Regulons Revealed with Gene Expression Data and
Studies on DNA Sequencing via Ion Conductance
A thesis presented
by
Frederick Phillip Roth
to
the Committee on Higher Degrees in Biophysics
in partial fulfillment of the requirements
for the degree of
Doctor of Philosophy
in the subject of
Biophysics
Harvard University
Cambridge, Massachusetts
May 1998
 1998 by Frederick Phillip Roth
I dedicate this thesis to my wife, Becca Marsh Roth,
who means more to me than any of it.
Table of Contents
Abstract
Acknowledgments
1
3
Chapter 1  Introduction
1-1
Chapter 2  Analyzing Affymetrix DNA microarrays
Overview of Affymetrix microarrays
Overview of data analysis
The GeneChip algorithm
Concerns with the GeneChip algorithm
An alternative method using median and median ratio
2-1
2-2
2-7
2-8
2-14
2-16
Chapter 3  Revealing regulons with transcript data and sequence alignment
Credits
Introduction
Results and Discussion
Whole genome expression monitoring
Sequence motifs found
False positive and false negative motifs
Candidate sets of co-regulated genes
Experimental protocol
3-1
3-2
3-3
3-4
3-4
3-9
3-19
3-23
3-34
Chapter 4  Prospects for DNA sequencing using ion conductance
Credits
Introduction
Results and Discussion
Modeling channel conductance
Conductance measurements of Shigella LamB and λ bacteriophage
Experimental Protocol
4-1
4-2
4-3
4-5
4-5
4-9
4-18
Appendix A  Guide to Software
Applications for analyzing Affymetrix microarray data
Applications for noncoding DNA sequences
A-1
A-2
A-8
Appendix B  Assessing Similarity between Intergenic DNA Motifs
B-1
Appendix C  Absolute and Relative Abundance of Detectable Transcipts of
Four S. cerevisiae Cultures, Ranked Alphabetically
C-1
Appendix D  ORFs Not Detected
ORFs not assayed by the Affymetrix microarrays used
Detection thresholds for each microarray experiment
D-1
D-2
D-3
ORFs assayed and not detected among any of four cultures
D-4
Appendix E  ORFs with the Highest Average Abundance
E-1
Appendix F  ORFs Most Changed in Abundance
In mating type α relative to mating type a strain
In mating type a relative to mating type α strain
In glucose-fed relative to galactose-fed culture
In galactose-fed relative to glucose-fed culture
In heat-shocked relative to 30 °C culture
In 30 °C relative to heat-shocked culture
F-1
F-4
F-6
F-8
F-10
F-12
F-14
Appendix G  Sizes of Intergenic Regions in S. cerevisiae,
E. coli and H. influenzae
Intergenic regions in S. cerevisiae
Intergenic regions in E. coli
Intergenic regions in H. influenzae
G-1
G-5
G-7
G-9
Abstract
The first part of this thesis contributes methods for the analysis of genome-scale
transcript abundance data using oligonucleotide microarrays (‘DNA chips’). This
technique can reveal the genes most responsive to environmental or genotypic change.
By searching for conserved elements among the upstream DNA sequences of these genes,
one can identify candidate regulatory elements and corresponding candidate sets of coregulated genes. This strategy was applied to three extensively studied regulatory systems
in the yeast Saccharomyces cerevisiae. Galactose-response data yielded the known
binding site of Gal4, and six of nine genes known to be induced by galactose, as well as
two ORFs that are good candidates for galactose regulation. Heat shock data yielded a set
of histone genes and CCA, a DNA element known to mediate cell-cycle dependent
activation. Mating type a and α-specificity data yielded most of the known a- and αspecific genes and all of the four relevant DNA elements. This work validates a rapid
approach for discovery of regulation mechanism and introduces ‘AlignACE’, a tool for
extracting conserved motifs from unaligned DNA sequence.
In the second part of the thesis, a novel method for sequencing single molecules of
DNA is proposed based on the hypothesis that DNA passing through a membranespanning channel can disrupt the flow of ions in a sequence-dependent fashion. The
method’s prospects are examined and an experimental system is suggested which uses
bacteriophage λ and the outer-membrane protein LamB from Shigella sonnei. To
characterize the components of this experimental system, the ion conductance through
single channels of Shigella LamB was measured to be 88 ± 5 picoSiemens (pS) and the
1
ion conductance through single channels associated with purified bacteriophage λ was
measured to be 2.1 ± 0.7 nS. The λ channels are present in the absence of LamB,
suggesting that bacteriophage λrather than its receptorprovides the channel used for
DNA transfer across the E. coli outer membrane.
2
Acknowledgments
For the work of finding motifs from expression data described in Chapter 1, I have
many people to thank. The direct and integral roles of Jason Hughes and Pete Estep are
described in more detail in the preface to Chapter 1. Our collaborators at
Affymetrixparticularly David Lockhart, Janet Warrington, Lisa Wodicka and Bob
Blalockmade this work possible and shared a preprint of their yeast expression analysis
article with us. George Church brought the Gibbs motif sampling algorithm to our
attention initially, and Andrew Neuwald provided the Gibbs motif sampling computer
code and advice in compiling it. Keith Robison brought DNA weight matrix methods
and their power to my attention. Nearly every member of our lab contributed to
conversations on how to analyze expression data from Affymetrix microarrays, but
particularly Jason Hughes, Pete Estep, Saeed Tavazoie, George Church, John Aach, Jason
Johnson, Martin Steffen and Tom Blackwell. Fred Winston and Aimee Dudley shared
their expertise in yeast biology, with which we had little previous experience. Saeed
Tavazoie suggested the use of clustering methods in the analysis of multiple gene
expression data sets, an idea which is mentioned but not explored in Chapter 1. Temple
Smith, Tom Schneider, and John Aach contributed to ideas on assessing similarity
between sets of aligned sites. Dereth Phillips, Martha Bulyk, Saeed Tavazoie, Mark
Johnston, Fred Winston, Temple Smith, Kevin Struhl, David Lockhart and Janet
Warrington were kind enough to critically review our manuscript.
For the work on a single molecule method for DNA sequencing, I am indebted to
many people. The central contributions of Richard Baldarelli and George Church are
3
described in detail in a preface to Chapter 2. Chuck Schultz aided Rich Baldarelli in
making a working apparatus for measuring small electrical currents on a picoampere
scale. Julie Gastier, Dereth Phillips, Martha Bulyk, Pete Estep were all laboratory rotation
students involved at one time on this or related projects and provided enthusiastic help
and advice. Pete Estep helped in developing a purification scheme for LamB porins.
James Chou did some exploratory work on modeling of ion conductance in transmembrane channels. Laura Richterich helped with figures used in earlier manuscript
versions. I am indebted to Magdalena Tosteson for her help with planar bilayer methods.
Jim Horn aided in design and constructed a Faraday cage and planar bilayer apparatus.
Martin Steffen shared his knowledge of density gradient centrifugation. John
Kasianowicz and Daniel Branton provided advice and collaboration. Howard Berg
helped with DNA thermal motion calculations. Cliff Christian and Axon Instruments
gave equipment and advice. John Greci and New England Biolabs generously supplied λ
bacteriophage.
Through my graduate career, Matt Temple, Kristen Landry, and Paul Johnson
have been invaluable in keeping things moving more smoothly than one could possibly
expect and were tolerant of ambushes as they walked into their offices.
Support for the work described in this thesis came from a variety of sources. The
National Science Foundation gave funding in the form of graduate fellowships for Jason
Hughes and myself. George Church was an investigator with the Howard Hughes
Medical Institute. Generous support came from the Department of Energy (grant # DEFG02-87-ER60565), Office of Naval Research (grant # N00014-97-1-0865), National
4
Institutes of Health (grant # HG000811) and Lipper Foundation. Use of an SGI Power
ChallengeArray was provided by the NCSA at the Univ. of Illinois at Urbana-Champaign.
Mary Beth Shertick, Abby Jacobs, Eva Marie Hylen and Bob Tanis have juggled
our finances with humor and grace, and kept me replete with toys. Terri Broderick put up
stoically with my tendency to ask for a FedEx package at exactly the last minute.
Members of the Church lab have been both good colleagues and good friends. In
particular, Dereth Phillips has been my neighbor leading a parallel existence, and is
always good for a spontaneous aria or a fierce hug. I owe Rich Baldarelli not only for
allowing me to join his project, but for late night pizzas and conversation, and for
dragging me out on a bike ride once in a while. Andy Link shared his knowledge of
molecular biology, his skills in tequila concoctions and his many ideals, and gave me my
first experience in thesis-writing. Pete Estep has been always willing to share his bagels
and his hot stock tips while challenging my every scientific assumption. Jason Johnson
and Martha Bulyk introduced me to the joys of ultimate frisbee, while Keith Robison,
Cory Kostrub, and Eugene Chang helped divert me with competitive hand-eye
coordination exercises. Saeed Tavazoie was always good for a pleasant conversation or a
physics lesson. Martin Steffen was a source of motivation and enthusiasm. Mark Poritz
gave lessons in bacteriology and in how to search for a job. Chris Harbison kept the
shouting to a minimum. It has been a pleasure working in the past year in the close
company of John Aach, Jason Hughes, Jason Johnson and Jong Park. They have been
remarkably patient with me. Ting Wu, an honorary member of the Church Lab, gave
praise and encouragment in some of my darkest moments in graduate school.
5
For what I have learned and accomplished in graduate school, thanks are due most
to my advisor, George Church, who is remarkable man in that he ranks among both the
kindest and most intelligent people I have ever known. George has created a chaotic
place filled with creative peoplea fantastic setting for thinking about science.
Meredith Wynne and Jim Hogle made me welcome in the Harvard Biophysics
program. Jim and Gina DeVivo (‘GB’) have continued to make this program great and
have always made time for helping and advising. Since arriving in graduate school, I’ve
become indebted in the friendship of Stephen Chan, Shashi Mathew, Eliza and Paresh
Shah, and Michelle Milne, Susan Alderman, Paul Diamond and Brian Gladstone. I thank
Dan Jay and Jack Szostak for welcoming me into their laboratories.
Mentors, teachers and role models prior to graduate school include Irene MacKay,
D. L. Smith, Barbara Woll, Craig Taylor, Richard Packard, Art Rosenfeld, Sumner Davis,
Jasper Rine, Kevin Hurley, Alex Nichols, Adrianus Kalmijn, and Robert Saul.
I thank my mother, Uta, who gave me the confidence to think I could play the
game of science, for knitting sweaters and sending cookies and calling often. I thank my
father, John, for being a role model who makes a career in science look both fun and easy.
He has given me good advice.
6
Chapter 1
An Introduction
1-1
The nature of an introduction encourages me to relate the two distinct parts of this
thesis to one another. If there is one theme to this thesis, it is that both parts were
motivated by a desire to develop more efficient methods in experimental molecular
biology. One might also say that the two parts are complementary, in that one method
uses DNA sequence information to develop hypotheses and guide experiments while the
other method seeks more DNA sequence information. However, since unifying these two
rather distinct topics seems contrived, I will treat them as the distinct subjects that they
are.
Revealing Regulons. The first chapter of this thesis describes a method for
developing hypotheses about the coordinate regulation of sets of genes, and the specific
mechanisms that might regulate them. The first step in the approach is to measure the
abundance of transcripts for every gene or putative gene in a genome (the yeast
Saccharomyces cerevisiae was examined for the present study) under two or more
conditions.
Recent technological developments have made the simultaneous quantitation of
many mRNA transcripts more tractable. Although, it has long been possible to measure
mRNA levels by a Northern blot assay1, scaling this approach up to thousands of genes is
quite impractical. Currently, there are two general approaches to the problem of mRNA
quantitationhybridization-based methods and counting methods.
Hybridization-based methods involve a surface with arrayed nucleic acid, either
oligonucleotides or larger gene fragments. These oligonucleotides or gene fragments are
deposited in a known arrangement and are generally of known sequence. The mRNA to
be quantitated is labeled fluorescently (or radioactively) and hybridized to the surface.
1-2
The level of fluorescence intensity (or radioactivity) is then used to infer the amount of
each transcript in the mRNA population. Hybridization-based methods can be
subclassified by the method used in producing the hybridization arrays. So-called
‘spotting methods’ produce DNAgenerally by PCRfor deposition and subsequent
cross-linking to the surface. This method was originally employed on the scale of
hundreds of genes by Chuang et al.2, has been further miniaturized and refined in the
laboratory of Patrick Brown 3-6, and is currently commercially available from Incyte
Pharmaceuticals and Molecular Dynamics, among others. In situ-synthesis methods
involve synthesis of oligonucleotides in place, i.e., directly onto the surface on which
hybridization will later occur. This method was developed by Affymetrix 7-9 and is also
currently commercially available.
Counting methods are based on the determination of RNA sequences sampled
randomly from the mRNA population to be quantitated. Sequence fragments of sufficient
length can be uniquely assigned to a transcript, so that relative abundance can be
calculated by simply counting the number of fragments obtained from each transcript.
One example of this approach is the ‘shotgun’ sequencing of expressed sequence tags,
assembly of these sequence fragments into contiguous sequences, and calculation of
abundance for each contiguous sequence based on the number fragments assigned to
each. Another example is the serial analysis of gene expression (SAGE) approach
developed by Velculescu et al. 10; 11, whereby very short sequence fragments are
subcloned on the basis of neighboring restriction sites. These fragments are then
concatenated and sequenced in a high-throughput manner. A third counting method has
been developed by Lynx and has been mentioned in print 12-14, although some details of
1-3
the method’s capabilities remain obscure. The approach requires the creation of many
beads, each bead containing many copies of a single DNA fragment isolated from an
mRNA population. The sequence corresponding to each bead is sequenced by a clever
process involving Type IIS restriction enzymes and sequence-dependent ligation of a
Type IIS restriction site-containing linker.
Once one of these methods has been applied to cells grown in two or more
conditions or to cells of two or more genotypes, relative transcript abundance in these
mRNA populations can be examined. A set of genes which are similar in relative
abundance are more likely to be coordinately regulated than a randomly chosen set of
genes. Although not discussed here, there has been recent work on quantitating protein
abundance on a whole-genome (or -proteome) scale. Finding a set of genes of similar
relative protein abundance is another approach to finding a set of coordinately regulated
genes. Whole-genome relative abundance approaches to finding a biologically interesting
set of genes are comparable and complementary to genetic approaches which might be
guided by isolation and identification of mutant genes. For example, a genetic approach
to the study of gene regulation of galactose response (in the absence of prior knowledge)
might be the isolation of mutants which will not grow in the presence of galactose,
separation of mutant strains into complementation groups, and subsequent cloning and
sequencing of the genes corresponding to complementation groups. The set of genes
which, when mutated, impair growth on galactose is a biologically interesting set of
genes.
Given a biologically interesting set of genes, we can ask if there is a subset of
these genes that has a common DNA element in their upstream non-coding regions. Such
1-4
a subset is likely to be further enriched for coordinately regulated genes. There are
several algorithms which have been previously developed for the purpose of finding
conserved elements in unaligned sequence data. A recent review by Frech et al. 15
compared the methods CONSENSUS, WCONSENSUS 16, Gibbs Site Sampling 17 and
Gibbs Motif Sampling 18, having found these to be the only algorithms that were readily
available, currently recommended by their inventors, and which did not rely heavily on
prior knowledge of the sought-after conserved element. A more recent method called
Multiple Expectation Maximization for Motif Elicitation (MEME) 19 has been developed
but has not been compared independently with other methods.
CONSENSUS and WCONSENSUS are based on a clustering algorithm for
multiple sequence alignment, wherein the starting point is a pairwise comparison of all
potentially conserved sites. The best-matching pairs are kept, and every possible
comparison with a third sequence is made and the best sets of three are kept. This
continues until one of several stopping criteria are met. A clustering algorithm is an
example of a greedy algorithm, discussed further below.
MEME is based on expectation maximization, which is another example of a
greedy algorithm. MEME chooses a number of starting estimates for the weight matrix
describing a set of aligned site, each starting estimate being derived from one of the sites
in the input set. Then, it calculates the probability that each site is a match to this matrix.
Next, it updates the matrix based on these probabilities, with the greatest contribution to
the weight matrix coming from the most probable sites. The preceding two steps are
repeated until a locally optimal solution is reached.
1-5
A greedy algorithm assumes that a locally optimal solution is part of the globally
optimal solution. In the case of CONSENSUS and WCONSENSUS this is the
assumption that the best pair of sites (or one of the best pairs) will be a part of the best set
of multiple aligned sites. In the case of MEME, it is the assumption that the globally
optimal weight matrix will be reached by locally optimizing weight matrices derived from
each site in the input set. That neither of these assumptions are necessarily true for subtle
sequence motifs is a disadvantage. However, greedy algorithms are quite efficient and
both CONSENSUS and MEME have had demonstrated success.
Gibbs Site Sampling and Gibbs Motif Sampling are both stochastic sampling
approaches, i.e., unlike the greedy algorithms described above they do not proceed
deterministically to a local optimum from a given starting point. The Gibbs sampling
algorithm is similar to an expectation maximization approach except that it has an
element of randomness, so that usuallybut not alwaysit proceeds toward an optimal
solution.
This allows the discovery of subtle sequence motifs, where the globally optimal
alignment may be difficult to find using a deterministic greedy algorithm. One might
think that this comes at some expense in efficiency for an exhaustive search, but Gibbs
Site Sampling performs comparably to CONSENSUS using approximate 10 times fewer
CPU cycles 15.
Once a conserved DNA element has been found and a hypothesis has been
generated that a set of genes is coordinately regulated, the hypothesis can guide
experiments for verifying the functional importance of the conserved DNA element.
Oligonucleotide-directed mutagenesis is a technique which allows one to make point
1-6
mutations at specific, desired locations. One can then assay for impaired gene regulation
in the mutated strain.
We can contrast this approach to cases where there are no guiding hypotheses
about the locations of regulatory DNA elements. There are two commonly used
approaches in this case, both called ‘promoter-bashing’ in the common parlance.
Promoter-bashing consists of creating many strains, each having a different mutation in
the upstream region of the gene of interest. Linker-scanning mutagenesis is one such
mutagenic approach where each strain has a different region deleted in its upstream
sequence. Deletion strains in which differential transcription of a gene has been
abolished can thus identify regions important to regulation. Smaller deletions are then
constructed until the critical region(s) has been narrowed to a few base pairs. Once the
size of the critical region(s) has been narrowed down sufficiently, oligonucleotidedirected mutagenesis can be used to make specific point mutations to determine the
critical bases of the DNA element. Another promoter-bashing approach is cassette
mutagenesis, wherein the upstream region is randomly point-mutagenized extensively and
then used to replace the upstream sequence in an unmutagenized strain, so that any
impairment of regulatory function can be attributed to mutations in this cassette region.
Mutant strains impaired for gene regulation are then sequenced to identify critical
regions. Both of the approaches described above are laborious, and would not be
preferred in cases where there exist strong hypotheses for the location of regulatory sites.
Little or nothing is known about the transcriptional (or post-transcriptional)
regulation of most S. cerevisiae genes, so that more efficient methods for developing and
testing hypotheses about gene regulation are needed.
1-7
Single-molecule DNA sequencing. The second chapter of this thesis is an
exploration of a method for sequencing single molecules of DNA that was first proposed
by George Church in 1989.
At the time of this proposal, it was generally accepted that a dramatically
improved method of DNA sequencing would be required to determine the sequence of the
entire human genome at reasonable cost within a reasonable period of time 20. Today’s
DNA sequencing technology of choice, Sanger dideoxy sequencing, was first described in
1977 21. Radioactivity-based detection has evolved into fluorescence-based detection,
different DNA polymerases have been employed and the method has become more
automated, but the underlying method remains essentially the same 22. Automation of the
multiple steps required for Sanger dideoxy sequencing and the need for significant
quantities of reagents contribute to the cost of this method. Methods which directly
determine the sequence of a single molecule of DNA have the potential to reduce these
costs significantly.
George Church’s proposal was based on the principle that DNA passing through a
transmembrane channel will impede ion flow through that channel. So, if each of the
four (possibly modified) nucleotides block the channel to a unique extent, then the DNA
can be sequenced by measuring ion conductance. George Church and Richard Baldarelli
began exploring this idea and settled on a biological system for effecting DNA transport
across a membranebacteriophage λ. Bacteriophage λ infects E. coli cells and is known
to require a membrane receptor, the bacterial LamB porin, in order to inject its DNA
1-8
across the E. coli membrane. It has not been shown whether bacteriophage λ creates its
own channel, or if it widens a pre-existing channel in the LamB pore.
That it is possible to measure ion current through a single molecular ‘hole’ in a
lipid membrane has been long established 23. Current blockages in single channels have
previously been observed, e.g., in the case of a protein-conducting channel in the
endoplasmic reticulum 24. More critical questions to the proposed method are: Can
nucleic acids be ‘threaded’ into a channel under suitable experimental conditions? Will
different nucleotides block channel conductance to measurably different extents? If not,
can modified nucleotides be used to achieve this aim? Will thermal diffusion of nucleic
acids cause back-and-forth motion on the scale of single bases that will be more rapid
than the time resolution in current measurement we are able to achieve?
Independently, another research group, consisting of David Deamer, Daniel
Branton, John Kasianowicz and Eric Brandin, hit upon the same idea of using ion
conductance to sequence nucleic acids. They decided to use S. aureus α-hemolysin, a
large channel which does not naturally transport nucleic acids, and use electrophoresis as
a means to drive the nucleic acid (either RNA or DNA in this case) through the channel
25.
I will briefly discuss the results of Kasianowicz et al. here, though since their
results were published after completion of the work described in Chapter 2, this
discussion might properly belong in an epilogue 25. When ion current through a single
channel of α-hemolysin was measured in the presence of poly(U) single-stranded RNA,
transient decreases of ion current were seen. These transient decreases were not seen in
the absence of poly(U), so these decreases were attributed to channel blockage by the
1-9
nucleic acid. This was confirmed by repeating the experiment with poly(U) ranging in
length from 150 to 450 nucleotides, and finding that the duration of channel blockage was
proportional to poly(U) sequence length. Recently, it was reported that the same group
was able to discern the difference between poly(A) and poly(C) by measuring ion
current26. Using an RNA sequence of 70 As followed by 30 Cs, it was found that
conductance changed during the transient decrease in ion current.
Apart from the proposed method of sequencing by ion conductance outlined in
Chapter 2 and the method of Kasianowicz et al. discussed above, proposals for singlemolecule sequencing fall into two categories. The first of these seeks to sequence DNA
directly using scanning tunneling microscopy (STM). STM is a technique which uses a
conductive probe to scan a surface. When the probe is in contact with the surface, there is
a measurable electric current due to electrons ‘tunneling’ through the surface. If the
probe is moved up and down so that the tunneling current remains constant, and the
height of the probe is known, a topographical map of the surface can be constructed.
Double-stranded DNA has been imaged by STM in aqueous solution with high enough
resolution to resolve helical pitch 27. Subsequently, individual adenine bases were
resolved in single-stranded poly(dA), lending credence to the idea that DNA might be
sequenced 28. Since that time, there has been little reported progress towards sequencing
DNA directly by STM. In 1994, a related proposal was made to cleave surface-deposited
DNA at specific positions using incorporation of 32P, and sequence by measuring the
lengths of cleaved fragments using STM 29. To date, no DNA sequencing by STM
methods has been reported.
1-10
The second category of single-molecule DNA sequencing relies on the
fluorescence-based detection of single-molecules in a flowing solution. It also requires
that a DNA or RNA polymerase faithfully incorporate and extend from nucleotides that
have been modified to be fluorescent. A single-stranded nucleic acid, having each of its
four bases modified with one of four spectrally distinct fluorophores, is attached to a solid
support. Fluid is passes across this solid support, with the flow leading to a sensitive
fluorescence detector. A 3’→5’ exonuclease is used to remove bases sequentially from
one end, and as the fluorescent bases are removed they are carried past the detector 30.
The sequence of the four different fluorescent bases moving past the detector will then
correspond to the nucleic acid sequence.
Single-molecule fluorescence detection has been accomplished in a flow system
using the fluorescent dye rhodamine-6G, with about 85% of molecules in the flow being
detected 30. Incorporation and extension of fluorescently labeled nucleotides has been
accomplished, but low efficiency incorporation of modified nucleotides remains a
technical problem 31. No DNA sequence has yet been determined using this method.
In 1995, sequencing of the human genome began on a production scale using the
conventional Sanger dideoxy method 22. Incremental improvements in this method had
made it possible to consider using this approach to complete the genome. At the same
time, however, it was noted that uses for DNA sequencing would not end with
completion of an individual human genome. Improved DNA sequencing would lead to
improved methods for measuring mRNA expression levels, using the counting methods
like the SAGE approach described above. Increased interest in genetic variation among
1-11
humans, and in genomes in all branches of life guarantees continued interest in
revolutionary approaches to DNA sequencing.
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Lawrence, C.E., Altschul, S.F., Boguski, M.S., Liu, J.S., Neuwald, A.F. and
Wootton, J.C., Detecting subtle sequence signals: a Gibbs sampling strategy for multiple
alignment, Science, 262(5131), 208-214, 1993.
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Neuwald, A.F., Liu, J.S. and Lawrence, C.E., Gibbs motif sampling: detection
of bacterial outer membrane protein repeats, Protein Science, 4(8), 1618-1632, 1995.
19.
Bailey, T.L. and Elkan, C., Unsupervised learning of multiple motifs in
biopolymers using expectation maximization, Machine Learning Journal, 21, 51-83,
1995.
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Olson, M.V., The human genome project. [Review] [80 refs], Proceedings of the
National Academy of Sciences of the United States of America, 90(10), 4338-44, 1993.
21.
Sanger, F., Nicklen, S. and Coulson, A.R., DNA sequencing with chain-
terminating inhibitors, Proceedings of the National Academy of Sciences of the United
States of America, 74(12), 5463-7, 1977.
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Olson, M.V., A time to sequence, Science, 270(5235), 394-6, 1995.
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Bean, R.C., Shepherd, W.C., Chan, H. and Eichner, J., Discrete conductance
fluctuations in lipid bilayer protein membranes, J. Gen. Physiol., 53(6), 741-757, 1969.
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Simon, S.M. and Blobel, G., A protein-conducting channel in the endoplasmic
reticulum, Cell, 65(3), 371-380, 1991.
25.
Kasianowicz, J.J., Brandin, E., Branton, D. and Deamer, D.W.,
Characterization of individual polynucleotide molecules using a membrane channel,
Proc. Natl. Acad. Sci. USA, 93, 13770-13773, 1996.
26.
Zacks, R., Hole in the wall offers cheaper sequencing, Technology
Review(May/June), 26, 1998.
27.
Lindsay, S.M. and Barris, B., Images of the DNA double helix in water,
Science, 244, 1063-1064, 1989.
28.
Dunlap, D.D. and Bustamante, C., Images of single-stranded nucleic acids by
scanning tunnelling microscopy, Nature, 342, 204-206, 1989.
29.
Kelson, I. and Nussinov, S., A scheme for sequencing large DNA molecules by
identifying local nuclear-induced effects, Proceedings of the National Academy of
Sciences of the United States of America, 91(15), 6963-6, 1994.
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Harding, J.D. and Keller, R.A., Single-molecule detection as an approach to
rapid DNA sequencing. [Review] [17 refs], Trends In Biotechnology, 10(1-2), 55-7,
1992.
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Zhu, Z. and Waggoner, A.S., Molecular mechanism controlling the
incorporation of fluorescent nucleotides into DNA by PCR, Cytometry, 28(3), 206-11,
1997.
1-15
Chapter 2
Analyzing Affymetrix DNA Microarrays
There were many, often intense, discussions among members of our laboratory on
alternative ways to analyze fluorescence intensity datathe primary data from
Affymetrix DNA microarrays (‘chips’). It was during these discussions that my thoughts
on chip data analysis became more clear. In this chapter, I will first describe the physical
characteristics of Affymetrix chips, making liberal use of excerpts from several papers on
the subject 1-2. I will discuss the analysis algorithms used by Affymetrix and also our
motivations for developing an alternative method. Finally, I will describe the method of
analysis outlined in Chapter 1 in greater detail and describe limitations and future
possibilities.
High-density synthetic oligonucleotide arrays. Synthetic oligonucleotide arrays
have been used to quantitate transcript abundance in mammalian mRNA populations 3
and more recently in yeast mRNA populations 1. Synthetic oligonucleotide arrays are
essentially glass slides with oligonucleotides attached at the surface. Through the use of
photolithographic masking it is possible to synthesize these oligonucleotides in situ,
allowing for the creation of defined regions on the surface (also called ‘features’) which
contain oligonucleotides of a single desired sequence (see Fig. 1).
2-2
hν
mas k 1
X
X
X
X
X
O
O
O
O
O
HO H O
X
X
X
O
O
O
photodeprotection
A- X
X
X
X
X
X
A
A
O
O
O
chemical
coupling
hν
mas k 2
X
X
X
X
X
A
A
O
O
O
C- X
X
X
X
X
X
A
A
C
C
O
C
A
T
A
T
A
G
C
T
G
A
A
C
C
G
repeat
Figure 1. Light-directed synthesis of oligonucleotides. A surface bearing photoprotected
hydroxyls (X-O) is illuminated through a photolithographic mask (‘mask 1’), generating
free hydroxyl groups in the photodeprotected region. The hydroxyl groups are then
coupled to a deoxynucleoside phosphoramidite (5’-photoprotected). A new mask pattern
(‘mask 2’) is applied, and a second photoprotected phosphoramidite is coupled. Rounds
of illumination and coupling are repeated until the desired set of products is obtained.
This figure legend was excerpted from ref. 2 and the figure was adapted from the same
source by Martha L. Bulyk.
2-3
The oligonucleotide arrays used to monitor gene expression in Saccharomyces
cerevisiae measure 1.28 × 1.28 cm and contain more than 65,000 50 × 50 µm synthesis
‘features’. Each synthesis feature consists of more than 107 copies of a particular 25-mer
oligonucleotide. The full set of oligonucleotide probes covering all open reading frames
(ORFs) are divided among four different arrays, comprising a total area of approximately
one square inch for the entire yeast genome. For each ORF, approximately 20
complementary 25-mers were chosen using selection criteria which have not been
publicly revealed by Affymetrix, but which include tests for sequence uniqueness relative
to the rest of the genome and the absence of sequence features (e.g., self-complementarity
or clusters of single nucleotides) that have been determined to adversely affect
hybridization on arrays.
Use of multiple oligonucleotides for each ORF provides redundancy in the
detection and analysis of the data and mitigates the potentially confounding effects of
occasional cross-hybridization. For each of the complementary 25-mers (called ‘PM’s,
for ‘perfect matches’) there is a closely related 25-mer which differs by only one base
(called an ‘MM’ for ‘mismatch’) at the central position. The MM probe of each pair
serves as an internal control that allows consistent hybridization to be recognized (a PM
signal larger than the corresponding MM signal). The difference between the PM and
MM intensities of a probe pair will also be referred to as ∆. Both of the algorithms
discussed here are based on the difference of PM and MM partners, so that when the
differences of several ‘probe pairs’ (a PM and its corresponding MM) are aggregated,
cross-hybridization and background hybridization tends to cancel. Specific hybridization
2-4
signals, on the other hand, tend to add constructively across the set of probe pairs for each
gene.
The chips are read out by hybridizing fluorescently labeled cDNA or ‘cRNA’
(produced from cDNA by reverse transcription) to the chip. Fluorescence intensity is
quantitated by a scanning confocal microscope. This fluorescence intensity data is the
primary data which must be interpreted to give the relative and/or absolute abundance of
a transcript.
2-5
A.
B.
Figure 2. Fluorescence intensity images from an Affymetrix S. cerevisiae expression
microarray. (A) contains the complete image of a yeast ‘A’ chip (the first of a set of 4
chips). The image was obtained from a chip which was hybridized with cRNA which
was biotinylated and conjugated to phycoerythrin. The RNA was isolated from a culture
grown in the presence of galactose, labeled and hybridized as descibed in Chapter 1. (B)
is an enlargement of part of the chip shown in (A). In this image, a clustering of intense
features can be seen within rows. These clusters are generally sets of PM probes derived
from one ORF, while the corresponding MM probes are located in the next lowest row.
2-6
Overview of microarray fluorescence intensity data analysis. Analysis of
fluorescence intensity data may be divided into four distinct steps:
1) Obtain feature intensities. Assign an intensity value to each feature on the
chip. In Fig. 1A, a checkerboard pattern of intensity can be seen around the perimeter of
the chip. Each of the intense features in this pattern is complementary to a fluorescently
labeled control DNA sequence which has been added to the chip along with the labeled
DNA or RNA to be examined. The checkerboard pattern aids the GeneChip software in
its placement of a deformable grid over the intensity image, so that regions of intensity
can be mapped to coordinates on the chip.
2) Subtract Background. Calculate and subtract background intensity from
each feature. This step is employed in the methods used by both Affymetrix and myself,
but is not essential to every method of analysis that might be envisioned, since MM
features serve as an additional ‘background’ subtraction.
3) Normalize. Normalize feature intensity between chips within an experiment,
and between experiments. Since the efficiency of mRNA isolation, labeling, and
hybridization can vary from experiment to experiment, and the amount of in situsynthesized oligonucleotide can vary considerably from chip to chip, normalization is an
important step.
4) Calculate ORF abundance. First, group the feature intensities into sets of
PM and MM intensities so that each correspond to a given gene or ORF, using the
knowledge of the oligonucleotide sequence that corresponds to each feature coordinate on
the chip. Then, use the set of background-subtracted, normalized, PM and MM features
2-7
for a given ORF to determine either a) the ORF’s absolute transcript abundance or b) its
abundance relative to another growth condition.
5) Establish a measure of confidence. Features with pixel intensities that are
less variable should be more reliable. Feature sets that have more features, are less
variable, or that are more easily distinguished from background are also likely to yield a
more reliable measurement.
The GeneChip algorithm for interpreting fluorescence intensity. Here I describe
the algorithm used by the Affymetrix GeneChip software. Past versions of the algorithm
is known to me by personal communication, while the current version is as described in
the help files of GeneChip 3.0, unless otherwise noted. I should mention that changes
have been made in successive versions of the GeneChip software, so there is no
guarantee the algorithm is the same as in previous versions of GeneChip, nor that it will
be unchanged in future versions. My chief purpose in describing the GeneChip algorithm
is to put the new method of data analysis in the context of an alternative method.
1) Obtain feature intensities. After the perimeter checkerboard is used to map a
grid onto the features, a set of pixels is associated with each feature. The pixels near the
edges of the feature are discarded, and a clustering algorithm is used to find a region of
intense pixels among those remaining. The average pixel intensity of this region is then
assigned to the feature. Details of this procedure have been unavailable to the general
public, but I have been told more recently that the GeneChip 3.0 software has been
altered so that, instead of choosing a cluster of intense pixels, the 75th percentile pixel
intensity is assigned to the feature after discarding pixels near the feature edge.
2-8
2) Subtract Background. The total chip area is divided into sectors (with 16 as
a default number of elements in a sector). The background is then calculated
independently for the features in each sector by averaging the lowest N (80 is the default
value for N) feature intensities in that sector.
3) Normalize. One of three different methods of normalization can be used, at
the user’s discretion: a) Normalize using selected genes. Typically the genes selected
for normalization are transcripts not naturally present in yeast, e.g., transcripts from E.
coli, that have been ‘spiked’ at known concentration into the hybridization mixture. This
method is best for normalizing between different chips that have been exposed to the
same hybridization mixture. This method can also be the best approach for normalizing
between different preparations of hybridization mixture if the bacterial transcripts are
‘spiked’ into the nucleic acid preparation at an earlier step. If spiking occurs before total
RNA is purified from cell lysate, variation in efficiencies of RNA isolation, mRNA,
cDNA and cRNA production can be normalized. b) Normalize with user-defined
constant. The user specifies the normalization factor to the GeneChip software. c)
Normalize using the total intensity of all genes on the array. Although the exact
procedure for doing this was not known to me at the time I developed our analysis
method, I have since been told that this is done by dividing each feature intensity by the
sum of PM − MM, i.e., the sum of ∆, for all probe pairs.
4) Calculate ORF abundance. a) An ORF’s absolute abundance is calculated
by taking the average of ∆ for that ORF. For ORFs with few probe pairs (≤8), no
measures are taken to lessen the impact of outliers (surprisingly high or low values of ∆).
For ORFs with ~20 probe pairs, a so-called ‘Olympic scoring’ method is employed
2-9
wherein the highest and lowest ∆ values are discarded before calculating the average of
∆. For ORFs with ~50 probe pairs, so-called ‘super-Olympic’ scoring is used, wherein
first the highest and lowest ∆ values are discarded, and then those ∆ values more than
three standard deviations from the resulting mean are discarded, and abundance is taken
to be the mean of the remaining ∆ values. b) To calculate abundance of an ORF relative
to another growth condition, i.e., fold change, the absolute abundance is calculated in
each case using the method described in (a), and fold change is simply calculated as the
ratio of these two absolute abundances. In the case of abundance calculation, there is a
heuristic method (described below) for determining whether a transcript is ‘present’ or
‘absent’. If the transcript is deemed absent, the abundance value calculated above is not
reported. Similarly for fold change calculations, there is a heuristic method for
determining if there is ‘no change’ in abundance, in which case the calculated value for
fold change is not reported. If a transcript is deemed ‘present’ in one condition and
‘absent’ in the other, the lower transcript is set to 20 for the purposes of calculating an
approximate fold change value.
5) Establish a measure of confidence. At this point, the GeneChip software
does not provide a numeric measure of confidence, e.g., a 95% confidence interval for
abundance measurements. However, GeneChip does use a heuristic method for declaring
a transcript to be either ‘present’, ‘marginal’ or ‘absent’ among the pool of transcripts
being assayed, although there is no measure of what the upper or lower limits of that
transcript’s abundance might be, or with what confidence this decision was made. The
presence, absence or marginality of a transcipt is determined by some unknown
combination of three measures: a) The average of log(PM/MM) for a given transcript.
2-10
This is a measure of how different the pattern of probe intensities is from random. An
average log(PM/MM) of 0 would indicate perfectly random cross-hybridization. The
GeneChip user is able to set ‘marginal’ or ‘present’ thresholds for this value. b) The
ratio of the number of ‘positive’ probe pairs to the total number of probe pairs. A
‘positive’ probe pair is defined as one for which both ∆ and PM/MM are greater than
user-defined thresholds (called ‘SDT’ and ‘SRT’, respectively). c) The ratio of number
of ‘positive’ to number of ‘negative’ probe pairs. ‘Positive’ is defined as above, while a
‘negative’ probe pair is one for which −∆ and MM/PM exceed those same user-defined
thresholds employed in defining ‘positive’.
For measurements of expression change between two conditions, ‘fold change’ is
calculated as the ratio of abundances (as calculated above) in each condition. As a nonquantitative measure of confidence a transcript is called ‘increased’ (I), ‘decreased’ (D),
‘increased moderately’ (MI), ‘decreased moderately’ (MD), or ‘not changed’ (NC).
These determinations are made heuristically. There is also a measure called ‘Sig’ (short
for significance) associated with each fold change value, using an empirical combination
of ‘fold change’ and the absolute difference in abundance.
For ratios of transcript abundance, the determination of ‘NC’, ‘I’, ‘D’, ‘MI’, or
‘MD’ is made using an unknown combination of the following five measures: a) The
ratio of the number of probe pairs ‘increased’ to the number of probe pairs ‘decreased’.
A probe pair is considered ‘increased’ if (∆experiment−∆baseline) is greater than a threshold
‘CT’, and (∆experiment−∆baseline)/∆baseline is greater than a threshold ‘PCT’. A probe pair is
considered ‘decreased’ if (∆baseline−∆experiment) is greater than a threshold ‘CT’, and
(∆baseline−∆experiment)/∆baseline is greater than a threshold ‘PCT’. b) The fraction of probe
2-11
pairs that are ‘increased’, according to the above definition. c) The fraction of probe
pairs that are ‘decreased’, according to the above definition. d) The difference in the ratio
of the number of ‘positive’-scoring probe pairs to the number of ‘negative’-scoring probe
pairs, i.e., (#Pos/#Neg)experiment − (#Pos/#Neg)baseline. e) The difference in average log
ratio for the set of probe pairs, i.e., avg{log(PM/MM)}experiment −
avg{log(PM/MM)}baseline. The exact method by which the ‘NC’, ‘I’, ‘D’, ‘MI’, and ‘MD’
calls are determined from the above measures has not been revealed to us.
With each fold change value, there is an associated measure of change in
abundance called ‘Sig’. Although the name implies a measure of significance, it is not.
It is an empirical formula combining difference in absolute fold change with the ratio of
fold change, for ranking purposes. The formula is as follows:
(
Sig = 10 (x−4 3) ⋅ avg∆expt - avg∆ base ⋅ log10 avg∆expt avg∆base
)
where avg∆ is the mean of the ∆ values for a given ORF for a given condition and
x=
max(20, avg∆ expt ) − max(20, avg∆ base)
max(20, avg∆ expt ) + max(20, avg∆ base) + 1
.
The preceding equation is heuristic and, although it may prove useful in ranking
transcripts, has no direct connection that I can find with probability or significance of
results.
Success of the GeneChip algorithm. Wodicka et al. have applied the GeneChip
algorithm to chip data derived from S. cerevisiae cultures grown in both rich and minimal
media 1, with great success. These assays were shown to be largely reproducible: The
2-12
same RNA sample (from rich media) was hybridized to different chip sets from the same
production lot, and of 6200 probe sets, only 14 showed a difference in abundance of more
than two-fold between hybridizations while only two showed differences greater than
three-fold. When independent preparations of labeled RNA from the same pellet of yeast
cells were hybridized, 74 probe sets changed by more than two-fold, and six showed a
greater than three-fold difference. Estimates of gene abundance from the GeneChip
analysis reportedly agreed well for all but one of the genes for which absolute abundance
had been measured in a previous study 4, although details of this agreement were not
presented 1.
Concerns with the GeneChip algorithm. In Chapter 1, an alternative data analysis
algorithm to the GeneChip algorithm above was presented. There were several
motivations for developing an alternative approach. The first is simply that some aspects
of the GeneChip algorithm are confidential, and it seems reasonable for one to know how
one’s data is being analyzed. A second, related, concern is that this algorithm has
changed over time in subsequent versions of the GeneChip software in ways that may or
may not have been shared with the public. Data analysis should be reproducible, and this
is not necessarily the case if the GeneChip software is used and later upgraded.
Another concern is that the approachs used by the GeneChip algorithm use a
number of parameters (thirty in GeneChip 3.0) set at the user’s discretion. The default
parameters used by GeneChip have reportedly been optimized by Affymetrix through a
series of spiking experiment wherein several known amounts of transcripts are ‘spiked’
into a hybridization pool, and also through repeated hybridizations to determine the
2-13
algorithm’s robustness to variation 1. However, we have no information about how these
parameters should vary depending upon the quality of the chip and nature of the
hybridization. This was a key point for us, since the first DNA chips we had to work
with had failed Affymetrix’s quality control procedure, so that it was entirely possible
that the algorithm parameters should be changed. For example, in the case where a
transcript called absent, the detection threshold, i.e., the ‘SDT’ threshold above, was set
to a value of 20. The default detection threshold then does not depend on the variance of
the data. Since the chips we had failed the Affymetrix quality control criteria due to
overall signal intensity, we expected that our detection threshold should be
correspondingly higher.
We also had some concerns about how the GeneChip method deals with outliers.
We and Affymetrix agree, I think, that the data acquired via Affymetrix chips contain a
substantial amount of unavoidable ‘contamination’ due to cross-hybridization and
variability in hybridization between probes of differing DNA sequence. Even in cases
where there is no cross-hybridization, variable binding energy (due to differences in GC
content) or secondary structure within a transcript can cause large differences in ∆, even
within a single transcript. The effect of data contamination should only increase with the
use of lower quality chips. So, even if the GeneChip parameters have been optimized for
most chips, they may not have been appropriate for ours. The GeneChip approach to
outlier detection was to toss the high and low ∆ values, and then remove those ∆ values
more than three standard deviations from the resulting mean. If we encounter more than
one high or one low outlier, we should use a method which can handle this occurrence.
Ideally, a method of outlier detection should be informed by a knowledge of the
2-14
distribution underlying ∆ values. Unfortunately, this distribution may be different for
every transcript, since each transcript has probe pairs of different sequence. Many of the
transcripts we analyzed have an asymmetric distribution of ∆ values, i.e., the median of ∆
values is consistently lower than the mean of ∆ values across the four conditions we
measured. If this is the case, it is inappropriate to apply a symmetric outlier detection
scheme since the distribution of ∆ is asymmetric. An alternative to outlier detection is to
use statistics that are robust to outliers, e.g., the median as opposed to the mean.
A further concern stemmed from my objection that one of the measures used in
deciding whether a transcript is ‘increased’ or ‘not changed’ between two conditions is
inappropriate. The measure (∆experiment−∆baseline)/∆baseline depends on which of two
conditions is considered the experimental condition and which is considered the baseline.
It is then possible for a transcript to be considered ‘not changed’ with one choice of
baseline, and ‘increased’ with the alternative choice. A representative of Affymetrix has
recently informed me (20 April 1998) that the above formula is no longer used in
GeneChip, but the literature distributed to users was not updated and unfortunately the
formula in actual use is considered confidential until further notice. This highlights the
potential danger of not being able to reproduce data analysis.
Median ∆ and median ∆-ratio algorithms for interpreting fluorescence data.
Although there are minor differences in the way that I performed background subtraction
and normalization in Chapter 1, I would not argue that the methods I used here were
significantly different or superior. Our methods for dealing with background and
normalization were developed without knowing the methods used by the GeneChip
2-15
software. With present knowledge, I would choose GeneChip’s methods for background
subtraction, and am ambivalent about the method of normalization. The GeneChip
method for background subtraction is superior to the method that I used in that it
accounts for variation in background levels across the chip, while the method I described
in Chapter 1 does not.
An alternative to GeneChip’s method of calculating transcript abundance is use of
the median as a measure of central tendency of ∆ values. The median is a measure of
central tendency that is robust to outliers. Use of a robust statistic seems preferable in a
case where the underlying distribution of ∆ has not been characterized. A related
measure of variance can then be usedmedian deviation. Median deviation is calculated
in the following way: median deviation = median{ med∆ − ∆1, med∆ − ∆2, . . . , med∆ −
∆n }, where med∆ = median{∆1,∆2, . . . ,∆n}. This method was not described in Chapter
1, since only relative abundance was used for that work.
An alternative to the GeneChip method of calculating relative abundance (also
described in Chapter 1) is the median ∆-ratio method. Using this method, relative
abundance is calculated in the following way: median {(∆1,expt / ∆1,base), (∆2,expt / ∆2,base),
(∆3,expt / ∆3,base), . . . , (∆n,expt / ∆n,base) }. This method has the advantage that variance
associated with the sequence differences of different probes is eliminated. When
absolute abundance is calculated for a given condition, individual probe intensities will
vary because of the sequence-dependence of binding energy, secondary structure and
hybridization kinetics. If the sequence in the transcript complementary to the probe has a
propensity to form secondary structure, this will also create probe-specific variation in
measured intensity. The sequence-dependence of intensity will create a large variance in
2-16
∆ intensities, which will be reflected in the ratio of two absolute abundances. The ∆-ratio
for a probe pair of given sequence is a less sequence-dependent measure than ∆. The
central tendency (I used the median) of these ∆-ratios is then a good representation of
ratio of abundance between conditions. An estimate of error in this number reflects
primarily uncertainty in the abundance ratio, rather than sequence-dependent variation in
hybridization kinetics.
An estimate of error in the ratio of abundance could be calculated by using the
median deviation of ∆-ratios, but since ∆-ratios are ratios, it is perhaps better to estimate
central tendency using the median of log-ratios and measure the error in this number by
measuring the median deviation of log-ratios, so that:

∆1,expt
∆ 2,expt
∆ 3,expt
∆ n,expt 
, log
, log
, ..., log

M = median log

∆1,base
∆ 2,base
∆ 3,base
∆ n,base 


∆1,expt
∆ 2,expt
∆ 3,expt
∆ n,expt
E = median  log
− M , log
− M , log
− M , ..., log
−M
∆ 1,base
∆ 2,base
∆ 3,base
∆ n,base


where M is the median of log(∆-ratios) and E is an estimate of error in this number.
The methods described here of calculating absolute and relative abundance have
the advantages that they are simpler, and allow for an estimate of error. What the user of
chip data would really like is a confidence interval for abundance and relative abundance,
i.e., a range of values and a statement that the true value lies within that range with a
confidence. Unfortunately, a supportable method for assigning confidence intervals to
this data does not exist. To assign a confidence interval, one should first obtain an
understanding of the underlying distribution of ∆ values for each ORF (or the underlying
distribution of ∆ ratios). This will almost be certainly done empirically, with data sets
that are not available to us at present. Several types of experiments will be required for
2-17
this purpose. To characterize the cross-hybridization of a transcript to all probes on a
chip, one might label and hybridize each probe alone to the chip. This would require
about 24,000 experiments (6,000 genes × four chips), so one might envision hybridizing
with pools containing a small number of labeled transcripts to reduce the number of
required hybridizations. One caveat to this already arduous experiment is that differential
mRNA degradation, differential transcription initiation or termination sites, and
differential splicing may make the total number of possible transcripts much greater than
6,000.
Neglecting cross-hybridization, the distribution of ∆ could be found by simply
hybridizing labeled genomic DNA to a chip, since the relative amount of ‘transcript’ is
the same for each ORF being assayed. To determine the relationship of ∆ ratios to the
true ratio of transcript abundance, one could hybridize with different mixtures each
‘spiked’ with known amounts of one or more transcripts.
2-18
References
1.
Wodicka, L., Dong, H., Mittmann, M., Ho, M.-H. and Lockhart, D.J.,
Genome-wide expression monitoring in Saccharomyces cerevisiae, Nature
Biotechnology, 15(13), 1359-1366, 1997.
2.
Pease, A.C., Solas, D., Sullivan, E.J., Cronin, M.T., Holmes, C.P. and Fodor,
S.P., Light-generated oligonucleotide arrays for rapid DNA sequence analysis,
Proceedings of the National Academy of Sciences of the United States of America,
91(11), 5022-6, 1994.
3.
Lockhart, D.J., Dong, H.L., Byrne, M.C., Follettie, M.T., Gallo, M.V., Chee,
M.S., Mittmann, M., Wang, C.W., Kobayashi, M., Horton, H. and Brown, E.L.,
Expression monitoring by hybridization to high-density oligonucleotide arrays, Nature
Biotechnology, 14(13), 1675-1680, 1996.
4.
Iyer, V. and Struhl, K., Absolute mRNA levels and transcription initiation rates
in Saccharomyces cerevisiae., Proceedings of the National Academy of Sciences of the
United States of America, 93, 5208-5212, 1996.
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Chapter 3
Revealing Regulons Using Transcript Abundance Data
and Upstream Sequence Alignment
Allocating Credit among Co-authors
Since the following chapter represents more than one person’s efforts, it seems
appropriate to a doctoral thesis that I describe which parts were my own work.
Contributions made by those who were not coauthors are creditedI sincerely hope
adequatelyelsewhere in the acknowledgments. The central concept of searching for
conserved upstream elements among genes chosen by expression analysis originated
jointly with Jason Hughes and myself. The work of growing cultures, isolating and
labeling RNA, and performing microarray hybridization experiments was performed
entirely by Preston Estep. The tools for data analysis were developed collaboratively by
Jason Hughes and myself, but our contributions are separable. Jason’s focus was on
rewriting the computer code for AlignACE, and implementing the changes that we made
from the original Gibbs motif sampling algorithm. Design and implementation of the
algorithms for analyzing data from Affymetrix microarrays and for assessing similarity
between two sets of aligned sites were primarily my own. I wrote the computer code used
for retrieving upstream DNA sequence for given ORFs, scoring motifs discovered by
AlignACE against the yeast genome by the Berg and von Hippel method, integrating site
locations with expression data, and for calculating consensus sequences by the method of
Day and McMorris. I applied the above-described tools to the galactose, heat shock and
mating type data sets, and assessed false negatives and the expected number of false
positives.
3-2
Complete DNA sequence is now known for more than ten different organisms 1.
For even the most intensely studied of these organisms, a large fraction of genes is
completely uncharacterized — about 40% and 50% for Escherichia coli and
Saccharomyces cerevisiae, respectively 2; 3. Furthermore, annotation of non-coding
regions has typically lagged behind discovery and prediction of gene function. Given that
sequence elements in non-coding regions often control gene expression, and that knowing
a gene’s place in the larger regulatory network of a cell is essential to understanding its
function, it is critical that we develop methods for rapidly characterizing non-coding
regions.
A common approach to the discovery of regulatory elements entails the
construction of a series of deletions or replacements in the 5’ untranslated region (UTR)
sequence of a gene, followed by a screen for altered regulation. An efficient method for
predicting the most likely locations of regulatory sequences can guide experiments more
quickly to the sought-after elements. Where there is a set of genes ‘enriched’ for coregulated members (obtained for example by genetic evidence), this prediction can be
based on sequence conservation among the upstream regions of several genes 4.
Recently, it has become possible to measure the abundance of mRNA transcripts
on a whole-genome scale 5-9. By comparing transcript levels in different conditions (or
different strains), we can find the set of genes whose transcript levels respond to a
difference in environment (or genotype). With this set of genes in hand, a number of
questions naturally arise: Which of these changes in expression constitute a primary
response to an environmental change, and which are indirect effects? Which are most
3-3
critical for adaptation to a new condition? By what mechanisms are changes in transcript
abundance achieved? What DNA (or RNA) sequence elements mediate the regulation of
transcript abundance?
Given a set of induced (or repressed) genes, one can use a computational
algorithm to search the regions upstream of translation start for short conserved DNA
sequence motifs. Such a conserved motif is a good candidate for a transcriptional control
element. Although they have been less extensively studied, sequence elements in the 5’
UTR may also be determinants of mRNA stability 10; 11. It has also been suggested that
long conserved sequences in the 5’ UTR are candidate sites for regulation by antisense
transcripts 12. Regardless of mechanism, a set of genes with similar expression responses
that also share a conserved upstream motif is a candidate for a set of co-regulated genes,
i.e., a regulon.
Results and Discussion
Whole genome expression monitoring. To test our strategy of combined expression
analysis and upstream sequence alignment, we examined three transcriptionally-regulated
systems in the yeast S. cerevisiae: galactose utilization, heat shock response, and mating
type regulation. We measured mRNA transcript abundances in S. cerevisiae in each of
four different cultures, which allowed three whole-genome comparisons to be made: 1)
growth on galactose vs. glucose; 2) strains of mating type a vs. mating type α and 3)
growth at 30 °C continuously vs. after a 39 °C heat shock.
Expression was measured for each of these three systems using
photolithographically synthesized oligonucleotide microarrays (‘chips’) 7; 9. Change in
3-4
transcript abundance for each open reading frame (ORF) was calculated for each
comparison described above by a variation on a previously described method (see
Protocols). Fig. 1 shows the distribution of change in expression for each of the three
systems. Complete data sets are available, including ranked lists of those ORFs that were
most changed between each pair of conditions 13.
3-5
3-6
Figure 1. Histograms of log ratio of expression level in each of three whole-genome
expression comparisons. (A) reflects the comparison between growth in galactose vs.
glucose, with transcripts more abundant in galactose having a higher log ratio. (B)
reflects the comparison of heat shock vs. 30 °C, with transcripts increased under heat
shock conditions having a higher log ratio. (C) reflects the comparison of mating type α
with a, where transcripts more abundant in mating type α have a higher log ratio.
Transcripts with low measured abundance in both conditions were assigned a log ratio
value of 1 for the purposes of this figure. The fraction of all ORFs in the yeast genome
which were below detection threshold in both conditions was 70%, 62% and 68% for
figures (A), (B) and (C) respectively.
3-7
Examining upstream non-coding DNA sequence. For each of the whole-genome
expression comparisons described above, we examined sets of upstream DNA sequences
from 1) the top ten ORFs, as ranked by ratio of first-condition to second-condition
abundance, e.g., ratio of galactose to glucose expression, 2) the top ten ORFs, as ranked
by ratio of second-condition to first-condition abundance, e.g., ratio of glucose to
galactose expression, and 3) the combination of the two preceding ORF sets. Upstream
DNA sequence for each ORF was bounded at the 3’ (or downstream) end by the ORF’s
translation start. The 5’ end was bounded by the translation start or stop of the nearest
upstream ORF, with the exception that this boundary was never more than 600 DNA base
pairs (bp) or less than 300 bp from translation start.
Several algorithms which discover recurring motifs in unaligned sequences have
been developed, and have been compared in Frech et al. 14. ‘Gibbs motif sampling’ is
one such algorithm that is both computationally efficient and tends not to become
‘trapped’ in sub-optimal alignments 15; 16. Although the Gibbs sampling strategy has
been applied primarily to protein sequence alignments, it has been applied previously to
DNA 14; 17. The Gibbs motif sampling algorithm 15 was modified in several ways,
primarily to make it more amenable to alignment of DNA (as opposed to protein)
sequence and to allow iterative searches for multiple motifs.
The modified Gibbs motif sampling algorithm (‘AlignACE’) was applied to each
set of upstream DNA sequence. Of the many resulting DNA site alignments, we
considered further only those motifs which: 1) exceeded a threshold AlignACE scorea
measure of ‘goodness’ of sequence alignment; and 2) had a specificity scorea measure
of the fraction of genes in the yeast genome with matching upstream sitesbelow 1% of
3-8
the ORFs in yeast. The latter criterion requires that motifs be selective, i.e., not similar to
elements (such as the TATA Box) commonly found among upstream regions.
DNA sequence motifs found from expression data. We first consider alignment
results from the galactose vs. glucose comparison. With the set of ten ORFs more
abundant in galactose than glucose, we identified a motif, ‘gal-1’ (Fig. 2A), which
matches the galactose upstream activation sequence (UASG) motif. It should be noted
that we developed an objective measure to assess the similarity of the motifs identified
here with previously described motifs, and that this measure isto our knowledgethe
only published method for quantitatively assessing similarity between DNA-binding site
motifs (see Protocols). UASG is known to regulate galactose-utilization genes via the
Gal4/Gal80 activation complex 18. No motif which met our criteria was obtained when
the top ten ORFs ranked more abundant in glucose were used. Another UASG-like motif,
‘gal-glu-1’ (Fig. 2B), was obtained when the preceding two ORF sets (a total of twenty
ORFs) were combined. Fig. 2C summarizes the motifs found by AlignACE and those
that might have been expected a priori given their previously defined roles in
transcriptional regulation.
3-9
C.
Motif
gal-1 (A)
gal-glu-1
Expected
UASG
URSG
Rap1-binding
Gcr1-binding
Score Specif
33.1
0.16
24.9
0.20
DNABP
Gal4/Gal8
Mig1
Rap1
Gcr1
Consensus
CGGAGNRVTSYBBNCCG
CGSBSVWSABYNBTCCG
Consensus
TTCGGMGVDMTSTBVHCC
CCCCRSNTWWWW
WRCACCCAKACAYY
CKRGCTTCCWNTWK
Similarity
gal-glu-1*, UASG
UASG*, gal-1*
Ref.
19
19
19
19
3-10
Figure 2. DNA sequence motifs obtained from a comparison between growth on
galactose- and glucose-containing media. (A) Motif (‘gal-1’) obtained from the ten ORFs
most abundant in galactose relative to glucose while (B) Motif (‘gal-glu-1’) obtained by
combining the preceding set with the ten ORFs most abundant in glucose relative to
galactose, and matches UASG. See Protocols for a description of sequence logos. (C)
lists those motifs returned by AlignACE as well as motifs which might have been
expected a priori. ‘Score’ refers to AlignACE score, ‘Specif’ is the specificity score, and
‘DNABP’ refers to the protein which binds an element, where known. Consensus
sequences and motif similarity were obtained by objective criteria (see Protocols). A ‘*’
indicates a motif’s reverse complement.
3-11
The ten ORFs most abundant in the heat shocked culture relative to 30 °C yielded
a single motif, ‘39C-1’ (Fig. 3A), which is similar to ‘39C-30C-2’ (Fig. 3E), but not
similar to any of the known binding sites considered in this study. The ten ORFs more
abundant in 30 °C relative to heat-shocked culture yielded two motifs. The first of these,
‘30C-1’ (Fig. 3B), matches the cell cycle activation (CCA) motif, a previously known
activator of histone genes 20; 21. The second motif, ‘30C-2’ (Fig. 3C), has not been
previously noted. When the combined set of twenty ORFs was used (genes abundant
either in heat shock or 30 °C), another CCA-like motif‘39C-30C-1’ (Fig. 3D)was
identified along with ‘39C-30C-2’ (Fig. 3E), a motif similar to ‘39C-1’. Fig. 3F
summarizes the motifs found by AlignACE and those that might have been expected a
priori given their previously defined roles in transcriptional regulation.
3-12
3-13
F.
Found
39C-1 (A)
30C-1 (B)
30C-2 (C)
39C-30C-1 (D)
39C-30C-2 (E)
Expected
HSE
STRE
CCA
NEG
MCB
SCB
ECB
Score
5.1
40.1
5.5
30.1
8.5
DNABP
HSF
Msn2/Msn4
?/Hir1/Hir2
?
Mbp1
Swi4/Swi6
Mcm1
Specif
0.04
0.26
0.44
0.20
0.10
Consensus
TCCGTRTBTAYCC
GTTCYSANMRHTTCK
RRKDWGVSGBGSWG
GTTCYSAVMRYTTCK
MMMTCCGTRKKYRSY
Consensus
CNVGAANNTTCBMG
HHAGGGGV
GCGAARWWNTSRGAAC
TDDACGCTMAAWSWC
ACGCGTWAM
RDDYCACGAAAA
TTWCCCDWTTAGGAAA
Similarity
39C-30C-2
39C-30C-1, CCA*
30C-1, CCA*
39C-1
Ref.
22
23; 24
20
21
25
25
26
Figure 3. DNA sequence motifs obtained from a comparison of growth between heat
shock and 30 °C conditions. (A), Motif (‘39C-1’) obtained from the ten ORFs most
abundant in heat shock relative to 30 °C, (B) and (C) Motifs (‘30C-1’ and ‘30C-2’,
respectively) obtained from the ten ORFs most abundant in 30 °C relative to heat shock,
while (D) and (E) Motifs (‘39C-30C-1’ and ‘39C-30C-2’ respectively) obtained from the
combined set of twenty ORFs. See Protocols for a description of sequence logos. (F)
lists those motifs returned by AlignACE as well as motifs which might have been
expected a priori. ‘Score’ refers to AlignACE score, ‘Specif’ is the specificity score, and
‘DNABP’ refers to the protein which binds an element, where known. Consensus
sequences and motif similarity were obtained by objective criteria (see Protocols). A ‘*’
indicates a motif’s reverse complement.
3-14
When the ten ORFs most abundant in mating typeα relative to type a were
examined, the motif ‘mtα-1’ (Fig. 4A) was found. ‘mtα-1’matches the P-Box and the
early cell cycle box (ECB; mediates activation of M/G1-specific transcription 25; 26), as
well as the Gcr1-binding site and the heat shock element (HSE). The P-box and ECB
elements are both known to be bound by Mcm1 27. Using the ten ORFs more abundant
in mating type a than type α, three motifs emerged. The first two of these, ‘mta-1’ and
‘mta-2’ (Fig.4B,C) have not been previously noted. The third motif, ‘mta-3’ (Fig. 4D),
matches the binding site of Matα2 27.
When the combined set of twenty ORFs was used, four motifs emerged. The first
of these, ‘mtα-mta-1’ (Fig. 4E), matches the known Matα2-binding site. The second,
‘mtα-mta-2’ (Fig. 4F), matches the pheromone-response element (PRE)—the known
binding site of Ste12 27. ‘mtα-mta-2’ is interesting, since a weak second match to the
PRE consensus suggests a conserved spacing of 7 bp between PRE elements. The third
motif, ‘mtα-mta-3’ (Fig. 4G), bears some resemblance to the PRE consensus, but had a
similarity score below the threshold applied here (see Protocols). The fourth motif, ‘mtαmta-4’ (Fig. 4H), corresponds to the Q-Box element, which is known to bind Matα1 27.
Fig. 4I summarizes the motifs found by AlignACE and those that might have been
expected a priori given their previously defined roles in transcriptional regulation.
3-15
3-16
I.
Motif
mtα-1 (A)
Score
8.9
Specif
0.22
Consensus
TTCCTAATTHG
mta-1 (B)
mta-2 (C)
mta-3 (D)
mtα-mta-1 (E)
mtα-mta-2 (F)
mtα-mta-3 (G)
mtα-mta-4 (H)
8.5
5.0
28.1
20.7
5.3
8.6
5.3
0.10
0.20
0.62
0.68
0.26
0.54
0.62
ADWHCWBKAAAWANAKTCWTH
AAAYCAWMAWKAMWA
GRWAWTTACATG
CATGTAMWTWYC
TWTDYWWHBKKMWTGTTTSA
TGAMATAWTDAAMA
AATGMCMGCMA
Expected
P-Box
Q-Box
α2-binding
PRE
DNABP
Mcm1
Matα1
Matα2
Ste12
Consensus
TTTCCTAATTAGGNAN
TCAATGVCAG
CRTGTAAWT
TGAAACA
Similarity
P-Box*, ECB*,
Gcr1-binding, HSE
α2-binding*, mtα-mta-1*
α2-binding, mta-3*
PRE*
Q-Box
Ref.
27
27
27
27
Figure 4. DNA sequence motifs obtained from a comparison of growth between mating
type a and α strains. (A) Motif (‘mtα-1’) obtained from the ten ORFs most abundant in
mating type α relative to mating type a. (B), (C), (D) Motifs (‘mta-1’, ‘mta-2’ and ‘mta3’ respectively) obtained from the ten ORFs most abundant in mating type a relative to
mating type α. (E), (F), (G), (H) Motifs (‘mtα-mta-1’, ‘mtα-mta-2’, ‘mtα-mta-3’ and
‘mtα-mta-4’ respectively) obtained from the combined set of twenty ORFs. See
Protocols for a description of sequence logos. (I) lists motifs returned by AlignACE as
well as motifs which might have been expected a priori. ‘Score’ refers to AlignACE
score, ‘Specif’ is the specificity score, and ‘DNABP’ refers to the protein which binds an
element, where known. Consensus sequences and motif similarity were obtained by
objective criteria (see Protocols). A ‘*’ indicates a motif’s reverse complement.
3-17
How do these results compare with what one might have expected from previous
work on these regulatory systems? Motifs common to many genes, e.g., the TATA box,
were neither found nor expected since these are excluded by the selectivity constraint
discussed above. In the case of ORFs more abundant in glucose than galactose, we might
have expected motifs corresponding to Rap1 or Gcr1-binding sites, but found neither of
these. Rap1 and Gcr1 are general transcription factors with diverse roles, including
regulation of glycolytic enzymes and ribosomal proteins 28. In the case of ORFs more
abundant in galactose than glucose we might have expected to find URSG (bound by
Mig1 28), but did not. As expected, our procedure did find UASG, an essential regulatory
element for galactose-utilizing genes.
The heat shock (HSE) and stress response promoter elements (STRE), known to
mediate heat shock response 29; 30, were notably absent from the motifs found by
AlignACE. Heat shock is known to have broad effects, including transient cell cycle
arrest in G1 31. As a result, we might also have expected to find genes with cell cyclespecific expression among genes affected by heat shock. Histone genes are strongly
transcribed during S phase, and are regulated both by a negative regulatory sequence
(NEG) and activated by the CCA motif (Fig. 3B, D) 20; 21. Not found among heat shock
data were the NEG motif, the Swi4/6-dependent cell cycle box (SCB) or MluI cell cycle
box (MCB) motifs which regulate G1/S-specific transcription, or the ECB element 25; 26.
AlignACE did find the CCA motif among a set of histone genes.
The α2 operator, P-Box, PRE and Q-Box elements represent the complete set of
DNA elements responsible for regulation of mating type-specific genes 27. All four of
these elements were found by AlignACE (Fig. 4C-H). The similarity of ‘mtα-1’ to both
3-18
HSE and the Gcr1-binding site was unexpected, and may represent false positive
determinations of motif similarity.
False positive and false negative motifs. We estimated the number of expected
false positives by generating and examining negative control sets of randomly chosen
genes and asking how many motifs passed both AlignACE and specificity criteria. The
AlignACE score criterion used here was chosen permissively, so that few biologically
relevant motifs would be excluded. The permissive AlignACE score threshold (5) was
examined as well as more stringent thresholds (8 and 20). For the permissive threshold,
an average of 1.7 motifs (Poisson distributed with a coefficient of dispersion (CD) of 0.9)
was obtained from negative control gene sets, which is consistent with the observation
that four motifs identified in this study from sets of 10 ORFs (Fig. 3A, 3C, 4B, 4C) did
not match known regulatory elements. The chance that a motif is a false positive
decreases with increasing AlignACE score, so that if a threshold score of 8 is applied the
mean number of false positives is reduced to 0.8 (CD = 1.0). If a threshold score of 20 is
applied, the mean number of false positives is further reduced to 0.2 (CD = 1.6). The
number of expected false positives for a variety of alternative AlignACE and specificity
score thresholds can be found in Fig. 5. All six of the six motifs identified in this study
which meet the most stringent threshold of 20 are similar to known regulatory elements.
This shows that these methods can be appliedat the discretion of the userto either
generate an inclusive set of testable hypotheses with a significant false positive rate, or to
more confidently predict a subset of biologically relevant motifs.
3-19
3.00-3.50
2.50-3.00
#of passing motifs from
100 random runs
3.50
2.00-2.50
3.00
1.50-2.00
1.00-1.50
2.50
0.50-1.00
0.00-0.50
2.00
1.50
1.00
5
0.50
0.00
20
MAP score
5.00%
4.00%
3.00%
Specificity
12
2.00%
1.00%
0.50%
0.40%
0.20%
8
Figure 5. Sets of 10 ORFs were drawn randomly 100 times from the complete set of
yeast ORFs. AlignACE was used to find conseved motifs for each random set.
AlignACE score and specificity score were obtained for each motif. The number of
motifs found that passed both AlignACE and specificity score thresholds is plotted as a
function of the thresholds chosen.
3-20
We were interested in understanding why our approach had ‘false negatives’, i.e.,
did not find all of the motifs we might have expected a priori. For each expected motif,
we applied our method to an ‘ideal’ set of genes derived from the literature. Motifs
corresponding to the URSG and NEG elements were not found among ‘ideal’ gene sets
using the permissive AlignACE score threshold, so that we attribute not finding these
motifs to AlignACE. Motifs corresponding to the Gcr1-binding, STRE and MCB
elements were obtained which passed both AlignACE score (13.9, 12.1, 10.6
respectively) and specificity score criteria (0.4%, 0.9% and 1.0%, respectively), so that
we attribute not finding these motifs to the input sets of ORFs derived from expression
data. Motifs corresponding to the Rap1-binding, HSE, SCB and ECB elements were
found using ‘ideal’ gene sets with passing AlignACE scores (8.1, 14.8, 20.2 and 12.1,
respectively) but unacceptable specificity scores (4.1%, 7.3%, 5.3% and 1.6%,
respectively). We re-examined the appropriate 10 most-increased genes using relaxed
specificity score criterion and still did not find these motifs, so that we also attribute not
finding these motifs to the input set of ORFs. However, even if Rap1-binding, HSE, SCB
and ECB motifs had been found, they would likely not have passed our chosen specificity
criterion of 1%.
That input sets of upstream regions contained too few sites for AlignACE to align
can be verified by scanning the upstream regions of the appropriate 10 most-increased
genes for matches to motifs found from among ideal gene sets. Among the 10 genes most
increased in heat shock, HSE matched only 2 sites upstream of HSP26 while STRE
matched a total of only 3 sites upstream of HSP12 and HSP26. Among the 10 genes most
decreased in heat shock, MCB matched no sites, SCB matched 1 site upstream of LYS1,
3-21
and ECB matched only 1 site in the upstream region shared by HHT1 and HHF1. Among
the 10 genes most decreased in galactose neither the Rap1-binding site nor the Gcr1binding motif matched any upstream sites.
Candidate sets of co-regulated genes. Once a candidate regulatory motif has been
found, we are particularly interested in those ORFs that are both altered in expression and
contain an upstream match to this motif. First, we search the complete S. cerevisiae
genome to find the set of ORFs that contain matches to each motif in the 600 bp region
upstream of translation start. Second, we consider the intersection of this set of ORFs
with those ORFs that changed more than two-fold in abundance between conditions. We
consider the resulting ORFs to be good candidates for membership in a transcriptionally
co-regulated set of genes.
ORFs that have a measured change of more than two-fold in expression between
galactose and glucose, and have an upstream match to at least one of the UASG-like
motifs ‘gal-1’ and ‘gal-glu-1’ are shown in Table 1, along with the remaining genes
known previously to be regulated by UASG. There are nine genes known previously to be
regulated by the Gal4/Gal80 complex: GAL1, GAL2, GAL3, GAL7, GAL10, GAL80,
GCY1, MEL1 and PGM2. The candidate set derived from Table 1 contains six of these
nine. One of the missing three is MEL1, which codes for alpha-galactosidase. The strain
used for this experiment (FY4) is a mel- strain. Furthermore, we could not find a good
match to UASG in the MEL1 upstream sequence from this strain, so that we should not
have necessarily expected to find MEL1 in our candidate set. Also missing from our
candidate set were PGM2 and GAL80, which are known to be Gal4/Gal80 regulated. For
3-22
both of these genes, absolute expression levels were too low in both galactose and
glucose for an accurate estimate of change in expression.
The candidate set for galactose vs. glucose contains three ORFs not previously
thought to be regulated by Gal4/Gal80. Two of these, YPL066W and YPL067C, are
particularly interesting since they have approximately the same measured change in
expression, and are divergently transcribed from the same intergenic region which
contains a single match to each of the UASG-like motifs. Another site in this intergenic
region matches the consensus CGG(N)10CCG, to which weak Gal4-binding has also been
shown in vitro 32. Both YPL066W and YPL067C are of unknown function according to
the Saccharomyces Genome Database (SGD) 33, with no significant homology to any
gene of known function. Also in the candidate set was YMR318C, which has a strong
homology to zinc-containing alcohol dehydrogenases 33. We are currently exploring the
possibility that these ORFs are regulated by Gal4/Gal80.
ORFs that have a measured change of more than two-fold in expression between
heat shock and 30 °C, and have an upstream match to at least one of the motifs in Fig. 3
are shown in Table 2, along with the remaining histone genes. There are eight
genesfour functionally redundant gene pairsin S. cerevisiae that code for the four
nucleosomal proteins: HTA1, HTA2, HTB1, HTB2, HHT1, HHT2, HHF1, and HHF2.
The candidate set of co-regulated genes with matches to both of the CCA-like motifs
(‘30C-1’ and ‘39C-30C-1’) contains five of these genescollectively coding for the
complete set of S. cerevisiae nucleosomal proteins. It is important to note that our results
by themselves do not necessarily indicate a role for the CCA motif in heat shock
regulation or in cell cycle regulation, since we seek any motif common to a set of ORFs
3-23
without information about which motif (if any) might be responsible for the observed
changes in expression. RPS8A (coding for ribosomal protein rp19), HOR2 (DL-glycerol3-phosphatase), YDR070C (an ORF of unknown function), and GSY1 (glycogen
synthase) have upstream matches to one of the CCA-like motifs (‘30C-1’) 33. None of
these genes have previously been noted to be heat shock repressed or to be regulated by
CCA. However, GSY2a homolog of GSY1is reportedly induced by heat shock 34.
This suggests, together with our data showing reduced abundance of GSY1 in heat shock,
that GSY2 is a thermotolerant variant of glycogen synthase. It is also worth mentioning
that along with the other histone genes discussed above we found the gene HHO1
(histone H1) to be reduced by more than two-fold in heat shock. HHO1 does not,
however, contain an upstream match to the CCA motif.
Another candidate set of co-regulated genes can be derived from heat shock data,
using those ORFs in Table 2 with upstream matches to the motifs ‘39C-1’ and ‘39C-30C2’. This set contains the genes HSP26, GND2, GCV1, UBI4, ERG11, SOL4, and YHB1.
Of these, only HSP26 and UBI4 have been reported to be differentially expressed as a
result of heat shock 29. We can see no apparent rationale for co-regulation of this set of
genes or of the set derived from ‘30C-2’. None of the motifs ‘39C-1’, ‘30C-2’, or ‘39C30C-2’ have previously been implicated as regulatory elements.
ORFs that have a measured change of more than two-fold in expression between
mating types a and α, and have an upstream match to at least one of the mating typederived motifs (Fig. 4) are shown in Table 3, along with the remaining genes known to
have mating type-specific expression. Genes MFα1, MFα2, STE3, SAG1, MATα1 and
MATα2 are known previously to have mating type α-specific expression. The genes
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MFA1, MFA2, STE2, STE6, BAR1, AGA2, MATa1 and MATa2 are known previously
to have mating type a-specific expression 35. The candidate set of co-regulated genes
corresponding to the P-Box-like motif ‘mtα-1’ contains twelve genes, including four of
fourteen known mating type-specific genes. Candidate sets derived from those motifs not
known to be involved in transcriptional regulation, ‘mta-1’ and ‘mta-2’, each contained
seven ORFs, two of which are mating type-specific. The candidate set of genes with
matches to either of the Matα2 binding site-like motifs (‘mta-3’ and ‘mtα-mta-1’)
contains seventeen genesincluding five of the eight known a-specific genes. That
MATα1 and MATα2 genes had an upstream match to ‘mtα-mta-1’ in their shared
intergenic region is consistent with the fact that this locus is repressed by the
Matα2/Mata1 complex in a/α cells 35.
The candidate set of genes having upstream sites matching ‘mtα-mta-2’a PRElike elementcontains nine genes, five of which are mating type regulated. The
candidate set for ‘mtα-mta-3’ (weakly similar to PRE as noted above) contains thirteen
genes, two of which are mating-type specific. The gene STE18 has an upstream match to
‘mtα-mta-3’. STE18 codes for the Gγ subunit of the G protein coupled to both a and α
mating factor receptors, and is known to be regulated via the PRE element. Although
STE18 is not thought to have mating type-specific expression, we found the STE18
transcript to be three-fold more abundant in a than α 35. The candidate set of genes with
upstream matches to the Q-Box-like motif, ‘mtα-mta-4’, contained seven genes,
including one a-specific and two α-specific genes. In all, forty genes were contained in at
3-25
least one of the candidate sets of co-regulated genes described above, and among those
forty were nine of fourteen known mating type-specific genes.
3-26
ORF ID
YBR020W
YBR018C
YBR019C
YOR120W
YLR081W
YPL066W
YPL067C
YMR318C
YDR009W
YML051W
YMR105C
YBR184W
Gene
GAL1
GAL7
GAL10
GCY1
GAL2
GAL3
GAL80
PGM2
MEL1
Change
>1.8
>1.6
>1.6
>1.1
>0.9
>0.8
>0.8
0.6
>0.5
ND
ND
ND
l-1
ga
5
2
5
1
4
1
1
1
2
2
1
-
1
lug
l
ga
4
2
4
1
4
1
1
1
2
2
1
-
Table 1. The number of matching sites that lie within 600 bp upstream of translation
start of genes/ORFs that were either measurably changed in expression or are known to
be galactose-responsive. Genes/ORFs in plain text had a greater than 0.3 (two-fold)
between galactose and glucose growth conditions. Genes/ORFs in italics have been
shown previously to be regulated by the Gal4/Gal80 complex, but had a measured change
of less than 0.3. Change calculation is as described (see Protocols) with positive change
indicating higher transcript abundance in galactose than glucose.
3-27
ORF ID
Gene
YPL223C
YBR072W
YGR256W
YDR219C
YLL039C
YDR070C
YER062C
YER103W
YHR007C
YER042W
YDL223C
YGR038W
YDL048C
YMR090W
YGR248W
YOR185C
YOR259C
YNL241C
YNL156C
YPL135W
YHR057C
YNL031C
YDR224C
YDR225W
YBL015W
YNL030W
YBR009C
YFR015C
YBL003C
YBL002W
YBL072C
YBR010W
YGR234W
YJL052W
HSP26
GND2
GCV1
UBI4
HOR2
SSA4
ERG11
ORM1
STP3
SOL4
GSP2
CRL13
ZWF1
CYP2
HHT2
HTB1
HTA1
ACH1
HHF2
HHF1
GSY1
HTA2
HTB2
RPS8A
HHT1
YHB1
TDH1
Change
>0.8
0.7
0.7
0.6
0.6
0.5
0.5
0.5
0.5
0.4
0.4
0.4
>0.3
>0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
ND
-0.1
-0.2
-0.3
-0.4
<-0.4
<-0.5
-0.5
-0.5
-0.5
-0.5
<-0.6
<-1.7
1
C39
1
2
1
1
2
1
1
1
1
1
1
1
1
1
1
2
2
-
1
C30
2
1
2
4
4
2
4
1
5
5
1
4
-
2
C30
1
1
1
1
1
1
1
1
3
1
3
2
1
1
2
CC0
0
3
3
CC39
39
2
1
1
1
1
1
2
1
2
2
1
2
1
4
4
4
1
4
1
-
3-28
Table 2. The number of matching sites that lie within 600 bp upstream of translation
start of genes/ORFs that were either measurably changed in expression or are known to
code for nucleosomal proteins. Genes/ORFs in plain text had a measured change of
greater than 0.3 (two-fold) between the heat shock and 30 °C growth conditions.
Genes/ORFs in italics are known to code for nucleosomal proteins, but had a measured
change of less than 0.3. Change calculation is as described (see Protocols) with positive
change indicating higher transcript abundance in heat shock than 30 °C.
3-29
ORF ID
Gene
YPL187W
YGL089C
YCL066W
YCR040W
YJR004C
YLR040C
YHR053C
YHR128W
YHR141C
YGR038W
YLR355C
YCR097W
YCR096C
YCR039C
YCL067C
YKL178C
YKL209C
YDR301W
YLR438W
YBR107C
YKL080W
YML133C
YDR342C
YLR028C
YJR103W
YML075C
YKL128C
YCR012W
YMR003W
YAL061W
YPL271W
YBR011C
YMR119W
YKL214C
YKR018C
YJR086W
YBR147W
YKR071C
YLL040C
YJL164C
YCR024C-A
YIL015W
YFL026W
YGL032C
YNL145W
YDR461W
MFα1
MFα2
MATα1
MATα1
SAG1
CUP1
FUR1
MAK18
ORM1
ILV5
MATa1
MATa2
MATα2
MATα2
STE3
STE6
YHH1
CAR2
VMA5
HXT7
ADE16
URA8
HMG1
PMU1
PGK1
ATP15
IPP1
STE18
VPS13
SRA3
PMP1
BAR1
STE2
AGA2
MFA2
MFA1
Change
>1.3
>1.2
>0.7
>0.6
0.5
>0.4
0.4
0.4
0.4
0.3
0.3
ND
ND
ND
ND
ND
ND
-0.3
-0.3
-0.3
-0.3
-0.3
-0.3
-0.3
-0.4
-0.4
-0.4
-0.4
-0.4
-0.4
<-0.4
-0.5
-0.5
-0.5
-0.5
-0.5
-0.5
-0.5
-0.6
-0.6
-0.6
<-0.7
<-0.8
<-0.9
<-1.6
2.0
1
αt
m
4
1
1
1
1
1
1
1
1
1
1
1
1
-
1
at
m
1
2
2
1
1
1
1
2
at
m
1
1
1
2
1
2
1
2
3
4
1
aaaat
t
t
t
m
m
m
m
ααααt
t
t
t
m
m
m
m
3
at
m
3
2
1
1
3
2
2
3
2
1
1
1
1
1
3
1
2
1
2
2
2
2
2
1
1
2
1
1
1
1
2
1
1
1
1
1
1
1
1
1
1
2
1
1
1
-
1
1
1
2
1
1
1
-
3-30
Table 3. The number of matching sites that lie within 600 bp upstream of translation
start of genes/ORFs that were either measurably changed in expression or are known to
be mating type-specific. Genes/ORFs in plain text had a measured change of greater than
0.3 (two-fold) between mating types a and α. Genes/ORFs in italics have been shown
previously to have mating-type specific expression, but had a measured change of less
than 0.3. Change calculation is as described (see Protocols) with positive change
indicating higher transcript abundance in mating type α than a.
3-31
The success of this approach in finding regulatory DNA sequence motifs was
dramatic. The same criteria, when applied to three whole-genome expression
comparisons, uncovered at least one biologically important regulatory motif in each case.
In the case of galactose vs. glucose, UASG — one of the two motifs involved in
regulating galactose-utilization genes — was found along with most of the known UASG
-regulated genes. In the case of heat shock vs 30 °C, a motif known to function in
nucleosomal gene regulation was found, along with a set of genes collectively coding for
every nucleosomal protein. In the case of mating type a vs. α, every one of the four
motifs involved in mating type-specific gene regulation was found, along with most of
the known mating type-specific genes.
Our experiments showed lower sensitivity to transcripts of low abundance
compared with previously published S. cerevisiae expression studies 9. As a result, some
ORFs which are known from previous studies to be differentially expressed between the
examined conditions fell below our detection threshold for transcript abundance and thus
were not measurably changed in our results. Our approach for finding co-regulated genes
should then become even more successful as we optimize experimental methods in
whole-genome expression measurement.
In this work, we have restricted ourselves to a search for upstream sequence
elements. However, this approach could also be applied to 3’ UTR sequences to discover
conserved determinants of transcript termination, stability, or post-transcriptional
processing (as in the case of higher eukaryotic histone genes 21). The search for DNA (or
RNA) sequence elements in coding regions of co-expressed genes is complicated by
codon usage bias, which will tend to increase the likelihood of obtaining strong
3-32
alignments by chance. However, a search for protein (as opposed to nucleic acid)
sequence motifs among co-expressed genes may prove useful, e.g., in the discovery of
shared N-terminal signal sequences.
The AlignACE algorithm promises to be more generally useful in finding motifs
in unaligned DNA sequences. Although we used whole-genome expression analysis to
obtain sets of genes enriched for conserved sites, AlignACE may also prove useful in
finding regulatory motifs among a variety of enriched sequence sets. A common
example of this might be the upstream sequence from a collection of genes whose
mutants share a phenotype. For gene expression data sets taken from many cell types or
growth environments, it will be useful to find clusters of genes that are correlated in their
expression 36 and apply the sequence analysis described here. AlignACE and all other
software written for this work is publicly available 13.
Experimental Protocol
Strains and growth conditions. S. cerevisiae strain FY4 MATa was used for all growth
conditions except as noted. FY4 is a prototroph whose genome is completely sequenced
3; 37.
Cultures were grown with aeration in yeast nitrogen base plus ammonium sulfate
without amino acids (YNB) at 30 °C in a rotary incubator, and supplemented with 2%
glucose except as noted. All cultures were harvested in mid log phase (2 - 4 x 107
cells/ml) as determined by cell count and dilution plating. Cells were pelleted, quickly
washed once with 50 ml dH2O, frozen in a dry ice-isopropanol bath, and stored at -80 °C.
For galactose growth, 2% galactose was used in place of glucose. For the heat shocked
culture, cells were transferred at mid-log phase to a 39 °C shaking water bath. After 13
3-33
minutes the culture had reached 39 °C, and the incubation was continued for an additional
20 minutes. This temperature profile was chosen since heat shock-related transcripts are
at maximal levels between 10 and 20 minutes after reaching the higher temperature 38.
For mating type α cultures, strain FY5—isogenic to FY5 except that it is MATα—was
used in place of FY4. All strains were kindly provided by A. Dudley and F. Winston,
Harvard Medical School.
RNA preparation and hybridization. Total cellular RNA was prepared from the frozen
cell pellets by hot phenol extraction method (Current protocols in Molecular Bio,
Ausubel et.al.). An additional phenol extraction and a phenol/chloroform/isoamyl
alcohol extraction were done before ethanol precipitation. The poly-A fraction of total
cellular RNA was purified by a PolyATract kit (Promega , Madison, WI). The resulting
eluant was lyophilized and resuspended in 1-2 µl H2O. Synthesis, purification, and
fragmentation of biotinylated RNA antisense to mRNA transcripts (cRNA) was
performed as previously described 9. For each culture, expression data was acquired
using a set of four chips (Affymetrix yeast ‘antisense’ A - D) designed for expression
monitoring of S. cerevisiae 9.
Hybridization, washing, and scanning were carried out as previously described 9
except where noted below. For all hybridizations, 15 µg fragmented cRNA in 250 µl
buffer. Hybridizations were carried out either in Affy buffer (Affymetrix, Inc.) at 40 °C
or in 6X SSPE-T (0.9 M NaCl, 60 mM NaH2PO4, 6mM EDTA, 0.005% Triton X-100,
pH 7.6) at 45 °C for 14 to 18 hours. For a given chip type, hybridizations were carried
out identically for each culture. After hybridization and washing, the chips were stained
for 10 minutes at room temperature with 2µg/ml streptavidin-phycoerythrin conjugate
3-34
(SAPE; Molecular Probes , Eugene, OR) in 6X SSPE-T with 1 mg/ml acetylated BSA
(New England Biolabs , Beverly, MA). Unbound SAPE was removed by rinsing with 6X
SSPE-T at 45 °C.
Expression data analysis. Perfect match (PM) and single-base mismatch (MM) probe
intensities are calculated from raw intensities by the GeneChipTM software (Affymetrix,
Inc.) as described 9. For this analysis, genes with MM probes that are perfect matches to
a sequence within the genome, e.g., YBL087C and YKL006W, were not considered
further. Intensities for PM and MM probes are background-subtracted using the average
intensity of a set of 36 chip features with consistently low intensity in all of our
experiments. For a given chip, PM and MM data are then normalized using the average
background-subtracted PM intensity on that chip. This is likely more reliable than
normalizing to transcripts of ‘constant’ expression level, e.g., ACT1 or PDA1, since these
can vary between conditions by more than three-fold 39. PM − MM (∆) is then calculated
for each probe pair, and if ∆ is less than detection threshold, then ∆ is set to this
threshold. A detection threshold for PM or MM values on a given chip was chosen to be
σ, the standard deviation of background probe intensities on that chip; the threshold for ∆
values is then 2 * σ by propagation of error. The ratio ∆A/ ∆B of transcript abundance in
one condition (A) vs. another (B) is calculated for each corresponding pair of ∆ values.
Application of the detection threshold prevents unreasonably high (or negative) values for
(∆A/ ∆B) where a transcript is absent or undetectable in one or both conditions. The
change in expression for a given ORF is then calculated as log( median {(∆A1/ ∆B1), (∆A2/
∆B2),,, (∆An/ ∆Bn)}), where n is the number of probe pairs for that ORF. If the median is
3-35
calculated using a ∆A/ ∆B value where both or the greater of ∆A and ∆B were thresholdadjusted, then change in expression for this ORF is not calculated (‘ND’). Otherwise, if
the median is calculated using a ∆A/ ∆B value where either ∆A or ∆B were thresholdadjusted, change in expression is stated as being greater than (or less than) the calculated
value. The median, as opposed to the mean, was chosen as a measure of central tendency
that is robust to outliers. Our rationale for using the median of ∆ ratios rather than the
ratio of ∆ medians was that while the magnitude of ∆ for features of different sequence
can vary considerably, ∆A/ ∆B should be less variant. An alternative measure of
expression change (not used here) is ‘fractional change’: median {(∆A1−∆B1)/(∆A1+∆B1),
(∆A2−∆B2)/(∆A2+∆B2),,, (∆An−∆Bn)/(∆An+∆Bn)}. This measure should be robust to cases
where a transcript is below detection threshold in one condition but not the other.
Optimality of these or previous methods 9 for intensity data analysis have yet to be
demonstrated experimentally. However, the lists of most-changed genes for each of our
condition comparisons were not greatly affected by the analysis method used.
Modifications to Gibbs motif sampling alteration. Alterations of the Gibbs motif
sampling algorithm described in ref. 15 are the following: 1) Consideration of both
strands of DNA, so that when a potential site is examined, either the site or its reverse
complement—but not both—may be added to the alignment; 2) Near-optimum sampling
method was improved so that it tends to result in higher scoring alignments and so that all
columns spanned by the initially-chosen columns were considered; 3) Simultaneous
multiple motif searching was replaced with an iterative masking approach, allowing a
more efficient search for subtle motifs; 4) The model for base frequencies of non-site
sequence was fixed using the background nucleotide frequencies of S. cerevisiae. 5) The
3-36
code is now portable to DEC Unix and Windows platforms, in addition to Silicon
Graphics and Sun Unix systems.
AlignACE settings. The program ‘AlignACE’ was used with the following settings:
inital alignment used a ‘column-sampling’ approach with 10 columns; the expected
number of sites was 10; maximum number of initial sampling runs was 500; iterative
masking to find multiple motifs was performed a maximum of 100 times; near-optimum
sampling commenced after 50 consecutive sampling runs without an increase in
alignment score; iterative masking was terminated after three consecutive cases of nonconvergence or non-positive alignment score.
AlignACE implemented a scoring method for ‘goodness’ of a site alignment that has
previously been described by eq. 10 in ref. 40, and motifs below a threshold AlignACE
score of five were not considered further. To ensure that this criterion was sufficiently
permissive, we searched for conserved motifs among randomly chosen sets of 10
upstream intergenic DNA sequences with AlignACE settings as described above except
that a maximum of three motifs were sought from each intergenic sequence set. Each of
1000 randomly chosen sequence sets returned at least one motif with a score greater than
our threshold of five. In 674 cases, all three motifs returned had scores greater than five.
Finding sites which match motifs and calculating motif specificity. Sites were scored
against motifs using the method of Berg and von Hippel 41. To define a threshold score
for a ‘good’ matching site, we first calculated the mean score µ and standard deviation σ
for the set of sites that were aligned by AlignACE. We determined our specificity
scorethe estimated fraction of genes bound by the putative protein corresponding to a
given motifin the following way: We found the fraction of genes with upstream
3-37
matches, defining a matching site as one with a Berg-Von Hippel scoregreater than or
equal to µ. The specificity score is then twice this fraction, since half of ‘real’ sites will
have scores better than µ if ‘real’ sites have a symmetric score distribution. For discovery
of specific upstream sites, the threshold score for a ‘good’ match was lowered to µ - 3σ to
avoid missing potential binding sites.
Measuring similarity between DNA motifs. To identify previously described motifs that
might be similar to the newly identified motif, the relevant literature was searched.
Additionally, the TRANSFAC Release 3.2 was searched 19 using PatternSearch or
MatInspector 2.1 42 with a threshold of 85% identity for ‘core’ nucleotides and 60% for
overall identity. To assess similarity more quantitatively once a putatively similar motif
has been identified, DNA site weight matrices 41 were examined pairwise in all possible
alignments. The alignment which minimizes the sum of squared differences between
matrix elements is chosen. When necessary, as in the case of imperfectly overlapping
matrices, matrix elements are taken as their expectation value, based on the base
composition of S. cerevisiae. If aligned matrices do not overlap by more than 5 bases,
they are considered not similar. To further compare a given matrix A with a matrix B, a
submatrix of A defined by the region of overlap between aligned A and B matrices is
constructed. Each site used in generating the A and B matrices is scored against
submatrix A. Student’s t-statistic is calculated from the set of A site scores and the set of
B site scores. Matrix A is said to ‘detect’ matrix B if t is above a threshold (described
below). The procedure is repeated using a submatrix of B, and matrix A is then said to be
‘similar’ to matrix B if either matrix detects the other. The threshold for t was obtained
using a negative control set of fourteen literature-derived matrices that are each bound by
3-38
different proteins (all of the ‘expected’ motifs in Fig. 2C, 3F, and 4I except the P-Box,
which is bound by the same protein as ECB). False positive rate for matrix similarity was
calculated to be the number of similar pairs in the negative control set divided by 91(the
number of pairwise comparisons). The value of t corresponding to a 5% false positive
rate was found to be 3.26 by linear interpolation.
Assessing false positives. To estimate the number of ‘passing’ motifs that we might
expect by chance, we ran AlignACE on 100 randomly chosen sets of 10 upstream
sequences with settings identical to those above, where a ‘passing’ motif has a AlignACE
score greater than a set threshold (alternative thresholds of 5, 8, and 20 were examined)
and a less than 1% specificity score.
Ideal Gene Lists. In trying to determine why our approach failed to find certain
regulatory motifs, the following ‘ideal’ ORF sets were used to search for these motifs:
ECB: CDC 6, CDC46, CDC47, CLN3 and SWI4; Gcr1-binding site: ADH1, CDC19,
ENO1, PGK1 and TPI1; HSE: CUP1, HSC82, HSP26, HSP82, PGK1, SIS1, SSA1 and
SSA3; MCB: CDC8, CDC9, CDC21 and CLB5; URSG: FBP1, FPS1, GAL1, GAL3,
GAL4, HAP4, MEL1, PDC1 and SUC2; NEG: HHT1, HHT2 and HTA1; Rap1-binding
site: CDC19, ENO1, PGK1, PDC1, PHO5, RNR2, Rpl16A, SRA1, TEF1, TEF2 and
TPI1; SCB: CLN1, CLN2, HO and PCL1; STRE: CTT1, CYC7, DDR2, GAC1, HSP12,
HSP26, HSP104, NTH2, PTP2 and TPS2.
Methods for visually representing sequence alignments. In sequence ‘logos’, the height
of each letter is made proportional to its frequency, and the letters are sorted so the most
common one is on top. The height of the entire stack is then adjusted to signify the
information content of the sequences at that position 43. Consensus sequences were
3-39
determined using the plurality method of Day and McMorris44. From a set of equally
valid consensus bases, we choose the most precise base (e.g., A is more precise than N)
that has a precision unique to this set. For example, V is chosen from the set {M, R, V,
N}.
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McInerny, C.J., Partridge, J.F., Mikesell, G.E., Creemer, D.P. and Breeden,
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promoters activates M/G1-specific transcription, Genes & Development, 11(10), 12771288, 1997.
27.
Herskowitz, I., Rine, J. and Strathern, J., Mating-type determination and
mating-type interconversion in Saccharomyces cerevisiae, in Gene Expression, Vol. 2,
Jones, E.W., Pringle, J.R. and Broach, J.R., Eds., Cold Spring Harbor, NY, Cold Spring
Harbor Laboratory Press, 1992, 583-656.
3-43
28.
Johnston, M. and Carlson, M., Regulation of Carbon and Phosphate Utilization,
in Gene Expression, Vol. 2, Jones, E.W., Pringle, J.R. and Broach, J.R., Eds., Cold
Spring Harbor, NY, Cold Spring Harbor Laboratory Press, 1992, 193-281.
29.
Craig, E.A., The Heat-Shock Response of Saccharomyces cerevisiae, in Gene
Expression, Vol. 2, Jones, E.W., Pringle, J.R. and Broach, J.R., Eds., Cold Spring Harbor,
NY, Cold Spring Harbor Laboratory Press, 1992, 501-537.
30.
Schmitt, A.P. and McEntee, K., Msn2p, a zinc finger DNA-binding protein, is
the transcriptional activator of the multistress response in Saccharomyces cerevisiae, Proc
Natl Acad Sci U S A, 93(12), 5777-5782, 1996.
31.
Rowley, A., Johnston, G.C., Butler, B., Werner-Washburne, M. and Singer,
R.A., Heat shock-mediated cell cycle blockage and G1 cyclin expression in the yeast
Saccharomyces cerevisiae, Molecular & Cellular Biology, 13(2), 1034-1041, 1993.
32.
Vashee, S., Xu, H., Johnston, S.A. and Kodadek, T., How do "Zn2 cys6"
proteins distinguish between similar upstream activation sites? Comparison of the DNAbinding specificity of the GAL4 protein in vitro and in vivo, Journal of Biological
Chemistry, 268(33), 24699-24706, 1993.
33.
http://genome-www.stanford.edu/Saccharomyces.
34.
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stress, Molecular Microbiology, 16(6), 1197-1205, 1995.
35.
Sprague, G.F. and Thorner, J.W., Pheromone Response and Signal
Transduction during the Mating Process ofSaccharomyces cerevisiae, in Gene
Expression, Vol. 2, Jones, E.W., Pringle, J.R. and Broach, J.R., Eds., Cold Spring Harbor,
NY, Cold Spring Harbor Laboratory Press, 1992, 657-744.
3-44
36.
Wen, X., Fuhrman, S., Michaels, G.S., Carr, D.B., Smith, S., Barker, J.L. and
Somogyi, R., Large-scale temporal gene expression mapping of central nervous system
development, Proceedings of the National Academy of Sciences of the United States of
America, 95(1), 334-339, 1998.
37.
Winston, F., Dollard, C. and Ricupero-Hovasse, S.L., Construction of a set of
convenient Saccharomyces cerevisiae strains that are isogenic to S288C, Yeast, 11(1), 5355, 1995.
38.
Miller, M.J., Xuong, N.H. and Geiduschek, E.P., Quantitative analysis of the
heat shock response of Saccharomyces cerevisiae, Journal of Bacteriology, 151(1), 311327, 1982.
39.
Wenzel, T.J., Teunissen, A.W. and de Steensma, H.Y., PDA1 mRNA: a
standard for quantitation of mRNA in Saccharomyces cerevisiae superior to ACT1
mRNA, Nucleic Acids Research, 23(5), 883-884, 1995.
40.
Liu, J.S., Neuwald, A.F. and Lawrence, C.E., Bayesian models for multiple
local sequence alignment and Gibbs sampling strategies, Journal of the American
Statistical Association, 90(432), 1156-1170, 1995.
41.
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proteins. Statistical-mechanical theory and application to operators and promoters,
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MatInspector: new fast and versatile tools for detection of consensus matches in
nucleotide sequence data, Nucleic Acids Research, 23(23), 4878-4884, 1995.
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consensus sequences, Nucleic Acids Research, 18(20), 6097-6100, 1990.
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Computer Applications in the Biosciences, 9(6), 653-656, 1993.
3-46
Chapter 4
Prospects for Single Molecule DNA Sequencing
Using Ion Conductance
Allocating Credit among Co-authors
Since the following chapter represents more than one person’s efforts, it seems
appropriate to a doctoral thesis that I describe which parts were my own work.
Contributions made by those who were not coauthors are creditedI sincerely hope
adequatelyelsewhere in the acknowledgments. Computer modeling of channel
conductance was done primarily by George Church, with minor help from me in
choosing pore dimensions and producing the van der Waals representation in Fig. 1.
Estimation of thermal motion of phage DNA during injection was my own work. Dr.
Richard Baldarelli expressed and purified Shigella LamB pores, and tested activity with
an in vitro time course of bacteriophage λ injection. Dr. Baldarelli initiated work with
this system by purchasing and assembling the apparatus for measuring ion currents on a
picoampere scale, and performing preliminary experiments with LamB and
bacteriophage λ using patch-clamp methods. The observation of a channel activity
associated with purified bacteriophage λ in the absence of LamB was my own.
Experiments which established the single-channel conductance of LamB, and that of the
bacteriophage λ-associated channel (data shown in Fig. 2 & 3) were also entirely my
own work. I used the planar bilayer method of conductance measurement which I
reduced to practice in our laboratory with advice from Dr. Baldarelli. Modifications of
this methodincluding a novel apparatus for static discharge production of narrow
apertures in thin polymer film, and the use of FEP fluoropolymer filmwere my own
innovations.
4-2
Advances in electrophoretic gel-based DNA sequencing, automated fluorescent
and multiplex methods, have made feasible the complete sequencing of genomes 1-3.
Given the growing desire to sequence other large genomes and to genotype many
individual human genomes, there remains a need to explore alternative approaches that
can increase data yields and decrease costs without increasing errors. Single-molecule
DNA sequencing approaches have the potential to overcome some limitations of gelbased sequencing 4-6, e.g., to reduce time, reagent costs, and amplification artifacts
associated with conventional sequencing approaches. However, no single-molecule
method has yet produced reliable sequence.
Observation of voltage-induced flow of ions through a single transmembrane
channel was first reported in 1969 7 and observations of transient blocking and rapid
gating of single ion channels are now made routinely. Within the last few years,
measurements of channel conductance blockage by individual polymers have been
reported. These include peptide transport through channels of the endoplasmic
reticulum, protein transport across nuclear pore complexes, poly(ethylene glycol)
diffusion through alamethicin channels, and supercoiled DNA interactions with bilayers
8-11. More recently, conductance blockage of S.
aureus α-hemolysin channels due to the
passage of ssDNA has been reported 12.
We propose a single-molecule DNA sequencing method that takes advantage of
the remarkable sensitivity of single-channel recording techniques. A DNA molecule
passing through a transmembrane channel will interfere with ion flow through that
channel. If it each of four nucleotide bases (or base pairs) of a DNA molecule forms a
blockage of a unique size, it may then be possible to correlate variations in ion
4-3
conductance with DNA sequence as DNA is passed through a transmembrane channel.
If the canonical four nucleotides are too similar in size, we might then consider the use
of modifying DNA with larger bases.
The low cost of solid state amplifiers and the routine data acquisition rate of
300,000 samples per second make an ion conductance-based system for sequencing
DNA attractive. Any such system will have three basic requirements: an ion channel
with suitable geometry (discussed below), some form of nucleic acid, and a means of
delivering the nucleic acid to the channel. A system consisting of ssDNA or ssRNA
driven electrophoretically through α-hemolysin channels has recently been proposed 12.
We have focused our attention on dsDNA and on a bacteriophage/receptor system to
deliver dsDNA to a channel, since dsDNA has more predictable and less variable
secondary structure than ssDNA or RNA and since the observation of DNA injection by
a single bacteriophage would be of great biological interest. The rate of phage DNA
injection (about 1000 bp/sec 13), the potentially large read length (50 kb for λ
bacteriophage), and the ease of packaging exogenous DNA into phage particles 14 also
make a bacteriophage/receptor system a good choice.
Results and discussion
Model for a hypothetical DNA-containing channel. To illustrate the proposed method
and to examine its feasibility, we explored a simple geometrical model for the
conductance of a hypothetical channel containing dsDNA (Fig. 1A). The ion
conductance of a channel is determined by the channel’s surface charge distribution,
4-4
bulk conductivity of its solution, the structure of water within the channel and, of course,
the geometric size and shape of the channel 15. Theory of ion channel conductance has
not advanced to the point where conductance can be accurately predicted given a
channel’s three-dimensional structure. The conductance of large cylindrical water-filled
channels has, however, been modeled with some success as g =
σ ⋅ A
, where σ is the
L
bulk conductivity of the solution, A is the ion-accessible cross-sectional area, and L is
the length of the channel 16. Although this approximation is an overestimate for smaller
channels, g is in any case a monotonically increasing function of A if all non-geometric
factors are held constant; i.e., if a channel conducts ions, a decrease in cross-sectional
area results in a decrease in channel conductance. We draw only qualitative conclusions
from our model since it incorporates only steric effects on channel conductance.
So that the conductance might be principally determined by passage of only one
base pair at a time, we designed a hypothetical channel with a single narrow constriction
or ‘bottleneck’. The constriction was designed to be slightly wider than the diameter of
dsDNA and have a thickness that is small compared to nucleotide spacing along dsDNA.
Conductance (in units relative to the channel’s conductance without DNA present) was
calculated as the position of either canonical (Fig. 1B, black line) or modified (Fig. 1B,
red line) dsDNA was shifted along the axis of the channel (see materials and methods).
The modified dsDNA has an identical base sequence, but for one of its strands, every dT
was replaced by dU and every dC replaced by d-5-methyl-C (dmC).
We draw three conclusions from the output of the model for unmodified dsDNA.
(i) There is a periodic pattern of conductance peaks and valleys as a function of dsDNA
4-5
position along the channel axis, reflecting the periodic structure of dsDNA. (ii)
Conductance ‘valleys’ follow a pattern, so that dG-dC base pairs are distinguishable
from dA-dT base pairs; i.e., dA-dT base pairs block a greater fraction of channel
conductance than do dG-dC base pairs. (iii) By observing the conductance ‘valleys’ of
canonical DNA, one cannot distinguish dA-dT from dT-dA or dC-dG from dG-dC. For
the modified dsDNA conductance trace, ‘valleys’ corresponding to dmC -dG base pairs
can now be distinguished from those of dC-dG, and dA-dT can be distinguished from
dA-dU. One can envision the use of bulkier modifications if more base-dependent
contrast in conductance is required.
4-6
A.
B.
Relative G (%)
76.5
76.0
T
75.5
0
C
C
10
A
G
G
20
G
C
G
A
30
T
C
A
40
DNA Position (Å)
4-7
Figure 1. Modeling conductance through an idealized DNA-containing channel to
examine feasibility of DNA sequencing. (A) The idealized pore (shown in red) is 38 Å in
diameter and 26 Å in length (the approximate length of the hydrophobic region of a lipid
bilayer). The channel has a constriction 28 Å in diameter (in yellow) which has the
thickness of one keto-oxygen (3.1 Å), so that it admits dsDNA (in blue) with
surrounding space to allow the passage of small ions. Fig. 1A was generated using
RASMOL, which can be obtained from http://klaatu.oit.umass.edu/microbio/rasmol/. (B)
Conductance of a dsDNA-containing channel as a function of DNA position along the
idealized channel axis in 0.1 Å increments (see materials and methods). Conductance is
plotted for the indicated sequence of canonical B-form dsDNA (black line) and dsDNA
modified as described in the text (red line). Comparing unmodified DNA with DNA
modified in one strand identifies which parts of the conductance curve are sensitive to
which atoms of the DNA helix. In terms of the base sequence of the modified strand, the
conductance of the valleys follow a pattern of dC = dG > dA = dT for canonical DNA
and dU > dG > dA > d5mC for the modified DNA.
4-8
Conductance measurements of Shigella LamB and bacteriophage λ. We chose to
investigate this approach experimentally using bacteriophage λ and its receptor, the outer
membrane porin LamB of Shigella sonnei. The advantages of this system are that λ is
genetically and structurally the best understood bacteriophage, and for the following
additional reasons: in vitro conditions for Shigella LamB-dependent DNA ejection have
been determined 17; bacteriophage λ, in combination with LamB, has previously been
shown to form stable transmembrane channels 18; and the structure of E. coli LamB has
been determined 19. Shigella rather than E. coli LamB was chosen for these studies,
since E. coli LamB requires ethanol or chloroform to trigger λ’s DNA ejection in vitro
20; 21. Other bacteriophages for which in vitro DNA ejection has been studied include
T4
and T5 22; 23.
LamB is a trimeric outer membrane protein whose physiological function is to
passively transport maltose 19; 24. The λ tail fiber initiates the phage/receptor interaction
by docking reversibly to surface-exposed residues of LamB 21; 25. This is followed by
irreversible association of λ with LamB and subsequent DNA ejection at a rate of 1000
base pairs per second 13. After DNA ejection, the complex of λ and LamB remains
associated, and a channel is present that is stable and permeable to larger molecules than
LamB alone can admit 18.
Although the conductance of E. coli LamB has been characterized 26; 27, the
conductance of Shigella LamB has not been reported. The LamB protein of Shigella
differs from that of E. coli by only a few residues on the outer surface of the molecule 28,
so that the overall structure and conductance of the two porins should be very similar.
4-9
We developed a method for affinity-purifying Shigella LamB (see materials and
methods) and have shown the single (trimeric) channel conductance of Shigella LamB to
be 88 ± 5 pS (based on 75 transitions measured) in 0.5 M KCl in a lipid bilayer (Fig. 2),
with occasional subconductance transitions of 29 ± 3 pS (based on 37 transitions).
Subconductance states have been described for mutants of E. coli LamB, but have not
been observed in wild-type LamB 26; 27. We ascribe the 29 pS transitions to transient
closure of monomers. For a direct comparison of Shigella LamB with its E. coli
counterpart, we measured Shigella LamB conductance to be 174 ± 7 pS (based on 63
transitions) in conditions (bilayer potential 20 mV, bath solution 1 M KCl, 10 mM Tris
(pH 7.5), 10 mM MgCl2) similar to those in which E. coli LamB conductance is known
to be 155 pS 26; 27.
4-10
G (pS)
800
400
0
0
100
200
T (sec)
Figure 2. Discrete conductance transitions due to single Shigella LamB trimers. Channel
conductance measurements were obtained by adding Shigella LamB detergent micelles
to a bath of 0.5 M KCl adjacent to a voltage-clamped asolectin bilayer. Conductance of
the trimers was found to be 88 ± 5 pS.
4-11
The conductance of single channels associated with bacteriophage T5 and with
filamentous phage fd has been studied 23; 24, and some inferences about behavior of
individual bacteriophage T4-induced channels have been made 29. Although previous in
vitro experiments suggested that the bacteriophage λ/LamB complex forms a channel 18,
single channel conductance has not been measured. We attempted to characterize the
conductance of the λ/LamB complex. When a preincubated mixture of λ and Shigella
LamB was added to a voltage-clamped lipid bilayer, large channels were observed (data
not shown). The initial conductance transition of these channels is to a level of 2.4 ± 0.5
nS (based on 88 transitions measured), followed by a drop to 2.1 ± 0.2 nS (based on 25
transitions) after a characteristic time of about 20 seconds. Subsequent to this drop, a
variety of gating behaviors between lower conductance levels was observed in some
channels. Estimating a characteristic time for complete channel closure was problematic,
since these events were quite rare. Observations of a single channel have persisted as
long as 2.8 hours, and were generally terminated by a second channel insertion or by
breakage of the lipid bilayer.
To our surprise, when λ was added to a lipid bilayer in the absence of LamB,
channels with similar characteristics were observed (Fig. 3). Examples of the gating
behaviors mentioned above are shown in Fig.3A and 3B. The mean initial conductance
transition for these channels is 2.1 ± 0.7 nS (based on 54 transitions), which is
statistically indistinguishable from the mean transition of the λ/LamB mixture. The
number of channels present with bacteriophage λ alone was not significantly different
from the number of channels present when λ was premixed with LamB. These channels
4-12
were not observed in experiments with bilayer alone, or with bilayer and Shigella LamB.
Therefore we conclude that purified λ bacteriophage can form a channel in vitro without
the aid of its in vivo receptor, LamB. We do not know if the channel is formed by intact
phage or by a subpopulation of phage, e.g., ‘ghosts’ that have spontaneously ejected their
DNA. The λ-associated channel is unlikely to be an E. coli porin contaminant, since
further equilibrium CsCl density-gradient purification of phage and extensive dialysis
with a 500,000 MWCO membrane did not significantly alter the amount of channel
activity. Also, the channel is unlike any described naturally occurring E. coli channel in
its behavior and conductance.
4-13
8
A.
G (nS)
c
b
4
0
0
5
10
15
T (min)
4
G (nS)
B.
2
0
0
50
100
T (msec)
6
G (nS)
C.
4
2
0
0
10
20
T (sec)
4-14
Figure 3. A conductance trace of single channels associated with λ bacteriophage. (A)
Discrete conductance transitions of three individual channels. Channel conductance
measurements were obtained by adding purified λ phage to a bath of 0.5 M KCl adjacent
to a voltage-clamped asolectin bilayer. (B) An expansion of the conductance profile
indicated by the b arrow in Fig. 3 A (C) An expansion of the conductance profile
indicated by the c arrow in Fig. 3 A.
4-15
Receptor-independent channel formation was unexpected, since previous work
showed that λ does not trigger release of ATP from E. coli LamB-containing liposomes,
but does trigger ATP release from Shigella LamB-containing liposomes 18. However,
several possibilities reconcile this observation with our own: receptor-independent
channel formation by λ may be particular to lipid composition (we used soy rather than
egg phosphatidylcholine) or lower salt conditions; E. coli LamB may inhibit channel
formation by λ in vitro; the λ channel may form, but only be permeable to ATP when
complexed with Shigella LamB; or the channel-forming activity of λ alone may be
below the sensitivity of the ATP detection assay used. Experiments demonstrating a
Shigella LamB requirement for λ DNA injection 13; 17; 30 do not conflict with our
observations, since channel-formation and DNA ejection may be independent processes.
We do not believe that DNA transfer is occurring during our observations of λ phage
alone, since previous work has clearly shown that LamB is required for in vitro DNA
ejection 13. Nor do we expect DNA transfer in our mixtures of LamB and λ, since any
DNA ejection would have taken place before conductance is measured.
Conductance measurements of the λ channel allow us to make general inferences
about the nature of the channel used by λ for DNA transfer across the outer membrane. It
has not been known whether λ widens a channel in LamB for DNA transport or if it
forms a distinct transmembrane channel. Using a cylindrical water-filled channel model
(described above) with the 58.5 mS/cm conductivity of 0.5M KCl 31, a channel with 2.1
nS conductance has the 2 nm diameter of dsDNA if it has an ‘effective’ length of 9 nm.
Although the phage tail is about 150 nm long, its ‘effective’ length will be determined by
4-16
the permeability of the tail wall to ions, so that 9 nm does not seem unreasonable. The
conductance of the λ channel is comparable to the 2.1 nS conductance of FhuA/T5
bacteriophage channel under similar salt conditions 23 and to the 3.0 nS conductance of
the adsorption protein of filamentous phage fd (observed in 1M rather than 0.5M KCl)
24.
The observation that λ can by itself form a channel large enough to pass DNA
removes any need to invoke LamB as the pore used for DNA transfer, but does not rule
out this possibility.
Experiments critical to the success of the proposed sequencing method will
involve the addition of λ bacteriophage to a LamB-containing bilayer, so that
conductance during DNA transport may then be observed. We do not know if λ‘s DNA
transport channel contains a single ‘bottleneck’ as we have modeled above, and so we
cannot predict whether the channel will have sequence-dependent variations in ion
conductance which exceed the noise inherent in our experimental system. We also
cannot be certain that random thermal motion of DNA as it passes through λ‘s tail tube
will permit unidirectional motion of DNA as we have modeled it above. However, a
calculation of the rate of this random motion based on frictional considerations indicates
that it will be slow when compared with achievable data acquisition rates. In any case,
distinguishing the conductance signature of DNA transport from that of λ alone is
possible now that the conductance of λ and Shigella LamB have been observed
individually.
We suggest bacteriophage λ/Shigella LamB as a system for investigating singlemolecule DNA sequencing. In addition, this system may allow us to elucidate details of
4-17
λ phage's mechanism of DNA transfer. Although other virus-associated channels have
been previously described, e.g., bacteriophage T5/FhuA, filamentous phage fd
adsorption protein, mammalian reovirus, and influenza A virus, no detailed mechanism
for transmembrane nucleic acid transfer has been established for these systems 23; 24; 3234.
Details of other DNA transport systems, e.g., bacterial conjugation or specific uptake
of DNA by Haemophilus influenzae are also unknown 35.
Experimental protocol
Bacteriophage λ and LamB preparations. Purified bacteriophage λ of strain
cI857ind1Sam7 was obtained from New England Biolabs and was purified further by
CsCl equilibrium density centrifugation 36. Yield was determined to be ~1012 pfu/ml.
Shigella LamB protein was affinity-purified from E. coli strain Pop154, which carries a
Shigella LamB gene in place of the endogenous gene 25. Solubilized outer membranes
prepared from 2 L culture as described 37 were mixed with 15 ml amylose/agarose
affinity resin (New England Biolabs) and equilibrated with 10 mM CAPS/10 mM Tris
(pH 8.0), 1% triton X-100 and 100 mM NaCl. The column was washed with 20 mls
equilibration buffer. LamB protein was eluted with a continuous pH gradient established
between equilibration buffer and otherwise-identical pH 11 buffer. Fractions were
neutralized and those containing LamB were pooled and dialyzed against an excess
volume of 10 mM Tris (pH 7.5), 1% triton X- 100, 100 mM NaCl. The yield of LamB
protein was 49 µg/ml (2.1x1014 trimers/ml). Consistent with its maltose-binding
function, LamB can also be eluted using 2% maltooligosaccharide mix (Pfanstiehl
4-18
Laboratories, Inc.). We tested Shigella LamB and λ by mixing the two preparations
1:250 by volume and assaying for λ DNA release using ethidium bromide-stained
agarose gel electrophoresis. Fluorescence increased upon λ addition -- plateauing after
~1 minute at 37° -- but did not increase when LamB dialysis buffer was used in place of
LamB. In preparation for conductance measurements, a mixture of 1:250 by volume of
LamB: λ preparations was incubated at 37° for 3 hours, and then mixed 1:1 with 1M
KCl to approximately equalize salt concentrations to bath solution. 150 µl of this
mixture was added to bilayer chamber. For lambda-only channel measurements, phage
was prepared in the same manner, replacing the LamB preparation with 10 mM Tris (pH
7.5), 1% triton X-100, 100 mM NaCl.
Estimation of thermal motion of DNA. To obtain an order of magnitude estimate for the
diffusion constant (D) of DNA during injection, we first assumed that -- in the manner of
a spring -- the driving force of DNA transport is that stored in the densely packed DNA
of the head. If the packaging energy for λ is similar to that measured for other
bacteriophages -- ~1 ATP for every 2 bp packaged 38; 39 -- and if about 10% of this
energy is available to drive DNA transport, then a force (F) of 1.6 * 10-11 J m-1 would
drive DNA the length of 48,500 bp ( F ⋅ distance = energy ). We can relate F to a
frictional coefficient (f) for our situation if we assume the ‘terminal velocity’ v of DNA
transport --where frictional force balances motive force -- to be the rate previously
measured (~103 bp/sec) 13, since f ⋅ v = F . Finally, using the Einstein-Smoluchowski
relation
D=
k⋅T
f , we can estimate D to be ~10-16 meter2/sec. Knowing D, and using the
one-dimensional diffusion equation X RMS = 2 ⋅ D ⋅ t , where XRMS is the root-mean4-19
square distance traveled by DNA in a time t, we can conclude that the characteristic time
for the segment of DNA which experiences the friction calculated above to move a
distance of 1 bp by random thermal motion is ~1 millisecond. This is slow compared
with our data acquisition time of 3 microseconds per sample. See ref. 40 for a discussion
of diffusion.
Model for conductance of a DNA-containing channel. Conductance was calculated using
g( x ) =
1
1
=
N
R( x )
 τ 

∑ 
i = 1  A(i, x ) , where g(x) and R(x) are the conductance and resistance,
respectively, of the DNA-containing channel as a function of DNA position x, A(i, x) is
the ion-accessible area of a particular ‘slice’ i for the DNA-containing channel,
respectively, and N is the number of axial ‘slices’ of thickness τ into which the channel
can be divided. We set τ at 0.1 Å, and chose the ion Be++ for its small radius (0.35 Å).
The total resistance of the channel is the sum of the resistances of all the ‘slices’. For
each slice, the resistance is proportional to slice thickness τ and inversely proportional to
the ion-accessible area. The ion-accessible area of each slice was calculated by adding
the ion radius to the van der Waals radius of each channel and DNA atom, and then
counting the number of points on a 0.1 Å grid that are not contained within any atom’s
resultant radius.
Conductance measurements. All conductance measurements employed a TeflonTM block
with two chambers, each of ~ 1 ml capacity. The chambers are separated by a .0005
inch-thick TeflonTM or KortonTM FEP film (Norton Performance Plastics) with a small
(~25-30 µm) aperture. The aperture is produced by static discharge from a ZerostatTM
4-20
piezoelectric gun (Discwasher). Unless otherwise indicated, bath solution was 0.5 M
KCl, 5 mM Tris (pH 7.5), 5 mM MgCl2. Bilayers were produced by the folded bilayer
method 41 using 3 µl of a 20 mg/ml solution of asolectin (Sigma #P-5638) in pentane for
each chamber, and with light application of 1% squalene in pentane to the aperture.
Unless otherwise indicated, all bilayers were voltage-clamped at 25 mV. Electrodes were
Ag/AgCl (Axon Instruments). An Axopatch 200A amplifier (Axon Instruments) was
used to monitor pipette current in the capacitive-feedback configuration with a CV201A
headstage. Internal low-pass Bessel filter was set at 1 KHz, and a sampling interval of
100 µsec was used. A TL-1 DMA A/D converter interface transferred data to acquisition
software PCLAMP 6.0.2 (Axon Instruments). Data were analyzed with PCLAMP 6.0.2
and Axograph 2.0 (Axon Instruments). Shigella LamB measurements were digitally
filtered at 10 Hz.
References
1.
Hunkapiller, T., Kaiser, R.J., Koop, B.F. and Hood, L., Large-scale and
automated DNA sequence determination, Science, 254(5028), 59-67, 1991.
2.
Fleischmann, R.D., Adams, M.D., White, O., Clayton, R.A., Kirkness, E.F.,
Kerlavage, A.R., Bult, C.J., Tomb, J.F., Dougherty, B.A., Merrick, J.M. and et, a.,
Whole-genome random sequencing and assembly of Haemophilus influenzae Rd [see
comments], Science, 269(5223), 496-512, 1995.
3.
Church, G.M. and Kieffer-Higgins, S., Multiplex DNA sequencing, Science,
240(4849), 185-188, 1988.
4-21
4.
Davis, L.M., Fairfield, F.R., Harger, C.A., Jett, J.H., Keller, R.A., Hahn,
J.H., Krakowski, L.A., Marrone, B.L., Martin, J.C., Nutter, H.L. and et al., Rapid
DNA sequencing based upon single molecule detection, Gen. Anal. Tech. Appl., 8(1), 17, 1991.
5.
Lindsay, S.M. and Philipp, M., Can the scanning tunneling microscope
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4-26
Appendix A
A Software Guide
Quite a number of applications, small and large, were written in the course of this
work. So that others may make some use of these, I’ve made an attempt here to list the
applications, their purpose, their proper usage, and the naming of input and output files.
For the sake of simplicity, I’ve divided the applications into two categories: 1)
applications for processing and analyzing Affymetrix microarray (‘chip’) data; 2)
applications for analyzing upstream noncoding DNA sequences. All of the applications
listed were written in Perl5, with the exception of ‘AlignACE’, which was written in C.
Usage for each of these applications can also be determined from the command line by
typing the name of the application with no arguments.
Applications for processing and analyzing Affymetrix microarray data. The
following is a summary table of chip analysis applications:
Application
make_SUM_file
make_FEA_file
make_BKG_file
make_NRM_file
make_ALL_file
Input
Files
.txt
.SUM,
.CEL
.FEA
.BKG
Output
Purpose
File
.SUM Converts Affymetrix chip summary file to less
ambiguous .SUM format
.FEA Groups Affymetrix .CEL file feature data by ORF
.BKG
.NRM
.BKG or
.NRM
.CEL
.ALL
make_XP_file
.ALL
.XP
make_DIF_file
.ALL
.DIF
chipbatch
.ALL
Background-subtracts feature intensity data
Normalizes between chips within an experiment using
in vitro transcription controls
Collection of data from complete chip set for a given
experiment
Batch file for running make_FEA_file,
make_BKG_file, make_NRM_file, make_ALL_file
Computes absolute expression levels for each ORF in
an experiment
Computes relative expression levels for each ORF
between two experiments
‘make_SUM_file’
Usage: “make_SUM_file ?.txt -o ?.SUM”.
A-2
Example: “make_SUM_file 1228a.txt -o Sc_A.SUM”.
The starting point for our analysis was a ‘.CEL’ file created by the Affymetrix
GeneChip software. The ‘.CEL’ file contains the mean and variance of fluorescence
intensity for every coordinate on the chip. An essential step in calculating abundance of
an ORF is knowing which positions on the chip correspond to which ORFs. To this end,
we received files from Affymetrix which give the number of probes for each ORF, and
the X and Y coordinates of the ‘upper leftmost’ and ‘lower rightmost’ positions for each
feature set. Unfortunately, this description is ambiguous in cases where this feature set
has been interrupted, since the two defining coordinates given do not tell us where the
interruption occurs. Examples of interruptions include some features near the chip edge
which do not contain DNA, and checkerboards of features complementary to a control
DNA sequence located at the center and periphery of the chip. The ‘.SUM’ file was
designed as an unambiguous format which contains the start and stop coordinates of
uninterrupted blocks of features. ‘make_SUM_file’ takes the Affymetrix ‘.txt’ files and
converts them to .SUM files, notifying the user of ambiguities. To resolve ambiguities, a
‘dummy’ .CEL file was created containing intensities each of which encodes its
corresponding coordinate, e.g., the feature at coordinate (133,54) is given the intensity
133054. When this .CEL file is examined using the GeneChip software, the intensities
corresponding to a given ORF determine the corresponding coordinates. The .SUM files
which have been hand-edited to remove ambiguities are called ‘Sc_A.SUM’,
‘Sc_B.SUM’, ‘Sc_C.SUM’, and ‘Sc_D.SUM’, corresponding to chips A through D in a
complete chip set for yeast.
‘make_FEA_file’
A-3
Usage: “make_FEA_file ?.CEL ?.SUM”.
Example: “make_FEA_file 062697GALA.CEL Sc_A.SUM”.
Given the unambiguous locations of features corresponding to a given chip set,
we can now group intensity data by ORF. ‘make_FEA_file’ does this, putting the result
into a ‘.FEA’ file. In addition, ‘make_FEA_file’ groups a set of intensities drawn from
36 non-DNA-containing features into a feature set called ‘BACKGROUND’, for the
purpose of determining background and detection threshold levels.
‘make_BKG_file’
Usage: “make_BKG_file ?.FEA”.
Example: “make_BKG_file 062697GALA.FEA”.
This program finds the mean of 36 non-DNA-containing features and subtracts it
from every intensity value in a .FEA file. The results are written to a .BKG file.
‘make_NRM_file’
Usage: “make_NRM_file ?.BKG”.
Example: “make_NRM_file 062697GALA.BKG”.
If one would like to compare absolute abundance of ORFs which were measured
on different chip types within the same experiment, it is important to normalize the
results between the four different .BKG files of a chip set, since the average amount of
oligonucleotide on a chip can vary. This is true even if each chip has been hybridized
with the same pool of labeled nucleic acid under identical conditions. A reasonable
approach to normalization is to spike the pool of nucleic acid with a fixed amount of a
known sequence which can be assayed on each chip in the set. The chips have been
designed with this in mind, so that each chip in a set contains probes for several bacterial
A-4
transcripts. ‘make_NRM_file’ gets the median value of ∆ for each of these transcripts
and averages it to obtain a normalization factor. This program was not used for the work
in this thesis, since we sought only to calculate transcript abundance in each
‘experimental’ condition relative to a ‘baseline’ condition, and were not interested in
comparing abundances of different ORFs within the same condition. Consequently,
absolute abundance values of ORFs found in the appendices should be compared with
absolute abundances of other ORFs measured on different chip types only with some
hesitation.
‘make_ALL_file’
Usage: “make_ALL_file ?A.NRM ?B.NRM ?C.NRM ?D.NRM or
make_ALL_file ?A.BKG ?B.BKG ?C.BKG ?D.BKG”.
Example: “make_ALL_file 062697GALA.NRM 062797GALB.NRM
062797GALC.NRM 062997GALD.NRM”.
Since measuring abundance of all transcipts in a single condition requires four
chip experiments, the data from these experiments should be gathered together and
treated as a single data set (a .ALL file). ‘make_ALL_file’ also normalizes the complete
data set so that it will be comparable to data sets from other .ALL files. Normalization is
as discussed in Chapters 2 and 3. Each intensity value is divided by a normalization
factor. The normalization factor is the average PM intensity over all four chip data sets
within a .ALL file.
‘chipbatch’
Usage: “chipbatch ?A.CEL ?B.CEL ?C.CEL ?D.CEL [-d]”.
A-5
Example: “chipbatch 062697GALA.CEL 062797GALB.CEL
062797GALC.CEL 062997GALD.CEL”.
This is simply a script which shepherds a set of .CEL files from the four chips
through ‘make_FEA_file’, ‘make_BKG_file’, ‘make_NRM_file’ (optional) and
‘make_ALL_file’. The -d option indicates a decision to skip the normalization between
chips using the in vitro transcription controls provided by ‘make_NRM_file’.
‘make_XP_file’
Usage: “make_XP_file ?.ALL ?.XP”.
Example: “make_XP_file 062697GALA.ALL”.
This program calculates absolute abundance for every ORF by the median of ∆
values method described in Chapters 2 and 3. The .XP output file contains a threshold
column. A value of 1 in this column indicates that the value (or one of the two values if
the feature set contains an even number of probes) used to calculate the ∆ median is
below the detection threshold determined for that chip’s hybridization. If there are MM
probes among the features for an ORF which are not unique in the genome, this fact is
indicated and the calculation is based on the median of PM values rather than the median
of ∆ values.
‘make_DIF_file’
Usage: “make_DIF_file ?.ALL ?.ALL ?.DIF”.
Example: “make_DIF_file 062697GALA.ALL 062697FY4A.ALL
GAL_GLU.DIF”.
Calculates relative abundance by the median of ∆-ratios method described in
Chapters 2 and 3. Median deviation of log ∆-ratios is calculated as described in Chapter
A-6
2. ORFs are categorized based on whether or not they exceeded detection thresholds for
the two conditions being compared. This categroization is based on the ∆ values used to
calculate the median log ∆-ratio value (there are two such values for features with an odd
number of probes, four for an even number). The following table is a guide to
interpreting the threshold codes returned by ‘make_DIF_file’.
∆expt
value(s) ≥
Texpt
yes
no
yes
no
∆base
value(s) ≥
Tbase
yes
yes
no
yes
∆expt
value(s) ≥
Tbase
yes
-
∆base
value(s) ≥
Texpt
yes
no
Threshold
Code
Comment
none
1
2
3
yes
no
no
-
4
no
no
-
-
5
Detected in both conditions
Detected in condition 2 only
Detected in condition 1 only
Detected in both conditions,
but in condition 2 is below
threshold for condition 1
Detected in both conditions,
but in condition 1 is below
threshold for condition 2
Detected in neither
condition
For the preceding table, the .ALL file that is first in the argument list is considered to be
the experimental condition, and the second .ALL in the argument list is the baseline
condition. Texpt and Tbase refer to the detection threshold in the experimental condition
and the baseline condition, respectively. If there are MM probes among the features for
an ORF which are not unique in the genome, this fact is indicated, and the calculation is
based on the median of PM-ratios rather than the median of ∆-ratios.
Applications for analyzing upstream noncoding DNA sequences. The following
is a summary table of upstream sequence analysis applications:
Application
Input
Files
Output
File
Purpose
A-7
pickup
.up,
.dat selects upstream regions from yeast sequence
Sc_table,
yeastseq
makeseqfile
.ascii yeastseq concatenates a set of SGD raw sequence files w/o line
feeds
AlignACE
.dat
.out finds and aligns conserved sequences
.out
.LGO creates logos from gibbs output file
make_LGO_files
make_aln_files
.out
.aln extracts set of aligned sites from gibbs into FASTA
format
matrix_comp
.aln
.cmp assesses similarity between sets of aligned sites
find_consensus
.aln
.cns gets consensus sequence for aligned sites
scoresites
.out
.sco finds sites matching an aligned sequence set
assignsites
.sco
.ass,.as2 assigns each site upstream of coding regions to its ORF(s)
mergeORFs
.DIF,.as2 .MRG takes a list of ORFs ranked by expression and merges
with site info
‘pickup’
Usage: “pickup yeastseq?? Sc_table?? [-l ?.up] [-r #ofrandom]
[-m widthmin] [-w widthmax] [-c]”.
Example: “pickup yeastseq8_97 Sc_table9_97 -l coolORFs.up -o
coolORFs.dat -m 300 -w 600”.
This application returns a FASTA-format file containing upstream non-coding
regions, given an input (.up) file with a list of ORF names, e.g., YJL052W. All of the
work described in this thesis used yeastseq8_97 and Sc_table9_97, which are the raw
DNA sequence and ORF tables from S. cerevisiae as obtained from SGD. The program
can be used without an input file to generate an upstream sequence file from randomly
chosen ORFs. The upstream region is delimited at one end by the translation start of the
ORF specified and at the other end by the start or stop of the nearest upstream ORF,
except where a minimum or maximum upstream sequence length is specified. The -c
option can be used to generate both forward and reverse strands of the upstream
A-8
sequence. If two ORFs which share an upstream region are listed in the input file, that
upstream sequence is returned without duplication of sequence.
‘makeseqfile’
Usage: “makeseqfile ?? [-s seqdir]”.
Example: “makeseqfile yeastseq8_97 -s ~/yeast/all_raw/”.
This program takes a set of raw sequence files (one per chromosome) that have
been obtained from SGD and are in the specified directory, concatenates them and writes
them into one file. Line feeds are removed for faster loading of raw sequence data by the
program ‘pickup’.
‘AlignACE’
Usage: “AlignACE [-? -? -? ...]”.
Example: “gibbs -w10 -x10 -t500 -r100 -u50 -q3 -igoodORFs.dat
-ogoodORFs.out”.
This is an application which finds conserved motifs among DNA (or RNA)
sequence. The ‘.dat’ input file contains the sequence data to be examined in FASTA
format. Differences between this application and Gibbs Motif Sampling are described in
Chapter 3.
AlignACE performs a series of motif searches. After each successful motif
search, bases at the most information-rich position in the discovered motif are ‘masked
out’ so that they cannot be found in subsequent motif searches. We call this an iterative
masking approach.
Each motif search consists of a series of ‘sampling runs’, after which the highest
scoring motif found thus far is further optimized in a ‘near-optimum sampling run’.
A-9
Each run consists of a ‘column sampling step’, a ‘pass’ through the input sequence, and a
recalculation of the motif (or ‘MAP’) score. If the MAP score is higher than any
previously encountered in the current run, the current alignment is saved.
When column sampling is employed, only the number of columns (sequence
positions) specified is used to optimize the alignment, even though the element may span
a larger number of bases (e.g., the Gal4 binding site spans 17 bases even though only
about 8 bases show conservation).
The command line options for AlignACE are summarized in the table below.
Switch
-d
-e
-f
-i
-m
-n
-o
-p
-q
-r
-s
-t
-u
Default
Value
1
stderr_outfile
0.1
none
3× (#columns)
500
infileoptions.out
0.8
10
10
100
100
100
-w
10
-x
-z
10
-
-c
Description
Number of cycles per column shift
Turn off column sampling
Save debugging information to a file
Ratio of pseudocounts to real counts
Input file name
Maximum width of site
Number of iterations of near-optimum sampling
Output file name
Fractional weight on prior expectation of # of sites
Exit after this number of failed motif searches
Maximum total number of iteratively masked motif searches
Cease sampling run after this many passes without improvement
Maximum number of sampling runs in motif search
Cease motif search after this many sampling runs without
improvement
Number of columns (maximum number of conserved positions
expected)
Expected # of elements in input sequence data
Show stderr output
‘make_LGO_files’
Usage: “make_LGO_files ?.out [-r ?] [-n]”.
Example: “make_LGO_files goodORFs.out -r 10”.
A-10
This application is a front end for a set of programs developed by Tom Schneider
for generating sequence logos (described in Chapter 3). The input is a .out file generated
by AlignACE, and the output is a set of .LGO files containing logos in postscript format.
Run numbers 1 through the maximum specified by the -r switch are used to make logos
(the default is all motifs in the AlignACE file). The -n switch is used to specify that the
name of the file not be included next to the logo image.
‘make_aln_files’
Usage: “make_aln_files
?.out [-r ?]”.
Example: “make_aln_files goodORFs.out -r 10”.
This application parses a AlignACE output file (.out) and writes each motif to a
separate output (.aln) file. The .aln file is a FASTA format file containing the sites
aligned by AlignACE. The -r switch is used to limit the number of motifs parsed.
‘matrix_comp’
Usage: “matrix_comp A.aln B.aln [C.aln D.aln etc.]”.
Example: “matrix_comp *.aln”.
This application takes as input a set of .aln files (FASTA format files containing
aligned sites). By a process outlined in Appendix B, each set of aligned sites is compared
against every other set, and the resulting similarity score (best t statistic) is printed out for
matrices which are found to be similar. Currently, the default output is printed to the
screen, but this can be redirected to an output file, e.g. “matrix_comp *.aln >
all_against_all.cmp”.
‘find_consensus’
Usage: “find_consensus A.aln [C.aln D.aln etc.] [-a]”.
A-11
Example: “find_consensus *.aln”.
This application takes as input one or more .aln files (FASTA format files
containing aligned sites). By the method of Day and McMorris, a consensus sequence is
determined for each set of aligned sites. Currently, the default output is printed to the
screen, but this can be redirected to an output file, e.g. “find_consensus *.aln >
all.cns”.
‘scoresites’
Usage: “scoresites ?.out ? [-t Sc_table??] [-s yeastseq??]
[-o ?] [-z ?] [-d]”.
Example: “scoresites goodORFs.out 2 -t Sc_table9_97 -s
yeastseq8_97 -d -z 0”.
This application takes as input a AlignACE (.out) output file, a table of ORFs,
and a raw sequence file. It creates a weight matrix by the Berg and von Hippel method
described in Appendix B, and scores every site in the raw sequence file. This weight
matrix is also used to score each of the aligned sites from which the weight matrix was
derived. Based on the mean and standard deviation of the aligned site scores, a threshold
score can be set such that only scores better than this threshold will be recorded. The -z
switch is used to set this threshold: A -z switch setting of ‘0’ corresponds to a threshold
equal to the mean score of the aligned sites, while a -z setting of 3 corresponds to 3
standard deviations below (worse) than the mean of the aligned sites . The -o switch can
be used to specify the name of the output file (default is a .sco file of the same prefix as
the input file). ‘scoresites’ saves the distribution of scores across the whole genome,
unless the -d switch is applied.
A-12
‘assignsites’
Usage: “assignsites ?.sco [-t Sc_table??] [-w ?]
[-n ?] [-z ?] [-d]”.
Example: “assignsites goodORFs.sco -t Sc_table9_97 -w 600 -n
50 -z 0”.
This application takes as input a ‘.sco’ file produced by ‘scoresites’ which
contains high-scoring sites matching a motif found by ‘AlignACE’. Each site is
examined and if it lies within 600 bases (or some other distance specified with the -w
switch) upstream of an ORF’s translation start, the site is assigned to that ORF. A site
may be assigned to more than one ORF, as will be the case if the site lies within a
divergent intergenic region. The output is saved in both of two alternative formats in .ass
and .as2 files.
The -n switch is used to limit the output to the specified number of top-ranked
ORFs. The -z switch is used to only consider sites better than a certain threshold, and is
used in the same way as ‘scoresites’, described above. The -d switch is used to
automatically fetch brief descriptions of the top-ranked ORFs from the web sites of YPD,
SwissProt, and MIPS. This should be avoided unless the list of ORFs is short, as this can
be time-consuming and may be considered an unfriendly act by the managers of the
databases being accessed.
‘mergeORFs’
Usage: “mergeORFs ?.DIF ?.as2 [?.as2 ?.as2...] [-o OUTFILE]”.
Example: “mergeORFs GAL_GLU.DIF goodORFs.as2”.
A-13
This application merges a .as2 file with a .DIF file, so that each ORF in a .DIF file
is associated with the number of upstream matching sites and the highest score of its
upstream sites.
A-14
Appendix B
Method for Quantitatively Assessing Similarity Between
Intergenic DNA Element Motifs
Since much of this appendix is concerned with weight matrices as a
representation of an aligned set of DNA sequences, I will first devote some attention to
weight matrices. A weight matrix of size 4 × L can be used to described a set of sites of
maximum length L. There are four rows since there are four nucleotides. Elements of
the matrix are measures of the propensity of a ‘real’ site (one which is presumably bound
by a DNA-binding protein) to have a given base at a given position. This matrix can then
be used to assign an objective score to any DNA sequence, where the score reflects the
similarity of that sequence to the set of aligned sequences. A number of methods have
been used for deciding what values to put in each of the matrix elements. The method we
used for building weight matrices throughout this work was that of Berg and von Hippel
1, wherein each element is given by
 n(b, p) + 0.5 
ln 
 . Here, n(b,p) is the number
 nmax (p) + 0.5 
of occurrences of base b at position p in the set of aligned sites, and nmax is the number of
occurences of the most commonly occuring base at position p. The result of this equation
is that the most common base at a position is given weight 0, while less common bases
are given increasingly negative weights. The addition of 0.5 in the numerator and
denominator is a pseudocount, which has the effect of lessening the penalty for bases that
do not occur in the aligned sites. The reduction in penalty is most dramatic in cases
where the matrix has been generated from very few aligned sites.
If a base occurs
commonly in upstream regions, we may want to adjust the score to reflect this. Imagine a
case where ten examples of the sequence AAAAAAA have been aligned to generate a
weight matrix. It would hardly be surprising to find a sequence matching this matrix in a
95% AT genome, but it would be very surprising to find matches to this matrix in a 5%
B-2
AT genome. The matrix weights can be adjusted based on the background nucleotide
frequency in upstream regions, i.e., the prior probability of a base’s occurrence, by adding
 fbkg(b) 
 to each matrix element, where fbkg(b) is the background frequency of the
ln 
 fmax 
base b corresponding to the matrix element and fmax is the background frequency of the
most common base.
Along with developing methods for discovery of regulatory sequence elements, a
major goal of the work described in Chapter 3 was to validate these methods. For this
purpose, yeast growth conditions and/or genotypes were chosen where we might predict
the outcome. In other words, conditions were chosen where we already knew which
upstream sequence motifs we might expect a priori. Having obtained a set of sequence
motifs by the ‘AlignACE’ method of sequence alignment and the specificity scoring
approach, we must then ask, “Did we find the motifs we expected”. It would be all too
easy to simply look at a motif and conclude that it ‘looks like’ the motif we expected, and
in some cases this would be perfectly reasonable and reliable. It is in the borderline cases
of similarity where a visual examination is subject to the risk of a bias based on
expectations. When confronted with the need for an objective method for quantifying
similarity between two sets of DNA elements, I was surprised to discover that no such
method existed in the literature.
The problem of comparing two sets of aligned sites can be separated into two
parts. The first part is alignment of the two motifs or site sets with each other. I viewed
this problem as equivalent to aligning two weight matrices. To achieve this, I simply
tried all possible alignments of the two matrices with each other. For each alignment, I
B-3
calculated the sum of the squared differences between corresponding matrix elements.
The alignment which minimized the sum of the squared differences is then the best
alignment. You may have noticed a difficulty with this approach. How do we handle the
fact that matrices may be of a different width, since they may represent aligned sequences
of differing widths? How do we handle the fact that even matrices of the same width will
overhang one another in all but one possible alignment? At overhanging positions there
will be’missing’ elements in one of the matrices. For these ‘missing’ elements, I use the
expectation value of elements, given the known background nucleotide frequencies. The
matrix elements are then just the background frequency adjustment used above:
 fbkg(b) 
 . A weight matrix is also calculated for the reverse complement of one set
ln 
 fmax 
of aligned sites, and all possible alignments are scored as above so that the best
alignments of two sets of sites are chosen from either forward or reverse complement
orientations.
The second step of motif comparison is quantitating similarity between the nowaligned sets of sites. The general approach is to reduce this problem to that of
comparison of two distributions of numbers. There are accepted measures of similarity
between two distributions in classical statistics. One such measure which is commonly
used is Student’s t-statistic, t =
µ1 − µ 2
, where µ1 and µ2 are the means of the
σ 1 N1 + 1 N 2
two distributions, N1 and N2 are the number of samples in each distribution, and
σ =
N1 ⋅ s 1 2 + N2 ⋅ s 2 2
, where s1 and s2 are the standard deviations of the two
N1 + N2 - 2
B-4
distributions. The smaller the absolute value of the t-statistic, the more similar the two
distributions.
The question remaining is how to assign a number (score) to each site, and then
how to decide on a value of t that indicates a significant similarity. Consider sets of sites
A and B and their corresponding weight matrices A and B. After aligning matrix A and
matrix B, we can define two submatrices A and B of equal width by taking the
overlapping portions of each matrix. Using submatrix A, we can assign a score to each A
sequence and each each B sequence, and calculate the t-statistic for the two score
distributions. Likewise, we can calculate a t-statistic for the scores of A sites and B sites
generated using submatrix B. The measure of similarity between matrix A and matrix B
is then tmin, the t-statistic with the smallest absolute value.
How then do we assign a threshold for tmin, below which the two matrices are
considered similar? In Chapter 3, we descibed fifteen regulatory motifs that we might
have expected from the literature. Sites corresponding to these motifs were derived from
the literature, and weight matrices were generated for each. These fifteen sets of DNA
elements provided 105 (
15 ⋅ 14
) that can serve as negative controls, since I did not
2
expect any of these motifs to be similar to one another. I calculated a t-statistic such that
a false positive rate of 5% is expected, and was surprised to see that the ECB and P-Box
motifs had a tmin which was well below the calculated threshold of similarity. The reason
for this similarity became apparent on further examination: ECB and P-Box elements are
both bound by the same transcription factor Mcm1, so that I should in fact have expected
the motifs to be similar. After removing one of these motifs, the P-Box, from the
B-5
negative control set, I was left with 91 pairwise comparisons as negative controls with
which to calculate a threshold for tmin. The graph below shows a the fraction of these
pairwise comparisons deemed similar, based on different possible thresholds of tmin. By
linear interpolation, a 5% false positive rate was achieved using a tmin of −3.26.
Fraction of Negative Control Comparisons Deemed Similar for
Various Cutoffs Threshold of Best t-Value
0
-1
y = -36.14x - 1.4554
R2 = 0.9586
-2
-3
-4
-5
-6
-7
-8
0
0.1
0.2
Fraction of comparisons that are False Positives
In addition to the criteria above, we also require that the best alignment of sites
has an overlap of at least five bases, since DNA regulatory sites generally have more than
five conserved positions.
References.
B-6
1.
Berg, O.G. and von Hippel, P.H., Selection of DNA binding sites by regulatory
proteins. Statistical-mechanical theory and application to operators and promoters,
Journal of Molecular Biology, 193(4), 723-750, 1987.
B-7
Appendix C
Absolute and Relative Abundance of Detectable Transcripts
in Four Saccharomyces cerevisiae Cultures Organized
Alphabetically by ORF Identifier.
This appendix contains a table of those absolute and relative transcript
abundances that were detectable in at least one of four Saccharomyces cerevisiae
cultures. The genotype and growth conditions of these cultures are described in Chapter
3, as are the method of data collection, background subtraction and normalization. Since
I took only one approach of many towards analyzing this rich data set in Chapter 3, it is
my hope that this appendix will serve as a resource to others in the future.
In addition to conclusions drawn from this data in Chapter 3, there are minor
observations drawn from this data with regard to ‘housekeeping’ genes commonly used as
standards in Northern mRNA quantitation experiments. Transcripts for TBP (YER148W;
TATA-binding protein, also known as SPT15 or TFIID), ACT1 (YFL039C; actin), SRB4
(YER022W; subunit of RNA polymerase II holoenzyme), and PDA1 (YER178W;
subunit of pyruvate dehydrogenase) are commonly used standards for quantitating
mRNA. Neither TBP nor SRB4 were above detection threshold in all of our experiments,
so that these are not useful standards for our data. The absolute abundance of ACT1 is
more promising as a standard, in that it is well above detection threshold in all conditions
and its measured absolute abundance varies by only about 20% at most (between mating
type α and heat-shock). Measured absolute abundance of PDA1 was above detection
threshold in all conditions but was low in galactose (more than seven-fold lower than in
heat-shock). This is surprising, given that PDA1 transcript level has been cited as being
more invariant to varying growth conditions than that of ACT1 1. The RPS2 gene
(YGL123W; also known as RPS4 or SUP44) is one of few genes whose absolute
transcript abundance has been reliably quantitated. It was found to be at 28 ± 5 copies per
cell under growth conditions similar to those for our ‘baseline’ culture (glucose minimal
C-2
medium without casamino acids grown at 30 °C to mid-log phase) 2. Measured in the
absolute abundance units of the table below, RPS2 has an absolute abundance of 7.1 in
our ‘baseline’ (mating type a, glucose, 30 °C) condition. Based on this, 0.25 absolute
abundance units corresponds roughly with a single transcript per cell. This is necessarily
approximate since growth conditions and strains varied..
Guide to abundance table. The first column in the abundance table (“ID”)
containsexcepting the ribosomal RNA genes at topthe ORF identifier as issued by
the Saccharomyces Genome Database. An ORF identifier printed in italics indicates that
the sequence of some of the mismatch probes for this ORF were not unique in the
cerevisiae genome. In this case PM values were substituted for ∆ values in calculating
absolute and relative abundance, so that the quantitation for these ORFs should be viewed
more critically.
The second column (“Gene”) contains the common gene names corresponding to
each ORF identifier. The gene names were taken from the current (10 April 98) SGD
table of gene names.
The third column (“Chip”) indicates which of the four Affymetrix microarrays
contain the probe pairs corresponding to this transcript. Some transcripts are measured
on all four of the microarrays, so that they are labeled “A-D”.
The fourth column (“#PP”) is the number of probe pairs corresponding to this
transcript contained on the microarrays. Most transcripts employed 20 or 21 probe pairs
but a few ‘housekeeping’ genes, namely YFL039C (ACT1), YER 148W (SPT15), and
C-3
YER022W (SRB4) employed many more probe pairs and were measured on all four
microarrays in each condition.
The fifth through the eighth columns (“a”, “α”,”gal”, and “heat”) contain absolute
transcript abundances. These values are calculated by taking the median of normalized ∆
values. If the central-most ∆ valueor either of the central-most ∆ values in cases where
there is an even number of ∆ valuesin a ranked list is below detection threshold
(described in Chapters 2 and 3) then a transcript is considered to be below detection
threshold. Transcripts which fell below the detection threshold of the corresponding
hybridization experiment are indicated by abundance values in italics. In this case, ∆
values used to calculate the abundance value were adjusted to the detection threshold if
they fell below it.
The last three columns (“log (α/a)”, “log (gal/a)” and “log (heat/a)”) contain
transcript abundances relative to the ‘a’ culturestrain FY4 (MAT a), grown on glucose
at 30 °C. These values are calculated by taking the median of the log-ratios of
normalized ∆ values. If any of the ∆ values used to calculate the ratios of the centralmost ∆ ratio value(s) in a ranked list are below detection threshold (described in Chapters
2 and 3) then a transcript is considered to be below detection threshold in one or both of
the conditions being compared. Transcripts considered below detection threshold in one
or both conditions being compared are indicated by median log ∆-ratio values in italics.
If a transcript is below detection threshold in both conditions being compared, the median
log ∆-ratio is set to zero.
C-4
For each of the relative abundance values, a measure of significance is calculated
by dividing the median log ∆-ratio by the median deviation of log ∆-ratios. If this
measure of significance is one or greater, and the median log ∆-ratio is 0.2 or greater, the
median log ∆-ratio value is in bold type.
The following table contains abundance values for 3399 Saccharomyces
cerevisiae ORFs. Appendix D contains a list of those ORFs which both fell below
detection threshold in all four cultures measured and were not measurably changed
between pairs of conditions, along with a list of ORFs not represented on the microarray
set. Appendix D also contains a table of detection thresholds for each microarray
assayed.
C-5
Absolute and Relative Abundance of Transcripts in Four Assayed Cultures
ID
18srRnaa
18srRnab
25srRnaa
25srRnab
25srRnac
25srRnae
YAL003W
YAL005C
YAL007C
YAL008W
YAL009W
YAL012W
YAL014C
YAL016W
YAL017W
YAL019W
YAL021C
YAL022C
YAL023C
YAL027W
YAL030W
YAL033W
YAL035W
YAL036C
YAL038W
YAL039C
YAL040C
YAL042W
YAL043C
YAL044C
YAL045C
YAL046C
YAL049C
YAL051W
YAL053W
YAL054C
YAL055W
YAL056W
YAL060W
YAL061W
YAL062W
YAL063C
YAL068C
YAR002AC
YAR003W
YAR007C
YAR009C
YAR010C
YAR015W
YAR020C
Gene
EFB1
SSA1
FUN14
SPO7
CYS3
TPD3
FUN31
FUN30
CCR4
FUN26
PMT2
SNC1
FUN53
FUN12
FUN11
CDC19
CYC3
CLN3
FUN9
PTA1
GCV3
YAF1
ACS1
GDH3
RFA1
ADE1
Chip
#PP
a
α
gal
heat
A-D
A-D
A-D
A-D
A-D
A-D
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
84
80
84
80
84
84
41
20
20
20
21
20
21
20
20
20
20
20
21
21
42
20
21
21
20
20
21
20
21
20
21
20
20
21
20
21
21
20
21
21
20
20
20
20
20
20
46
20
20
20
0.17
0.11
1.54
0.11
0.11
0.35
1.58
1.37
0.26
0.18
0.09
1.53
0.15
0.32
0.09
0.09
0.09
0.1
0.38
0.09
0.42
0.13
0.26
0.09
7.32
0.22
0.12
0.2
0.09
0.83
0.09
0.16
0.36
0.09
0.14
0.09
0.09
0.09
0.56
0.46
0.09
0.09
0.24
0.56
0.09
0.09
0.56
0.12
0.12
0.26
0.12
0.09
1.02
0.08
0.08
0.26
1.47
0.99
0.16
0.15
0.04
1.72
0.12
0.23
0.05
0.04
0.08
0.08
0.29
0.05
0.29
0.12
0.18
0.1
4.36
0.11
0.09
0.19
0.05
0.52
0.04
0.07
0.32
0.04
0.07
0.04
0.04
0.05
0.17
0.16
0.08
0.1
0.21
0.57
0.09
0.05
0.31
0.08
0.05
0.11
0.16
0.09
0.32
0.07
0.07
0.25
1.28
1.38
0.22
0.14
0.07
1.19
0.1
0.26
0.07
0.07
0.1
0.08
0.29
0.07
0.31
0.1
0.21
0.11
4.35
0.16
0.14
0.19
0.07
0.71
0.07
0.15
0.49
0.07
0.17
0.08
0.07
0.07
0.66
0.28
0.09
0.07
0.26
0.72
0.07
0.07
0.5
0.16
0.19
0.2
0.15
0.1
0.84
0.09
0.09
0.24
1.01
2.42
0.13
0.16
0.09
1.42
0.09
0.31
0.09
0.09
0.09
0.09
0.24
0.09
0.27
0.09
0.14
0.09
5.25
0.15
0.09
0.17
0.09
1.13
0.09
0.14
0.87
0.09
0.12
0.09
0.09
0.09
0.48
1.07
0.09
0.09
0.17
0.43
0.11
0.09
0.97
0.23
0.15
0.16
log
(α/a)
0
0
-0.17
-0.1
-0.2
0.08
-0.1
-0.29
-0.13
-0.14
0
0.03
-0.22
-0.1
0
0
0
-0.15
-0.23
0
-0.13
-0.17
-0.15
-0.1
-0.11
-0.26
-0.16
-0.01
0
-0.11
0
0
-0.05
0
0
0
0
0
0
-0.45
0
0.06
-0.21
-0.09
0
0
-0.13
0
0
0
log
log
(gal/a) (heat/a)
-0.12
0
0
0
-0.51
-0.22
0
0
0
0
0
0
-0.12
-0.18
-0.04
0.21
-0.04
-0.11
-0.2
-0
0
0
-0.12
0
0
0.01
-0.04
0.01
0
0
0
0
0
0
0
0
0
-0.08
0
0
-0.07
-0.1
0
0
0
0
0.02
0
-0.1
-0.26
0
-0.09
0
0
0
-0
0
0
-0.12
0.09
0
0
0
0
0.05
0.24
0
0
0.06
0
0
0
0
0
0
0
-0.03
0
-0.1
0.32
0
0
0
0
0
-0.1
-0.02
-0.1
0
0.09
0
0
-0.03
0.32
-0.01
0.21
0.01
0
0
-0.05
C-6
YAR023C
YAR027W
YAR028W
YAR033W
YAR035W
YAR042W
YAR066W
YAR071W
YAR073W
YAR075W
YBL001C
YBL002W
YBL003C
YBL005W
YBL006C
YBL007C
YBL011W
YBL015W
YBL016W
YBL017C
YBL021C
YBL022C
YBL024W
YBL025W
YBL026W
YBL027W
YBL030C
YBL032W
YBL033C
YBL034C
YBL038W
YBL039C
YBL040C
YBL041W
YBL042C
YBL043W
YBL045C
YBL047C
YBL048W
YBL049W
YBL050W
YBL051C
YBL053W
YBL055C
YBL056W
YBL057C
YBL058W
YBL063W
YBL064C
YBL068W
YBL069W
YBL071C
YBL072C
YBL076C
YBL077W
YAT1
SWH1
PHO11
ECM15
HTB2
HTA2
PDR3
SLA1
SCT1
ACH1
FUS3
PEP1
HAP3
PIM1
RRN10
SNP3
RPL19B
PET9
RIB1
STU1
MRPL16
URA7
ERD2
PRE7
FUI1
ECM13
COR1
SEC17
PTC3
SHP1
KIP1
PRS4
AST1
RPS8A
ILS1
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
21
21
20
24
21
21
20
20
22
20
20
20
16
21
21
21
20
21
20
21
20
20
21
21
36
54
20
20
21
21
21
20
20
20
20
21
21
20
21
20
20
20
21
20
20
20
21
20
20
21
21
21
16
20
20
0.09
0.29
0.09
0.09
0.13
0.1
0.09
0.09
0.11
0.22
0.51
2.74
1.31
0.09
0.19
0.16
0.13
0.46
0.11
0.09
0.09
0.11
0.09
0.09
0.09
0.64
2.41
0.17
0.13
0.09
0.09
0.11
0.24
0.26
0.1
0.09
0.4
0.09
0.09
0.09
0.1
0.09
0.09
0.09
0.09
0.09
0.21
0.09
0.34
0.25
0.09
0.09
23.04
0.41
0.09
0.04
0.22
0.08
0.06
0.11
0.15
0.06
0.05
0.04
0.22
0.24
2.63
1.11
0.05
0.12
0.13
0.06
0.11
0.06
0.06
0.04
0.08
0.1
0.1
0.04
0.57
1.44
0.11
0.05
0.04
0.1
0.14
0.12
0.11
0.04
0.05
0.17
0.05
0.04
0.06
0.18
0.07
0.15
0.04
0.05
0.06
0.05
0.04
0.18
0.24
0.04
0.05
18.06
0.48
0.06
0.08
0.17
0.08
0.07
0.1
0.07
0.12
0.07
0.08
0.2
0.54
1.92
1.39
0.07
0.16
0.17
0.1
0.66
0.07
0.15
0.08
0.1
0.07
0.07
0.08
0.37
2.61
0.13
0.28
0.07
0.13
0.11
0.18
0.16
0.12
0.07
0.78
0.09
0.07
0.07
0.17
0.07
0.07
0.1
0.09
0.07
0.15
0.07
0.73
0.22
0.07
0.07
17.16
0.37
0.07
0.09
0.16
0.11
0.09
0.09
0.09
0.09
0.09
0.09
0.16
0.7
0.73
0.47
0.09
0.15
0.14
0.1
0.14
0.09
0.12
0.09
0.11
0.09
0.1
0.09
0.23
1.98
0.09
0.15
0.09
0.09
0.1
0.11
0.24
0.11
0.09
0.33
0.09
0.18
0.1
0.16
0.09
0.09
0.09
0.09
0.09
0.21
0.09
0.54
0.22
0.1
0.09
7.03
0.4
0.09
0
-0.21
0
0
-0.17
0
0
0
0
0
-0.13
0.08
-0.05
-0.25
-0.23
-0.24
0
-0.44
-0.18
-0.19
0
0
-0.14
0.04
0
-0.06
-0.19
0
0
0
-0.23
-0.1
-0.27
-0.28
0
0
-0.37
0
0
0
-0.05
0
0.01
0
0
0
0
0
-0.2
0
0
0
-0.13
0.06
0
0
0
0
0
0
-0.1
0
0
0
0
0
-0.08
-0.01
0
0
0
0
0.17
0
0
0
0
0
0
0
0
0
0
0.26
0
-0.08
0
0
0
0.01
0
0.18
0
0
0
-0.08
0
0
0
0
0
0
0
0.14
0
0
0
-0.13
-0.06
0
0
0.01
0
0
-0.1
-0
0
0
-0
-0.13
0.26
-0.48
-0.48
0
-0.02
0
0
-0.33
0
0
0
0
0
0
0
-0.3
-0.2
-0.12
0
0
0
0
-0.2
0
0
0
-0.11
0
0.29
0
0
0
0
0
0
0
0
0
0.09
-0.01
0
0
-0.49
0
0
C-7
YBL078C
YBL081W
YBL082C
YBL083C
YBL084C
YBL085W
YBL087C
YBL089W
YBL091C
YBL092W
YBL099W
YBL101C
YBL101W-A
YBL102W
YBL103C
YBL106C
YBL112C
YBL113C
YBR001C
YBR004C
YBR005W
YBR006W
YBR008C
YBR009C
YBR010W
YBR011C
YBR012W-A
YBR012W-B
YBR013C
YBR014C
YBR015C
YBR016W
YBR018C
YBR019C
YBR020W
YBR022W
YBR023C
YBR024W
YBR025C
YBR026C
YBR028C
YBR029C
YBR031W
YBR034C
YBR035C
YBR036C
YBR037C
YBR038W
YBR039W
YBR041W
YBR042C
YBR043C
YBR046C
YBR048W
YBR049C
RHK1
CDC27
BOI1
RPL23A
MAP2
RPL32
ATP1
ECM21
SFT2
RTG3
SNI2
NTH2
FLR1
HHF1
HHT1
IPP1
TTP1
GAL7
GAL10
GAL1
CHS3
SCO2
MRF1'
CDS1
RPL4A
HMT1
PDX3
CSG2
SCO1
CHS2
ATP3
FAT1
ZTA1
RPS11B
REB1
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
20
21
20
26
20
21
53
21
20
20
21
21
20
21
21
21
20
24
20
21
20
20
21
20
20
20
20
40
21
21
21
21
21
20
21
20
21
21
21
20
20
21
20
20
20
20
20
20
21
20
20
20
20
84
20
0.09
0.09
0.09
0.2
0.09
0.09
2.07
0.09
0.41
3.47
1.71
0.12
0.09
0.51
0.09
0.09
0.09
0.75
0.09
0.15
0.36
0.12
0.33
1.7
5.04
1.17
0.21
0.09
0.09
0.09
0.11
0.96
0.09
0.09
0.09
0.1
0.11
0.09
0.75
0.09
0.09
1.12
17.42
0.1
0.48
0.62
0.1
0.09
0.65
0.31
0.1
0.1
0.31
0.32
0.09
0.05
0.08
0.05
0.13
0.05
0.06
1.37
0.06
0.37
2.96
0.68
0.09
0.05
0.35
0.04
0.04
0.08
0.49
0.04
0.14
0.2
0.04
0.24
1.06
3.84
0.63
0.17
0.09
0.04
0.13
0.07
0.6
0.04
0.04
0.04
0.04
0.13
0.05
0.76
0.1
0.04
1.09
15.97
0.1
0.35
0.44
0.05
0.05
0.41
0.23
0.11
0.04
0.2
0.37
0.07
0.11
0.08
0.08
0.23
0.08
0.07
1.01
0.07
0.42
2.1
1.2
0.07
0.08
0.42
0.07
0.07
0.07
0.53
0.08
0.16
0.23
0.1
0.16
1.47
5.29
0.41
0.25
0.19
0.09
0.14
0.07
0.77
3.59
3.24
7.12
0.07
0.07
0.07
0.72
0.09
0.08
0.89
11.76
0.11
0.54
0.38
0.08
0.1
0.98
0.18
0.15
0.07
0.14
0.37
0.07
0.13
0.09
0.09
0.1
0.09
0.09
2.2
0.12
0.36
1.7
1.02
0.14
0.1
0.3
0.09
0.09
0.1
0.69
0.11
0.19
0.13
0.28
0.28
0.55
1.29
1.46
0.57
0.22
0.09
0.15
0.13
0.68
0.09
0.09
0.09
0.09
0.13
0.09
1.06
0.21
0.09
0.84
11.71
0.1
0.44
0.57
0.11
0.09
0.63
0.23
0.13
0.09
0.46
0.31
0.09
0
-0.2
0
-0.19
0
-0.16
-0.2
-0.26
0
-0.06
0
-0.3
0
-0.16
0
0
0
-0.14
0
-0.11
0
0
-0.18
-0.11
-0.11
-0.46
-0.14
0
0
0.01
-0.26
-0.22
0
0
0
0
-0.01
0
0.01
0
0
-0.07
-0.04
0
-0.14
-0.16
0
0
-0.09
-0.16
0
0
-0.13
0.02
0
0
0
0
-0.04
0
0
-0.4
0
-0.04
-0.22
0.01
0
0
0
0
0
0
0
0
-0.08
0
0
-0.23
-0.09
-0.02
-0.58
0.01
0.01
-0.09
0.02
0
-0.16
1.62
1.57
1.81
0
0
0
-0.08
0
0
-0.07
-0.14
0.05
0.06
-0.1
0
0
0.19
-0.11
0
0
-0.1
0
0
0.05
0
0
-0.1
0
0
-0.11
0
0
-0.32
-0.12
0
0
0.02
0
0
0
0.03
0
0
0
0.16
-0.1
-0.4
-0.53
0.01
0.36
0
0
0
0
-0.15
0
0
0
0
0.04
0
0.07
0.22
0
-0.13
-0.14
0
0.06
-0
0
0
-0.07
0
0
0
0.16
-0.02
0
C-8
YBR050C
YBR052C
YBR053C
YBR054W
YBR056W
YBR058C
YBR061C
YBR062C
YBR063C
YBR066C
YBR067C
YBR068C
YBR069C
YBR070C
YBR071W
YBR072W
YBR073W
YBR077C
YBR078W
YBR079C
YBR080C
YBR082C
YBR083W
YBR084C-A
YBR084W
YBR085W
YBR086C
YBR087W
YBR088C
YBR090C
YBR090C-A
YBR091C
YBR092C
YBR093C
YBR096W
YBR101C
YBR105C
YBR106W
YBR107C
YBR108W
YBR109C
YBR111C
YBR115C
YBR116C
YBR117C
YBR118W
YBR121C
YBR122C
YBR123C
YBR125C
YBR126C
YBR127C
YBR129C
YBR132C
YBR133C
REG2
YRO2
UBP14
TIP1
BAP2
VAP1
HSP26
RDH54
ECM33
RPG1
SEC18
UBC4
TEC1
RPL19A
MIS1
AAC3
RFC5
POL30
NHP6B
MRS5
PHO3
PHO5
PHO88
CMD1
YSA1
LYS2
TKL2
TEF2
GRS1
MRPL36
TFC1
TPS1
VMA2
OPY1
AGP2
HSL7
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
21
20
21
21
20
20
21
20
21
20
21
20
20
20
20
20
20
21
41
20
21
26
20
46
20
20
20
20
20
54
21
20
20
21
20
20
20
21
21
21
21
21
21
21
20
20
20
20
20
20
20
21
20
20
21
0.09
0.69
0.32
1.05
0.12
0.09
0.09
0.23
0.09
0.09
2.24
0.52
0.24
0.19
0.13
0.68
0.09
0.1
0.8
0.17
0.14
1.58
0.12
0.43
0.1
0.09
0.98
0.11
0.38
0.12
0.39
0.09
0.35
0.15
0.39
0.29
0.15
2.11
0.09
0.09
1.34
0.73
1.82
0.09
0.09
16.27
0.46
0.11
0.09
0.09
0.91
0.79
0.09
0.12
0.09
0.04
0.34
0.29
0.91
0.05
0.08
0.06
0.2
0.06
0.05
2.16
0.38
0.23
0.13
0.05
0.24
0.07
0.06
0.64
0.25
0.13
1.2
0.07
0.33
0.1
0.12
1.04
0.11
0.43
0.08
0.3
0.11
0.41
0.14
0.33
0.23
0.06
0.76
0.06
0.04
0.96
0.63
0.72
0.05
0.04
7.88
0.41
0.1
0.04
0.07
0.58
0.87
0.04
0.07
0.1
0.08
0.68
0.31
0.85
0.1
0.07
0.15
0.22
0.07
0.12
2.05
0.32
0.27
0.17
0.09
0.18
0.07
0.11
0.55
0.15
0.14
1.69
0.09
0.24
0.07
0.07
0.68
0.08
0.44
0.13
0.25
0.14
0.15
0.07
0.23
0.11
0.12
0.34
0.07
0.07
1.1
0.71
0.9
0.09
0.07
7.86
0.31
0.11
0.1
0.09
0.68
0.64
0.08
0.07
0.07
0.09
0.93
0.55
2.94
0.16
0.09
0.09
0.36
0.1
0.1
4.78
0.57
0.22
0.13
0.09
4.62
0.09
0.09
0.69
0.27
0.16
2.78
0.34
0.5
0.12
0.09
1.01
0.09
0.13
0.22
0.59
0.1
0.4
0.19
0.55
0.17
0.22
1.85
0.09
0.09
1.52
0.93
0.66
0.17
0.3
9.63
0.41
0.11
0.09
0.09
1.53
0.86
0.09
0.09
0.09
0
-0.2
-0.15
-0.16
0
-0.23
0
-0.04
0
0
-0.03
-0.12
0.03
0
0
-0.4
0
-0.25
-0.03
0.04
0
-0.06
0
0.02
0
-0.08
-0.04
0
0.04
-0.26
-0.07
0
0.07
-0.11
-0.02
-0.1
0
-0.46
-0.32
0
-0.05
-0.11
-0.29
0
0
-0.14
0.03
-0.09
0
0
-0.23
-0.01
0
0
0
0
-0.07
-0.06
-0.17
0
0
0.11
0
0
0
-0.03
-0.14
0
-0.09
0
-0.39
0
0
-0.13
0
0
0.07
0
0
0
0
-0.2
0
0.03
-0.06
-0.07
0.08
-0.28
0
0
-0.32
0
-0.7
0
0
-0.01
-0.01
-0.26
0
0
-0.24
-0.05
0
0
0
-0.14
-0.09
0
0
0
0
0.11
0.15
0.39
0
0
0
0.18
0
0
0.29
0.03
0
0
0
0.75
0
0
0.01
0
0
0.24
0.13
0
0
0
0
0
-0.1
0.03
0.19
0
0
0
0.15
-0.18
0.17
-0.03
0
0
0.06
0.14
-0.28
0.17
0.44
-0.1
0
0
0
0
0.12
0.06
0
0
0
C-9
YBR135W
YBR137W
YBR139W
YBR140C
YBR143C
YBR145W
YBR146W
YBR147W
YBR149W
YBR151W
YBR154C
YBR157C
YBR158W
YBR159W
YBR160W
YBR162C
YBR162W-A
YBR163W
YBR164C
YBR165W
YBR166C
YBR169C
YBR171W
YBR173C
YBR175W
YBR177C
YBR181C
YBR183W
YBR185C
YBR187W
YBR188C
YBR189W
YBR191W
YBR196C
YBR198C
YBR199W
YBR201W
YBR205W
YBR206W
YBR207W
YBR210W
YBR211C
YBR212W
YBR213W
YBR214W
YBR218C
YBR220C
YBR221C
YBR222C
YBR227C
YBR230C
YBR231C
YBR234C
YBR235W
YBR239C
CKS1
IRA1
SUP45
ADH5
MRPS9
RPB5
CDC28
YSY6
ARL1
UBS1
TYR1
SSE2
SEC66
UMP1
RPS6B
MBA1
NTC20
RPS9B
RPL21A
PGI1
TAF90
KTR4
DER1
KTR3
MAE1
NGR1
MET8
PYC2
PDB1
FAT2
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
20
20
21
20
21
20
21
20
20
20
21
20
20
20
20
21
21
20
20
20
20
20
20
20
21
20
40
20
21
21
20
20
17
20
21
20
20
20
21
21
20
21
21
21
20
20
21
21
20
20
21
20
20
21
21
0.18
0.13
0.36
0.11
0.22
0.58
0.15
0.39
0.69
0.19
0.11
0.1
0.58
0.88
0.21
0.6
0.09
0.09
0.09
0.11
0.09
0.2
0.21
0.11
0.11
0.6
0.85
0.24
0.28
0.93
0.09
2.94
28.82
1.85
0.09
0.14
0.09
0.11
0.09
0.42
0.1
0.09
0.09
0.09
0.34
0.24
0.22
0.75
0.15
0.09
0.87
0.09
0.62
0.09
0.09
0.16
0.1
0.19
0.07
0.2
0.22
0.16
0.11
0.45
0.09
0.1
0.06
0.57
0.72
0.23
0.61
0.13
0.06
0.09
0.12
0.04
0.06
0.18
0.11
0.09
0.4
0.86
0.22
0.29
0.7
0.05
2.79
26.13
1.73
0.07
0.09
0.05
0.08
0.05
0.32
0.06
0.04
0.04
0.04
0.2
0.09
0.14
0.63
0.16
0.04
0.35
0.04
0.56
0.09
0.06
0.14
0.2
0.13
0.07
0.16
0.59
0.14
0.37
0.87
0.07
0.11
0.08
0.69
1.01
0.21
0.54
0.15
0.07
0.07
0.11
0.07
0.07
0.15
0.14
0.12
0.45
0.9
0.2
0.36
0.54
0.08
1.98
15.15
1.52
0.07
0.15
0.15
0.07
0.07
0.31
0.12
0.07
0.07
0.1
0.23
0.11
0.17
0.61
0.21
0.07
0.78
0.07
0.51
0.07
0.07
0.12
0.14
0.46
0.11
0.18
0.26
0.18
0.18
1.05
0.19
0.19
0.09
0.81
0.77
0.26
0.48
0.14
0.09
0.11
0.09
0.09
0.26
0.14
0.14
0.09
0.46
1.07
0.38
0.4
0.61
0.09
1.94
13.93
1.88
0.09
0.19
0.09
0.11
0.11
0.37
0.09
0.09
0.09
0.09
0.53
0.09
0.13
0.62
0.27
0.09
0.76
0.11
0.63
0.09
0.09
0
0
-0.25
0
0.01
-0.29
-0.21
-0.52
-0.17
0
0
0
-0.01
-0.14
0
0.05
-0.18
0
0
-0.02
0
0
-0.04
-0.02
-0.12
-0.14
-0.01
-0.2
-0.09
0
0
-0.08
0
-0.02
-0.18
-0.19
0
0
0
-0.07
0
0
0
0
-0.27
0
-0.1
-0.08
0.01
0
-0.32
0
-0.14
0
-0.17
0.01
0.13
-0.15
0
-0.04
0.04
0
-0.03
0.06
-0.15
-0.03
0
0.04
0
0
-0.07
0
0
0
0.01
0
-0.2
0.02
0.01
0
0
-0.09
-0.13
-0.02
-0.23
0
-0.15
-0.1
-0.14
0
0
0.12
0
0
-0.04
0
0
0
-0.05
0
0
-0.08
-0.09
0.07
0
-0.06
0
-0.1
0
0
0
0
0
0
0
-0.22
0
-0.17
0.25
0.01
0.14
0
0.14
-0.02
0
-0.05
0
0
0
0
0
0.17
0
0.16
0
-0.11
0
0
0.09
-0.15
0
-0.21
-0.18
0
0
0
0
0
0
0
0
0
0
0
0.09
-0.1
-0.1
-0.11
0.18
0
-0.1
0
0.01
0
0
C-10
YBR241C
YBR242W
YBR243C
YBR244W
YBR246W
YBR248C
YBR249C
YBR252W
YBR253W
YBR254C
YBR256C
YBR258C
YBR260C
YBR261C
YBR262C
YBR263W
YBR264C
YBR265W
YBR268W
YBR269C
YBR274W
YBR276C
YBR279W
YBR280C
YBR282W
YBR283C
YBR286W
YBR287W
YBR288C
YBR290W
YBR291C
YBR293W
YBR297W
YBR301W
YBR302C
YCL001W
YCL002C
YCL008C
YCL009C
YCL011C
YCL016C
YCL017C
YCL018W
YCL019W
YCL025C
YCL027W
YCL028W
YCL029C
YCL030C
YCL033C
YCL034W
YCL035C
YCL036W
YCL037C
YCL038C
ALG7
HIS7
ARO4
DUT1
SRB6
RIB5
SHM1
MRPL37
PPS1
PAF1
MRPL27
SSH1
APE3
APM3
BSD2
CTP1
MAL33
RER1
ILV6
GBP2
NFS1
LEU2
AGP1
FUS1
BIK1
HIS4
SRO9
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
21
21
21
20
21
20
20
21
20
21
20
20
21
21
21
21
21
20
20
21
21
20
20
21
21
21
20
20
20
20
21
20
20
20
20
20
20
20
20
21
20
21
20
20
20
21
21
21
21
20
20
20
21
20
20
0.49
0.09
0.17
0.09
0.11
0.09
2.24
0.55
0.09
0.09
0.09
0.09
0.09
0.15
0.27
0.75
0.09
0.38
0.26
0.39
0.09
0.1
0.09
0.12
0.13
0.52
3.04
0.48
0.09
0.09
0.9
0.09
0.09
0.14
0.93
0.1
0.19
0.15
1.26
0.25
0.09
0.52
1.04
0.1
0.51
0.09
0.24
0.09
0.38
0.16
0.27
1.16
0.09
0.11
0.12
0.18
0.07
0.11
0.06
0.08
0.08
1.79
0.58
0.04
0.1
0.09
0.06
0.06
0.18
0.21
0.55
0.06
0.26
0.05
0.18
0.07
0.11
0.06
0.08
0.08
0.43
2.18
0.31
0.05
0.07
0.47
0.04
0.04
0.08
0.54
0.08
0.2
0.12
0.91
0.25
0.05
0.64
0.85
0.09
0.27
0.08
0.16
0.06
0.32
0.2
0.14
0.43
0.04
0.11
0.07
0.31
0.07
0.1
0.07
0.11
0.15
2.23
0.62
0.12
0.1
0.14
0.07
0.07
0.22
0.37
0.5
0.08
0.38
0.14
0.32
0.08
0.13
0.14
0.07
0.14
0.31
2.54
0.38
0.07
0.07
0.46
0.08
0.08
0.08
0.58
0.07
0.14
0.07
1.04
0.26
0.07
0.52
1.17
0.15
0.47
0.07
0.18
0.07
0.33
0.27
0.27
1.09
0.07
0.08
0.11
0.58
0.09
0.09
0.09
0.15
0.12
0.92
0.35
0.09
0.09
0.09
0.09
0.09
0.12
0.26
0.52
0.09
0.21
0.11
0.33
0.09
0.18
0.12
0.09
0.13
0.42
4.85
0.54
0.09
0.09
0.56
0.11
0.09
0.15
0.65
0.09
0.16
0.1
0.75
0.27
0.09
0.45
1.21
0.09
0.65
0.09
0.21
0.11
0.36
0.33
0.26
1.7
0.09
0.11
0.2
-0.23
0
0
0
-0.13
0
0.06
-0.01
0
0.01
-0.21
-0.19
0
-0.08
-0.13
-0.05
0
-0.1
-0.42
-0.11
0
-0.02
-0.25
0
0
-0.01
-0.13
0
0
-0.25
-0.21
0
0
0
-0.17
0
-0.06
-0.15
-0.1
0.01
0
0.01
-0.22
0
-0.2
0
-0.19
0
-0.1
-0.08
-0.13
-0.16
0
-0.06
0
0
0
0
0
0
0.01
0.11
-0.03
0.01
0
0
0
0
-0.07
0.12
-0.06
-0.05
-0.05
-0.12
0.1
0
0
0.05
0
0
-0.12
-0.15
-0.06
0
0
-0.21
0
0
0
0
0
-0.1
0
-0.01
0
0
0.03
-0.08
0
-0.02
0
0
0
-0.08
0.12
-0.06
0.03
0
0
0
0.14
0
-0.08
0
0.04
0
-0.17
-0.18
0
0
0
0
0
0
0
-0.11
0
-0.1
-0.24
0.08
0
0
0
0
0
-0.02
0.15
0.14
0
0
-0.22
0
0
0
-0.06
0
0
0
-0.12
0
0
0
0
0
0
0
0
0
0
0.23
-0.05
0.39
0
0
0.15
C-11
YCL039W
YCL040W
YCL042W
YCL043C
YCL044C
YCL045C
YCL047C
YCL049C
YCL050C
YCL056C
YCL057W
YCL064C
YCL066W
YCL067C
YCL073C
YCLX06C
YCLX12W
YCR002C
YCR004C
YCR005C
YCR008W
YCR009C
YCR011C
YCR012W
YCR013C
YCR017C
YCR018C
YCR020C
YCR020C-A
YCR021C
YCR023C
YCR024C-A
YCR029C
YCR029C-A
YCR030C
YCR031C
YCR034W
YCR035C
YCR036W
YCR037C
YCR039C
YCR040W
YCR043C
YCR044C
YCR046C
YCR047C
YCR048W
YCR051W
YCR052W
YCR053W
YCR057C
YCR059C
YCR060W
YCR061W
YCR062W
GLK1
PDI1
APA1
PRD1
CHA1
ALPHA1
ALPHA2
CDC10
YCP4
CIT2
SAT4
RVS161
ADP1
PGK1
SRD1
PET18
MAK31
HSP30
PMP1
RIM1
RPS14A
FEN1
RRP43
RBK1
PHO87
ALPHA2
ALPHA1
IMG1
ARE1
RSC6
THR4
PWP2
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
20
21
20
21
20
20
20
20
20
20
21
20
20
20
20
20
21
21
21
20
21
20
20
20
21
21
21
20
20
21
21
20
21
40
20
20
20
21
20
20
20
20
21
20
20
20
21
20
20
20
20
21
20
20
20
0.09
4.56
0.31
2.02
0.09
0.11
0.11
0.18
0.42
0.09
0.09
0.7
0.09
0.09
0.12
0.09
0.09
0.51
0.5
1.05
0.09
0.3
0.09
23.1
0.14
0.33
0.09
0.09
0.09
2.85
0.28
1.83
0.09
0.88
0.09
8.73
0.75
0.09
0.09
0.09
0.09
0.09
0.21
0.25
0.36
0.09
0.16
0.17
0.11
0.87
0.09
0.17
0.11
0.28
0.17
0.05
2.52
0.15
1.06
0.05
0.05
0.07
0.09
0.37
0.11
0.04
0.62
0.51
0.12
0.12
0.07
0.06
0.48
0.5
0.53
0.05
0.31
0.07
5.85
0.14
0.25
0.04
0.08
0.11
2.05
0.16
0.54
0.09
0.53
0.05
4.9
0.4
0.08
0.08
0.06
0.14
0.37
0.22
0.26
0.19
0.06
0.06
0.2
0.07
1.16
0.06
0.2
0.12
0.11
0.11
0.08
5.11
0.19
2.34
0.08
0.1
0.12
0.15
0.35
0.14
0.08
0.7
0.07
0.13
0.11
0.1
0.07
0.35
0.57
0.19
0.07
0.48
0.08
9.14
0.09
0.17
0.13
0.13
0.13
3.07
0.17
0.8
0.07
0.95
0.07
6.89
0.55
0.07
0.07
0.08
0.14
0.07
0.2
0.23
0.34
0.07
0.1
0.16
0.09
0.76
0.07
0.23
0.13
0.1
0.12
0.09
4.42
0.37
2.3
0.09
0.09
0.09
0.2
0.52
0.13
0.11
1
0.09
0.12
0.11
0.12
0.09
0.3
0.84
0.48
0.09
0.44
0.15
8.72
0.15
0.26
0.09
0.1
0.1
7.83
0.13
1.02
0.11
0.71
0.09
6.4
0.22
0.11
0.09
0.14
0.1
0.09
0.15
0.29
0.32
0.09
0.17
0.14
0.09
0.83
0.09
0.22
0.13
0.14
0.19
0
-0.32
0
-0.1
0
0
0
0
-0.04
-0.09
0
-0.07
0.67
0
0
0
-0.28
-0.09
-0.14
-0.21
0
-0.01
0
-0.44
-0.21
-0.11
0
0
-0.05
-0.18
-0.12
-0.6
-0.27
-0.06
0
0
0
0
0
0
0.01
0.63
-0.06
-0.11
0
0
-0.26
0.02
-0.27
0.08
0
0
-0.09
-0.3
-0.22
0
-0.09
0
0.12
0
0
-0.01
0
0
-0.09
0
0
0
0
0
0
0
-0.03
0
-0.52
0
0.1
0
-0.35
0
-0.19
0.06
0
0
0.02
0
-0.38
0
0.03
0
-0.09
-0.2
0
0
0
0
0
0
0
-0.05
0
0
0
0
-0.02
0
0.01
-0.08
0
0
0
0.01
0
0.12
0
0
0
0
0.09
0
0
0.12
0
0
0
0
0
-0.06
0.04
-0.24
0
0.07
0.09
-0.23
0
-0.09
0
0
0
0.35
-0.03
-0.32
0
-0.1
0
-0.2
-0.37
0
0
0
0
0
-0.14
0
0
0
0
0
0
0.06
0
0
0
0
0
C-12
YCR065W
YCR067C
YCR069W
YCR070W
YCR071C
YCR072C
YCR075C
YCR076C
YCR077C
YCR079W
YCR080W
YCR082W
YCR083W
YCR084C
YCR087W
YCR088W
YCR090C
YCR096C
YCR104W
YCRX07W
YCRX08W
YCRX13W
YCRX17W
YCRX19W
YCRX21C
YDL001W
YDL004W
YDL005C
YDL007W
YDL008W
YDL009C
YDL010W
YDL012C
YDL014W
YDL015C
YDL018C
YDL022W
YDL024C
YDL029W
YDL033C
YDL038C
YDL039C
YDL040C
YDL042C
YDL046W
YDL047W
YDL048C
YDL049C
YDL051W
YDL052C
YDL053C
YDL054C
YDL055C
YDL057W
YDL059C
HCM1
SED4
SCC3
SCC3
IMG2
ERS1
PAT1
TUP1
ABP1
A2
PAU3
SOL2
ATP16
MED2
RPT2
APC11
NOP1
GPD1
ARP2
NAT1
SIR2
SIT4
STP4
KNH1
YLA1
SLC1
PSA1
RAD59
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
21
21
20
20
21
20
21
20
20
20
21
20
20
20
21
21
20
20
20
21
20
20
20
21
21
21
20
21
20
20
21
20
41
20
20
20
20
21
20
20
21
21
21
20
21
21
20
21
21
20
20
20
20
21
21
0.13
0.09
0.37
0.38
0.09
0.09
0.13
0.12
0.16
0.27
0.09
0.15
0.24
0.25
0.09
0.11
0.09
0.12
0.15
0.09
0.11
0.3
0.3
0.09
0.09
0.09
1.08
0.09
0.18
0.14
0.11
0.12
0.24
0.63
0.46
0.09
4.4
0.09
0.52
0.09
0.09
0.14
0.09
0.09
0.78
0.09
0.83
0.09
0.11
0.44
0.33
0.09
1.88
0.09
0.09
0.07
0.08
0.14
0.27
0.04
0.04
0.1
0.09
0.21
0.24
0.08
0.1
0.18
0.32
0.04
0.11
0.09
0.17
0.22
0.06
0.14
0.2
0.22
0.06
0.05
0.05
0.83
0.06
0.19
0.13
0.1
0.07
0.17
0.94
0.29
0.06
2.94
0.04
0.4
0.07
0.14
0.1
0.06
0.06
0.43
0.05
0.35
0.04
0.1
0.35
0.23
0.06
1.18
0.05
0.05
0.07
0.1
0.21
0.27
0.08
0.09
0.1
0.18
0.15
0.24
0.07
0.16
0.27
0.19
0.07
0.07
0.11
0.18
0.12
0.1
0.08
0.22
0.25
0.07
0.07
0.07
3.21
0.09
0.2
0.13
0.14
0.07
0.19
0.77
0.39
0.07
2.84
0.07
0.63
0.07
0.09
0.12
0.15
0.07
0.47
0.08
1.1
0.1
0.12
0.42
0.4
0.13
1.55
0.07
0.07
0.09
0.14
0.2
0.38
0.09
0.09
0.09
0.19
0.19
0.25
0.09
0.21
0.42
0.21
0.09
0.1
0.09
0.17
0.16
0.09
0.17
0.3
0.48
0.09
0.09
0.09
0.77
0.09
0.39
0.15
0.09
0.09
0.19
0.71
0.49
0.12
3.92
0.14
0.54
0.09
0.2
0.23
0.09
0.1
0.62
0.09
1.77
0.09
0.16
0.42
0.4
0.12
2.28
0.09
0.09
0
-0.14
0
-0.17
0
0
-0.12
-0.15
-0.05
-0.02
-0.05
-0.16
-0.1
-0.05
0
-0.19
0.01
0.01
-0.08
0
-0.12
-0.11
-0.05
0
0
0
-0.16
-0.28
-0.12
0
-0.13
0
0
0.13
-0.17
0
-0.21
0
-0.05
-0.13
-0.08
-0.16
0
0
-0.15
-0.33
-0.18
0
0
-0.11
-0.15
0
-0.11
-0.27
0
0
0
-0.12
-0.1
0
0
-0.1
0
0
0.02
0
-0.01
0.08
0
0
0
0.02
0.02
0
0
0
-0.04
0.03
0
0
0
0.21
0
-0.05
0
0
0
0
-0.06
0
0
-0.13
0
0.12
0
0
-0.05
-0.03
0
-0.18
0
0.21
0.07
0.01
-0.02
0.04
0.07
0.02
0
0
-0.07
0
-0.02
0
0
0
-0.03
0
0
0
0
0.1
0.35
0
0
0
0
0
0
0
0.03
0.07
0.16
0
0
0
-0.08
0
0.26
0
0
0
-0
-0.04
0.01
0
-0.06
0
0.05
0
0.13
0.05
0.02
0
0.06
0
0.29
0
0
0
0
0
0.05
0
0
C-13
YDL061C
YDL064W
YDL066W
YDL067C
YDL072C
YDL075W
YDL076C
YDL078C
YDL080C
YDL081C
YDL082W
YDL083C
YDL084W
YDL085W
YDL086W
YDL092W
YDL093W
YDL095W
YDL097C
YDL100C
YDL102W
YDL103C
YDL109C
YDL110C
YDL111C
YDL112W
YDL120W
YDL122W
YDL123W
YDL124W
YDL125C
YDL126C
YDL128W
YDL130W
YDL131W
YDL132W
YDL133W
YDL134C
YDL135C
YDL136W
YDL137W
YDL140C
YDL141W
YDL142C
YDL143W
YDL144C
YDL145C
YDL147W
YDL153C
YDL155W
YDL157C
YDL158C
YDL160C
YDL165W
YDL168W
RPS29B
IDP1
COX9
RPL31A
MDH3
THI3
RPP1A
RPL13A
RPS16B
SRP14
PMT5
PMT1
RPN6
CDC2
QRI1
RRP42
YFH1
UBP1
HNT1
CDC48
VCX1
RPP1B
LYS21
CDC53
PPH21
RDI1
RPL35B
ARF2
RPO21
BPL1
CRD1
CCT4
COP1
RPN5
SAS10
CLB3
DHH1
CDC36
SFA1
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
22
21
20
20
20
66
20
21
20
20
20
20
20
21
20
20
20
20
20
20
20
20
21
21
20
21
20
20
20
21
41
20
21
41
20
21
21
20
20
20
20
20
20
20
20
21
20
21
20
20
20
20
21
20
20
3.87
0.25
0.64
1.43
1.46
1.57
0.09
0.3
0.1
7.2
2.42
5.9
0.53
0.09
0.51
0.09
0.11
0.29
0.13
0.46
0.09
0.09
0.1
0.19
0.14
0.1
0.1
0.09
0.17
1.19
4.95
0.57
1.07
20.92
1.46
0.09
0.09
0.13
0.13
1.57
2.71
0.13
0.09
0.13
0.1
0.26
0.09
0.09
0.09
0.09
0.22
0.11
0.23
0.26
0.25
3.76
0.25
0.5
1.01
0.79
1.75
0.08
0.25
0.05
5.21
4.59
4.64
0.37
0.04
0.15
0.07
0.05
0.16
0.08
0.3
0.05
0.07
0.06
0.13
0.12
0.08
0.09
0.07
0.11
0.81
3.51
0.3
0.8
22.16
0.62
0.07
0.04
0.08
0.09
1.19
1.8
0.09
0.04
0.07
0.09
0.29
0.11
0.05
0.05
0.05
0.21
0.1
0.15
0.15
0.15
2.79
0.17
0.92
2.49
1.3
1.45
0.07
0.25
0.1
6.1
2.31
3.26
0.43
0.12
0.25
0.07
0.11
0.2
0.11
0.59
0.07
0.12
0.09
0.22
0.11
0.1
0.19
0.11
0.09
2.02
8.1
0.57
1.22
14.29
1.4
0.07
0.07
0.13
0.1
1.52
3.3
0.2
0.08
0.07
0.1
0.24
0.07
0.07
0.07
0.07
0.28
0.07
0.15
0.31
0.27
2.04
0.28
0.54
1.15
1.58
1.03
0.1
0.37
0.09
2.72
2.23
3.72
0.42
0.09
0.31
0.11
0.09
0.28
0.21
0.6
0.09
0.09
0.14
0.21
0.24
0.1
0.13
0.09
0.12
1.83
4.01
0.78
1.58
13.86
0.8
0.09
0.09
0.13
0.11
0.87
1.96
0.19
0.09
0.1
0.11
0.33
0.09
0.13
0.09
0.09
0.21
0.09
0.18
0.27
0.41
-0.07
0
-0.08
-0.07
-0.12
-0.07
0
-0.17
0
-0.08
0.11
-0.04
-0.07
0
0
0
0
-0.14
0
-0.12
0
-0.2
-0.17
-0.25
-0.09
-0.04
0
0
0
-0.18
-0.14
-0.18
-0.07
0.02
-0.26
-0.26
0
-0.2
0
-0.01
-0.16
0
0
0
-0.09
-0.01
0
0
0
0
0
-0.21
-0.21
-0.11
-0.17
-0.14
-0.02
0.18
0.28
-0.08
0
0
-0.01
0
-0.26
-0.05
-0.16
0
0
0
0
0
0
0
0.06
0
0
-0.08
0.03
-0.03
0
0.13
-0.07
0
0.13
0.2
0.02
-0.03
-0.16
-0.02
0
0
0.03
0
-0.05
0.05
0
0
0
0
-0.05
0
0
0
0
0.04
-0.2
0
0.07
-0.08
-0.22
0
-0.03
-0.09
0
-0.1
0
0.09
0
-0.31
-0.03
-0.21
-0.1
0
0
0
-0
0
0.16
0.08
0
0
0
0
0.11
0
0
0
0
0.21
-0.08
0.15
0.16
-0.25
-0.22
0
0
0
0
-0.18
-0.07
0
0
0
0
0
0
0.06
0
0
0.01
0
0
0.08
0.13
C-14
YDL171C
YDL173W
YDL174C
YDL178W
YDL179W
YDL180W
YDL181W
YDL182W
YDL185W
YDL188C
YDL190C
YDL191W
YDL192W
YDL193W
YDL195W
YDL198C
YDL200C
YDL201W
YDL202W
YDL204W
YDL205C
YDL208W
YDL212W
YDL213C
YDL215C
YDL217C
YDL220C
YDL222C
YDL223C
YDL224C
YDL226C
YDL228C
YDL229W
YDL230W
YDL232W
YDL234C
YDL235C
YDL236W
YDL237W
YDL241W
YDL246C
YDR001C
YDR002W
YDR003W
YDR005C
YDR006C
YDR007W
YDR009W
YDR011W
YDR012W
YDR016C
YDR017C
YDR019C
YDR020C
YDR023W
GLT1
DLD1
AIP2
PCL9
INH1
LYS20
TFP1
PPH22
UFD2
RPL35A
ARF1
SEC31
YHM1
MGT1
MRPL11
HEM3
NHP2
SHR3
GDH2
TIM22
CDC13
WHI4
GCS1
SSB1
PTP1
OST4
GYP7
YPD1
PHO13
TRP1
GAL3
SNQ2
RPL4B
KCS1
GCV1
SES1
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
20
20
21
20
21
20
20
21
21
20
20
20
20
20
21
21
21
21
20
20
20
20
20
21
20
20
20
21
20
20
20
21
20
21
21
20
20
21
21
20
20
20
20
20
21
20
21
20
20
35
20
21
21
20
20
0.29
0.09
0.25
0.09
0.09
0.09
1.31
6.35
0.77
0.9
0.1
2.15
3.84
0.09
0.41
0.56
0.09
0.09
0.09
0.17
0.09
0.46
0.7
0.09
0.11
0.09
0.13
0.23
0.11
0.09
0.17
0.09
5.02
0.09
1.16
0.09
0.09
0.25
0.34
0.09
0.14
0.17
0.52
0.13
0.12
0.09
0.21
0.09
0.24
8.95
0.11
0.09
0.16
0.09
0.47
0.27
0.06
0.18
0.06
0.04
0.05
1.63
3.03
0.52
0.78
0.07
2.03
4.11
0.05
0.31
0.38
0.06
0.08
0.07
0.1
0.07
0.72
0.51
0.04
0.07
0.08
0.07
0.05
0.06
0.11
0.1
0.05
5.31
0.04
1.19
0.04
0.05
0.18
0.25
0.05
0.15
0.09
0.3
0.08
0.06
0.04
0.12
0.04
0.1
6.22
0.07
0.04
0.17
0.05
0.38
0.27
0.07
0.19
0.11
0.07
0.07
1.78
4.98
0.64
0.9
0.1
2.42
7.41
0.1
0.17
0.54
0.08
0.07
0.11
0.08
0.07
0.57
0.54
0.07
0.12
0.11
0.07
0.07
0.07
0.07
0.17
0.08
3.74
0.07
1.12
0.08
0.12
0.27
0.3
0.07
0.16
0.11
0.46
0.13
0.1
0.1
0.27
0.29
0.17
4.99
0.07
0.07
0.13
0.07
0.33
0.32
0.12
0.31
0.1
0.09
0.09
1.27
3.4
0.94
0.72
0.1
1.82
4.11
0.15
0.32
0.36
0.1
0.09
0.09
0.46
0.09
0.44
0.36
0.09
0.14
0.09
0.09
0.97
0.42
0.1
0.18
0.1
3.35
0.11
1.17
0.09
0.1
0.32
0.29
0.09
0.09
0.28
0.32
0.09
0.11
0.1
0.27
0.09
0.3
5.42
0.09
0.09
1
0.09
0.42
-0.05
0
-0.24
0
0
0
-0.03
-0.29
-0.13
-0.13
0
0
0.06
0
-0.12
-0.16
-0.25
0
-0.15
0
0
0.17
-0.15
0
0
0
0
0
0
0
-0.13
0
0.04
0
-0.06
0
0
-0.11
-0.13
0
-0.23
0
-0.15
-0.18
-0.25
0
-0.28
0
-0.17
-0.11
-0.14
0
-0.13
0
-0.05
-0.06
0
-0.13
0
-0.08
0
0.12
-0.15
-0.09
-0.08
0
-0.03
0.13
-0
0
-0.05
0
0
0
-0.1
0
0.07
0
0
0
0
0
-0.2
0
0
-0.06
0
-0.14
0
-0.08
0
0
-0.01
-0.05
0
-0.01
0
-0.03
0
-0.05
-0.03
0.03
0.49
0
-0.18
0
0
-0.07
0
-0.1
0
0
-0.03
0
0
0
-0.05
-0.27
0.08
0
0
-0.13
0.04
0
0.02
-0.06
0
0
0
0.37
0
0
-0.13
0
0.05
0
0
0.45
0.39
0
0
0
-0.15
0.07
-0.02
0
0
0.07
0.08
0
0
0.31
-0.1
0
0
0.07
0.12
0
0
-0.17
0
0
0.64
0
-0.07
C-15
YDR024W
YDR025W
YDR027C
YDR031W
YDR032C
YDR033W
YDR035W
YDR036C
YDR037W
YDR038C
YDR039C
YDR041W
YDR043C
YDR044W
YDR045C
YDR046C
YDR047W
YDR050C
YDR051C
YDR055W
YDR056C
YDR059C
YDR062W
YDR063W
YDR064W
YDR067C
YDR070C
YDR071C
YDR072C
YDR073W
YDR074W
YDR077W
YDR079W
YDR082W
YDR084C
YDR086C
YDR090C
YDR091C
YDR092W
YDR093W
YDR094W
YDR097C
YDR098C
YDR099W
YDR100W
YDR101C
YDR103W
YDR105C
YDR107C
YDR111C
YDR115W
YDR116C
YDR117C
YDR119W
YDR120C
RPS11A
ARO3
KRS1
ENA5
ENA2
HEM13
BAP3
HEM12
TPI1
UBC5
LCB2
RPS13
IPT1
SNF11
TPS2
SED1
PET100
STN1
SSS1
UBC13
MSH6
BMH2
STE5
TRM1
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
20
94
20
20
20
20
20
21
20
20
20
20
20
20
20
20
21
21
20
21
20
38
20
20
21
20
21
20
21
20
20
20
21
21
20
21
21
20
20
20
21
20
21
20
20
20
20
20
21
21
20
20
20
20
20
0.09
1.05
0.09
0.09
1.87
9.07
0.73
0.09
0.34
0.11
0.24
0.1
0.09
0.4
0.11
0.31
0.25
20.73
0.09
1.54
0.17
0.17
0.52
0.25
7.08
0.09
0.51
0.17
0.37
0.09
0.29
6.78
0.12
0.09
0.45
0.88
0.16
0.13
0.44
0.09
0.1
0.09
0.12
0.72
0.87
0.09
0.09
0.19
0.29
0.09
0.2
0.11
0.09
0.11
0.09
0.08
1.34
0.05
0.04
1.2
6.59
0.63
0.1
0.42
0.08
0.27
0.06
0.07
0.22
0.07
0.21
0.23
18.17
0.05
1.32
0.18
0.12
0.22
0.23
6.41
0.09
0.08
0.12
0.27
0.06
0.09
5.06
0.09
0.04
0.3
0.62
0.11
0.16
0.42
0.05
0.04
0.06
0.1
0.56
0.46
0.06
0.05
0.11
0.18
0.08
0.15
0.05
0.07
0.1
0.05
0.08
1.27
0.07
0.09
1.29
5.58
1.11
0.1
0.43
0.09
0.24
0.12
0.07
0.39
0.08
0.19
0.28
15.12
0.1
1.82
0.34
0.22
0.13
0.32
4.79
0.08
0.52
0.16
0.32
0.07
0.15
6.65
0.13
0.07
0.34
0.66
0.15
0.16
0.73
0.1
0.11
0.07
0.1
0.48
0.5
0.08
0.07
0.24
0.23
0.07
0.23
0.07
0.07
0.08
0.07
0.09
1.25
0.09
0.1
3.17
6.13
0.66
0.15
0.43
0.09
0.38
0.09
0.1
0.31
0.11
0.37
0.3
12.24
0.09
5.63
0.23
0.23
0.19
0.28
4.32
0.09
2.18
0.16
0.43
0.09
0.21
7.48
0.13
0.09
0.36
0.48
0.18
0.19
0.66
0.09
0.1
0.09
0.13
0.7
0.82
0.09
0.09
0.18
0.15
0.09
0.24
0.09
0.09
0.14
0.09
0
0.03
0
0
-0.25
-0.06
-0.08
0
0.03
0
-0.01
0
0
0
0
-0.15
-0.09
-0.1
0
-0.14
-0.13
-0.16
0
-0.06
-0.08
0
0
0
-0.13
0
0
-0.14
-0.17
0
-0.12
-0.09
-0.1
0
-0.04
0
0
0
-0.17
-0.12
-0.26
0
0
-0.2
-0.14
-0.16
-0.07
0
0
0
0
0
-0.05
0
0
-0.2
-0.16
0.17
-0.09
0.02
0
-0.02
0.07
0
0
0
0
-0.09
-0.2
0
0.08
0.04
0.04
-0.19
-0.04
-0.22
-0.05
-0.05
-0.02
-0.06
0
-0.11
-0.1
0.06
0
0
-0.08
-0.08
0
0.1
0
-0.06
0
0
0
-0.2
0
0
0
-0.07
0
0
0
0
0
0
0
-0.03
0
0
0.16
-0.22
0
0.1
0.1
0
0.1
0
0
0.01
0
0.18
0.03
-0.12
0
0.57
0
0.1
-0.1
-0.08
-0.26
0
0.52
0
0
0
0
0.03
0
0
-0.05
-0.15
0
0
0.09
0
0
0
0
0.05
-0.03
0
0
0
-0.06
0
0.09
0
0
0
0
C-16
YDR121W
YDR123C
YDR126W
YDR127W
YDR128W
YDR129C
YDR130C
YDR133C
YDR134C
YDR138W
YDR139C
YDR140W
YDR141C
YDR142C
YDR143C
YDR144C
YDR146C
YDR147W
YDR148C
YDR151C
YDR152W
YDR153C
YDR154C
YDR155C
YDR156W
YDR158W
YDR160W
YDR161W
YDR163W
YDR165W
YDR166C
YDR167W
YDR170C
YDR171W
YDR172W
YDR174W
YDR177W
YDR178W
YDR182W
YDR185C
YDR187C
YDR188W
YDR190C
YDR194C
YDR196C
YDR204W
YDR205W
YDR208W
YDR209C
YDR210W
YDR212W
YDR214W
YDR216W
YDR220C
YDR222W
INO2
ARO1
SAC6
HPR1
RUB1
PEX7
SAN1
MKC7
SWI5
KGD2
CTH1
CPH1
RPA14
HOM2
SSY1
TCI1
SEC5
TAF25
SEC7
HSP42
SUP35
UBC1
SDH4
CDC1
CCT6
MSS116
COQ4
MSS4
TCP1
ADR1
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
20
21
20
21
21
21
20
16
34
21
40
21
20
20
21
21
20
20
20
20
20
20
21
20
20
20
21
20
21
20
21
20
21
20
20
21
21
20
20
20
20
20
20
20
20
21
21
20
21
20
21
20
20
20
21
0.09
0.09
0.09
0.2
0.09
0.41
0.09
10.29
14.56
0.09
0.24
0.12
0.09
0.09
0.09
0.09
0.09
0.09
0.31
0.09
0.09
0.1
39.53
9.71
0.5
2.28
0.09
0.09
0.09
0.09
0.09
0.1
0.09
0.5
0.23
0.57
0.21
2.47
0.13
0.09
0.09
0.32
0.15
0.11
0.1
0.12
0.09
0.09
0.09
0.25
0.18
0.27
0.09
0.09
0.09
0.05
0.06
0.12
0.16
0.04
0.2
0.05
8.07
12.15
0.04
0.17
0.22
0.04
0.06
0.04
0.09
0.06
0.04
0.17
0.08
0.08
0.05
32.8
8.33
0.42
1.68
0.04
0.07
0.06
0.06
0.05
0.04
0.06
0.34
0.27
0.42
0.21
1.95
0.1
0.05
0.06
0.26
0.18
0.09
0.07
0.11
0.06
0.05
0.07
0.23
0.11
0.16
0.07
0.1
0.12
0.07
0.09
0.07
0.21
0.07
0.31
0.07
6.47
12.18
0.07
0.19
0.12
0.08
0.09
0.07
0.07
0.07
0.07
0.4
0.07
0.07
0.12
36.58
8.09
0.54
2.78
0.07
0.07
0.07
0.07
0.07
0.09
0.07
0.27
0.23
0.49
0.26
4.61
0.21
0.08
0.07
0.26
0.16
0.07
0.1
0.11
0.07
0.07
0.07
0.3
0.11
0.23
0.08
0.07
0.08
0.09
0.09
0.14
0.19
0.09
0.3
0.09
5.16
9.7
0.09
0.22
0.33
0.09
0.1
0.09
0.09
0.09
0.12
0.19
0.1
0.09
0.09
35.26
10.17
0.44
1.61
0.09
0.09
0.09
0.09
0.09
0.09
0.09
0.36
0.26
0.9
0.24
2.07
0.11
0.09
0.09
0.32
0.23
0.09
0.1
0.23
0.1
0.09
0.09
0.22
0.17
1.09
0.09
0.09
0.26
0
-0.31
-0.16
-0.1
0
-0.18
0
-0.13
-0.12
0
-0.11
-0.1
0
-0.23
0
-0.18
-0.22
0
0
-0.11
0
0
-0.06
-0.11
0
-0.07
0
0
0
0
0
0
-0.22
-0.3
-0.19
-0.13
-0.04
-0.14
-0.1
0
0
-0.06
0.01
0
0
-0.3
0
0
-0.21
-0.15
-0.24
-0.24
0
-0.17
-0.15
0
0
0
0
0
-0.07
0
-0.19
-0.13
0
-0.02
-0.01
0
0
0
0
0
0
0.11
0
0
0
-0.1
-0.14
-0.01
0.14
0
0
0
0
0
0
0
-0.3
0
0
0.11
0.2
-0.02
0
0
-0.06
0
0
0
0
0
0
0
0.08
-0.18
-0.02
0
0
0
0
0
0
0
0
-0.04
0
-0.24
-0.18
0
0.01
0.09
0
0
0
0
0
0.09
-0.05
0
0
0
-0.02
0
0
-0
0
0
0
0
0
0
0
-0.15
0
0.09
0.06
-0.06
0
0
0
0.07
0
0
0
0.19
0
0
0
-0.01
0.05
0.53
0
0
0.3
C-17
YDR224C
YDR225W
YDR226W
YDR231C
YDR232W
YDR233C
YDR234W
YDR235W
YDR236C
YDR238C
YDR239C
YDR242W
YDR245W
YDR247W
YDR248C
YDR252W
YDR258C
YDR260C
YDR261C
YDR262W
YDR264C
YDR266C
YDR267C
YDR271C
YDR272W
YDR275W
YDR276C
YDR280W
YDR284C
YDR286C
YDR287W
YDR291W
YDR292C
YDR293C
YDR294C
YDR296W
YDR297W
YDR298C
YDR300C
YDR301W
YDR302W
YDR303C
YDR304C
YDR306C
YDR307W
YDR308C
YDR309C
YDR315C
YDR318W
YDR319C
YDR320C
YDR321W
YDR322W
YDR323C
YDR328C
HTB1
HTA1
ADK1
HEM1
LYS4
PRP42
SEC26
AMD2
MNN10
BTT1
HSP78
EXG2
AKR1
GLO2
DPP1
SRP101
SSD1
DPL1
SUR2
ATP5
PRO1
CFT1
CYP5
SRB7
MCM21
ASP1
MRPL35
PEP7
SKP1
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
19
32
20
20
21
20
20
20
21
21
21
21
20
20
20
20
20
20
21
21
20
21
21
20
20
20
21
21
21
20
20
20
20
21
20
20
20
20
20
21
20
20
21
20
21
20
21
20
21
21
21
20
20
20
20
1.72
4.13
3.57
0.29
0.7
2.35
1.09
0.09
0.13
0.19
0.1
0.09
0.13
0.23
0.11
0.09
0.13
0.09
0.18
0.18
0.11
0.11
0.09
0.09
0.21
0.11
8.06
0.09
0.54
0.1
0.09
0.09
0.09
0.09
0.16
0.17
1.38
2.2
0.09
0.09
0.09
0.09
1.16
0.09
0.11
0.09
0.13
0.09
0.09
0.11
0.09
0.26
0.12
0.09
0.93
2
2.61
2.45
0.1
0.57
2.2
0.81
0.04
0.13
0.19
0.05
0.05
0.11
0.16
0.07
0.04
0.04
0.09
0.14
0.11
0.06
0.08
0.06
0.06
0.16
0.1
5.35
0.09
0.3
0.07
0.05
0.06
0.06
0.06
0.15
0.11
0.95
1.67
0.07
0.04
0.1
0.05
0.83
0.05
0.08
0.05
0.14
0.04
0.04
0.1
0.05
0.2
0.1
0.06
0.84
1.75
3.02
4.6
0.29
0.6
2.24
0.87
0.07
0.11
0.25
0.07
0.09
0.11
0.29
0.11
0.08
0.08
0.14
0.13
0.11
0.12
0.07
0.1
0.07
0.26
0.13
6.18
0.09
0.26
0.08
0.07
0.07
0.09
0.07
0.17
0.18
1.3
3.27
0.13
0.07
0.09
0.07
1.11
0.12
0.07
0.07
0.22
0.07
0.09
0.16
0.07
0.18
0.16
0.07
1.16
1.31
2.54
3.44
0.17
0.71
2.57
0.46
0.09
0.17
0.31
0.09
0.09
0.12
0.28
0.12
0.09
0.19
0.09
0.29
0.2
0.2
0.09
0.1
0.09
0.33
0.24
6.68
0.09
0.33
0.13
0.09
0.09
0.13
0.1
0.3
0.16
1.66
1.49
0.09
0.09
0.09
0.09
1.48
0.11
0.09
0.09
0.12
0.09
0.09
0.11
0.1
0.17
0.17
0.09
1.18
-0.01
-0.07
-0.11
-0.18
-0.08
-0.06
-0.15
0
0
-0.12
0
0
0
-0.21
-0.17
0
0
0
-0.11
-0.17
0
-0.23
0
0
0
-0.05
-0.21
-0.08
-0.21
0
0
0
0
0
0
-0.24
0
-0.09
-0.12
-0.31
-0.23
0
-0.09
0
-0.25
0
0
0
0
0
0
-0.09
0
0
-0.05
0.02
-0.07
0.02
0.13
-0.04
-0.05
0
0
0
0.01
0
0.02
0
0.03
0
-0.07
0
0
0
-0.01
0
0
0
0
0.06
0.02
-0.11
0
-0.19
0
0
0
0
0
0
0
-0.03
0.12
0
0
0
0
-0.06
0
0
0
-0.03
0
0
-0.09
0
0
0
0
0.04
-0.13
-0.19
-0.05
0
0
-0.01
-0.19
0
0
0.02
0
0
0
0.11
0
0
0.17
0
0.1
0.09
0.16
0
0
0
0.16
0.18
-0.03
0
-0.15
0
0
0
0
0
0.15
0
0.11
-0.15
0
0
0
0
0.09
0
0
0
0
0
0
0
0.07
-0.1
0
0
0
C-18
YDR329C
YDR335W
YDR337W
YDR338C
YDR339C
YDR341C
YDR342C
YDR343C
YDR345C
YDR346C
YDR347W
YDR348C
YDR349C
YDR350C
YDR352W
YDR353W
YDR354W
YDR357C
YDR358W
YDR362C
YDR364C
YDR365C
YDR367W
YDR368W
YDR373W
YDR375C
YDR376W
YDR377W
YDR378C
YDR381W
YDR382W
YDR384C
YDR385W
YDR387C
YDR388W
YDR389W
YDR390C
YDR391C
YDR392W
YDR394W
YDR395W
YDR397C
YDR398W
YDR399W
YDR400W
YDR404C
YDR407C
YDR408C
YDR409W
YDR410C
YDR411C
YDR415C
YDR418W
YDR422C
YDR423C
PEX3
MSN5
MRPS28
HXT7
HXT6
HXT3
MRP1
YPS4
TCM10
TRR1
TRP4
TFC6
CDC40
YPR1
BCS1
ARH1
ATP17
YRA1
RPP2B
EFT2
RVS167
SAC7
UBA2
SPT3
RPT3
SXM1
NCB2
HPT1
RPB7
ADE8
STE14
RPL12B
SIP1
CAD1
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
20
21
20
20
20
20
20
20
20
20
21
20
20
21
21
20
20
20
21
21
20
20
20
20
20
21
20
20
20
20
20
21
20
21
21
21
20
20
21
21
20
20
21
21
21
20
20
21
20
20
20
20
20
20
21
0.09
0.09
0.12
0.09
0.09
0.32
6.13
6
3.77
0.11
0.22
0.09
0.24
0.09
0.14
2.74
0.19
0.09
0.09
0.09
0.09
0.09
0.34
0.91
0.09
0.09
0.09
0.48
0.13
0.41
30.31
0.5
3.6
0.09
2.09
0.09
0.09
0.31
0.09
0.15
0.1
0.09
0.09
0.22
0.11
1.63
0.09
0.26
0.09
0.4
0.33
0.09
4.88
0.09
0.11
0.06
0.06
0.05
0.06
0.14
0.26
3.01
2.42
2.58
0.13
0.18
0.05
0.24
0.04
0.1
2.43
0.16
0.08
0.05
0.05
0.04
0.08
0.31
0.78
0.05
0.04
0.07
0.33
0.15
0.47
23.08
0.37
3.35
0.04
1.5
0.05
0.05
0.22
0.04
0.1
0.11
0.04
0.11
0.38
0.11
1.23
0.06
0.27
0.05
0.27
0.33
0.06
4.53
0.05
0.07
0.07
0.1
0.12
0.08
0.15
0.36
4.56
4.84
0.09
0.13
0.32
0.07
0.24
0.07
0.14
2.49
0.22
0.09
0.08
0.07
0.08
0.07
0.41
1.03
0.07
0.07
0.07
0.62
0.16
0.5
17.09
0.12
2.35
0.09
1.57
0.07
0.07
0.27
0.09
0.09
0.13
0.13
0.15
0.22
0.18
0.9
0.07
0.24
0.07
0.25
0.59
0.07
3.91
0.07
0.09
0.1
0.09
0.12
0.09
0.18
0.29
4.07
3.68
2.42
0.09
0.3
0.09
0.24
0.09
0.09
2.49
0.09
0.09
0.09
0.09
0.09
0.09
0.37
1.03
0.1
0.09
0.09
0.39
0.18
0.26
13.72
0.34
3
0.11
2.45
0.09
0.09
0.34
0.09
0.16
0.13
0.1
0.09
0.29
0.09
1.17
0.09
0.27
0.09
0.42
0.28
0.11
2.88
0.09
0.09
0
0
0
0
-0.02
-0.05
-0.33
-0.42
-0.16
-0.17
-0.19
0
-0.09
0
-0.18
-0.01
-0.05
-0.22
-0.25
0
0
0
-0.1
-0.13
0
0
-0.17
-0.2
-0.2
0
-0.08
-0.07
-0.07
0
-0.11
0
0
-0.24
0
-0.23
-0.06
0
0.1
0.12
-0.11
-0.04
0
-0.06
0
-0.16
-0.05
0
-0.09
0
0
0
-0.02
-0.04
0
0.06
-0.01
-0.24
-0.16
-1.4
0
1E-16
0
0
0
0
-0.02
-0.06
0
-0.06
0
0
0
-0.07
0.03
0
0
0
0.19
0
-0.01
-0.25
-0.25
-0.19
0
-0.11
0
0
-0.07
-0.02
0
-0.06
0
0.07
-0.04
0.18
-0.14
0
0
0
0
0.18
0
-0.17
0
0
0
0
0
0
0.04
-0.03
-0.19
-0.18
-0.18
0
0
0
0.1
0
0
-0.06
-0.1
0
0
0
0
0
0.01
0.08
0
0
0
-0.05
0
-0.16
-0.33
-0.07
-0.09
0
0.04
0
0
0.07
0
0
0
0
0.04
0.11
0
-0.07
0
0.01
0
0.06
-0.04
0
-0.18
0
0
C-19
YDR424C
YDR427W
YDR429C
YDR432W
YDR433W
YDR434W
YDR435C
YDR436W
YDR441C
YDR447C
YDR450W
YDR451C
YDR452W
YDR453C
YDR454C
YDR456W
YDR457W
YDR459C
YDR461W
YDR462W
YDR463W
YDR464W
YDR465C
YDR466W
YDR468C
YDR470C
YDR471W
YDR472W
YDR474C
YDR476C
YDR477W
YDR479C
YDR481C
YDR482C
YDR483W
YDR486C
YDR487C
YDR489W
YDR490C
YDR492W
YDR493W
YDR494W
YDR497C
YDR498C
YDR500C
YDR502C
YDR503C
YDR504C
YDR505C
YDR506C
YDR508C
YDR510W
YDR511W
YDR512C
YDR513W
DYN2
RPN9
TIF35
NPL3
PPZ2
APT2
RPS17B
RPS18A
GUK1
NHX1
TOM1
MFA1
MRPL28
STP1
SPP41
TLG1
RPL27B
SNF1
PHO8
KRE2
RIB3
ITR1
SEC20
RPL37B
SAM2
LPP1
PSP1
GNP1
SMT3
TTR1
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
20
21
20
20
31
20
21
20
20
20
26
20
20
20
21
20
21
21
21
21
21
20
21
20
21
20
20
20
20
21
21
21
21
21
20
20
20
21
21
21
20
21
20
21
21
20
20
20
20
21
20
21
20
20
21
0.12
0.19
0.35
0.19
1.23
0.17
0.13
0.09
0.33
3.3
1.45
0.09
0.15
0.2
3.37
0.09
0.09
0.19
4.42
0.1
0.09
0.1
0.09
0.09
0.09
0.09
0.82
0.14
0.09
0.72
0.29
0.15
0.25
0.09
0.67
0.09
0.13
0.09
0.12
0.24
0.09
0.09
4.04
0.11
5.12
2.5
0.14
0.18
0.09
0.09
0.53
0.28
0.09
0.09
0.68
0.08
0.16
0.32
0.13
1.3
0.28
0.07
0.04
0.46
3.09
3.12
0.06
0.11
0.07
2.96
0.14
0.12
0.12
0.04
0.08
0.09
0.12
0.09
0.08
0.05
0.08
1.28
0.11
0.06
0.52
0.16
0.09
0.26
0.04
0.58
0.06
0.21
0.06
0.05
0.28
0.06
0.04
3.86
0.11
7.72
2.08
0.12
0.16
0.06
0.07
0.66
0.5
0.07
0.04
0.55
0.15
0.22
0.3
0.1
0.93
0.26
0.16
0.07
0.36
3.09
2.91
0.07
0.17
0.14
3.18
0.07
0.11
0.17
4.53
0.18
0.1
0.11
0.07
0.07
0.09
0.07
1.39
0.17
0.1
0.93
0.13
0.1
0.26
0.1
0.85
0.09
0.35
0.07
0.08
0.4
0.08
0.07
6.05
0.2
8.36
2.09
0.18
0.18
0.07
0.07
0.5
0.55
0.18
0.11
1.36
0.14
0.28
0.35
0.14
1.98
0.29
0.09
0.09
0.34
1.85
2.15
0.09
0.22
1.66
2.07
0.11
0.09
0.2
5.25
0.17
0.11
0.09
0.09
0.09
0.11
0.09
1.35
0.17
0.1
0.62
0.29
0.13
0.37
0.09
1.13
0.09
0.22
0.09
0.09
0.42
0.09
0.09
3.14
0.14
5.04
2.01
0.14
0.22
0.1
0.09
0.69
0.36
0.16
0.09
1.2
-0.2
-0.16
-0.04
-0.19
0.02
-0.01
0
0
0.02
-0.03
0.2
0
0
0
-0.06
-0.19
0.06
-0.23
-1.98
0
0
0.01
-0.05
-0.2
-0.3
0
0.21
0
0
-0.05
-0.1
-0.19
-0.04
0
0
0
0.09
-0.25
-0.33
0.09
-0.24
0
0.01
-0.02
0.15
-0.04
-0.21
-0.12
0
-0.33
0.1
0.12
0
0
-0.01
0.07
-0.05
0
0
-0.08
0.14
0
0
-0.01
-0.11
0.23
0
0
0
-0.02
0
-0.05
0
0.02
0.07
0
0
0
0
0
0
0.25
0.07
0
0.08
0
-0.07
0
0
0.02
-0.06
0.31
0
0
0.12
0
0
0.25
0.11
0.21
-0.04
0
0
0
0
0
0.18
0.07
0
0.28
0.04
0.14
0
0
0.17
0.11
-0
0
0
-0.14
0.01
0
0
0.88
-0.21
0
0
-0.03
0.08
0.13
0.06
0
0
0
0
0
0.19
0.13
0.06
-0.03
0
0
0.16
0
0.16
0
0.19
0
0
0.18
0
0
-0.13
0
-0.01
-0.07
0.05
0
0
0
0
0
0.09
0
0.25
C-20
YDR514C
YDR516C
YDR517W
YDR518W
YDR519W
YDR520C
YDR529C
YDR531W
YDR533C
YDR534C
YDR538W
YDR539W
YDR541C
YDR542W
YDR543C
YDR545W
YEL001C
YEL002C
YEL006W
YEL007W
YEL009C
YEL011W
YEL012W
YEL013W
YEL015W
YEL017C-A
YEL017W
YEL020C
YEL021W
YEL024W
YEL026W
YEL027W
YEL031W
YEL034W
YEL036C
YEL037C
YEL038W
YEL040W
YEL042W
YEL043W
YEL046C
YEL047C
YEL049W
YEL050C
YEL051W
YEL052W
YEL054C
YEL056W
YEL057C
YEL058W
YEL059C-A
YEL059W
YEL060C
YEL063C
YEL066W
EUG1
FKB2
QCR7
PAD1
WBP1
GCN4
GLC3
UBC8
VAC8
PMP2
URA3
RIP1
CUP5
SPF1
HYP2
ANP1
RAD23
UTR4
UTR2
GDA1
GLY1
PAU2
RML2
VMA8
AFG1
RPL12A
HAT2
PCM1
SOM1
PRB1
CAN1
HPA3
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
21
21
20
21
20
20
21
20
20
21
20
20
20
20
20
20
20
20
20
20
20
21
21
20
20
31
21
21
21
20
20
21
21
20
21
21
20
21
20
21
20
21
20
20
20
20
21
20
20
21
21
21
20
20
20
0.09
0.54
0.4
0.14
0.97
0.09
0.75
0.09
1.53
0.09
0.09
0.09
0.09
0.26
0.14
0.65
0.44
0.31
0.16
0.1
4.55
0.12
0.07
0.11
0.07
4.02
0.13
0.07
0.14
0.7
1.59
6.11
0.21
3.65
0.13
0.07
0.19
0.36
0.16
0.07
0.51
0.18
0.15
0.15
0.15
0.09
1.73
0.12
0.07
0.31
0.16
0.07
0.26
0.09
0.07
0.05
0.32
0.27
0.17
0.92
0.07
0.24
0.08
1.01
0.09
0.14
0.05
0.06
0.21
0.11
0.39
0.61
0.23
0.08
0.14
3.37
0.11
0.07
0.07
0.07
3.44
0.12
0.07
0.13
0.33
2.96
8.08
0.07
2.59
0.14
0.07
0.17
0.75
0.07
0.07
0.35
0.12
0.08
0.11
0.09
0.08
1.94
0.07
0.07
0.17
0.17
0.07
0.17
0.07
0.07
0.07
0.51
0.37
0.2
0.84
0.07
1.27
0.1
2.53
0.07
0.08
0.1
0.07
0.29
0.09
0.62
0.57
0.27
0.18
0.22
3.05
0.23
0.07
0.1
0.07
3.85
0.07
0.07
0.14
1.21
2.14
4.37
0.21
4.14
0.22
0.12
0.21
0.28
0.29
0.07
0.86
0.18
0.13
0.13
0.17
0.11
2.37
0.08
0.13
0.2
0.34
0.07
0.4
0.07
0.19
0.09
0.26
0.21
0.2
1.13
0.09
0.46
0.09
9.8
0.09
0.14
0.12
0.16
0.21
0.13
0.75
0.38
0.31
0.16
0.3
4.88
0.05
0.05
0.14
0.08
6.39
0.21
0.08
0.13
0.58
3.21
7.51
0.51
5.92
0.18
0.13
0.25
0.36
0.25
0.09
0.96
0.27
0.13
0.18
0.26
0.15
1.57
0.12
0.05
0.27
0.29
0.05
0.49
0.1
0.28
0
-0.31
-0.15
-0.14
0.02
0
-0.3
0
-0.16
0
-0.11
0
0
-0.12
0
-0.24
0
0
0
0.08
-0.09
0
0
-0.1
0
-0.11
0
0
0
-0.18
0.24
0.02
-0.32
-0.05
0
0
-0.04
0.2
0
0
-0.2
0
0
0
-0.1
0
0
-0.12
0
-0.14
0
0
-0.15
0
0
0
-0.02
-0.09
0.01
0.14
0
0.23
0
0.16
0
0
0
0
0
0
0.04
0.1
0
0
0.15
0.01
0.06
0
0
0
-0.05
0
0
-0.01
0.18
0.14
-0.06
0
0
0.01
0
0
-0.03
0.18
0
0.2
0
0
0
0.03
0
0.08
0
0.24
0.15
0.21
0
0.16
0
0.27
0
-0.3
-0.02
0
0.05
0
-0.17
0
0.65
0
0
0
0.1
0
0
0.05
0.11
0.01
0.05
0.32
0.02
0
0
0
0
0.15
0.01
-0.1
-0.08
-0.09
0.27
0.07
0.29
-0.01
0.1
0.16
-0.01
0
0.07
0.09
0.12
0.21
-0.08
-0.07
0.13
0.1
-0.01
0
0
0.01
0.12
0
0.16
-0.09
0.38
C-21
YEL071W
YEL073C
YEL074W
YEL075C
YEL077C
YER001W
YER003C
YER004W
YER005W
YER007C-A
YER009W
YER010C
YER011W
YER012W
YER014W
YER016W
YER017C
YER019C-A
YER019W
YER020W
YER021W
YER022W
YER023W
YER024W
YER025W
YER026C
YER027C
YER028C
YER029C
YER030W
YER031C
YER034W
YER035W
YER036C
YER037W
YER039C
YER042W
YER043C
YER044C
YER045C
YER046W
YER048C
YER049W
YER050C
YER052C
YER053C
YER055C
YER056C
YER056C-A
YER057C
YER058W
YER060W
YER060W-A
YER061C
YER062C
MNN1
PMI40
NTF2
TIR1
PRE1
HEM14
BIM1
AFG3
SBH2
GPA2
RPN3
SRB4
PRO3
GCD11
CHO1
GAL83
SMB1
YPT31
HVG1
SAH1
CAJ1
HOM3
HIS1
FCY2
RPL34A
HIG1
PET117
FCY21
FCY22
CEM1
HOR2
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
A-D
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
20
20
10
20
22
21
21
21
20
21
20
20
20
21
21
20
21
20
21
21
21
625
20
20
21
20
21
21
20
20
20
21
20
20
21
21
20
21
21
21
21
20
20
20
20
20
20
20
20
21
20
20
20
20
20
0.2
0.26
0.07
0.07
0.29
0.07
0.23
0.36
0.07
0.13
1.33
0.14
2.52
0.27
0.07
0.1
0.07
0.93
0.16
0.28
0.09
0.11
0.94
0.08
0.21
0.97
0.09
0.09
0.07
0.07
0.29
0.07
0.31
0.16
0.07
0.07
0.07
4.32
0.65
0.07
0.07
0.07
0.07
0.07
0.16
0.75
0.97
0.68
2.49
0.89
0.07
0.07
0.09
0.07
0.59
0.16
0.15
0.07
0.07
0.22
0.07
0.07
0.27
0.07
0.07
1.02
0.1
3.07
0.22
0.07
0.07
0.07
0.56
0.11
0.19
0.09
0.08
1.03
0.07
0.2
0.41
0.07
0.07
0.07
0.07
0.12
0.07
0.18
0.17
0.07
0.07
0.07
2.8
0.33
0.07
0.07
0.07
0.07
0.07
0.17
0.33
0.6
0.79
1.66
0.77
0.07
0.07
0.07
0.07
0.65
0.21
0.25
0.07
0.07
0.35
0.08
0.27
0.62
0.07
0.07
1.42
0.17
1.9
0.18
0.07
0.07
0.07
0.61
0.11
0.37
0.18
0.07
1.4
0.07
0.12
0.64
0.07
0.07
0.08
0.09
0.34
0.07
0.21
0.21
0.07
0.07
0.07
3.21
0.44
0.07
0.07
0.08
0.07
0.07
0.27
0.71
0.86
0.79
1.83
1.13
0.07
0.07
0.07
0.07
0.4
0.31
0.26
0.06
0.05
0.44
0.1
0.18
0.38
0.13
0.09
0.9
0.23
2.23
0.41
0.05
0.05
0.06
0.63
0.15
0.4
0.23
0.09
0.5
0.06
0.15
0.67
0.1
0.05
0.05
0.09
0.23
0.05
0.98
0.3
0.15
0.05
0.29
2.86
0.72
0.12
0.08
0.1
0.05
0.1
0.24
1.03
0.79
1.41
1.35
1.21
0.07
0.16
0.16
0.07
2.05
-0.1
-0.21
0
0
-0.11
0
-0.2
-0.1
0
0
0.06
-0.01
0.06
0
0
-0.03
0
-0.1
-0.02
-0.08
0
-0.11
-0.05
0
0
-0.32
-0
0
0
0
-0.1
0
0
0
0
0
0
-0.16
-0.19
0
0
0
0
0
0
-0.26
-0.19
-0.05
0
0.02
0
0
0
0
-0.07
0
0.05
0
0
0
0
0.19
0.13
0
0
0.07
0
-0.03
0.11
0
0
0
-0.03
-0.02
0.01
0.1
0
0.07
0
0
-0.19
0
0
0
0
0
0
0
0
0
0
0
-0.14
-0.19
0
0
0
0
0
0.31
0
-0.01
-0.05
-0.14
0.06
0
0
0
0
-0.04
0.15
0
0
0
0.2
0.03
0
0.15
0.08
0
-0.08
0.16
0.03
0.27
0
0
-0.11
-0.06
0
0.04
0.17
0
-0.07
0
0
-0.2
-0.07
0
0
0.05
-0.08
0
0.3
0.22
0.28
0
0.41
-0.2
0
0.19
-0.14
0
0
0
0.14
0.15
-0.12
0.17
-0.17
0.08
0
0.18
0.01
0
0.5
C-22
YER063W
YER064C
YER066W
YER067W
YER068W
YER069W
YER072W
YER073W
YER074W
YER076C
YER078C
YER079W
YER080W
YER081W
YER082C
YER083C
YER084W
YER086W
YER087C-A
YER087W
YER088C
YER089C
YER090W
YER091C
YER092W
YER093C-A
YER094C
YER095W
YER099C
YER100W
YER102W
YER103W
YER106W
YER107C
YER112W
YER113C
YER114C
YER115C
YER117W
YER118C
YER119C
YER120W
YER121W
YER122C
YER124C
YER125W
YER126C
YER127W
YER130C
YER131W
YER133W
YER134C
YER136W
YER138C
YER141W
MOT2
ARG5,6
RPS24A
ILV1
SBH1
DOT6
PTC2
TRP2
MET6
PUP3
RAD51
PRS2
UBC6
RPS8B
SSA4
GLE2
USS1
BOI2
SPR6
RPL23B
SSU81
SCS2
GLO3
RSP5
LCP5
RPS26B
GLC7
GDI1
COX15
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
21
20
20
21
20
20
21
21
42
21
20
21
21
21
20
20
21
20
20
20
21
20
21
20
21
41
20
21
21
20
33
20
20
20
20
20
20
20
50
20
21
20
20
20
21
20
21
20
20
21
40
20
20
40
20
0.15
0.08
0.11
0.35
0.07
0.27
1.02
0.1
0.49
0.11
0.07
0.08
0.08
0.07
0.07
0.24
0.07
0.13
0.47
0.07
0.25
0.41
0.08
2.23
0.07
0.07
0.68
0.15
0.1
0.14
6.12
0.26
0.07
0.11
0.08
0.07
0.1
0.16
1.82
0.27
0.07
1.47
0.07
0.09
0.07
0.14
0.07
0.07
0.07
0.6
0.07
0.18
0.17
0.27
0.58
0.07
0.07
0.08
0.22
0.08
0.13
1.05
0.13
0.72
0.08
0.07
0.09
0.07
0.07
0.07
0.24
0.07
0.36
0.56
0.07
0.26
0.17
0.07
3.16
0.07
0.07
0.7
0.17
0.07
0.07
5.21
0.09
0.07
0.13
0.07
0.07
0.07
0.19
3.53
0.25
0.09
1.53
0.07
0.09
0.07
0.11
0.07
0.07
0.09
0.76
0.07
0.1
0.16
0.17
0.54
0.08
0.09
0.12
1.03
0.07
0.5
0.91
0.18
0.57
0.08
0.07
0.12
0.09
0.07
0.07
0.64
0.08
0.3
0.83
0.07
0.51
0.33
0.13
1.47
0.07
0.07
1.18
0.13
0.08
0.09
5.47
0.12
0.07
0.1
0.07
0.07
0.07
0.21
1.68
0.27
0.11
0.98
0.07
0.15
0.07
0.13
0.07
0.07
0.07
0.46
0.07
0.16
0.19
0.24
0.54
0.05
0.14
0.06
0.23
0.1
0.27
1.14
0.13
0.63
0.06
0.07
0.11
0.1
0.09
0.07
0.55
0.05
0.27
0.48
0.1
0.57
0.34
0.13
3.65
0.06
0.06
1.14
0.16
0.18
0.09
4
0.84
0.05
0.11
0.1
0.06
0.06
0.13
1.83
0.38
0.19
2.03
0.09
0.12
0.15
0.17
0.07
0.07
0.17
0.41
0.08
0.17
0.39
0.55
1.24
-0.06
0
-0.08
-0.19
0
-0.07
0.07
0.09
0.17
0
0
0
0.02
0
0
0
0
0.21
0
0
-0
-0.1
0
0
0
0
0
0
0
0
0.01
-0.16
0
0
0
0
0
0
0.21
-0.03
0
0.07
0
-0.01
0
0
0
0
0
0
0
-0.04
-0.01
0
-0.04
0
0
0
0.36
0
0.37
0.11
0.11
0.07
0
0
0
0
0
0
0.12
0
0.13
0.07
0
0
0
0.05
-0.21
0
0
0.1
0
0
0
-0.08
-0.1
0
0.06
0
0
0
0
0.03
-0.05
0
-0.05
0
0
0
0
0
0
0
0
0
0
0
0.05
-0.05
0
0.11
0
-0.17
-0.03
0.03
0.16
0.15
0.02
-0.14
0
-0.05
0
0.03
0
0.12
0
0.03
-0.04
0.03
0.29
-0.03
0
0.15
0
-0.12
0.3
-0.07
0.08
-0.03
-0.23
0.5
0
-0.05
0
0
0
-0.04
0.07
0.03
0.11
0.1
0
0
0.33
-0.12
-0.09
0
0.12
0
-0.05
0
0.18
0.29
0.26
C-23
YER143W
YER145C
YER146W
YER148W
YER150W
YER151C
YER152C
YER154W
YER155C
YER156C
YER157W
YER158C
YER159C
YER160C
YER163C
YER164W
YER165W
YER166W
YER167W
YER170W
YER174C
YER175C
YER176W
YER177W
YER178W
YER183C
YER185W
YER186C
YER190W
YFL-TYA
YFL-TYB
YFL002C
YFL005W
YFL006W
YFL007W
YFL009W
YFL010C
YFL011W-A
YFL013C
YFL014W
YFL016C
YFL017C
YFL018C
YFL018W-A
YFL019C
YFL020C
YFL021W
YFL022C
YFL026W
YFL027C
YFL028C
YFL030W
YFL031W
YFL034W
YFL035C-A
DDI1
FTR1
SPT15
UBP3
OXA1
BEM2
BUR6
CHD1
PAB1
BCK2
ADK2
ECM32
RPL23B
PDA1
SPB4
SEC4
CDC4
AUA1
HSP12
MDJ1
LPD1
SNP2
PAU5
GAT1
FRS2
STE2
CAF16
HAC1
B
B
B
A-D
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
20
20
20
624
20
20
21
20
20
20
21
20
21
40
20
21
20
20
20
21
21
20
21
20
20
21
20
21
20
20
20
20
21
20
21
20
20
21
21
20
20
20
20
21
21
20
20
20
20
21
20
21
21
21
20
0.07
0.07
0.12
0.28
5.59
0.07
0.2
0.38
0.08
0.16
0.07
0.07
0.09
0.12
0.2
0.07
0.28
0.07
0.07
0.07
0.17
0.07
0.07
4.58
1.88
0.07
0.07
0.07
0.73
0.07
0.07
0.1
0.14
0.1
0.07
0.09
1.22
0.11
0.07
2.53
0.11
0.14
0.44
0.22
0.07
0.12
0.17
0.56
0.57
0.07
0.13
0.14
1.89
0.07
0.08
0.07
0.07
0.07
0.18
3.51
0.07
0.16
0.31
0.07
0.18
0.07
0.15
0.07
0.11
0.18
0.07
0.43
0.07
0.07
0.07
0.11
0.07
0.08
2.63
1.91
0.09
0.07
0.07
0.39
0.07
0.07
0.08
0.14
0.12
0.07
0.09
0.76
0.07
0.07
1.62
0.08
0.13
0.53
0.23
0.08
0.12
0.14
0.64
0.07
0.07
0.11
0.09
1.74
0.07
0.07
0.08
0.1
0.07
0.26
4.4
0.07
0.18
0.38
0.08
0.22
0.07
0.08
0.07
0.2
0.19
0.07
0.11
0.07
0.07
0.07
0.23
0.09
0.07
6.59
0.32
0.1
0.07
0.08
0.1
0.07
0.08
0.07
0.19
0.08
0.07
0.07
1.01
0.07
0.07
2.65
0.1
0.15
0.9
0.24
0.07
0.1
0.07
0.39
0.69
0.07
0.25
0.69
1.18
0.07
0.07
0.08
0.15
0.13
0.24
8.47
0.06
0.21
0.51
0.11
0.14
0.06
0.22
0.06
0.39
0.42
0.05
0.28
0.06
0.08
0.05
0.2
0.08
0.06
6.89
2.46
0.1
0.06
0.08
0.91
0.06
0.05
0.1
0.15
0.14
0.07
0.13
1.45
0.05
0.05
16.82
0.17
0.1
0.69
0.25
0.05
0.14
0.22
1
1.21
0.05
0.16
0.31
2.07
0.06
0.06
0
0
0
-0.02
-0.2
0
-0.1
0.03
0
0.07
0
0
0
0
-0.01
-0
0.06
0
0
0
0
0
0
-0.22
0.05
0
0
0
-0.05
0
0
0
0
0
0
0
-0.15
-0.01
0
-0.05
0
0
-0.02
0
0
0
0
0.11
-0.8
0
0
0
-0.04
0
0
0
0
0
0
-0.09
0
-0.03
0
0
0.31
0
0
0
0
0
0
-0.2
0
0
0
0.07
0
0
-0.02
-0.54
0.04
0
0
-0.7
0
0
0
0
0
0
0
-0.05
-0.1
0
0.19
0
0
0.27
0.17
0
0
-0.3
0.03
0.06
0
0.09
0.32
-0.2
0
0
0
0.1
0.03
0.02
0.19
0
-0.06
0.2
0
-0.1
-0.16
0.04
-0.14
0.39
0.25
0
0.03
0
-0.14
0
-0.15
-0.14
0
0.08
0.12
0.06
0
0
0.12
0
0
0
0
0.04
-0.15
0
0.1
0
0
0.89
0.01
0
0.07
-0.04
0
0
-0.01
0.23
0.29
0
-0.06
0.14
0.05
0
0
C-24
YFL035C-B
YFL037W
YFL038C
YFL039C
YFL041W
YFL043C
YFL044C
YFL045C
YFL048C
YFL054C
YFL057C
YFL058W
YFL059W
YFL062W
YFL066C
YFR001W
YFR003C
YFR004W
YFR006W
YFR007W
YFR009W
YFR010W
YFR011C
YFR015C
YFR017C
YFR018C
YFR020W
YFR021W
YFR022W
YFR024C
YFR024C-A
YFR025C
YFR026C
YFR028C
YFR030W
YFR031C
YFR031C-A
YFR033C
YFR034C
YFR036W
YFR037C
YFR041C
YFR042W
YFR044C
YFR045W
YFR047C
YFR048W
YFR049W
YFR050C
YFR051C
YFR052W
YFR053C
YGL001C
YGL002W
YGL003C
TUB2
YPT1
ACT1
FET5
SEC53
EMP47
THI5
SNZ3
COS4
RPN11
GCN20
GSY1
HIS2
CDC14
MET10
SMC2
RPL2A
QCR6
PHO4
CDC26
RSC8
YMR31
PRE4
RET2
RPN12
HXK1
CDH1
B
B
B
A-D
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
20
21
20
629
21
20
20
21
21
21
25
20
20
20
23
20
20
20
20
21
20
20
21
21
21
20
21
21
20
20
26
20
21
20
20
21
52
20
21
20
20
21
20
21
21
21
21
21
20
20
20
21
20
20
20
0.15
0.48
0.74
3.67
0.15
0.07
0.07
1.25
0.12
0.08
0.15
0.07
0.1
0.58
0.12
0.07
0.09
0.26
0.13
0.07
0.17
0.15
0.08
0.16
0.23
0.27
0.07
0.07
0.08
0.27
0.14
0.07
0.07
0.09
0.07
0.07
2.22
0.37
0.08
0.07
0.13
0.07
0.07
0.72
0.07
0.43
0.07
0.23
0.45
0.55
0.07
2.94
0.31
0.1
0.07
0.26
0.6
0.74
3.35
0.14
0.07
0.07
1.49
0.09
0.07
0.25
0.07
0.07
0.47
0.07
0.07
0.07
0.27
0.07
0.07
0.26
0.12
0.07
0.07
0.31
0.18
0.1
0.07
0.07
0.26
0.08
0.07
0.07
0.07
0.07
0.07
5.11
0.35
0.07
0.07
0.1
0.07
0.08
0.86
0.07
0.53
0.07
0.29
0.57
1.02
0.13
2.87
0.2
0.09
0.07
0.22
0.75
1.07
3.59
0.15
0.07
0.07
0.29
0.07
0.07
0.21
0.07
0.07
0.61
0.07
0.07
0.07
0.42
0.14
0.07
0.2
0.17
0.16
0.07
0.36
0.17
0.07
0.07
0.09
0.07
0.1
0.07
0.12
0.07
0.07
0.07
5.37
0.32
0.07
0.08
0.15
0.08
0.07
1.03
0.07
0.95
0.07
0.83
0.52
0.16
0.09
6.72
0.2
0.13
0.07
0.36
0.54
1.14
4.14
0.14
0.08
0.06
1.42
0.19
0.08
0.34
0.07
0.07
0.93
0.08
0.05
0.08
0.73
0.12
0.07
0.27
0.22
0.07
0.05
0.47
0.16
0.14
0.07
0.36
0.47
0.15
0.07
0.05
0.09
0.11
0.06
2.57
0.26
0.12
0.07
0.24
0.07
0.15
1.57
0.11
1.28
0.08
0.41
0.98
0.99
0.29
5
0.41
0.15
0.09
0.1
0.01
-0.01
-0.04
0
0
0
0.09
0
0
0
0
-0
-0
0.01
0
0
0
0
0
0.08
0
0
-0.21
-0.09
0
0
0
0
0
-0.1
0
0
0
0
0
0.22
0
0
0
0
0
0
0
0
-0.01
0
0.04
-0.01
0.1
0
-0.29
-0.03
0
0
0.02
0
0.06
-0.06
0
0
0
-0.71
0
-0.1
0
0
0
0.06
-0.1
0
0
0.12
0
0
0
0
0
-0.2
0.18
0
0
0
0
-0.5
-0.1
0
0
0
0
0
0.14
0
0
0
0
0
0
0.11
0
0.3
0
0.23
0
-0.43
0
0.1
0
0
0
0.37
-0.05
0.16
0.05
0.02
-0.08
0
-0.14
0.18
0
-0.05
0
0
0.17
0
0
0
0.25
-0.06
-0.08
0.05
0.01
-0.05
-0.5
0.14
-0.14
-0.04
0
0.27
0.02
0.1
0
0
-0.06
0.07
0
0.01
-0.14
-0.07
0
0
0
0
0.25
0.07
0.39
0
0
0.17
0.21
0.18
0.03
0.12
-0.07
0
C-25
YGL004C
YGL006W
YGL008C
YGL009C
YGL010W
YGL011C
YGL012W
YGL013C
YGL019W
YGL020C
YGL021W
YGL022W
YGL023C
YGL024W
YGL026C
YGL028C
YGL029W
YGL030W
YGL031C
YGL032C
YGL035C
YGL036W
YGL037C
YGL038C
YGL039W
YGL040C
YGL044C
YGL045W
YGL047W
YGL048C
YGL051W
YGL053W
YGL054C
YGL055W
YGL056C
YGL057C
YGL058W
YGL062W
YGL067W
YGL068W
YGL070C
YGL076C
YGL077C
YGL078C
YGL079W
YGL080W
YGL081W
YGL082W
YGL084C
YGL087C
YGL088W
YGL089C
YGL091C
YGL096W
YGL097W
PMC1
PMA1
LEU1
SCL1
ERG4
PDR1
CKB1
ALK1
STT3
TRP5
RPL30
RPL24A
AGA2
MIG1
MTC2
OCH1
HEM2
RNA15
RPT6
OLE1
RAD6
PYC1
RPB9
RPL7A
HNM1
DBP3
MMS2
MFα2
NBP35
SRM1
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
20
20
20
21
21
21
20
21
20
20
20
21
20
20
21
20
20
21
20
20
20
20
21
20
20
20
20
20
20
21
20
20
20
20
20
20
21
21
21
20
20
41
20
20
20
20
20
20
20
20
20
21
20
21
20
0.08
0.07
6.06
0.42
0.15
0.39
0.69
0.07
0.17
0.25
0.07
0.21
0.07
0.07
0.97
0.16
0.09
4.86
2.6
0.6
0.07
0.07
1.34
0.1
0.16
0.77
0.07
0.07
0.07
0.27
0.07
0.07
0.78
0.65
0.07
0.07
0.07
0.08
0.25
0.14
0.07
3.81
1.04
0.15
0.1
0.21
0.07
0.07
0.09
0.18
0.07
0.07
0.07
0.09
0.07
0.07
0.08
5.38
0.53
0.18
0.3
0.82
0.07
0.18
0.18
0.07
0.21
0.08
0.07
1.08
0.17
0.08
9.72
2.56
0.07
0.07
0.07
1.59
0.14
0.16
0.54
0.07
0.07
0.07
0.4
0.07
0.07
0.5
1.19
0.11
0.07
0.07
0.11
0.18
0.2
0.14
4.11
0.97
0.16
0.07
0.24
0.07
0.07
0.07
0.11
0.09
3.67
0.07
0.07
0.07
0.07
0.08
7.72
0.76
0.16
0.67
0.78
0.07
0.19
0.25
0.07
0.13
0.07
0.07
1.26
0.17
0.07
0.89
2.74
0.53
0.07
0.07
1.91
0.11
0.08
0.44
0.07
0.07
0.07
0.49
0.07
0.07
0.43
2.44
0.07
0.08
0.11
0.16
0.28
0.2
0.11
4.26
0.77
0.12
0.07
0.28
0.07
0.07
0.1
0.21
0.07
0.07
0.08
0.07
0.07
0.06
0.09
8.74
0.65
0.24
0.54
0.87
0.12
0.31
0.3
0.05
0.2
0.09
0.07
1.04
0.4
0.09
5.39
3.71
1.09
0.07
0.08
4.48
0.14
0.27
0.82
0.08
0.08
0.14
0.77
0.07
0.11
0.6
3.08
0.1
0.07
0.12
0.22
0.34
0.26
0.17
2.99
1.03
0.16
0.06
0.29
0.05
0.06
0.1
0.2
0.1
0.05
0.12
0.07
0.07
0
0
0.05
0.09
0
0.03
0.07
0
-0
0
0
0.03
0
0
0
0
0
0.32
-0.1
-0.9
0
0
-0.21
0
0
0
0
0
0
0.06
0
0
-0.01
0.22
0.08
0
0
0
-0.09
0
0
0.06
0
0
0
-0.03
0
0
-0
0
0
1.22
0
0
0
0
0
0.14
0.19
0
0.23
0
0
0
0.06
0
0
0
0
0.02
0.07
0
-0.73
-0.05
0
0
0
0.08
-0.01
0
-0.05
0
0
0
0.03
0
0
0
0.51
0
0
0.03
0.03
0.12
0.18
0
0.01
-0.04
-0.02
0
0.03
0
0
0
0.11
0
0
0
0
0
0
-0
0.17
0.19
0.08
0.24
0.03
-0.06
0.02
0.12
0
0.16
0.05
0
0.01
0.25
-0.11
0.03
0.09
0.13
-0.12
0.04
0.26
0
0.12
0.09
0
-0.11
0.03
0.31
0
-0.02
0.05
0.62
0
0
0.03
0.09
0.11
0.17
0.11
-0.17
-0.06
0
0
0.02
0
0
-0.02
0.07
-0.03
0
-0.02
-0.15
-0.1
C-26
YGL099W
YGL100W
YGL101W
YGL102C
YGL103W
YGL104C
YGL105W
YGL106W
YGL107C
YGL111W
YGL112C
YGL114W
YGL115W
YGL117W
YGL119W
YGL121C
YGL122C
YGL123W
YGL124C
YGL125W
YGL126W
YGL127C
YGL128C
YGL130W
YGL134W
YGL135W
YGL137W
YGL141W
YGL142C
YGL143C
YGL147C
YGL148W
YGL151W
YGL153W
YGL154C
YGL155W
YGL156W
YGL157W
YGL159W
YGL160W
YGL161C
YGL162W
YGL166W
YGL167C
YGL172W
YGL173C
YGL178W
YGL179C
YGL181W
YGL184C
YGL186C
YGL187C
YGL188C
YGL189C
YGL191W
SEH1
RPL28
ARC1
MLC1
TAF60
SNF4
ABC1
NAB2
RPS2
MET13
SCS3
SOH1
CEG1
PCL10
RPL1B
SEC27
GPI10
MRF1
RPL9A
ARO2
NUT1
PEX14
LYS5
CDC43
AMS1
SUT1
CUP2
PMR1
NUP49
KEM1
MPT5
GTS1
COX4
RPS26A
COX13
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
20
21
20
20
41
21
21
20
21
20
20
21
21
20
20
20
20
21
20
21
21
20
21
21
21
20
20
21
21
20
26
21
20
21
21
20
21
20
20
21
20
20
21
21
21
20
21
20
20
20
20
21
20
19
21
0.09
0.11
0.08
0.08
3.2
0.12
0.65
0.16
0.07
0.08
0.12
0.09
0.27
0.08
0.07
0.15
0.07
4.64
0.07
0.1
0.31
0.17
0.07
0.07
0.07
7.5
0.14
0.07
0.07
0.07
1.35
0.9
0.07
0.07
0.1
0.07
0.12
0.26
0.07
0.07
0.64
0.08
0.1
0.12
0.07
0.08
0.07
0.1
0.39
0.07
0.13
0.88
0.08
14.83
0.19
0.1
0.09
0.09
0.08
4.77
0.1
0.84
0.51
0.07
0.07
0.08
0.08
0.13
0.07
0.07
0.13
0.08
7.09
0.07
0.21
0.25
0.17
0.07
0.07
0.07
7.35
0.17
0.07
0.07
0.07
2.2
0.74
0.07
0.07
0.07
0.07
0.07
0.23
0.07
0.07
0.43
0.07
0.09
0.16
0.1
0.09
0.07
0.08
0.23
0.07
0.12
0.81
0.07
22.84
0.36
0.07
0.13
0.08
0.07
5.05
0.08
0.67
0.07
0.07
0.07
0.12
0.11
0.3
0.28
0.07
0.43
0.12
5.63
0.07
0.16
0.81
0.2
0.07
0.07
0.11
8.23
0.23
0.07
0.07
0.07
0.73
0.83
0.07
0.08
0.11
0.07
0.08
0.07
0.08
0.07
0.54
0.08
0.11
0.2
0.07
0.1
0.07
0.18
0.22
0.07
0.16
1.94
0.1
1.19
1.31
0.08
0.09
0.05
0.05
4.78
0.14
0.99
0.46
0.05
0.1
0.11
0.1
0.31
0.09
0.1
1.53
0.14
7.69
0.06
0.25
0.43
0.26
0.07
0.06
0.07
10.97
0.22
0.07
0.07
0.08
1.46
0.84
0.05
0.08
0.15
0.1
0.2
0.4
0.05
0.07
0.76
0.09
0.14
0.18
0.09
0.16
0.12
0.18
0.35
0.1
0.31
1.2
0.06
14.56
0.36
0
0
0
0
0.04
-0.04
-0.05
0.35
0
0
0
0
0
0
0
-0.07
0
0.18
0
0.1
0
0
0
0
0
-0.02
0
0
0
0
0.13
0
0
0
0
0
0
0
0
0
-0.08
0
0
0.09
0
0
0
0
-0.1
0
0
0
0
0.03
0
-0
0
0
0
0.09
-0.09
0
-0.22
0
0
0
0
-0.01
0.34
0
0.44
0
0.08
0
0
0.39
0.15
0
0
0.19
0.01
0.08
0
0
0
0.14
0.12
0
0
0
0
0
-0.3
0
0
0.02
0
0
0
0
0
0
0.04
-0.09
0
0
0.37
0
-0.89
0.27
0
-0.05
0
0
0.02
0
0.05
0.33
0
-0.02
0
-0.07
-0.05
0
0.16
0.82
0
0.12
0
0.07
0.1
-0.03
0
0
0
0.07
0.04
-0.11
0
0
-0.03
0.03
0
0
0.01
0
0.07
0.13
0
0.03
0.12
0
0.03
0.16
0
0
0.05
0.14
0.04
0.16
0.28
0.02
0
-0.16
-0.04
C-27
YGL193C
YGL195W
YGL196W
YGL197W
YGL198W
YGL199C
YGL200C
YGL202W
YGL203C
YGL206C
YGL207W
YGL208W
YGL209W
YGL210W
YGL213C
YGL215W
YGL216W
YGL219C
YGL220W
YGL221C
YGL223C
YGL224C
YGL225W
YGL231C
YGL234W
YGL236C
YGL238W
YGL242C
YGL244W
YGL245W
YGL247W
YGL248W
YGL252C
YGL253W
YGL255W
YGL256W
YGL261C
YGR001C
YGR004W
YGR007W
YGR008C
YGR009C
YGR010W
YGR011W
YGR014W
YGR015C
YGR017W
YGR019W
YGR020C
YGR021W
YGR023W
YGR024C
YGR026W
YGR027C
YGR028W
GCN1
MDS3
EMP24
ARO8
KEX1
CHC1
SPT16
SIP2
MIG2
YPT32
SKI8
CLG1
KIP3
NIF3
GOG5
ADE5,7
CSE1
RTF1
PDE1
RTG2
HXK2
ZRT1
ADH4
MUQ1
STF2
SEC9
MSB2
UGA1
VMA7
RPS25A
MSP1
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
21
21
20
21
21
21
21
20
21
20
20
21
20
20
20
21
21
20
20
21
20
20
20
21
20
21
20
20
20
20
21
20
20
21
20
20
20
40
21
20
20
21
20
20
20
21
20
20
20
21
20
20
20
20
21
0.33
0.09
0.31
0.07
0.21
0.14
1.24
1.03
0.07
0.17
0.07
0.07
0.21
0.07
0.11
0.09
0.07
0.07
1.03
0.4
0.07
0.07
1.24
0.15
0.09
0.07
0.07
0.08
0.07
0.74
0.07
0.17
0.07
1.57
4.53
2.66
0.22
0.07
0.07
0.15
1.26
0.07
0.07
0.07
0.12
0.09
0.07
0.33
0.52
0.07
0.07
0.13
0.52
0.81
0.07
0.17
0.07
0.32
0.07
0.82
0.07
1.12
1.05
0.07
0.17
0.08
0.07
0.25
0.07
0.07
0.09
0.07
0.07
0.85
0.29
0.07
0.09
1.22
0.18
0.09
0.07
0.07
0.07
0.07
0.45
0.07
0.14
0.07
2.17
4.95
3.48
0.1
0.07
0.07
0.15
0.66
0.07
0.07
0.07
0.07
0.07
0.07
0.33
0.47
0.07
0.07
0.2
0.34
0.9
0.07
0.17
0.1
0.55
0.07
0.12
0.07
2.5
1.58
0.07
0.23
0.07
0.07
0.08
0.07
0.09
0.11
0.09
0.07
1.06
0.4
0.07
0.07
1.77
0.17
0.09
0.07
0.07
0.09
0.07
0.57
0.08
0.19
0.1
0.79
3.95
0.52
0.19
0.07
0.07
0.11
1.79
0.07
0.09
0.07
0.1
0.07
0.07
0.49
0.68
0.07
0.07
0.12
0.53
0.89
0.09
0.18
0.12
0.96
0.05
0.34
0.08
2.29
1.33
0.1
0.23
0.05
0.06
0.28
0.07
0.1
0.16
0.05
0.05
1.14
0.61
0.08
0.05
1.21
0.21
0.09
0.07
0.09
0.16
0.06
0.77
0.09
0.36
0.08
2.01
1.99
0.99
0.3
0.07
0.06
0.24
1.42
0.08
0.05
0.06
0.07
0.06
0.05
1.37
0.44
0.06
0.08
0.22
0.93
0.81
0.05
0
0
-0.03
0
0.2
-0.05
0.07
-0
0
0
0
0
0
0
0
0
0
0
0
0.01
0
0.05
0
0
0
0
0
0
0
-0.14
0
-0.06
0
0
0.05
0.05
-0.1
0
0
0
-0.2
0
0
0
0
0
0
-0
0
0
0
0.07
-0.01
-0.03
0
-0.03
0
0.14
0
-0.02
-0.03
0.21
0.12
0
0.05
0
0
-0.3
0
0
0
0
0
0.16
0.04
0
0
0.02
0.16
0
0
0
0
0
-0.1
0
0.06
0
-0.02
0.01
-0.39
0
0
0
0
0.33
0
0
0
0
0
0
0
0
0
0
0
0.1
0.09
0.03
0
-0.06
0.48
-0.17
0.22
0
0.1
-0.06
-0.07
0
0
0
-0.05
0
0
-0.02
0
0
0.03
0.06
-0
0
0
0.11
0
0
0
0.02
0
-0.04
0
0.21
-0.04
-0.18
-0.34
-0.38
-0.08
0
0
-0.06
0.12
0
0
0
0
0
0
0.37
0
0
0
0.09
0.2
-0.11
0
C-28
YGR029W
YGR031W
YGR032W
YGR033C
YGR034W
YGR036C
YGR037C
YGR038W
YGR041W
YGR043C
YGR044C
YGR049W
YGR050C
YGR052W
YGR054W
YGR055W
YGR060W
YGR061C
YGR062C
YGR063C
YGR065C
YGR069W
YGR073C
YGR074W
YGR075C
YGR076C
YGR077C
YGR078C
YGR079W
YGR080W
YGR082W
YGR083C
YGR084C
YGR085C
YGR086C
YGR088W
YGR090W
YGR094W
YGR095C
YGR097W
YGR101W
YGR102C
YGR105W
YGR106C
YGR108W
YGR110W
YGR111W
YGR118W
YGR121C
YGR124W
YGR125W
YGR126W
YGR127W
YGR132C
YGR133W
ERV1
GSC2
RPL26B
CWH8
ACB1
ORM1
BUD9
RME1
SCM4
MUP1
ERG25
ADE6
COX18
SPT4
SMD1
PRP38
MRPL25
PEX8
PAC10
TWF1
TOM20
GCD2
MRP13
RPL11B
CTT1
VAS1
ASK10
VMA21
CLB1
RPS23A
MEP1
ASN2
PHB1
PEX4
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
20
21
20
20
17
20
21
21
20
20
20
21
20
21
20
20
20
21
21
20
20
20
20
20
21
20
20
20
20
20
21
20
20
32
20
21
20
20
21
20
21
20
20
20
20
20
20
80
21
21
21
20
20
20
20
0.15
0.07
0.22
0.09
3.2
0.08
2.26
0.17
0.07
0.07
0.29
0.1
0.09
0.16
0.08
0.43
1.96
0.2
0.18
0.65
0.07
0.07
0.11
0.1
0.07
0.07
0.21
0.07
0.07
0.07
0.3
0.07
0.07
3.17
0.22
0.11
0.07
0.19
0.2
0.08
0.23
0.09
0.09
0.7
0.11
0.07
0.07
1.4
0.07
0.25
0.07
0.07
0.13
0.08
0.08
0.14
0.07
0.25
0.07
3.19
0.07
2.95
0.3
0.07
0.07
0.18
0.09
0.07
0.11
0.08
0.49
2.6
0.37
0.08
0.57
0.07
0.07
0.07
0.08
0.07
0.08
0.15
0.07
0.07
0.07
0.54
0.07
0.08
7.72
0.3
0.08
0.07
0.19
0.16
0.1
0.18
0.09
0.1
0.82
0.12
0.07
0.07
1.92
0.08
0.25
0.07
0.07
0.09
0.12
0.07
0.22
0.09
0.48
0.07
3.23
0.09
6.31
0.07
0.07
0.07
0.22
0.12
0.08
0.07
0.07
0.65
1.84
0.14
0.18
0.67
0.1
0.07
0.07
0.15
0.07
0.07
0.15
0.08
0.07
0.08
0.47
0.07
0.07
5.4
0.27
0.07
0.07
0.26
0.19
0.09
0.17
0.1
0.17
1.01
0.07
0.14
0.08
1.71
0.14
0.22
0.07
0.07
0.13
0.18
0.08
0.14
0.13
0.44
0.09
2.08
0.16
2.21
0.32
0.06
0.37
0.3
0.21
0.09
0.33
0.11
0.57
2.88
0.33
0.2
0.7
0.09
0.05
0.09
0.09
0.07
0.07
0.3
0.1
0.06
0.08
0.69
0.09
0.07
5.16
0.34
0.67
0.09
0.2
0.35
0.19
0.31
0.12
0.11
0.74
0.08
0.11
0.09
1.33
0.09
0.42
0.09
0.06
0.21
0.17
0.07
-0.08
0
0
0
-0.04
0
0.05
0.35
0
0
-0.12
0
-0
-0.05
0
0
0.14
0.05
-0.1
0
0
0
0
0
0
0
-0.03
0
0
0
0.06
0
0
0.17
0
0
0
0
0
0
-0.08
0
0
0.04
0
0
0
0.12
0
0.2
0
0
0
0
0
0.1
0
0.19
0
-0.13
0
0.33
-0.24
0
0
0.04
0
0
-0.04
0
0.12
0.02
-0.16
0
0.01
0
0
0
0
0
0
0
0
0
0
-0.01
0
0
0.2
0
0
0
0.05
0
0
-0.06
0
0.1
0
0
0.02
0
0.13
0
-0.01
0
0
0
0.07
0
0.01
-0.02
0.1
0
-0.19
0.05
0.09
0.37
0
0.41
0.22
0.17
0
0.27
0
0.22
0.29
0.05
0
-0.02
0
0
0
0
0
0
0.19
-0.04
0
0
0.16
-0.07
0
0.05
0
0.44
0
-0.04
0.02
-0.06
-0.16
-0.07
-0.05
0.06
0
0.03
0.1
-0.07
-0.11
0.19
-0.06
0
0.14
0.01
0
C-29
YGR135W
YGR136W
YGR137W
YGR138C
YGR141W
YGR143W
YGR144W
YGR146C
YGR147C
YGR148C
YGR149W
YGR155W
YGR157W
YGR159C
YGR161C
YGR162W
YGR163W
YGR165W
YGR167W
YGR169C
YGR172C
YGR173W
YGR174C
YGR175C
YGR178C
YGR180C
YGR181W
YGR182C
YGR183C
YGR184C
YGR185C
YGR189C
YGR191W
YGR192C
YGR193C
YGR194C
YGR195W
YGR197C
YGR199W
YGR200C
YGR201C
YGR203W
YGR204W
YGR206W
YGR207C
YGR209C
YGR210C
YGR211W
YGR214W
YGR215W
YGR216C
YGR217W
YGR218W
YGR220C
YGR222W
PRE9
SKN1
THI4
NAT2
RPL24B
CYS4
CHO2
NSR1
TIF4631
CLC1
YIP1
CBP4
ERG1
PBP1
RNR4
QCR9
UBR1
TYS1
HIP1
TDH3
PDX1
SKI6
SNG1
ADE3
TRX2
RPS0A
GPI1
CCH1
CRM1
MRPL9
PET54
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
20
20
21
21
20
21
21
20
20
19
21
21
20
20
21
20
20
20
20
20
21
21
20
20
21
20
21
20
21
21
20
21
20
20
20
20
21
20
21
21
20
21
21
20
20
21
21
21
41
20
20
20
20
20
21
0.4
0.12
0.1
0.6
0.07
0.15
0.2
0.16
0.07
1.23
0.46
0.68
0.45
0.21
0.17
0.09
0.07
0.07
0.13
0.08
0.18
0.07
0.07
0.66
0.24
0.9
0.64
0.4
1.45
0.07
0.17
0.62
0.24
22.18
0.09
0.24
0.13
0.1
0.07
0.07
0.07
0.13
0.38
0.07
0.08
2.07
0.2
0.07
1.38
0.07
0.07
0.08
0.07
0.12
0.07
0.56
0.07
0.08
0.38
0.07
0.09
0.16
0.11
0.1
1.66
0.24
0.59
0.65
0.48
0.1
0.08
0.07
0.07
0.15
0.07
0.25
0.07
0.07
0.78
0.16
1.29
0.75
0.27
1.09
0.07
0.22
0.47
0.29
6.67
0.07
0.07
0.16
0.07
0.07
0.07
0.07
0.07
0.35
0.07
0.07
1.93
0.25
0.11
1.64
0.07
0.07
0.07
0.07
0.12
0.07
0.28
0.08
0.1
0.69
0.07
0.1
0.17
0.16
0.09
0.93
0.51
0.86
0.7
0.3
0.21
0.07
0.07
0.07
0.19
0.07
0.12
0.07
0.08
0.43
0.13
0.98
1.07
0.49
3.17
0.07
0.1
0.87
0.46
29.62
0.07
0.08
0.16
0.07
0.07
0.07
0.12
0.1
0.44
0.07
0.08
1.6
0.22
0.07
2.3
0.07
0.07
0.07
0.07
0.12
0.07
0.94
0.46
0.2
1.35
0.07
0.15
0.2
0.27
0.1
1.35
0.77
1.15
0.97
0.44
0.21
0.11
0.08
0.05
0.2
0.05
0.11
0.08
0.07
0.73
0.24
0.96
0.97
0.2
0.85
0.07
0.17
0.8
0.46
29.71
0.07
0.07
0.2
0.06
0.11
0.05
0.3
0.08
0.78
0.06
0.07
2.79
0.24
0.07
1.27
0.05
0.09
0.05
0.07
0.15
0.06
0.1
0
-0
-0.14
0
-0.05
-0.06
0
0
0
-0.16
0.08
0.06
0.31
-0.1
0
0
0
0
0
0.02
0
0
-0.02
-0.12
0
0.05
0
-0.11
0
0.04
0
0
-0.05
0
-0.1
0
0
0
0
0
0
-0.03
0
0
0
0.03
0.02
0.09
0
0
0
0
0
0
-0.1
0
0
-0.02
0
-0.06
-0.03
0.05
0
-0.09
0.11
0.21
0.1
0
0.04
0
0
0
0.03
0
0
0
0
0.04
-0.13
0.1
0.09
0
0.34
0
-0.11
0.03
0
0.19
0
0
0
0
0
0
0
0
0
0
0
0.15
0
0
0.14
0
0
0
0
0.03
0
0.27
0.31
0.25
0.3
0
-0.04
-0.07
0.22
0
0.12
0.19
0.21
0.01
0.25
0.01
0
-0.07
0
0.06
0
0
0
0
0.14
-0.02
-0.13
0.11
0
-0.07
-0.14
0.07
0.19
0.22
0.1
0
0
0.02
0
0.07
-0.12
0.21
0
0.17
0
0
0.23
-0.03
-0.16
-0.04
0
-0.1
0
-0.13
-0.08
0
C-30
YGR224W
YGR227W
YGR229C
YGR231C
YGR232W
YGR234W
YGR235C
YGR240C
YGR241C
YGR243W
YGR244C
YGR246C
YGR248W
YGR250C
YGR252W
YGR253C
YGR254W
YGR255C
YGR256W
YGR257C
YGR258C
YGR260W
YGR262C
YGR263C
YGR264C
YGR267C
YGR268C
YGR270W
YGR275W
YGR277C
YGR279C
YGR281W
YGR282C
YGR284C
YGR285C
YGR286C
YGR294W
YGR295C
YGR296W
YHL001W
YHL002W
YHL003C
YHL004W
YHL006C
YHL008C
YHL011C
YHL015W
YHL017W
YHL019C
YHL020C
YHL021C
YHL024W
YHL025W
YHL026C
YHL027W
DIE2
SMI1
PHB2
YHB1
PFK1
YAP1802
BRF1
SOL4
GCN5
PUP2
ENO1
COQ6
GND2
RAD2
MES1
FOL2
YTA7
YOR1
BGL2
ZUO1
BIO2
COS6
RPL14B
LAG1
MRP4
PRS3
RPS20
APM2
OPI1
SNF6
RIM101
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
21
20
20
20
20
20
21
20
21
21
20
20
21
20
21
20
20
20
20
20
20
20
20
21
20
20
20
20
20
20
20
20
21
20
21
20
20
20
20
63
20
20
20
21
20
20
20
20
20
21
21
20
20
21
20
0.07
0.09
0.09
0.17
0.19
0.37
0.07
0.67
0.1
0.07
0.17
0.07
0.23
0.07
0.07
0.21
7.04
0.23
0.08
0.1
0.07
0.3
0.17
0.12
0.07
0.14
0.2
0.07
0.1
0.09
3.4
0.08
1.89
0.27
0.88
0.07
0.24
1.27
0.37
3.27
0.07
0.14
0.07
0.07
0.15
0.11
3.39
0.15
0.07
0.2
0.16
0.07
0.19
0.08
0.09
0.07
0.08
0.07
0.14
0.54
0.59
0.16
0.56
0.07
0.07
0.11
0.08
0.14
0.07
0.07
0.17
5.36
0.21
0.08
0.08
0.07
0.26
0.23
0.22
0.08
0.11
0.14
0.07
0.19
0.08
2.96
0.07
1.66
0.32
1.37
0.08
0.15
0.77
0.45
3.71
0.08
0.15
0.12
0.07
0.07
0.19
5.46
0.18
0.07
0.26
0.07
0.07
0.15
0.11
0.07
0.07
0.07
0.12
0.2
0.56
1.38
0.22
0.87
0.07
0.12
0.53
0.07
0.19
0.1
0.07
0.22
5.52
0.31
0.13
0.1
0.08
0.44
0.2
0.13
0.09
0.15
0.3
0.07
0.11
0.1
4.15
0.07
1.81
0.65
1.32
0.17
0.12
0.52
0.62
3.21
0.08
0.11
0.15
0.07
0.18
0.21
3.79
0.23
0.07
0.32
0.27
0.07
0.17
0.09
0.07
0.07
0.13
0.12
0.22
0.6
0.11
0.13
1.18
0.08
0.05
0.22
0.07
0.72
0.52
0.05
0.29
18.48
0.27
0.53
0.09
0.05
0.36
0.16
0.26
0.14
0.19
0.36
0.08
0.15
0.11
2.65
0.1
2.69
0.53
1.06
0.05
0.3
0.65
0.59
2.67
0.1
0.12
0.14
0.07
0.16
0.24
3.35
0.19
0.05
0.38
0.25
0.06
0.17
0.22
0.14
0
0
0
0
0.26
0.05
0
0
0
0
0
0
-0.2
0
0
0.06
0
0
0
0
0
0
0.11
0
0
0
-0.07
0
0.09
0
0
0
0.18
-0.01
0.12
0
0
-0.1
0.03
0.1
0
0
0
0
-0.05
0.09
0.1
0
0
0
-0.06
0
-0.1
0
0
0
0
0
0.05
0.42
0.41
0.1
0.06
0
0
0.48
0
-0.14
0.11
0
0.21
0.05
0.1
0.04
0
0
0.05
0.05
0
0
0.01
0.1
0
0
0
0.13
0
0.14
0.19
0
0.3
0
-0.17
0.08
0.09
0
0
0.1
0
0
0.12
0.09
0
0
0
-0.02
0
-0.04
0
0
0
-0.03
-0.08
0.09
0.39
-0.6
0.1
0.28
0
0
0.02
0
0.35
0.59
0
0.28
0.3
0.06
0.75
0
0
0
-0.04
0.09
0.15
0.07
0.16
0
0.04
0.07
-0.04
0.06
0.29
0.12
0.03
0
0
-0.04
0.12
0
0
0.02
0.05
-0.16
-0.09
0.15
-0.25
0
0
-0.03
0.01
0
0
0.15
-0.14
C-31
YHL028W
YHL029C
YHL031C
YHL032C
YHL033C
YHL034C
YHL035C
YHL039W
YHL040C
YHL044W
YHL046C
YHL048W
YHL049C
YHL050C
YHR001W
YHR001W-A
YHR003C
YHR004C
YHR005C
YHR007C
YHR008C
YHR009C
YHR010W
YHR012W
YHR013C
YHR016C
YHR017W
YHR018C
YHR019C
YHR020W
YHR021C
YHR022C
YHR024C
YHR025W
YHR026W
YHR027C
YHR028C
YHR030C
YHR032W
YHR033W
YHR034C
YHR037W
YHR039BC
YHR039C
YHR041C
YHR042W
YHR043C
YHR045W
YHR046C
YHR049W
YHR050W
YHR051W
YHR052W
YHR053C
YHR054C
WSC4
GOS1
GUT1
RPL8A
SBP1
COS8
QCR10
GPA1
ERG11
SOD2
RPL27A
VPS29
ARD1
YSC84
YSC83
ARG4
DED81
RPS27B
MAS2
THR1
PPA1
RPN1
DAP2
SLT2
PUT2
VMA10
SRB2
NCP1
DOG2
SMF2
COX6
CUP1
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
21
20
20
20
20
20
20
21
20
20
20
21
10
40
20
21
20
20
20
20
21
20
20
41
20
38
21
20
21
21
20
20
20
21
20
21
21
20
21
20
20
21
21
21
21
20
20
21
21
21
20
21
20
20
21
0.09
0.07
0.07
0.07
1.4
0.53
0.07
0.07
0.09
0.07
0.1
0.24
0.16
0.23
0.08
0.81
0.07
0.07
0.07
1.02
0.62
0.24
3.58
0.07
0.07
0.07
0.07
1.11
0.35
0.24
12.82
0.07
0.08
1.54
6.83
0.13
0.09
0.07
0.16
0.21
0.07
0.1
0.71
0.2
0.41
0.33
0.11
0.13
0.07
0.28
0.18
0.56
0.07
5.96
0.07
0.1
0.07
0.07
0.07
1.72
0.52
0.07
0.11
0.07
0.07
0.1
0.38
0.21
0.15
0.08
0.73
0.08
0.07
0.08
1.3
0.4
0.17
2.94
0.07
0.1
0.07
0.07
0.61
0.39
0.19
13.16
0.07
0.11
2.18
6.49
0.17
0.19
0.07
0.15
0.07
0.07
0.07
1.09
0.18
1.08
0.5
0.07
0.11
0.07
0.54
0.19
0.66
0.07
17.01
0.07
0.07
0.07
0.07
0.29
1.64
1.1
0.07
0.09
0.07
0.07
0.14
0.33
0.13
0.21
0.07
2.1
0.07
0.07
0.07
0.71
1.24
0.22
5.14
0.07
0.12
0.07
0.07
2.01
0.68
0.22
10.02
0.07
0.14
2.38
7.25
0.2
0.14
0.07
0.12
0.65
0.09
0.17
1.17
0.17
0.46
0.34
0.2
0.11
0.07
0.55
0.18
2.02
0.07
5.98
0.07
0.05
0.08
0.08
0.16
1.49
0.95
0.06
0.07
0.07
0.09
0.19
0.48
0.07
0.23
0.1
0.56
0.06
0.05
0.08
2.6
1.05
0.22
2.49
0.07
0.09
0.06
0.07
1.33
0.6
0.38
10.05
0.12
0.16
1.38
4.63
0.24
0.17
0.09
0.17
0.05
0.05
0.12
0.98
0.14
0.64
0.7
0.07
0.14
0.11
0.25
0.14
0.85
0.06
16.67
0.06
0
0
0
0
0.06
-0.02
0
0
0
0
0
0
0
0
0
0.09
0
0
0
0.02
-0.2
-0
0.04
0
0.05
0
0
-0.08
0
0
0.03
0
0
0.12
0.17
0.05
0
0
0
-0.2
0
-0.07
0.02
0
0.16
0
-0.1
0
0
0.06
0
0
0
0.4
0
-0.05
0
0
0.09
0.09
0.18
0
0.04
0
0
0
-0.01
-0.12
0
0
0.35
0
0
0
-0.03
0.34
0
0.16
0
0.11
0
0
0.35
0.14
0
-0.05
0
0
0.11
0.05
0.06
0
0
0
0.5
0
0.06
0.22
0
0
0
0.22
0
0
0.18
0
0.33
0
0.02
0
0
0
0
0.11
0.03
0.29
0
-0.15
0
0
0
0.03
-0.2
-0.04
0
-0.11
-0.1
0
-0
0.47
0.28
-0.04
-0.02
-0.12
0
0
0
0.08
0.11
0.08
-0.12
0.08
0.01
-0.07
-0.09
0.13
0.17
0.13
0.12
-0.22
0
-0.01
0
-0.13
-0.09
0.1
0
-0.13
0.13
-0.19
0
0.06
0
0.34
0
C-32
YHR055C
YHR056C
YHR057C
YHR062C
YHR063C
YHR064C
YHR065C
YHR067W
YHR068W
YHR069C
YHR070W
YHR071W
YHR072W
YHR074W
YHR076W
YHR078W
YHR082C
YHR083W
YHR084W
YHR086W
YHR087W
YHR089C
YHR091C
YHR092C
YHR094C
YHR096C
YHR097C
YHR098C
YHR100C
YHR104W
YHR106W
YHR107C
YHR108W
YHR110W
YHR112C
YHR113W
YHR114W
YHR115C
YHR116W
YHR123W
YHR128W
YHR132C
YHR133C
YHR135C
YHR138C
YHR139C
YHR140W
YHR141C
YHR142W
YHR143W
YHR143W-A
YHR145C
YHR146W
YHR147C
YHR161C
CUP1
CYP2
RPP1
PDR13
RRP3
DYS1
RRP4
PCL5
ERG7
KSP1
STE12
NAM8
GAR1
MSR1
HXT4
HXT1
HXT5
GRE3
TRR2
CDC12
EPT1
FUR1
ECM14
YCK1
SPS100
RPL42B
RPB12
MRPL6
YAP1801
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
20
20
21
21
21
20
20
20
20
20
21
20
20
21
21
20
20
20
20
20
20
20
20
20
20
20
40
21
20
20
20
20
20
20
20
20
20
21
20
41
21
21
20
20
20
20
20
20
20
20
20
21
20
20
20
6.8
0.08
0.11
0.07
0.18
0.94
0.07
0.07
0.23
0.07
0.09
0.07
0.07
0.11
0.12
0.13
0.07
0.2
0.07
0.19
0.82
0.55
0.08
0.76
0.84
0.07
0.12
0.1
0.07
0.43
0.13
0.12
0.07
0.2
0.14
0.27
0.07
0.1
0.07
0.14
0.44
0.14
0.42
0.11
0.35
0.07
0.07
1.03
0.27
0.48
0.12
0.1
0.07
0.11
0.09
6.52
0.07
0.15
0.09
0.17
1.16
0.07
0.07
0.32
0.07
0.14
0.07
0.09
0.15
0.08
0.1
0.07
0.25
0.07
0.25
0.7
0.65
0.07
0.41
1.34
0.07
0.07
0.11
0.07
0.19
0.11
0.11
0.1
0.14
0.1
0.19
0.07
0.11
0.08
0.14
1.09
0.18
0.69
0.09
0.33
0.07
0.07
1.98
0.27
0.54
0.23
0.07
0.07
0.14
0.08
4.94
0.07
0.51
0.07
0.26
1.05
0.09
0.08
0.19
0.08
0.21
0.18
0.14
0.19
0.14
0.08
0.07
0.35
0.07
0.22
0.88
0.4
0.09
0.12
0.07
0.07
0.08
0.11
0.08
0.78
0.1
0.09
0.12
0.25
0.15
0.21
0.07
0.16
0.07
0.13
0.48
0.33
0.7
0.07
0.51
0.08
0.08
2.78
0.39
0.89
0.32
0.07
0.14
0.08
0.1
15.95
0.08
0.43
0.05
0.1
0.87
0.05
0.05
0.29
0.13
0.22
0.08
0.12
0.15
0.09
0.1
0.06
0.3
0.06
0.11
0.52
0.24
0.07
0.61
1.57
0.16
0.07
0.09
0.05
1.63
0.18
0.09
0.06
0.11
0.2
0.22
0.05
0.14
0.07
0.05
0.69
0.16
0.23
0.11
0.51
0.07
0.05
1.45
0.37
0.57
0.16
0.05
0.06
0.12
0.08
0.05
0
0.06
0.09
0
0.06
0
0
0
0
0
0
0
0
-0.1
0
0
0.05
0
0
-0.11
0.03
0
-0.02
0.06
0
-0.1
0
0
-0.12
0
0
0
0
0
-0.02
0
0
0
0
0.38
0.16
0.02
0
-0.17
0
0
0.35
-0.07
0.05
0.1
0
0
0
0
-0.05
0
0.35
0
0.1
0
0
0.05
0
0
0
0.32
0
0.06
0
0
0
0.18
0
0
-0.09
-0.05
0
-0.5
-0.8
0
0
0
0
0.14
0
0
0
0.03
0
0
0
0
0
0
0.14
0.21
0.01
0
0.14
0
0
0.33
0.04
0.24
0.25
0
0.15
0
0
0.43
-0.13
0.32
0
-0.16
-0.05
0
0
-0.03
0
0.01
-0
0
0
0
-0.12
0
0.04
0
0
0
-0.21
-0.12
-0.13
0.14
0.16
0
0
0
0.57
-0.02
0
0
-0.2
0.04
-0.04
0
0
0
-0.22
0.15
0
0
0
0.07
0
0
0.04
0.08
0.05
0
0
0
0
0
C-33
YHR162W
YHR163W
YHR170W
YHR171W
YHR174W
YHR175W
YHR176W
YHR179W
YHR180W
YHR181W
YHR183W
YHR187W
YHR188C
YHR190W
YHR191C
YHR192W
YHR193C
YHR194W
YHR195W
YHR198C
YHR199C
YHR200W
YHR201C
YHR202W
YHR203C
YHR205W
YHR206W
YHR208W
YHR214C-B
YHR215W
YHR217C
YHR219W
YIL001W
YIL007C
YIL008W
YIL009W
YIL010W
YIL011W
YIL014W
YIL015C-A
YIL015W
YIL018W
YIL020C
YIL021W
YIL022W
YIL023C
YIL027C
YIL030C
YIL033C
YIL034C
YIL036W
YIL038C
YIL039W
YIL040W
YIL041W
SOL3
NMD3
ENO2
CTR2
OYE2
GND1
IKI1
ERG9
CTF8
EGD2
RPN10
PPX1
RPS4B
SCH9
SKN7
BAT1
PHO12
FAA3
DOT5
BAR1
RPL2B
HIS6
RPB3
TIM44
SSM4
SRA1
CAP2
NOT3
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
20
20
21
20
20
20
20
20
20
21
20
21
20
21
21
20
21
21
21
21
21
21
21
20
20
20
21
20
40
20
10
20
21
20
21
20
20
21
21
20
20
26
20
20
20
20
20
20
21
20
20
20
21
20
20
1.38
0.47
0.07
0.09
15.27
0.4
0.12
0.78
0.07
0.35
1.99
0.09
0.3
0.54
0.07
0.07
1.12
0.07
0.07
0.11
0.36
0.31
0.07
0.07
4.69
0.13
0.07
0.47
0.23
0.07
0.26
0.35
0.07
0.07
0.07
0.07
0.08
0.64
0.07
0.07
0.45
8.69
0.07
0.12
0.07
0.26
0.07
0.14
0.38
0.62
0.07
0.09
0.13
0.31
0.81
2.26
0.59
0.15
0.07
25.96
0.55
0.07
0.66
0.07
0.71
2.73
0.07
0.31
0.69
0.09
0.07
2.16
0.1
0.07
0.07
0.29
0.44
0.07
0.07
7.32
0.07
0.08
0.89
0.19
0.07
0.19
0.47
0.07
0.07
0.11
0.07
0.09
0.49
0.07
0.08
0.07
15.94
0.11
0.11
0.09
0.13
0.08
0.12
0.36
0.51
0.07
0.07
0.25
0.38
1.1
1.85
0.84
0.09
0.07
21.33
0.7
0.07
1.1
0.07
0.5
3.45
0.11
0.33
0.76
0.08
0.08
2.79
0.11
0.07
0.1
0.33
0.5
0.08
0.09
9.08
0.07
0.08
1.18
0.28
0.07
0.16
0.69
0.08
0.07
0.07
0.07
0.2
0.33
0.07
0.08
0.42
13.08
0.08
0.14
0.08
0.21
0.14
0.14
0.52
0.52
0.07
0.12
0.34
0.61
1.22
1.21
0.7
0.09
0.05
13.1
0.24
0.05
1.42
0.06
0.41
1.46
0.08
0.3
0.51
0.06
0.11
2.23
0.08
0.06
0.07
0.27
0.42
0.06
0.06
4.42
0.09
0.09
0.57
0.63
0.07
0.06
0.57
0.05
0.06
0.05
0.07
0.13
0.34
0.07
0.07
0.64
7.97
0.09
0.17
0.12
0.23
0.07
0.09
0.59
1.26
0.06
0.07
0.15
0.24
0.8
0.13
0
0.02
0
0.04
0.11
0
0
0
0.13
0.07
0
-0.04
0.03
0
0
0.19
0
0
0
-0.02
0.06
0
0
0.13
0
0
0.04
0.08
0
-0.11
0
0
0
0.04
0
0
0
0
0
-0.7
0.2
0
0
0
-0.14
0
0
-0.02
-0.08
0
0
0
0
0.09
0.19
0.14
0
0
-0.07
0.26
-0
0.35
0
0.15
0.31
0
0.01
0.09
0
0
0.38
0
0
0
-0
0.07
0
0
0.19
0
0
0.11
0.09
0
-0.15
0.18
0
0
0
0
0.1
-0.11
0
0
-0
0.05
0
0
0
0
0.12
0.01
0
0
0
0.02
0
0.19
0.17
-0.11
-0.01
0
0
-0.13
-0.2
0
0.33
0
0.04
-0.09
-0.14
-0.07
0.02
0
-0.04
0.15
-0.11
0
0
-0.05
0.17
0
-0.16
-0.14
-0
0
0
0.21
0
0
0.01
0
-0.15
0
0
0.02
-0.19
-0.14
0
0.11
-0.14
0.01
0.01
0
-0.1
0
0
0.12
0.15
0
0
0
0
0.04
C-34
YIL042C
YIL043C
YIL044C
YIL045W
YIL046W
YIL047C
YIL048W
YIL049W
YIL050W
YIL051C
YIL052C
YIL053W
YIL056W
YIL059C
YIL062C
YIL064W
YIL065C
YIL066C
YIL067C
YIL069C
YIL070C
YIL074C
YIL075C
YIL076W
YIL077C
YIL078W
YIL083C
YIL085C
YIL087C
YIL088C
YIL090W
YIL093C
YIL094C
YIL098C
YIL099W
YIL101C
YIL104C
YIL106W
YIL108W
YIL109C
YIL111W
YIL113W
YIL114C
YIL115C
YIL116W
YIL117C
YIL118W
YIL119C
YIL121W
YIL123W
YIL124W
YIL125W
YIL129C
YIL131C
YIL133C
CBR1
PIG2
MET30
SYG1
NEO1
DFG10
PCL7
MMD1
RPL34B
RHR2
ARC15
RNR3
RPS24B
RPN2
SEC28
THS1
KTR7
FMC1
SGA1
XBP1
MOB1
SEC24
COX5B
POR2
NUP159
HIS5
RHO3
RPI1
SIM1
KGD1
FKH1
RPL16A
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
21
20
20
20
21
20
21
20
20
21
20
20
20
21
20
20
20
21
21
44
20
20
21
20
20
20
20
20
21
21
20
21
21
21
20
20
21
20
20
20
20
20
21
20
21
20
21
20
20
21
20
20
20
21
20
0.12
2.69
0.07
0.09
0.09
0.14
0.17
0.12
0.1
2.45
2.34
2.53
0.07
0.07
0.73
0.07
0.08
0.07
0.07
0.45
0.27
0.12
0.16
0.1
0.09
0.8
0.26
0.07
0.37
0.26
0.11
0.07
0.85
0.07
0.09
0.12
0.07
0.11
0.1
0.37
0.23
0.07
0.16
0.08
0.08
0.07
0.08
0.07
0.16
0.68
0.69
0.15
0.12
0.07
4.77
0.07
2.41
0.07
0.07
0.08
0.19
0.15
0.13
0.1
3.98
4.11
3.14
0.07
0.12
1.21
0.1
0.08
0.14
0.07
0.93
0.23
0.12
0.13
0.13
0.07
1.46
0.39
0.07
0.34
0.16
0.1
0.07
0.98
0.07
0.07
0.08
0.07
0.13
0.12
0.36
0.13
0.07
0.15
0.07
0.07
0.07
0.07
0.08
0.2
1.15
0.69
0.1
0.13
0.1
8.84
0.11
2.93
0.07
0.07
0.07
0.13
0.19
0.16
0.29
4.11
5.06
4.93
0.07
0.13
1.28
0.08
0.15
0.1
0.09
0.74
0.31
0.11
0.19
0.28
0.07
0.94
0.39
0.07
0.54
0.26
0.12
0.08
1.97
0.08
0.07
0.22
0.08
0.12
0.11
0.47
0.2
0.07
0.22
0.08
0.1
0.07
0.1
0.07
0.21
1.03
0.65
0.27
0.15
0.07
5.2
0.09
1.48
0.08
0.05
0.19
0.22
0.16
0.09
0.12
3.06
1.76
3.29
0.06
0.09
1.19
0.05
0.12
0.06
0.08
0.48
0.29
0.2
0.2
0.14
0.05
0.65
0.54
0.08
0.33
0.1
0.08
0.05
0.86
0.06
0.05
0.06
0.11
0.07
0.15
0.38
0.33
0.06
0.11
0.05
0.08
0.16
0.08
0.1
0.14
1.1
1.08
0.08
0.15
0.06
3.77
-0.02
0
0
0
0
0
0
0
0
0.17
0.28
0.05
0
0
0.02
0.05
0
0
0
0.2
0
0
-0.1
0.1
-0.1
0.04
0.05
0
-0.06
0
0
0
-0.09
0
0
0
0
0
0
-0.03
-0.2
0
0
0
0
0
0
0
0.11
0.12
0
-0.03
0
0
0.26
0
0.04
0.03
-0.1
0
0
-0.03
0.06
0.34
0.12
0.24
0.19
0
0
0.21
0
0.14
0
0
0.1
0
0
0
0.29
-0.1
0.05
0.09
0
0.14
0.03
0
0.03
0.2
0
0
0
0
0
0
0.13
0
0
0
0
-0.01
0
0.03
0
0.08
0.04
0.2
0.24
0
0
0.11
0
0
0.06
0
0
0.14
-0.09
0
0
0.02
-0.25
0.04
0
-0.15
0.16
0
0.03
0
-0.07
0.01
-0.02
0.07
-0.12
-0.03
0
0
0.05
0
-0.07
-0.14
0
0
-0.05
0
0
0
-0.14
-0.12
0.02
0.01
0.21
0
0
0
0
0.15
-0.15
-0.09
0
0.07
0.19
0
-0.04
0
-0.09
C-35
YIL134W
YIL135C
YIL136W
YIL137C
YIL140W
YIL142W
YIL145C
YIL148W
YIL152W
YIL154C
YIL155C
YIL156W
YIL157C
YIL158W
YIL160C
YIL162W
YIL164C
YIL165C
YIL169C
YIL170W
YIL176C
YIL177C
YIR003W
YIR006C
YIR007W
YIR011C
YIR012W
YIR013C
YIR016W
YIR018W
YIR019C
YIR021W
YIR022W
YIR024C
YIR026C
YIR028W
YIR034C
YIR035C
YIR036C
YIR037W
YIR038C
YIR041W
YIR043C
YIR044C
YJL001W
YJL002C
YJL004C
YJL008C
YJL011C
YJL012C
YJL014W
YJL015C
YJL016W
YJL017W
YJL020C
FLX1
OM45
SRO4
CCT2
RPL40A
IMP2'
GUT2
UBP7
POT1
SUC2
NIT1
HXT12
PAN1
STS1
SQT1
YAP5
MUC1
MRS1
SEC11
GIF1
YVH1
DAL4
LYS1
HYR1
PRE3
OST1
SYS1
CCT8
CCT3
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
21
20
21
21
21
21
20
32
20
21
21
20
20
21
20
20
21
21
20
23
20
40
20
20
21
21
21
21
20
21
21
21
20
21
20
20
20
21
20
20
20
20
26
20
29
20
20
20
21
20
20
21
21
21
21
0.07
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0.08
0.28
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0.14
0.07
0.18
0.07
0.08
0.34
0.09
0.07
0.13
0.8
0.07
0.08
0.07
4.01
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0.36
2.43
0.66
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0.09
0.25
0.39
0.57
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0.09
0.09
0.14
0.23
0.07
0.12
0.09
0.09
0.07
0.18
0.09
0.07
0.1
0.19
0.23
4.12
0.07
0.22
0.07
0.07
0.39
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0.07
0.09
0.07
0.07
0.07
0.07
0.24
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0.12
0.17
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0.2
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0.07
0.2
0.07
0.07
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0.12
0.07
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0.6
0.23
3.06
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0.07
0.41
0.61
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0.12
0.07
0.2
0.23
0.07
0.11
0.07
0.07
0.07
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0.07
0.08
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0.07
0.13
0.11
0.18
0.07
0.07
0.22
0.07
0.09
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0.07
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0.07
0.07
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0.06
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0.05
0.06
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0.08
0.07
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0.46
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YJL021C
YJL026W
YJL027C
YJL030W
YJL032W
YJL034W
YJL041W
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YJL171C
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RNR2
MAD2
KAR2
NSP1
MHP1
GYP6
TDH1
PEP8
IKS1
NUP82
MRPL8
PRY3
PRY1
SCP160
ARP4
ARG3
CCT7
NCA3
PHO86
RPE1
SPB8
URA2
MRS3
LCB3
RPS21B
TIF2
TIM17
INO1
FAR1
CIS3
SRA3
QCR8
ERG20
RFA3
KRE9
RPL17B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
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B
B
B
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
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20
21
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21
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21
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21
20
20
20
20
21
21
21
20
20
20
21
21
20
20
20
20
20
38
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0.07
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0.51
0.12
0.1
0.1
0.26
0.25
0.19
0.09
0.5
0.08
1.44
0.27
0.09
0.12
0.12
0.28
0.35
0.5
0.35
0.35
0.35
0.84
0.35
0.35
0.35
0.35
5.56
2.78
0.42
2.34
0.35
0.35
0.36
9.57
2.11
0.47
0.37
0.57
0.55
0.43
0.5
4.7
0.07
0.88
0.07
0.07
0.07
0.99
0.07
0.14
0.07
0.07
0.07
8.02
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0.07
0.07
0.07
0.08
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0.16
0.09
0.36
0.07
0.61
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0.11
0.54
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0.1
0.17
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7.42
2.74
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2
0.11
1.25
0.16
6.6
1.73
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0.07
0.72
0.07
0.07
0.07
2.07
0.1
0.2
0.09
0.07
0.23
6.58
0.18
0.57
0.07
0.07
0.07
0.09
0.11
0.15
0.11
0.57
0.08
2.1
0.23
0.07
0.08
0.09
0.23
0.26
0.39
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0.26
0.26
0.45
0.26
0.4
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1.81
1.89
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2.44
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1.27
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3.2
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0.37
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2.6
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0.21
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0.89
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0.45
0.29
0.61
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0.56
0.24
0.3
7.58
2.45
0.66
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0.4
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4.62
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-0
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0.07
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C-37
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YJR001W
YJR004C
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YJR009C
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YJR014W
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YJR096W
YJR101W
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YJR104C
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YJR115W
YJR116W
RPL39
RPS22A
RPS14B
ELO1
NCE101
PEX2
SAG1
SUI2
TDH2
SPC1
ILV3
ESS1
TES1
BNA1
SSC1
CYC1
APS2
PTK2
RPA12
CCT5
ARP3
HAM1
OPI3
HOC1
CDC11
MIR1
STE18
RPL43B
URA8
SOD1
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
20
20
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20
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20
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21
20
20
21
20
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21
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21
21
21
21
20
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21
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0.35
5.75
19.08
2.33
0.37
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0.6
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7.93
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14.51
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2.68
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0.35
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1.17
0.35
0.35
0.35
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4.06
8.49
1.56
0.3
0.67
0.11
0.39
0.26
0.3
0.19
1.74
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0.1
10.33
0.21
0.14
0.3
0.34
0.28
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4.83
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0.3
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1.1
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0.42
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0.24
3.73
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2.57
0.24
5.1
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C-38
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YKL024C
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YKL034W
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YKL086W
YKL087C
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YKL094W
YKL096W
YKL097W-A
STE24
ATP2
RPS5
ZMS1
HOM6
PMT4
RPS4A
BAT2
COS5
MET14
MRP17
AUR1
RPL14A
CAP1
MRT4
UFD4
ARC19
ATP7
RAM2
URA6
TFA1
PTM1
PHD1
TOA2
FBA1
MSN4
YET1
YNK1
VMA5
TEF4
MDH1
CYT2
YJU3
CWP1
CWP2
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
20
20
21
20
20
20
20
21
21
20
20
20
20
20
20
20
20
59
21
20
20
21
21
21
21
20
21
20
21
21
20
21
20
21
21
21
20
20
20
20
20
20
21
20
20
20
40
20
21
21
20
20
20
21
20
0.35
0.35
0.8
5.23
0.35
0.35
0.35
0.46
1.05
0.49
2.08
0.35
0.35
0.35
0.35
0.35
0.72
5.69
0.35
0.35
0.35
0.35
0.35
0.4
0.35
0.35
0.35
0.35
0.35
0.35
2.32
0.35
0.53
0.35
0.35
0.35
0.35
10.71
0.35
11.55
0.35
0.53
0.35
0.78
0.35
1.29
0.51
0.35
1.47
0.35
0.35
0.35
0.35
4.38
40.86
0.1
0.17
1.3
7.14
0.12
0.15
0.14
0.63
1.09
0.35
3.91
0.09
0.23
0.11
0.19
0.17
0.42
3.42
0.13
0.31
0.17
0.09
0.4
0.51
0.14
0.1
0.29
0.11
0.12
0.14
2.48
0.35
0.09
0.32
0.11
0.09
0.21
10.33
0.29
22.12
0.19
0.68
0.13
0.78
0.32
0.8
0.84
0.19
0.86
0.12
0.2
0.1
0.21
5.54
25.7
0.26
0.26
0.7
1.26
0.26
0.26
0.26
0.63
1
0.26
1.25
0.26
0.26
0.26
0.26
0.26
0.29
2.67
0.26
0.26
0.26
0.26
0.26
0.55
0.26
0.26
0.26
0.26
0.26
0.26
0.81
0.26
0.26
0.26
0.26
0.26
0.26
5.08
0.26
8.98
0.26
0.46
0.26
0.9
0.26
1.11
0.34
0.26
1.04
0.26
0.28
0.26
0.26
1.36
15.05
0.37
0.24
1.16
3.89
0.24
0.24
0.44
0.83
1.55
0.4
2.76
0.25
0.3
0.29
0.24
0.32
0.81
3.55
0.26
0.37
0.24
0.25
0.48
0.85
0.24
0.26
0.43
0.28
0.4
0.24
3.08
0.69
0.24
0.52
0.24
0.24
0.36
8.56
0.45
25.53
0.51
1.2
0.24
1.91
0.48
1.24
0.37
0.24
1.45
0.26
0.47
0.27
0.46
9.13
33.07
0
0
0.05
0.07
0
0
0
0.03
0.03
0
0.26
0
0
0
0
0
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-0.3
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0
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0
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0
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0.03
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0
0.08
0
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0
0.14
0.17
0
0.02
0
0
0
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0
0.05
0.01
0.2
0
0.24
0.04
-0.02
0
0
0
0
0
0
0.07
0.31
-0.12
C-39
YKL100C
YKL103C
YKL104C
YKL117W
YKL120W
YKL122C
YKL126W
YKL127W
YKL128C
YKL140W
YKL141W
YKL142W
YKL144C
YKL145W
YKL146W
YKL148C
YKL150W
YKL151C
YKL152C
YKL156W
YKL157W
YKL160W
YKL163W
YKL164C
YKL165C
YKL167C
YKL170W
YKL172W
YKL174C
YKL175W
YKL178C
YKL180W
YKL181W
YKL182W
YKL184W
YKL185W
YKL186C
YKL190W
YKL191W
YKL192C
YKL196C
YKL199C
YKL207W
YKL210W
YKL211C
YKL212W
YKL213C
YKL214C
YKL216W
YKR004C
YKR006C
YKR013W
YKR018C
YKR025W
YKR026C
LAP4
GFA1
SBA1
SRP21
YPK1
PGM1
PMU1
TGL1
SDH3
MRP8
RPC25
RPT1
SDH1
MCR1
GPM1
RPS27A
APE2
PIR3
PIR1
MCD4
MRP49
MRPL38
STE3
RPL17A
PRS1
FAS1
SPE1
ASH1
MTR2
CNB1
DPH2
YKT6
YKT9
UBA1
TRP3
SAC1
DOA1
URA1
ECM9
MRPL13
PRY2
GCN3
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
21
21
20
20
20
20
20
21
21
20
20
20
20
20
20
20
20
20
20
20
20
20
20
21
20
20
21
20
20
21
20
43
21
20
21
20
20
41
20
20
21
21
21
21
20
20
21
21
20
20
20
21
21
20
20
0.35
0.35
0.35
0.42
0.35
0.35
0.45
0.35
0.35
0.35
0.6
0.37
0.35
0.56
0.38
0.51
0.62
0.35
8.38
2.36
0.35
0.35
1.28
5.07
0.35
0.35
0.35
0.35
0.35
0.65
0.35
11.66
0.44
0.77
0.35
0.35
0.35
0.35
0.35
2.87
0.35
0.35
0.35
0.35
0.35
0.35
0.35
0.35
0.35
0.35
0.35
1.31
0.35
0.35
0.35
0.12
0.25
0.36
0.33
0.14
0.11
0.24
0.21
0.15
0.16
0.42
0.2
0.09
0.53
0.35
0.15
0.43
0.16
7.69
1.5
0.24
0.17
0.88
5.54
0.17
0.14
0.12
0.11
0.16
1.27
0.43
11.93
0.37
1.43
0.52
0.3
0.16
0.25
0.34
3.42
0.16
0.21
0.56
0.22
0.35
0.2
0.12
0.14
0.21
0.13
0.16
1.85
0.19
0.13
0.15
0.26
0.26
0.28
0.45
0.26
0.26
0.27
0.26
0.26
0.26
0.82
0.37
0.26
0.44
0.27
0.36
0.92
0.26
4.91
2.3
0.26
0.29
1.3
2.62
0.47
0.26
0.26
0.26
0.26
0.32
0.26
8.58
0.45
0.59
0.26
0.28
0.26
0.3
0.31
2.83
0.26
0.26
0.26
0.26
0.37
0.26
0.26
0.26
0.3
0.26
0.26
1.08
0.26
0.26
0.26
0.24
1
0.46
1.51
0.25
0.25
0.28
0.24
0.24
0.39
0.59
0.64
0.24
0.82
0.37
0.24
1.02
0.9
9.57
3.31
0.43
0.24
9.38
7.47
0.24
0.29
0.24
0.24
0.41
0.53
0.24
9.2
0.65
1.36
0.34
0.3
0.24
0.52
0.44
5.54
0.24
0.24
0.52
0.26
0.46
0.42
0.3
0.24
0.24
0.24
0.26
2.67
0.4
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0.24
0
-0.29
-0.05
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0
0
0
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0
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0
0
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0
0
0
0
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0
0.03
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0
0
0.09
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0.12
0.05
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0
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0
0
0
0
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0
0
0
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0
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0
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0.07
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0.01
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0
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0
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0
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0
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0
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0
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0
0
0
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0
0.28
0
0
0
0
0
0
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0.13
0
0.11
0
0
0.27
0.35
0.1
0.15
0
0
0.49
0.21
0
0
0
0
0.05
0
0
-0.1
-0.02
0.15
0
0
0
-0.07
0.01
0.23
0
0
-0.01
0
0
-0.03
0
0
0
0
0
0.2
-0.11
0
0
C-40
YKR030W
YKR038C
YKR039W
YKR042W
YKR043C
YKR046C
YKR048C
YKR049C
YKR056W
YKR057W
YKR059W
YKR062W
YKR065C
YKR066C
YKR067W
YKR068C
YKR070W
YKR071C
YKR074W
YKR076W
YKR080W
YKR088C
YKR093W
YKR094C
YKR100C
YLL009C
YLL010C
YLL014W
YLL018C
YLL020C
YLL022C
YLL023C
YLL024C
YLL025W
YLL026W
YLL027W
YLL028W
YLL031C
YLL039C
YLL040C
YLL041C
YLL043W
YLL044W
YLL045C
YLL048C
YLL049W
YLL050C
YLL051C
YLL053C
YLL056C
YLL058W
YLL064C
YLL066C
YLL067C
YLR001C
GAP1
UTH1
NAP1
RNC1
RPS21A
TIF1
TFA2
CCP1
BET3
ECM4
MTD1
PTR2
RPL40B
COX17
DPS1
HIF1
SSA2
HSP104
UBI4
VPS13
SDH2
FPS1
RPL8B
YBT1
COF1
FRE6
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
20
21
20
21
21
21
21
21
20
29
20
21
20
20
20
21
20
21
20
21
20
20
20
29
20
21
20
21
20
24
20
21
20
22
20
21
21
20
20
20
21
20
20
20
20
20
21
20
20
21
21
20
40
45
21
0.35
0.35
0.49
4.61
0.36
0.35
0.38
0.35
0.35
2.86
1.57
0.35
0.92
1.09
0.35
0.47
0.35
0.35
0.35
0.35
0.35
0.35
0.35
1.16
0.35
0.35
0.35
0.77
0.36
0.35
0.35
1.04
2.07
0.35
0.47
0.35
0.35
0.35
0.35
0.35
1.13
0.35
0.35
1.68
0.35
0.35
1.14
0.35
0.35
0.35
0.35
0.37
0.35
0.35
0.35
0.19
0.1
0.2
6.54
0.65
0.16
0.29
0.2
0.09
8.27
4.14
0.1
0.88
1.22
0.1
0.39
0.15
0.11
0.36
0.11
0.15
0.15
0.33
1.48
0.1
0.12
0.1
1.1
0.81
0.34
0.1
0.93
3.05
0.27
0.25
0.24
0.26
0.17
0.43
0.11
0.79
0.19
0.12
3.2
0.16
0.1
2.89
0.09
0.25
0.09
0.15
0.33
0.16
0.19
0.09
0.26
0.26
0.26
2.7
0.57
0.29
0.26
0.26
0.26
4.07
1.34
0.26
0.61
0.63
0.26
0.29
0.26
0.26
0.26
0.26
0.26
0.26
0.26
1.19
0.26
0.26
0.26
0.49
0.3
0.26
0.26
0.28
0.76
0.36
0.4
0.26
0.26
0.26
0.71
0.26
1.73
0.26
0.26
0.74
0.26
0.26
1.57
0.26
0.26
0.26
0.26
0.52
0.26
0.26
0.26
0.34
0.24
0.44
7.27
0.8
1.21
0.4
0.53
0.24
5.08
2.32
0.24
1.22
3.07
0.28
0.54
0.29
0.24
0.38
0.27
0.3
0.25
0.43
0.98
0.24
0.26
0.24
0.86
0.76
0.63
0.24
1.53
4.73
0.42
1.25
0.24
0.37
0.24
2.2
0.24
1.32
0.24
0.24
2.01
0.24
0.24
3.83
0.24
0.31
0.26
0.24
0.42
0.32
0.43
0.33
0
0
0
0.1
0
0
-0.12
0
0
0.17
0.14
0
-0.08
-0.13
0
-0.03
0
-0.53
0
0
0
0
0
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0
0
0
0.05
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0
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0.17
0
0
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-0.21
-0.49
-0.19
-0.55
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0
0
0.12
0
0
0.18
0
0
0
0
0
0
0
0
0
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0
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0
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0
0
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0
0
0
0
0
0
0
0
0
0
0.08
-0.01
0.32
0.05
0.18
0
-0.09
0
0
0.1
0.22
0
0.11
0
0
-0.01
0
0
0
-0.13
-0.05
0
0
0
-0.09
0.09
0.22
0
0.01
0.26
0
0.27
0
0
0
0.57
0
-0.04
0
0
0
0
0
0.3
0
0
0
0
0
0
-0.16
-0.05
C-41
YLR005W
YLR008C
YLR017W
YLR018C
YLR019W
YLR023C
YLR025W
YLR027C
YLR028C
YLR029C
YLR034C
YLR037C
YLR038C
YLR040C
YLR042C
YLR043C
YLR044C
YLR048W
YLR050C
YLR056W
YLR058C
YLR059C
YLR060W
YLR061W
YLR064W
YLR065C
YLR066W
YLR069C
YLR073C
YLR074C
YLR075W
YLR076C
YLR078C
YLR079W
YLR081W
YLR083C
YLR088W
YLR089C
YLR093C
YLR095C
YLR099C
YLR100W
YLR104W
YLR109W
YLR110C
YLR112W
YLR113W
YLR118C
YLR120C
YLR121C
YLR129W
YLR130C
YLR132C
YLR133W
YLR134W
SSL1
MEU1
SNF7
AAT2
ADE16
RPL15A
COX12
TRX1
PDC1
RPS0B
ERG3
SHM2
YNT20
FRS1
RPL22A
SPC3
MEF1
RPL10
BOS1
SIC1
GAL2
EMP70
GAA1
HOG1
YPS1
YPS3
DIP2
ZRT2
CKI1
PDC5
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
20
20
20
20
21
20
21
21
21
21
20
20
20
20
20
21
20
41
20
20
21
20
20
20
20
20
20
20
21
21
21
20
20
21
21
21
20
20
20
20
20
20
20
21
20
21
21
20
20
20
20
21
20
20
20
0.35
0.35
0.35
0.35
0.35
0.35
0.35
0.84
0.35
0.97
0.53
0.44
0.6
0.35
0.35
2.64
11.63
2.25
0.4
0.65
1.52
0.35
0.4
7.13
0.35
0.35
0.35
0.35
0.35
0.35
5.4
0.5
0.35
0.35
0.35
0.35
0.35
0.35
0.35
0.35
0.35
0.35
0.35
3.58
13.2
0.35
0.41
0.35
0.57
0.35
0.35
0.35
0.35
0.35
0.35
0.14
0.2
0.63
0.15
0.14
0.13
0.09
0.97
0.23
2.84
0.6
0.34
0.64
1
0.1
5.22
13.96
3.36
0.32
1.53
3.52
0.19
0.55
9.29
0.21
0.48
0.13
0.12
0.22
0.16
8.55
0.19
0.11
0.21
0.09
0.18
0.12
0.15
0.11
0.16
0.27
0.27
0.18
9.66
35.7
0.11
0.57
0.26
0.53
0.1
0.13
0.33
0.16
0.12
0.14
0.26
0.26
0.36
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0.26
0.27
0.26
0.99
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0.88
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0.52
1.16
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0.26
2.07
6.64
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0.28
0.63
1.05
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0.31
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0.28
0.26
0.26
0.26
0.26
3.96
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0.26
2.84
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0.26
0.26
0.26
0.26
0.43
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0.26
1.96
17.05
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0.26
0.28
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0.26
0.26
0.26
0.26
0.26
0.24
0.36
0.82
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0.24
0.35
0.24
1.5
0.36
1.24
1.24
0.46
0.72
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0.24
5.41
15.05
2.04
0.57
1.57
6.78
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0.62
6.95
0.46
0.25
0.24
0.24
0.41
0.45
6.55
0.37
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0.3
0.24
0.24
0.24
0.24
0.24
0.24
0.3
0.44
0.38
8.52
34.4
0.24
0.71
0.68
1.34
0.42
0.24
0.6
0.24
0.24
0.24
0
0
0.09
0
0
0
0
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-0.34
0.32
0
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0.42
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0.1
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0.28
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0
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0
0.07
0.03
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0.05
0.23
0.59
0
0
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0
0
0
0
0.01
0.01
0
0
0
0
0
0
0
0
0
0
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0
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0.34
0.09
0
0.22
0.26
0.17
0.08
0
0.1
0
0
0
C-42
YLR146C
YLR150W
YLR153C
YLR154C
YLR155C
YLR157C
YLR160C
YLR167W
YLR172C
YLR175W
YLR177W
YLR178C
YLR179C
YLR180W
YLR185W
YLR186W
YLR192C
YLR194C
YLR195C
YLR197W
YLR199C
YLR201C
YLR202C
YLR203C
YLR204W
YLR206W
YLR208W
YLR209C
YLR212C
YLR216C
YLR220W
YLR222C
YLR224W
YLR229C
YLR231C
YLR237W
YLR241W
YLR244C
YLR248W
YLR249W
YLR250W
YLR251W
YLR252W
YLR253W
YLR256W
YLR257W
YLR258W
YLR259C
YLR264W
YLR268W
YLR270W
YLR285W
YLR286C
YLR287C-A
YLR290C
SPE4
MPT4
ACS2
ASP3
ASP3
ASP3
RPS31
DPH5
CBF5
TFS1
SAM1
RPL37A
NMT1
SIK1
MSS51
QRI5
SEC13
TUB4
CPR6
CCC1
CDC42
THI7
MAP1
RCK2
YEF3
SSP120
HAP1
GSY2
HSP60
RPS28B
SEC22
CTS1
RPS30A
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
20
21
20
21
20
20
20
20
21
20
20
21
21
20
21
20
21
20
21
20
20
20
18
21
20
20
21
21
20
21
20
20
21
20
20
21
21
20
20
20
20
20
20
21
20
21
21
21
20
21
20
21
20
40
20
0.35
0.77
0.47
0.35
0.35
0.35
0.35
4.08
0.36
0.35
0.35
0.39
0.83
0.6
4.65
0.35
0.35
0.35
0.35
0.35
0.35
0.35
0.35
0.45
0.35
0.35
0.94
0.35
0.35
0.35
0.35
0.35
0.35
0.72
0.35
0.35
0.35
0.35
0.43
1.04
0.35
0.36
0.35
0.35
0.35
0.35
0.35
0.98
2.16
0.35
0.35
0.35
1.1
3.45
0.35
0.22
1.74
0.8
0.14
0.09
0.09
0.15
7.94
0.44
0.34
0.13
0.47
1.58
1.41
5.62
0.24
0.32
0.49
0.11
0.22
0.26
0.38
0.15
0.67
0.18
0.26
0.91
0.4
0.09
0.43
0.41
0.12
0.16
1.6
0.3
0.12
0.16
0.44
0.31
1.8
0.16
0.22
0.22
0.09
0.09
0.11
0.48
1.19
3.08
0.21
0.15
0.15
1.61
4.59
0.09
0.26
1.09
0.28
0.26
0.26
0.26
0.26
3.51
0.32
0.36
0.26
0.31
0.63
0.33
2.88
0.28
0.26
0.78
0.26
0.26
0.27
0.46
0.26
0.26
0.26
0.28
0.7
0.26
0.26
0.26
0.26
0.26
0.26
0.41
0.26
0.26
0.26
0.26
0.28
0.83
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0.34
0.26
0.26
0.26
0.26
0.42
0.81
0.52
0.26
0.26
0.26
0.79
2.83
0.26
0.24
1.29
0.55
0.24
0.38
0.26
0.45
3.94
0.42
0.44
0.24
3.31
1.38
1.28
5.18
0.33
0.27
1.01
0.24
0.25
0.59
0.65
0.3
0.6
0.24
0.3
1.46
0.41
0.24
1.4
0.55
0.24
0.33
1.89
0.39
0.24
0.3
0.57
0.33
1.68
0.27
0.59
0.47
0.24
0.29
0.24
0.58
3.58
2.38
0.34
0.3
0.24
1.21
3.33
0.25
0
0.25
0.07
0
0
0
0
0.18
0.02
0
0
0
0.14
0.1
0.08
0
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0
0
0
0
0
0
0
0
0
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0
0
0
0
0
0.26
0
0
0
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0.19
0
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0
0
0
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0.03
0.07
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0
0
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0
0
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0
0
0
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0
0
0
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0
0.04
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0
0
0
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0
0.06
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0
0
0
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0.02
0.1
0
0.65
0.07
0.23
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0
0
0.15
0
0
0.08
0.09
0
0.1
0
0
0.03
0
0
0.53
0
0
0
0.22
0
0
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-0.11
0
0.14
0
0.18
0.11
0
0
0
0.04
0.32
-0.06
0
0
0
0.14
0
0
C-43
YLR291C
YLR292C
YLR293C
YLR294C
YLR295C
YLR297W
YLR300W
YLR301W
YLR303W
YLR304C
YLR317W
YLR325C
YLR327C
YLR328W
YLR330W
YLR333C
YLR335W
YLR340W
YLR342W
YLR344W
YLR347C
YLR348C
YLR350W
YLR351C
YLR354C
YLR355C
YLR356W
YLR359W
YLR364W
YLR367W
YLR370C
YLR372W
YLR375W
YLR378C
YLR380W
YLR384C
YLR388W
YLR390W
YLR391W
YLR395C
YLR404W
YLR405W
YLR406C
YLR412W
YLR413W
YLR414C
YLR420W
YLR421C
YLR426W
YLR429W
YLR432W
YLR437C
YLR438W
YLR439W
YLR441C
GCD7
SEC72
GSP1
ATP14
EXG1
MET17
ACO1
RPL38
RPS25B
NUP2
RPP0
FKS1
RPL26A
KAP95
DIC1
NIT3
TAL1
ILV5
ADE13
RPS22B
ARC18
SUR4
STP3
SEC61
IKI3
RPS29A
ECM19
COX8
RPL31B
URA4
CRN1
CAR2
MRPL4
RPS1A
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
20
21
20
20
20
21
21
20
21
20
20
20
21
20
20
28
20
20
20
30
20
20
21
21
20
20
20
20
21
90
20
20
20
21
20
20
21
20
21
20
20
20
55
21
20
20
20
20
41
20
20
20
21
21
29
0.35
0.35
1.16
0.45
0.35
0.5
6.8
0.35
0.39
0.54
0.35
1.24
0.35
0.35
0.35
1.58
0.35
8.13
0.4
0.58
0.35
0.36
1.57
0.45
1.04
1.09
0.48
0.51
0.35
0.67
0.58
1.33
0.76
0.85
0.35
0.35
5.94
0.35
2.73
1.2
0.35
0.35
1.33
0.35
0.35
0.67
0.35
0.35
0.35
0.35
0.35
0.35
0.35
0.35
2.69
0.21
0.12
2.37
1.1
0.53
0.57
4.85
0.29
0.51
0.44
0.16
2.24
0.18
0.11
0.13
2.59
0.13
9.17
0.47
0.45
0.17
0.59
1.94
0.4
1.35
2.59
0.29
0.44
0.1
0.97
0.83
2.24
0.93
1.03
0.24
0.11
10.34
0.2
4.58
1.6
0.1
0.12
2.85
0.1
0.15
0.61
0.15
0.49
0.12
0.15
0.59
0.21
0.22
0.14
3.96
0.26
0.26
0.72
1.05
0.62
0.4
2.29
0.26
0.81
0.52
0.26
1.16
0.42
0.26
0.26
0.72
0.26
3.54
0.26
0.26
0.26
0.26
1.86
0.29
0.83
1.31
0.39
0.33
0.26
0.73
0.42
0.68
0.57
0.59
0.26
0.26
2.44
0.26
2.53
0.95
0.26
0.26
1.27
0.26
0.26
0.53
0.26
0.26
0.26
0.26
0.26
0.26
0.26
0.26
1.15
0.44
0.24
2.02
1.06
0.33
1.2
8.56
0.31
3.15
0.98
0.25
2.24
0.6
0.26
0.24
1.71
0.24
4.96
0.64
0.4
0.24
0.55
2.09
0.47
1.8
2.74
1.13
0.53
0.24
0.79
0.87
1.53
2.35
1.14
0.26
0.24
6.05
0.36
6.49
1.23
0.24
0.24
2.5
0.24
0.37
1.1
0.24
0.52
0.24
0.24
0.42
0.24
0.68
0.24
2.87
0
0
0.24
0.12
0
0.05
0.03
0
0.01
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0.12
-0.31
0
0
0.21
0
0.04
0.02
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0
0
0.05
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0.03
0.33
-0.26
-0.02
0
0.07
0.04
0.12
0.05
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0
0
0.14
0
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-0.01
0
0
0.08
0
0
0
0
0
0
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0.09
0
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0
0.02
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0
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0.2
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0
0.12
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0
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0
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0
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0
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0
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0
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0
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0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0.06
0
0.17
0.27
0
0.19
0.08
0
0.77
0.09
0
0.01
0.03
0
0
0.09
0
-0.19
0.12
0
0
-0.09
0.16
0
0.2
0.29
0.32
0.1
0
-0.03
0.11
0.02
0.39
0.06
0
0
-0.08
0
0.16
-0.11
0
0
0.1
0
0.02
0.15
0
0.01
0
0
0
0
0.29
0
-0.01
C-44
YLR447C
YLR448W
YLR449W
YLR459W
YLR461W
YLR466W
YLR467W
YML001W
YML004C
YML008C
YML009C
YML010W
YML010W-A
YML010W-B
YML012W
YML014W
YML018C
YML019W
YML022W
YML024W
YML025C
YML026C
YML027W
YML028W
YML029W
YML030W
YML031W
YML039W
YML040W
YML045W
YML048W
YML051W
YML052W
YML055W
YML056C
YML057W
YML058W
YML063W
YML064C
YML067C
YML070W
YML072C
YML073C
YML074C
YML075C
YML078W
YML079W
YML085C
YML086C
YML092C
YML100W
YML101C
YML105C
YML106W
YML110C
VMA6
RPL6B
FPR4
CDC91
PAU4
YPT7
GLO1
ERG6
MRPL39
SPT5
ERV25
OST6
APT1
RPS17A
RPS18B
YOX1
TSA1
NDC1
GSF2
GAL80
SUR7
SPC2
CMP2
RPS1B
TEM1
DAK1
RPL6A
NPI46
HMG1
CPR3
TUB1
ALO1
PRE8
TSL1
SEC65
URA5
DBI56
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
20
20
21
20
20
20
20
20
21
20
21
20
20
41
20
20
21
20
20
20
21
19
21
21
21
20
21
40
20
40
20
21
21
20
41
20
20
20
21
20
20
21
20
20
21
21
21
20
21
20
21
21
20
20
20
0.58
4.37
0.35
0.35
0.35
0.75
0.6
0.36
0.35
0.4
0.35
0.35
0.37
0.35
1.59
0.35
0.35
0.35
0.76
3.63
0.35
0.84
0.35
4.04
0.35
0.35
0.35
0.35
0.35
0.35
0.35
0.35
0.88
0.35
0.41
0.35
1.15
0.39
0.35
0.46
0.42
0.35
3.12
0.35
0.35
1.42
0.35
0.44
0.39
0.56
1.12
0.35
0.35
2.55
0.62
1.07
6.39
0.13
0.15
0.16
0.55
0.58
0.32
0.33
0.42
0.34
0.11
0.26
0.09
2.25
0.1
0.1
0.15
0.81
4.98
0.15
2.28
0.15
7.95
0.1
0.23
0.15
0.19
0.13
0.15
0.3
0.19
1.32
0.21
0.58
0.11
2.37
0.45
0.13
0.33
0.26
0.41
4.4
0.37
0.17
1.64
0.1
0.7
0.69
0.95
0.67
0.58
0.28
4.41
0.49
0.43
3.19
0.26
0.26
0.28
0.57
0.54
0.34
0.26
0.26
0.31
0.26
0.26
0.26
1.25
0.26
0.26
0.27
0.39
1.43
0.26
0.97
0.26
6.35
0.26
0.26
0.26
0.26
0.26
0.26
0.26
0.61
0.29
0.26
0.36
0.26
0.85
0.26
0.26
0.26
0.26
0.26
1.66
0.29
0.26
0.83
0.26
0.26
0.4
0.48
0.51
0.33
0.26
1.56
0.31
0.85
3.25
0.24
0.26
0.24
1.03
1.18
0.53
0.64
0.39
0.54
0.24
0.52
0.24
2.25
0.24
0.24
0.34
0.82
3.27
0.24
1.38
0.24
6.44
0.24
0.3
0.29
0.53
0.55
0.55
0.43
0.35
0.89
0.24
0.6
0.74
2.24
0.24
0.24
0.75
0.94
0.35
1.81
0.36
0.24
2.07
0.24
0.26
0.54
2.15
1.58
0.32
0.33
3.48
1.05
0.1
0.15
0
0
0
-0.24
0
0
0
-0.05
0
0
0
0
0.08
0
0
0
-0.11
0.14
0
0.14
-0.5
0.1
0
0
0
0
0
0
0
0
0
0
0.06
0
0.17
0
0
-0.2
0
-0.02
0.11
0
-0.38
0
0
0.04
0.08
0.09
-0.25
0.1
0
0.15
-0.09
0
-0.26
0
0
0
-0.05
0
0
0
0
-0.11
0
0
0
0
0
0
0
-0.1
-0.2
0
-0.06
0
0.08
0
0
0
0
0
0
0
0.17
-0.3
0
0
0
-0.23
0
0
0
-0.2
0
-0.35
0
0
-0.19
0
0
0
-0.2
-0.2
0
0
-0.29
-0.2
0.09
-0.1
0
0
0
0.17
0.2
0.03
0.13
0
0
0
0
0
0.07
0
0
0
0.03
-0.09
0
-0.02
0
0.14
0
0
-0.13
0.04
0.2
0.11
0.03
0
0
0
0.02
0.12
0.16
0
0
0.07
0.37
-0.16
-0.25
0
0
0.07
0
0
0
0.39
0.2
0
0
0.08
0.19
C-45
YML112W
YML113W
YML114C
YML116W
YML117W-A
YML121W
YML123C
YML124C
YML125C
YML126C
YML127W
YML128C
YML129C
YML130C
YML131W
YML132W
YML133C
YMR002W
YMR003W
YMR005W
YMR006C
YMR008C
YMR009W
YMR010W
YMR011W
YMR012W
YMR015C
YMR022W
YMR024W
YMR027W
YMR035W
YMR038C
YMR042W
YMR043W
YMR047C
YMR049C
YMR050C
YMR051C
YMR054W
YMR055C
YMR056C
YMR058W
YMR062C
YMR067C
YMR071C
YMR072W
YMR073C
YMR074C
YMR079W
YMR081C
YMR083W
YMR087W
YMR088C
YMR089C
YMR090W
CTK3
DAT1
ATR1
GTR1
PHO84
TUB3
HMGS
COX14
ERO1
COS3
MPT1
PLB1
HXT2
CLU1
ERG5
QRI8
HRT2
IMP2
LYS7
ARG80
MCM1
NUP116
STV1
BUB2
AAC1
FET3
ECM40
ABF2
SEC14
ISF1
ADH3
YTA12
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
21
20
21
21
20
20
21
21
20
20
20
20
20
21
20
20
40
21
21
21
21
21
21
21
20
20
20
20
21
21
20
21
21
20
21
21
40
20
21
20
20
20
20
20
20
20
21
21
21
21
20
20
20
21
20
0.35
0.35
0.35
0.35
0.35
0.35
0.35
0.37
0.46
1.23
0.53
0.35
0.35
0.35
0.35
0.82
0.35
1.24
0.35
0.35
0.35
0.92
0.35
0.35
0.35
0.35
0.35
0.5
0.35
0.35
0.35
0.35
0.35
0.52
0.35
0.35
0.35
0.35
0.35
0.35
0.35
0.36
0.35
0.35
0.41
0.35
0.35
0.35
0.35
0.35
2.24
0.35
0.35
0.35
0.35
0.09
0.16
0.09
0.17
0.27
0.1
0.56
0.53
0.41
1.35
0.4
0.21
0.15
0.09
0.18
0.88
0.24
1.96
0.13
0.16
0.11
0.65
0.12
0.11
0.17
0.26
0.17
0.43
0.14
0.11
0.22
0.22
0.14
0.41
0.15
0.25
0.21
0.15
0.15
0.12
0.17
0.2
0.22
0.13
0.4
0.26
0.13
0.3
0.44
0.09
1.96
0.12
0.11
0.27
0.21
0.26
0.26
0.26
0.26
0.26
0.26
0.26
0.42
0.26
0.99
0.26
0.26
0.26
0.26
0.26
0.51
0.26
1.43
0.26
0.26
0.26
0.76
0.26
0.26
0.26
0.26
0.26
0.26
0.26
0.26
0.26
0.26
0.26
0.54
0.26
0.26
0.26
0.26
0.26
0.26
0.29
0.26
0.26
0.26
0.27
0.26
0.26
0.26
0.27
0.6
1.42
0.26
0.26
0.26
0.3
0.24
0.35
0.29
0.27
0.85
0.25
0.68
0.5
0.52
1.63
0.67
1.06
0.43
0.31
0.24
0.96
0.27
2.02
0.24
0.31
0.24
1.73
0.42
0.24
0.24
0.26
0.24
0.94
0.24
0.25
0.31
0.24
0.24
0.97
0.24
0.3
0.43
0.59
0.24
0.24
0.58
0.43
0.24
0.24
0.79
0.29
0.29
0.35
0.24
0.24
4.37
0.24
0.24
0.26
0.83
0
0
0
0
-0.26
0
0.14
-0.1
0
0.03
0
0
0
0
0
-0.11
-0.32
0.02
-0.44
0
0
-0.22
0
0
0
0
0
-0.13
0
0
0
-0.34
-0.5
-0.28
-0.5
-0.19
0
0
0
0
0
0
0
0
-0.12
0
0
-0.23
-0.13
0
-0.09
0
0
0
-0.39
0
0
0
0
0
0
0
0
0
0
-0.14
0
0
0
0
0
0
-0.03
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0.05
-0.1
0
0
0
0
0
0
0
0
0.3
0
-0.06
-0.09
0.06
0.08
-0.09
0.47
0
0
0
0.01
0
0.03
0
-0.09
0
0.14
0.08
0
0
0
0
0.22
0
0
0
0
0
0
0
0
0.05
0.23
0
0
0
-0
0
0
0.31
0
-0.12
0
0
0
0.27
0
0
0
0.35
C-46
YMR091C
YMR092C
YMR099C
YMR105C
YMR108W
YMR110C
YMR113W
YMR116C
YMR119W
YMR119W-A
YMR120C
YMR121C
YMR123W
YMR128W
YMR131C
YMR135C
YMR136W
YMR142C
YMR143W
YMR145C
YMR146C
YMR148W
YMR149W
YMR150C
YMR152W
YMR157C
YMR161W
YMR169C
YMR171C
YMR173W
YMR173W-A
YMR174C
YMR175W
YMR177W
YMR181C
YMR184W
YMR186W
YMR189W
YMR191W
YMR194W
YMR195W
YMR200W
YMR202W
YMR203W
YMR205C
YMR208W
YMR211W
YMR215W
YMR216C
YMR217W
YMR221C
YMR222C
YMR224C
YMR226C
YMR230W
NPL6
AIP1
PGM2
ILV2
BEL1
ADE17
RPL15B
ECM16
RPL13B
RPS16A
TIF34
SWP1
IMP1
HLJ1
ALD3
DDR48
PAI3
SIP18
MMT1
HSC82
GCV2
RPL36A
ROT1
ERG2
TOM40
PFK2
ERG12
SKY1
GUA1
MRE11
RPS10B
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
20
21
20
20
21
21
21
40
20
20
20
20
20
20
20
20
20
20
33
20
21
20
20
21
20
20
20
21
20
20
21
20
20
21
21
21
20
20
21
19
21
20
20
21
20
21
21
21
21
21
21
21
20
21
23
0.35
0.35
0.35
0.35
0.35
0.35
0.35
9.06
0.35
0.35
0.35
0.35
0.85
0.35
0.35
0.35
0.35
1.95
2.01
0.69
0.36
0.4
0.71
0.35
0.35
0.35
0.35
0.35
0.35
0.35
11.18
0.35
0.35
0.35
0.35
0.35
0.48
0.35
0.35
5.47
0.98
0.35
1.87
0.4
0.8
0.35
0.35
0.92
0.35
0.35
0.35
0.42
0.35
1.5
0.61
0.1
0.18
0.26
0.17
0.37
0.17
0.11
8.98
0.14
0.1
0.18
0.27
1.03
0.1
0.16
0.12
0.34
2.96
2.16
0.91
0.88
0.5
0.69
0.17
0.14
0.1
0.16
0.09
0.09
0.13
7.89
0.09
0.09
0.11
0.25
0.2
0.41
0.21
0.11
4.55
0.97
0.21
2.57
0.39
0.75
0.12
0.09
1.29
0.09
0.61
0.18
0.23
0.09
1.42
0.76
0.26
0.26
0.26
0.38
0.47
0.26
0.26
3.58
0.26
0.26
0.26
0.26
0.56
0.26
0.26
0.26
0.26
1.08
0.86
0.94
0.42
0.36
0.44
0.26
0.26
0.26
0.26
0.26
0.26
0.26
5.6
0.28
0.26
0.26
0.26
0.55
0.51
0.26
0.26
4.29
0.64
0.26
1.39
0.26
0.43
0.26
0.26
0.68
0.26
0.27
0.26
0.26
0.26
1.04
0.56
0.24
0.67
0.33
0.58
0.91
0.32
0.24
7.36
0.35
0.24
0.71
0.52
0.56
0.24
0.24
0.59
0.37
1.69
1.55
0.98
0.87
0.71
0.86
0.24
0.29
0.25
0.27
0.6
0.24
0.25
14.76
1.45
1.33
0.24
0.57
0.47
0.86
0.72
0.24
4.64
2.27
0.37
2.24
0.58
1.33
0.24
0.24
0.44
0.24
0.3
0.24
0.36
0.28
2.48
0.45
0
0
0
0
-0.13
0
0
0.03
-0.47
0
0
0
0
0
0
0
-0.3
0.11
-0.01
0
0.16
0
0.05
0
0
0
0
0
0
0
-0.08
0
0
0
-0.23
-0.34
-0.22
0
0
0.06
0.03
0
0.07
0.01
-0.06
0
0
0.16
0
0.18
0
0
0
-0.17
-0.02
0
0
0
0
-0.1
0
0
-0.29
0
0
0
0
0
0
0
0
0
-0.23
-0.25
0.1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
-0.06
0
0
0
0
-0.13
0
0
0
-0.14
0
0
0
0
0
0
0
0
0
0
0
0.02
0
0.1
0.09
0
0
-0.1
0
0
0
-0.07
-0.13
0
0
0
0
-0.07
-0.12
0.12
0.12
-0.13
0.01
0
0
0
0
0.24
0
0
0.18
0.51
0.5
0
0.16
-0.09
0.03
0.24
0
0
0.2
0
0
0.01
0.13
0
0
0
0
0
0
-0.1
0
0.17
-0.15
C-47
YMR234W
YMR235C
YMR236W
YMR237W
YMR238W
YMR239C
YMR240C
YMR241W
YMR242C
YMR243C
YMR244C-A
YMR244W
YMR245W
YMR246W
YMR247C
YMR250W
YMR251W-A
YMR252C
YMR253C
YMR255W
YMR256C
YMR257C
YMR258C
YMR259C
YMR260C
YMR261C
YMR262W
YMR263W
YMR264W
YMR266W
YMR267W
YMR269W
YMR271C
YMR272C
YMR274C
YMR275C
YMR276W
YMR278W
YMR281W
YMR283C
YMR286W
YMR289W
YMR290C
YMR290W-A
YMR291W
YMR292W
YMR293C
YMR294W-A
YMR295C
YMR296C
YMR297W
YMR298W
YMR299C
YMR300C
YMR301C
RNH1
RNA1
TAF17
DFG5
RNT1
CUS1
RPL20A
ZRC1
FAA4
HOR7
COX7
PET111
TIF11
TPS3
CUE1
PPA2
URA10
SCS7
RCE1
BUL1
DSK2
RIT1
MRPL33
HAS1
LCB1
PRC1
ADE4
ATM1
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
20
20
21
21
21
20
21
21
17
21
20
21
20
20
20
20
20
20
20
21
21
20
21
20
20
21
20
20
21
21
20
20
21
20
20
21
21
20
20
21
20
20
20
20
20
20
21
21
20
20
20
21
20
20
20
0.11
0.19
0.23
0.11
0.25
0.11
0.11
0.94
0.58
0.75
0.11
0.11
0.11
0.2
0.11
0.65
10.08
0.2
0.11
0.11
0.54
0.11
0.11
0.11
0.27
0.13
0.11
0.11
0.42
0.11
0.11
0.11
0.11
0.72
0.11
0.11
0.54
0.11
0.11
0.11
0.29
0.11
0.11
0.11
0.18
0.48
0.11
0.13
1.83
0.41
1.65
0.5
0.11
0.11
0.11
0.08
0.16
0.47
0.08
0.33
0.08
0.08
1.18
1.15
0.75
0.16
0.08
0.08
0.28
0.08
0.46
12.08
0.22
0.08
0.09
0.58
0.08
0.08
0.08
0.38
0.21
0.08
0.08
0.43
0.08
0.1
0.08
0.08
0.84
0.2
0.08
0.64
0.08
0.11
0.09
0.42
0.08
0.11
0.08
0.16
0.86
0.1
0.09
1.7
0.53
2.6
0.63
0.08
0.12
0.08
0.06
0.25
0.43
0.2
0.26
0.04
0.04
1.16
0.85
0.69
0.22
0.04
0.04
0.3
0.05
0.67
12.88
0.32
0.06
0.07
2.43
0.08
0.06
0.06
0.46
0.17
0.04
0.11
0.49
0.13
0.09
0.05
0.04
0.84
0.19
0.05
0.51
0.09
0.16
0.08
0.29
0.05
0.04
0.04
0.34
0.68
0.14
0.12
1.94
0.34
2.59
0.65
0.04
0.1
0.08
0.04
0.28
0.75
0.16
0.46
0.06
0.06
0.86
0.7
0.81
0.27
0.06
0.06
0.65
0.06
1.3
7.72
0.34
0.14
0.08
0.87
0.07
0.08
0.06
0.28
0.21
0.06
0.11
0.7
0.2
0.07
0.05
0.11
0.76
0.14
0.04
1.2
0.09
0.24
0.06
0.43
0.13
0.06
0.07
0.39
0.6
0.08
0.07
2.39
0.61
2.87
0.91
0.05
0.11
0.07
0
0
0.17
0
0.07
0
0
0.02
0.12
0.13
0
0
0
0.08
0
0
-0.02
0
0
0
0.08
0
0
0
0.12
-0.02
0
0
0.15
0
0
0
0
-0.11
0
0
0.21
0
0
0
0.11
0
0
0
0
0.23
0
0
0.09
0
0.14
0.15
0
0.06
0
0
0.13
0.12
-0.07
-0.02
0
0
0
0.06
-0.06
0.14
0
0
0.09
0
-0.03
-0.05
0.03
0
0
0.45
0
-0.26
0
0.21
-0.1
0
-0.14
0.17
-0.04
0
0
0
0
-0.04
0
0.01
0
0.02
-0.17
0.02
0
0
0
0.15
0.14
0.02
-0.17
0.09
-0.08
0.13
0.02
0
0
0
0
0.08
0.29
0.03
0.22
0
-0.29
-0.12
-0.08
0.16
0.26
0
0
0.47
0
0.29
-0.01
0.11
0.06
0
0.07
0
0
0
-0.04
0
0
-0.16
0.37
0.19
0
0
0.01
0.03
-0.09
0
0.43
0
0.14
-0.34
0.16
0.05
0
0
0.13
-0.04
0
0
0.07
0.1
0.24
0.14
0
0
0
C-48
YMR302C
YMR303C
YMR304C-A
YMR304W
YMR305C
YMR308C
YMR309C
YMR310C
YMR311C
YMR312W
YMR314W
YMR315W
YMR316C-A
YMR316W
YMR318C
YMR319C
YMR321C
YMR322C
YMR323W
YMR325W
YNL001W
YNL002C
YNL003C
YNL004W
YNL005C
YNL006W
YNL007C
YNL008C
YNL009W
YNL010W
YNL011C
YNL013C
YNL015W
YNL016W
YNL021W
YNL022C
YNL023C
YNL025C
YNL026W
YNL029C
YNL030W
YNL031C
YNL032W
YNL035C
YNL036W
YNL037C
YNL038W
YNL039W
YNL040W
YNL042W
YNL043C
YNL044W
YNL045W
YNL046W
YNL048W
PRP12
ADH2
PSE1
NIP1
GLC8
PRE5
FET4
DOM34
RLP7
PET8
HRB1
MRP7
LST8
SIS1
IDP3
PBI2
PUB1
HDA1
SSN8
KTR5
HHF2
HHT2
SIW14
NCE103
IDH1
TFC5
ALG11
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
20
20
20
21
20
20
21
20
20
20
20
20
20
21
20
20
21
20
20
20
20
20
20
21
21
21
20
20
20
21
20
20
20
20
20
21
20
21
20
21
20
20
21
20
20
21
21
20
21
20
20
20
20
21
20
0.11
0.15
0.11
0.11
0.75
0.29
0.11
0.12
0.11
0.13
0.31
0.82
0.11
0.11
0.37
0.15
0.46
0.11
0.11
0.11
0.11
0.11
0.22
0.11
0.11
0.22
1.29
0.11
0.11
0.23
0.11
0.11
0.95
0.14
0.11
0.11
0.11
0.11
0.11
0.11
2.55
5.59
0.11
0.11
0.11
0.36
0.11
0.11
0.11
0.11
0.12
2.07
0.11
0.51
0.11
0.1
0.27
0.08
0.08
1.37
0.24
0.08
0.21
0.09
0.16
0.31
0.57
0.08
0.08
0.56
0.14
0.63
0.08
0.08
0.12
0.08
0.12
0.18
0.09
0.09
0.3
1.28
0.18
0.08
0.37
0.08
0.08
0.47
0.17
0.08
0.08
0.08
0.08
0.08
0.08
1.8
7.11
0.08
0.08
0.08
0.21
0.08
0.08
0.1
0.08
0.15
1.62
0.16
0.56
0.08
0.11
0.34
0.15
0.06
1.02
0.35
0.07
0.3
0.11
0.08
0.43
1.35
0.05
0.16
1.89
0.05
0.7
0.05
0.04
0.04
0.04
0.1
0.32
0.05
0.11
0.24
1.37
0.16
0.04
0.56
0.07
0.04
3.03
0.22
0.05
0.06
0.07
0.04
0.07
0.05
3.38
11.01
0.11
0.05
0.12
0.78
0.07
0.04
0.04
0.04
0.09
2.68
0.29
0.63
0.11
0.17
0.36
0.07
0.04
0.95
0.6
0.08
0.29
0.15
0.09
0.6
1.33
0.06
0.15
0.93
0.09
0.33
0.07
0.06
0.09
0.05
0.09
0.35
0.06
0.1
0.14
1.83
0.18
0.09
0.49
0.05
0.09
2.58
0.25
0.06
0.15
0.06
0.04
0.07
0.11
1.03
5.71
0.07
0.04
0.05
0.85
0.06
0.08
0.12
0.11
0.11
1.55
0.41
0.37
0.11
0
0.02
0
0
0.1
0.08
0
0.13
0
0
0.02
0
0
0
0.11
0
0.2
0
0
0
0
0.05
0.03
0
0
0
-0.06
0.03
0
0.12
0
0
-0.09
0
0
0
0
0
0
0
0.04
0.01
0
0
0
-0.09
0
0
0
0
0
-0.03
0
0.08
0
-0.09
0.18
0
0
0.05
0.09
0
0.14
0
0
0.1
0.28
0
0
0.6
0
0.2
0
0
0
0
0
-0.02
0
0
0.01
-0.05
0.03
0
0.26
0
0
0.59
0.18
0
0
0
0
0
0
0.1
0.13
-0.04
0
0.02
0.18
0
0
0
0
0
0.1
-0.11
0.02
0
0.1
0.12
0
0
0.05
0.27
0
0.24
0.16
0
0.18
0.26
0
0.04
0.2
-0.18
-0.13
0
0
0
0
0
0.06
0
0
0.04
0.09
0.12
0
0.12
0
0
0.38
0.05
0
0.09
0
0
0
0.02
-0.39
0
0
0
0
0.17
0
0
0.05
0.01
-0.21
-0.09
0.13
-0.13
0
C-49
YNL050C
YNL051W
YNL052W
YNL053W
YNL054W
YNL055C
YNL056W
YNL058C
YNL061W
YNL062C
YNL063W
YNL064C
YNL065W
YNL066W
YNL067W
YNL069C
YNL070W
YNL071W
YNL072W
YNL073W
YNL074C
YNL075W
YNL076W
YNL078W
YNL079C
YNL080C
YNL081C
YNL084C
YNL085W
YNL086W
YNL087W
YNL088W
YNL090W
YNL091W
YNL092W
YNL093W
YNL094W
YNL096C
YNL097C
YNL098C
YNL099C
YNL100W
YNL101W
YNL103W
YNL104C
YNL107W
YNL108C
YNL110C
YNL111C
YNL112W
YNL113W
YNL114C
YNL115C
YNL116W
YNL117W
COX5A
MSG5
VAC7
POR1
NOP2
GCD10
YDJ1
SUN4
RPL9B
RPL16B
TOM7
LAT1
RNH35
MSK1
YMK1
MKS1
TPM1
END3
MKT1
TOP2
RHO2
YPT53
RPS7B
PHO23
RAS2
MET4
LEU4
CYB5
DBP2
RPC19
MLS1
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
20
21
20
20
21
21
21
20
20
20
20
20
20
20
34
20
20
21
20
20
20
20
20
20
21
20
21
21
21
21
20
21
20
20
20
20
20
42
20
20
21
20
21
20
21
20
20
20
20
42
20
21
20
20
21
0.11
0.11
1.09
0.11
0.11
6.5
0.14
0.11
0.11
0.11
0.11
0.49
0.11
0.32
1.48
5
0.35
0.8
0.11
0.11
0.11
0.11
0.11
0.2
0.19
0.13
0.13
0.11
0.11
0.13
0.11
0.11
0.11
0.11
0.11
0.11
0.11
0.82
0.11
0.16
0.11
0.19
0.11
0.11
1.2
0.11
0.16
0.11
0.11
0.16
0.13
0.11
0.11
0.11
0.11
0.1
0.08
0.9
0.08
0.08
5.85
0.21
0.2
0.1
0.11
0.08
0.72
0.08
0.42
1.54
7.52
0.54
0.81
0.08
0.08
0.08
0.16
0.08
0.29
0.29
0.22
0.11
0.09
0.08
0.18
0.08
0.08
0.16
0.08
0.08
0.08
0.09
1.58
0.12
0.15
0.24
0.16
0.17
0.08
0.85
0.08
0.16
0.09
0.19
0.33
0.15
0.08
0.08
0.09
0.08
0.08
0.05
2.69
0.15
0.05
8.2
0.15
0.12
0.05
0.12
0.07
0.86
0.04
0.35
2.52
3.46
0.56
0.71
0.06
0.15
0.15
0.1
0.06
0.15
0.45
0.24
0.21
0.07
0.09
0.21
0.06
0.05
0.17
0.07
0.04
0.04
0.09
1.07
0.06
0.16
0.17
0.35
0.13
0.06
1.98
0.07
0.14
0.1
0.17
0.44
0.2
0.06
0.05
0.08
0.04
0.05
0.05
1.08
0.17
0.04
8.19
0.14
0.17
0.06
0.05
0.15
1.54
0.09
0.63
1.93
4.06
0.94
1.04
0.04
0.08
0.12
0.08
0.04
0.29
0.44
0.33
0.19
0.08
0.11
0.22
0.08
0.04
0.14
0.1
0.14
0.05
0.16
1.4
0.09
0.21
0.22
0.24
0.19
0.12
1.85
0.05
0.23
0.08
0.26
0.13
0.16
0.05
0.1
0.07
0.05
-0.1
0
0.04
0
0
0.02
-0.03
0.03
0
0.01
0
0.16
0
0.11
0.16
0.07
0.08
0
0
0
0
0.13
0
0.08
0.03
0
-0.09
0
0
0.05
0
0
0
0
0
0
0
0.16
0
-0.07
0.13
0.02
0.09
0
0.02
0
0.02
0
0
0.27
0
0
0
0
0
-0.19
0
0.47
0.05
-0.37
0.24
-0.05
0
0
-0
0
0.17
0
0.07
0.27
-0.11
0.05
-0.07
0
0.15
0.1
0
0
0
0.2
0.02
0.07
-0.31
0
0.11
-0.27
0
0.1
0
0
0
0
0.02
0
-0.04
-0.03
0.22
0.1
0
0.35
0
-0.11
0
0.1
0.35
0.06
0
0
0
0
0
0
-0.03
0.16
0
0.18
0
0.1
0
0
0.06
0.34
0
0.26
0.22
-0.12
0.13
0.05
0
0
-0.04
0
0
0.14
0.18
0.23
0.14
0
0
0.07
-0.23
0
0
0
0
0
0.12
0.14
0
0.14
0.09
0.02
0.22
0
0.22
0
0.05
0
0.12
-0.15
0.09
0
0
0
-0.36
C-50
YNL118C
YNL121C
YNL122C
YNL123W
YNL124W
YNL125C
YNL129W
YNL130C
YNL131W
YNL132W
YNL133C
YNL134C
YNL135C
YNL136W
YNL137C
YNL138W
YNL141W
YNL142W
YNL144C
YNL145W
YNL147W
YNL149C
YNL150W
YNL151C
YNL153C
YNL154C
YNL155W
YNL156C
YNL157W
YNL158W
YNL159C
YNL160W
YNL162W
YNL163C
YNL165W
YNL166C
YNL167C
YNL168C
YNL169C
YNL170W
YNL173C
YNL174W
YNL175C
YNL176C
YNL177C
YNL178W
YNL180C
YNL181W
YNL183C
YNL184C
YNL185C
YNL186W
YNL189W
YNL190W
YNL191W
PSU1
TOM70
ESBP6
CPT1
TOM22
FPR1
NAM9
SRV2
AAH1
MEP2
MFA2
RPC31
PFD4
YCK2
YGP1
RPL42A
SKO1
PSD1
MDG1
RPS3
NPR1
DOT4
SRP1
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
21
20
20
21
21
21
21
20
21
20
20
20
20
20
20
21
21
21
20
21
20
21
20
21
21
21
20
20
21
21
21
21
44
20
21
20
20
20
20
21
20
20
20
20
21
20
20
20
20
20
20
20
20
20
21
0.11
0.11
0.11
0.11
0.11
0.14
0.11
0.82
0.46
0.11
0.11
2.28
4.35
0.11
0.11
0.39
0.11
0.13
0.11
7.14
0.11
0.11
0.11
0.11
0.11
0.13
0.11
0.44
0.37
0.11
0.11
2.57
1.22
0.11
0.11
0.11
0.11
0.21
0.41
0.11
0.11
0.11
0.11
0.11
0.11
7.05
0.19
0.11
0.11
0.12
0.18
0.11
0.14
1.14
0.11
0.08
0.1
0.08
0.08
0.13
0.23
0.08
0.79
0.59
0.11
0.08
2.07
9.95
0.08
0.08
0.61
0.18
0.12
0.08
0.09
0.13
0.14
0.08
0.11
0.18
0.3
0.08
0.45
0.45
0.11
0.09
3.77
2.11
0.08
0.09
0.08
0.08
0.25
0.43
0.08
0.08
0.08
0.1
0.08
0.08
7.67
0.25
0.08
0.09
0.14
0.17
0.08
0.23
1.61
0.08
0.06
0.07
0.05
0.08
0.18
0.3
0.07
1.04
0.71
0.08
0.05
3.28
7.86
0.04
0.14
0.51
0.14
0.12
0.13
6.35
0.16
0.18
0.05
0.06
0.14
0.16
0.06
0.55
0.48
0.09
0.1
4.97
1.22
0.04
0.08
0.06
0.05
0.4
0.57
0.06
0.12
0.06
0.04
0.06
0.07
6.58
0.25
0.09
0.07
0.09
0.17
0.06
0.23
1.95
0.04
0.07
0.09
0.06
0.1
0.19
0.35
0.07
1.03
0.75
0.08
0.05
2.58
6.05
0.06
0.04
0.45
0.09
0.13
0.04
10.97
0.12
0.12
0.08
0.11
0.15
0.18
0.13
0.89
0.78
0.11
0.19
7.09
1.51
0.07
0.08
0.05
0.05
0.31
0.46
0.06
0.09
0.04
0.04
0.04
0.04
6.59
0.23
0.11
0.05
0.11
0.33
0.13
0.28
2.99
0.15
0
0
0
0
0
0
0
0.03
0.08
0
0
0
0.13
0
0
0.15
0.16
0.05
0
-1.6
0
0.1
0
-0.03
-0.03
0.02
0
0.04
0.01
0
0
0.05
0.09
0
0
0
0
0.06
-0
0
0
0
0
0
0
0.07
0.01
0
0
-0.03
0.02
0
-0.01
0.13
0
0
0
0
0
-0.07
0.17
-0.21
0.13
0.08
0
0
0.17
0.07
0
0.03
0.12
0.03
-0.17
0.04
0.04
0.1
0.08
0
0
0.07
0
0
0.2
0.2
0
-0.22
0.09
-0.11
0
0
0
0
0.09
0.15
0
0
0
0
0
0
0.05
0.01
0
0
0
0
0
0.13
0.24
0
-0.21
0
0
0
0.01
0.29
0
0.11
0.12
0
0
0.12
0
0
0
0.16
-0.22
-0.1
0
0.14
0
0
-0.22
0
-0.07
0.06
0.06
0.32
0.27
0
0
0.27
-0.07
0
0
0
0
0.18
-0.07
0
0
0
0
0
0
-0.12
0
0
0
-0.1
0.05
0
0.11
0.31
0.12
C-51
YNL192W
YNL193W
YNL194C
YNL195C
YNL199C
YNL200C
YNL201C
YNL202W
YNL206C
YNL208W
YNL209W
YNL211C
YNL213C
YNL216W
YNL217W
YNL219C
YNL220W
YNL221C
YNL222W
YNL223W
YNL229C
YNL230C
YNL231C
YNL232W
YNL234W
YNL236W
YNL237W
YNL238W
YNL239W
YNL240C
YNL241C
YNL243W
YNL244C
YNL245C
YNL246W
YNL247W
YNL248C
YNL249C
YNL251C
YNL252C
YNL255C
YNL256W
YNL259C
YNL261W
YNL262W
YNL263C
YNL264C
YNL265C
YNL268W
YNL271C
YNL274C
YNL277W
YNL278W
YNL280C
YNL281W
CHS1
GCR2
SPS19
SSB2
RAP1
ALG9
ADE12
POP1
SSU72
URE2
SIN4
YTP1
KEX2
LAP3
ZWF1
SLA2
SUI1
RPA49
MPA43
NRD1
ATX1
ORC5
POL2
YIF1
LYP1
BNI1
MET2
ERG24
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
20
20
21
20
20
20
20
20
20
20
20
20
21
20
21
20
20
20
21
20
21
21
20
21
20
21
20
21
20
21
20
21
20
20
20
20
20
20
20
20
21
20
21
21
21
21
21
20
21
20
21
20
21
21
21
0.13
0.11
0.11
0.11
0.11
0.31
0.11
0.11
0.11
2.81
2.31
0.11
0.11
0.11
0.11
0.13
0.22
0.11
0.11
0.11
0.11
0.11
0.12
0.11
0.11
0.11
0.11
0.11
0.26
0.12
0.27
0.13
0.88
0.11
0.18
0.11
0.11
0.11
0.11
0.11
0.25
0.11
0.22
0.11
0.11
0.49
0.11
0.11
0.96
0.11
0.19
0.11
0.11
0.26
0.16
0.14
0.13
0.08
0.08
0.11
0.29
0.08
0.08
0.08
2.76
3.13
0.08
0.08
0.09
0.09
0.17
0.22
0.08
0.08
0.08
0.11
0.08
0.18
0.16
0.08
0.08
0.08
0.11
0.25
0.13
0.36
0.16
0.81
0.08
0.17
0.17
0.17
0.08
0.19
0.12
0.51
0.08
0.2
0.1
0.08
0.75
0.09
0.09
1.53
0.08
0.32
0.08
0.08
0.26
0.24
0.25
0.04
0.04
0.05
0.04
0.36
0.04
0.26
0.05
5.52
2.16
0.09
0.05
0.06
0.18
0.15
0.2
0.04
0.08
0.06
0.15
0.04
0.28
0.1
0.04
0.06
0.09
0.06
0.88
0.15
0.34
0.18
1.14
0.1
0.13
0.17
0.1
0.1
0.07
0.11
0.4
0.05
0.35
0.06
0.05
0.44
0.09
0.04
0.89
0.05
0.64
0.04
0.1
0.29
0.35
0.31
0.06
0.12
0.16
0.08
0.48
0.07
0.14
0.09
7
2.51
0.09
0.06
0.11
0.1
0.15
0.33
0.08
0.06
0.04
0.11
0.07
0.16
0.13
0.07
0.09
0.14
0.13
0.41
0.22
0.62
0.15
1.12
0.12
0.15
0.15
0.09
0.11
0.08
0.11
0.37
0.05
0.31
0.1
0.05
0.67
0.17
0.07
0.89
0.14
0.75
0.06
0.11
0.34
0.69
0
0
0
0
0
0
0
0
0
0.09
0.17
0
0
0
0
-0.01
0.07
0
0
0
0.03
0
0.06
0.15
0
0
0
0
0.06
0.01
0.15
0.04
0.11
0
0
0.07
0.12
0
0.05
0
0.22
0
0
0
0
0.07
0
0
-0.02
0
0
0
0
-0.05
0.17
0.18
0
0
0
0
-0.13
0
0.17
0
0.26
0
0
0
0
0.09
-0.07
0.03
0
0
0
0.01
0
0.13
0
0
0
-0.27
0
0.41
0.11
0.15
-0.01
0.21
0
-0.18
0.08
0
0
0
0
0.17
0
0.32
0
0
-0.23
-0.18
0
-0.05
0
0.07
0
0
-0.04
0.19
0.27
0
-0.02
0.08
-0.35
0.22
-0.18
0
0
0.3
-0.11
0
0
0
0
0
0.14
0
0
0
0.02
0
0.03
-0.05
0
0
0
0.07
0.19
0.21
0.33
0.07
0.18
0
-0.04
0.02
0
-0.1
0
0
0.24
0
0.17
0
0
-0.01
0.07
0
-0.13
-0.04
0.39
0
0
0.12
0.51
C-52
YNL283C
YNL284C
YNL287W
YNL288W
YNL289W
YNL290W
YNL291C
YNL292W
YNL293W
YNL294C
YNL300W
YNL301C
YNL302C
YNL303W
YNL304W
YNL305C
YNL306W
YNL307C
YNL308C
YNL310C
YNL312W
YNL313C
YNL314W
YNL315C
YNL316C
YNL317W
YNL320W
YNL321W
YNL322C
YNL323W
YNL326C
YNL327W
YNL328C
YNL329C
YNL330C
YNL331C
YNL332W
YNL333W
YNL334C
YNL336W
YNL337W
YNL339C
YNR001C
YNR002C
YNR006W
YNR007C
YNR009W
YNR010W
YNR011C
YNR012W
YNR013C
YNR014W
YNR015W
YNR016C
YNR017W
WSC2
MRPL10
SEC21
PCL1
RFC3
MID1
PUS4
MSB3
RPL18B
RPS19B
MCK1
RFA2
DAL82
ATP11
PHA2
KRE1
EGT2
MDJ2
PEX6
RPD3
SNZ2
SNO2
COS1
CIT1
FUN34
VPS27
AUT1
CSE2
PRP2
URK1
SMM1
ACC1
MAS6
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
21
21
20
20
21
20
21
20
20
21
21
56
40
20
20
20
20
20
20
20
21
20
20
21
20
21
20
21
20
21
20
21
20
20
20
21
20
20
20
30
20
20
20
20
20
21
21
21
20
21
20
20
20
20
20
0.23
0.18
0.17
0.23
0.11
0.11
0.11
0.11
0.11
0.11
3.3
1.8
2.55
0.11
0.11
1.14
0.21
0.14
0.11
0.11
0.28
0.11
0.11
0.11
0.11
0.11
0.23
0.14
1.45
0.11
0.11
1.57
0.11
0.11
0.16
0.11
0.11
0.11
0.11
0.31
0.11
0.42
1.13
0.12
0.11
0.11
0.11
0.11
0.11
0.11
0.11
0.49
0.11
0.41
0.36
0.35
0.18
0.19
0.3
0.08
0.08
0.18
0.08
0.08
0.08
1.49
1.97
2.95
0.1
0.08
0.57
0.25
0.28
0.08
0.08
0.65
0.08
0.08
0.08
0.1
0.08
0.25
0.22
1.29
0.17
0.09
2.13
0.08
0.08
0.15
0.08
0.08
0.08
0.08
0.22
0.08
0.43
0.82
0.12
0.08
0.08
0.11
0.08
0.08
0.08
0.13
0.19
0.09
0.5
0.58
0.29
0.25
0.2
0.22
0.1
0.04
0.13
0.09
0.05
0.09
1.98
1.74
2.83
0.06
0.04
0.6
0.36
0.26
0.09
0.07
0.51
0.05
0.05
0.1
0.05
0.07
0.29
0.2
1.97
0.08
0.08
2.34
0.09
0.13
0.16
0.04
0.1
0.16
0.11
0.5
0.06
0.57
1.91
0.24
0.04
0.09
0.07
0.04
0.05
0.07
0.09
0.1
0.1
0.6
0.87
0.29
0.38
0.21
0.32
0.04
0.11
0.11
0.07
0.05
0.2
1.34
1.52
2.03
0.06
0.05
1.72
0.29
0.13
0.1
0.06
0.41
0.07
0.05
0.17
0.14
0.04
0.3
0.22
1.41
0.11
0.09
2.31
0.07
0.13
0.25
0.1
0.04
0.06
0.06
0.37
0.04
0.65
1.63
0.14
0.06
0.09
0.04
0.06
0.05
0.08
0.17
0.33
0.08
0.64
0.92
0.1
0
-0.08
0.05
0
0
0.02
0
0
0
0.06
0.1
0.04
0
0
-0.2
-0.05
0.05
0
0
0.15
0
0
0
0
0
0
-0.1
0.1
0
0
0.17
0
0
0
0
0
0
0
0
0
-0.06
0
0
0
0
-0.08
0
0
0
0
0
0
0.12
0.06
-0.02
0.1
-0.02
0
0
0
0
0
0
0
0.08
0.07
0.03
0
0
-0.17
0
0.04
0
-0.19
0.1
0
0
0
0
0
0.14
-0.02
0.01
0
0
0.15
0
0
-0.05
0
0
0.11
0
0.11
0
0.12
0.2
0.24
0
-0.25
0
0
0
0
0
0
0
0.13
0.21
0.06
0.03
0.02
0.09
0
0
0.02
0
0
0.01
-0.17
-0.01
-0.11
0
0
0.14
0.03
-0.02
0
0
0.03
0
0
0.08
0.12
0
0.13
0.05
0.09
0
-0.18
0.19
0
0
0.11
-0.07
0
0
0
0.04
0
0.09
0.08
0
0
-0.22
0
0
0
-0.18
0.04
0
0
0.16
0.19
C-53
YNR018W
YNR019W
YNR020C
YNR021W
YNR022C
YNR025C
YNR026C
YNR027W
YNR028W
YNR029C
YNR030W
YNR031C
YNR032W
YNR033W
YNR034W
YNR035C
YNR036C
YNR037C
YNR038W
YNR039C
YNR040W
YNR041C
YNR043W
YNR044W
YNR046W
YNR047W
YNR048W
YNR049C
YNR050C
YNR051C
YNR052C
YNR053C
YNR054C
YNR055C
YNR057C
YNR058W
YNR061C
YNR065C
YNR067C
YNR068C
YNR071C
YNR074C
YNR075W
YNR076W
YOL001W
YOL002C
YOL003C
YOL004W
YOL005C
YOL007C
YOL008W
YOL009C
YOL010W
YOL011W
YOL012C
ARE2
SEC12
CPR8
ECM39
SSK2
PPG1
ABZ1
SOL1
ARC35
DBP6
COQ2
MVD1
AGA1
MSO1
LYS9
POP2
HOL1
BIO4
BIO3
COS10
PAU6
PHO80
SIN3
RPB11
CSI2
MDM12
HTA3
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
20
21
20
20
21
21
20
20
20
20
20
20
20
21
20
20
20
20
21
20
20
21
20
20
20
20
20
20
20
20
20
41
21
21
21
21
21
21
21
20
21
20
20
20
21
20
20
20
21
21
21
21
20
21
20
1.45
0.11
0.11
0.59
0.11
0.11
0.11
0.11
0.11
0.11
0.14
0.11
0.11
0.11
0.13
0.16
0.96
0.18
0.11
0.12
0.11
0.2
0.35
0.18
0.14
0.11
0.11
0.11
2.88
0.11
0.12
0.11
0.11
0.31
0.11
0.11
0.16
0.11
0.12
0.11
0.11
0.11
0.11
0.26
0.11
0.32
0.11
0.11
0.44
0.11
0.11
0.11
0.11
0.15
0.5
1.95
0.08
0.08
0.61
0.08
0.08
0.08
0.08
0.09
0.08
0.16
0.08
0.11
0.08
0.09
0.26
0.94
0.18
0.1
0.14
0.08
0.23
0.44
0.28
0.45
0.08
0.08
0.08
1.54
0.08
0.18
0.14
0.08
0.39
0.11
0.08
0.27
0.1
0.19
0.08
0.08
0.08
0.08
0.28
0.08
0.28
0.08
0.09
0.42
0.08
0.14
0.1
0.1
0.1
0.6
2.94
0.04
0.06
0.59
0.09
0.05
0.05
0.07
0.08
0.06
0.2
0.04
0.1
0.11
0.09
0.29
1.07
0.18
0.1
0.24
0.11
0.19
0.52
0.12
0.46
0.05
0.06
0.07
4.73
0.07
0.23
0.14
0.05
0.39
0.29
0.19
0.31
0.15
0.28
0.04
0.06
0.1
0.04
0.67
0.04
0.48
0.05
0.08
0.41
0.11
0.17
0.15
0.05
0.17
0.8
2.36
0.11
0.07
0.72
0.07
0.04
0.05
0.13
0.08
0.05
0.18
0.06
0.1
0.07
0.21
0.36
0.87
0.21
0.13
0.19
0.16
0.22
0.65
0.44
0.47
0.06
0.08
0.08
1.52
0.06
0.2
0.14
0.04
0.52
0.33
0.09
0.19
0.11
0.59
0.05
0.04
0.16
0.06
0.54
0.1
0.56
0.09
0.1
0.43
0.04
0.19
0.13
0.11
0.3
0.43
0.06
0
0
0.03
0
0
0
0
0
0
0.03
0
0.02
0
0
0.08
0.03
0
0
0
0
-0.03
0.1
0.16
0.12
0
0
0
-0.16
0
0.06
0.09
0
0.01
0
0
0.07
0
-0.02
0
0
0
0
-0
0
0.03
0
0
0
0
0
0
0
0
0.1
0.28
0
0
0
-0.08
0
0
0
0
0
0.03
0
0
0
0
0.01
0.06
0
-0.2
0.14
0
0
0.16
-0.22
0.05
0
0
0
0.3
0
0
0.02
0
0
0.26
0.19
-0.06
0.03
0.12
0
0
0
0
0.11
0
0.17
0
0
0.09
-0.04
0.07
0.01
0
0
0.01
0.14
0.01
0
0.05
0
0
0
0.02
0
0
0.07
0
0
0
0.09
0.23
0.14
0.1
0.07
0.14
0.07
0
0.16
0.2
0.13
0
0
0
-0.21
0
-0.01
-0.04
0
0.08
0.17
-0.1
-0.09
0
0.35
0
0
0.1
0
0.08
0
0.12
0
0
0.03
0
0.09
0
-0
0.17
-0.1
C-54
YOL013C
YOL014W
YOL016C
YOL019W
YOL020W
YOL021C
YOL022C
YOL026C
YOL027C
YOL030W
YOL031C
YOL032W
YOL033W
YOL035C
YOL036W
YOL038W
YOL039W
YOL040C
YOL042W
YOL043C
YOL048C
YOL049W
YOL051W
YOL052C
YOL053C-A
YOL053W
YOL055C
YOL056W
YOL057W
YOL058W
YOL059W
YOL060C
YOL061W
YOL062C
YOL063C
YOL064C
YOL065C
YOL066C
YOL068C
YOL070C
YOL071W
YOL072W
YOL073C
YOL075C
YOL077C
YOL080C
YOL081W
YOL082W
YOL083W
YOL084W
YOL086C
YOL087C
YOL088C
YOL090W
YOL092W
HRD1
CMK2
TAT2
DIS3
MSE1
PRE6
RPP2A
RPS15
NTG2
GSH2
GAL11
SPE2
DDR2
GPM3
ARG1
GPD2
PRPS5
APM4
MET22
INP54
RIB2
HST1
IRA2
ADH1
MPD2
MSH2
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
20
20
20
20
21
20
21
20
21
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
21
20
21
20
21
21
21
20
20
21
20
20
20
20
21
21
20
20
20
20
21
21
20
21
20
20
21
20
20
0.11
0.14
0.24
0.15
0.11
0.11
0.11
0.36
0.17
1.07
0.11
0.11
0.11
0.11
0.11
0.51
8.1
10.86
0.11
0.11
0.17
0.13
0.11
0.24
5.4
0.11
0.11
0.11
0.16
0.65
0.43
0.11
0.45
0.11
0.11
0.11
0.11
0.11
0.11
0.11
0.11
0.11
0.46
0.11
0.11
0.11
0.11
0.11
0.11
0.11
7.45
0.11
0.14
0.11
0.39
0.08
0.23
0.13
0.29
0.15
0.21
0.14
0.34
0.11
0.98
0.08
0.12
0.08
0.1
0.08
0.54
11.06
20.6
0.12
0.08
0.17
0.11
0.08
0.18
5.24
0.08
0.09
0.08
0.21
0.22
0.5
0.14
0.74
0.15
0.09
0.13
0.08
0.08
0.12
0.08
0.1
0.08
0.47
0.08
0.18
0.08
0.09
0.12
0.11
0.08
8.52
0.08
0.11
0.08
0.62
0.05
0.05
0.35
0.36
0.17
0.16
0.06
0.27
0.2
1.31
0.43
0.07
0.08
0.04
0.06
0.57
13.38
12.74
0.1
0.06
0.24
0.11
0.07
0.23
8.5
0.06
0.09
0.05
0.22
1.99
0.97
0.15
0.57
0.13
0.06
0.2
0.08
0.06
0.16
0.04
0.13
0.07
0.34
0.05
0.19
0.07
0.08
0.15
0.14
0.04
12.76
0.06
0.18
0.04
0.54
0.08
0.04
0.31
0.27
0.13
0.11
0.08
0.68
0.24
0.83
0.13
0.09
0.05
0.04
0.07
0.96
10.26
8.63
0.09
0.06
0.24
0.12
0.04
0.37
16.53
0.06
0.07
0.08
0.17
0.38
0.67
0.16
0.93
0.16
0.07
0.17
0.06
0.04
0.19
0.06
0.23
0.08
0.55
0.06
0.13
0.04
0.21
0.19
0.22
0.07
12.09
0.04
0.18
0.06
0.45
0
0.11
0
0.11
0.05
0.21
-0.01
0
-0.1
0.06
0
0
0
0
0
0.05
0.1
0.24
0.06
0
0
0
0
0
-0.07
0
0
0
0.02
-0.35
0.03
0
0.13
0
0
0
0
0
0
0
-0.06
0
0.1
0
0.14
0
0
0
0
0
0.11
0
0
0
0.17
0
0
0.12
0.21
0.17
0.1
0
-0.1
0.07
0.11
0.45
0
0
0
0
0.12
-0.09
0
0
0
0.12
0
0
0.03
0.19
0
0
0
-0.06
0.53
0.27
0
0.07
0
0
0.16
0
0
0
0
0
0
0
0
0
0
0
0.04
-0.11
0
0.11
0
-0.06
0
0.06
0
0
0.03
0.03
0
-0.02
-0.14
0.12
0.07
-0.02
0
0
0
0
0
0.3
-0.12
-0.19
0
0
0.1
0
0
0.15
0.44
-0.3
0
0
-0.07
0
0.19
-0.01
0.17
0.05
0
0.07
0
0
0.03
0
0.17
0
-0.03
0
-0.05
0
0.2
0.16
0.11
0
0.12
0
-0.01
0
-0.02
C-55
YOL094C
YOL096C
YOL097C
YOL098C
YOL101C
YOL102C
YOL103W
YOL106W
YOL107W
YOL108C
YOL109W
YOL110W
YOL111C
YOL112W
YOL119C
YOL120C
YOL121C
YOL122C
YOL123W
YOL124C
YOL125W
YOL126C
YOL127W
YOL128C
YOL129W
YOL130W
YOL133W
YOL135C
YOL136C
YOL137W
YOL139C
YOL140W
YOL142W
YOL143C
YOL146W
YOL147C
YOL148C
YOL149W
YOL151W
YOL153C
YOL154W
YOL155C
YOL158C
YOL159C
YOL162W
YOL164W
YOL165C
YOR001W
YOR002W
YOR004W
YOR006C
YOR007C
YOR008C
YOR009W
YOR010C
RFC4
COQ3
TPT1
ITR2
INO4
ZEO1
SHR5
MSB4
RPL18A
RPS19A
SMF1
HRP1
MDH2
RPL25
ALR1
HRT1
MED7
PFK27
CDC33
ARG8
RIB4
PEX11
SPT20
DCP1
GRE2
RRP6
ALG6
SGT2
SLG1
TIR2
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
20
21
20
20
20
20
20
20
20
20
20
20
20
20
20
40
40
21
21
20
20
21
20
21
21
21
20
20
20
20
21
20
20
20
20
20
21
20
20
21
21
20
21
20
20
20
20
20
20
21
20
20
20
21
20
0.11
0.11
0.29
0.11
0.11
0.11
0.22
0.11
0.15
0.13
1.59
0.19
0.47
0.11
0.11
7.79
3.34
0.23
0.12
0.11
0.11
0.18
2.08
0.11
1.56
0.11
0.19
0.11
0.14
0.11
1.27
0.11
0.14
0.32
0.11
0.79
0.11
0.11
0.64
0.17
1.89
0.13
0.11
0.11
0.11
0.11
0.11
0.11
0.18
0.11
0.11
0.71
0.21
0.26
1.16
0.17
0.11
0.52
0.1
0.08
0.08
0.23
0.08
0.16
0.17
1.89
0.36
0.51
0.08
0.08
6.78
3.89
0.23
0.14
0.08
0.09
0.14
3.37
0.08
1.5
0.08
0.15
0.09
0.15
0.08
1.24
0.11
0.24
0.48
0.09
0.81
0.08
0.08
0.42
0.15
1.48
0.13
0.09
0.13
0.08
0.11
0.1
0.18
0.13
0.08
0.08
0.54
0.18
0.09
1.62
0.17
0.11
0.49
0.04
0.11
0.11
0.2
0.06
0.23
0.15
2.5
0.31
0.56
0.06
0.07
8.19
4.38
0.35
0.18
0.09
0.06
0.45
2.36
0.05
1.61
0.09
0.25
0.11
0.19
0.13
1.21
0.13
0.28
0.66
0.08
0.77
0.04
0.09
0.8
0.2
0.17
0.21
0.05
0.2
0.05
0.15
0.07
0.12
0.18
0.07
0.07
1.09
0.22
0.24
1.59
0.17
0.1
0.63
0.1
0.06
0.07
0.33
0.07
0.21
0.11
2.26
0.6
0.78
0.06
0.08
7.15
2.9
0.36
0.11
0.07
0.06
0.24
1.38
0.05
2.13
0.1
0.28
0.09
0.26
0.1
0.99
0.1
0.25
0.47
0.08
0.48
0.08
0.05
0.79
0.24
0.08
0.28
0.1
0.19
0.06
0.09
0.05
0.11
0.14
0.09
0.04
1.86
0.25
0.4
0.81
0
0
0.16
0
0
0
0
0
0.03
-0.04
0.16
0.07
0.05
0
0
0.1
0.04
-0.06
0.07
0
0
0
0.18
0
0.04
0
0
0
0.11
0
0.13
0
0.09
0.17
0
0.05
0
0
0
0
0.18
0
0
0
0
0
0
-0.04
0
0
0
0.01
-0.09
0
0.13
0
-0.18
0.1
0
0
0
0
0
0.13
-0
0.28
0.13
0.02
0
0
0.11
0.07
0.27
0.07
0
0
0.2
0.02
0
0.13
0
0.06
0
0.03
0
0.18
0
0.13
0.34
0
0.01
0
0
0.17
-0.12
-0.78
0
-0.33
0.09
0
0.05
-0.23
-0.11
-0.02
0
0
0.19
-0.02
-0.17
0.11
0
-0.1
0.18
0
0
0
0.17
0
0
-0.18
0.15
0.26
0.13
0
0
-0.02
-0.11
0.24
-0.19
0
0
-0.06
-0.13
0
0.07
-0.17
0.04
0
0.27
0
0.05
0
0.04
0.23
0
-0.18
0
0
0.24
-0.04
-0.99
0.01
0
0.1
0
0
0
0
-0.19
-0.14
0
0.41
0.1
-0.06
-0.07
C-56
YOR013W
YOR014W
YOR015W
YOR016C
YOR018W
YOR020C
YOR021C
YOR022C
YOR023C
YOR027W
YOR031W
YOR034C
YOR035C
YOR036W
YOR039W
YOR040W
YOR042W
YOR043W
YOR044W
YOR045W
YOR046C
YOR047C
YOR051C
YOR052C
YOR053W
YOR054C
YOR056C
YOR057W
YOR059C
YOR061W
YOR062C
YOR063W
YOR064C
YOR065W
YOR066W
YOR067C
YOR069W
YOR071C
YOR072W
YOR074C
YOR078W
YOR079C
YOR081C
YOR084W
YOR085W
YOR086C
YOR087W
YOR088W
YOR089C
YOR090C
YOR091W
YOR092W
YOR094W
YOR095C
YOR096W
RTS1
ROD1
HSP10
STI1
CRS5
AKR2
PEP12
CKB2
GLO4
WHI2
TOM6
DBP5
STD1
SGT1
CKA2
RPL3
CYT1
ALG8
VPS5
CDC21
ATX2
OST3
VPS21
ECM3
ARF3
RKI1
RPS7A
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
21
21
20
20
21
21
21
20
21
21
20
20
20
20
20
20
21
20
20
21
20
21
21
20
20
21
20
20
21
20
20
20
20
20
20
21
21
21
21
45
20
21
21
20
20
20
20
20
21
20
20
20
20
20
42
0.11
0.11
0.11
0.18
0.11
1.22
0.11
0.11
0.11
0.3
0.16
0.11
0.11
0.11
0.2
0.11
0.11
0.11
0.16
1.6
0.14
0.11
0.11
0.17
0.11
0.11
0.11
0.11
0.14
0.13
0.11
4.77
0.11
0.28
0.11
0.18
0.11
0.11
0.11
0.11
0.11
0.11
0.11
0.18
0.25
0.11
0.11
0.11
0.11
0.11
0.11
0.12
0.11
0.11
2.93
0.11
0.08
0.15
0.35
0.08
0.77
0.23
0.12
0.16
0.21
0.17
0.1
0.09
0.08
0.18
0.08
0.13
0.09
0.12
2.22
0.18
0.1
0.12
0.15
0.08
0.08
0.08
0.08
0.13
0.18
0.15
6.58
0.08
0.23
0.11
0.16
0.08
0.09
0.09
0.08
0.09
0.12
0.09
0.17
0.23
0.13
0.08
0.08
0.12
0.08
0.15
0.21
0.08
0.13
3.29
0.09
0.08
0.16
0.32
0.05
1.63
0.24
0.08
0.06
0.41
0.24
0.08
0.04
0.05
0.25
0.08
0.13
0.11
0.19
2.09
0.26
0.05
0.04
0.3
0.06
0.07
0.08
0.04
0.16
0.15
0.11
5.5
0.1
0.92
0.1
0.21
0.05
0.11
0.04
0.04
0.09
0.18
0.12
0.21
0.31
0.11
0.05
0.07
0.18
0.08
0.08
0.24
0.06
0.13
4.26
0.17
0.07
0.23
0.27
0.05
2.71
0.16
0.07
0.17
0.89
0.51
0.11
0.05
0.06
0.27
0.12
0.28
0.15
0.26
2.27
0.25
0.11
0.09
0.41
0.07
0.09
0.04
0.06
0.19
0.17
0.11
4.18
0.05
0.28
0.17
0.18
0.04
0.12
0.04
0.05
0.06
0.12
0.11
0.17
0.2
0.19
0.04
0.13
0.24
0.16
0.08
0.33
0.07
0.07
2.03
0
0
0.05
0.13
0
0.06
0.2
0
0.08
0
0
0
0
0
-0.03
0
-0.07
0
0
0.13
0.11
0
0.05
0
0
0
0
0
-0.06
0.05
0
0.09
0
0
0
0
0
0
0
0
0
-0.07
0
0
0.1
0
0
0
0.02
0
0
0.11
0
0.08
0.13
0
0
0.01
-0.07
0
0.24
0.22
0
0
0.01
0
0
0
0
0.08
0
-0.06
0
-0.09
0.08
0.05
0
0
0.18
0
0
0
0
0
0
-0.27
0.03
0
0.17
0
0.02
0
-0.05
0
0
0
0.05
0
0.07
0.09
-0.1
0
0
0.05
0
0
0.01
0
0.07
0.11
0.02
0
0.16
0
0
0.42
-0.05
0
0.12
0.38
0.34
0
0
0
0.05
0.07
0.18
0
0.2
0.06
0.09
0
-0.08
0.28
0
0
0
0
0.1
0
0
-0.15
0
-0.02
0.16
0.01
0
-0.1
0
0
0
0
-0.31
-0.19
-0.02
0
0
0
0.14
-0.04
0
0.23
0
0
-0.1
C-57
YOR097C
YOR098C
YOR099W
YOR101W
YOR102W
YOR103C
YOR104W
YOR106W
YOR107W
YOR108W
YOR109W
YOR110W
YOR112W
YOR115C
YOR116C
YOR117W
YOR119C
YOR120W
YOR121C
YOR122C
YOR123C
YOR124C
YOR125C
YOR126C
YOR128C
YOR129C
YOR130C
YOR131C
YOR132W
YOR133W
YOR134W
YOR135C
YOR136W
YOR137C
YOR138C
YOR140W
YOR141C
YOR142W
YOR143C
YOR145C
YOR147W
YOR149C
YOR150W
YOR151C
YOR152C
YOR153W
YOR154W
YOR155C
YOR157C
YOR158W
YOR159C
YOR160W
YOR161C
YOR163W
YOR164C
NUP1
KTR1
RAS1
OST2
VAM3
INP53
RPO31
RPT5
RIO1
GCY1
PFY1
LEO1
UBP2
CAT5
IAH1
ADE2
ARG11
VPS17
EFT1
BAG7
IDH2
SFL1
ARP8
THI80
SMP3
RPB2
PDR5
PUP1
PET123
SME1
MTR10
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
20
20
20
20
20
20
20
21
20
21
21
21
21
21
20
21
20
20
20
21
20
20
21
20
20
20
21
20
20
20
21
20
20
20
21
20
20
20
20
20
20
21
20
20
20
20
21
20
20
20
21
21
20
21
20
0.14
0.11
1.34
0.11
0.11
0.37
0.11
0.11
0.11
0.27
0.11
0.11
0.11
0.11
0.11
0.33
0.11
0.11
0.11
2.73
0.11
0.11
0.11
0.11
0.19
0.11
0.11
0.11
0.11
2.91
0.11
0.11
1.42
0.11
0.11
0.11
0.11
0.52
0.11
0.11
0.11
0.11
0.3
0.11
0.11
0.46
0.11
0.11
0.47
0.11
0.11
0.11
0.25
0.11
0.17
0.19
0.1
1.16
0.09
0.08
0.32
0.08
0.11
0.08
0.34
0.08
0.08
0.08
0.08
0.08
0.23
0.08
0.14
0.08
4.46
0.1
0.08
0.1
0.08
0.24
0.08
0.12
0.18
0.1
3.52
0.08
0.08
0.88
0.08
0.08
0.08
0.08
0.49
0.08
0.08
0.08
0.08
0.16
0.18
0.1
0.52
0.08
0.08
0.68
0.11
0.14
0.09
0.16
0.08
0.17
0.18
0.09
2.53
0.1
0.04
0.71
0.06
0.11
0.06
0.27
0.04
0.04
0.07
0.1
0.04
0.33
0.1
3.21
0.13
4.22
0.06
0.06
0.2
0.19
0.21
0.09
0.16
0.19
0.1
3.39
0.08
0.04
3.46
0.04
0.08
0.06
0.07
0.74
0.05
0.13
0.05
0.07
0.36
0.18
0.08
0.8
0.04
0.08
0.7
0.05
0.13
0.04
0.16
0.12
0.19
0.18
0.11
1.54
0.05
0.06
0.42
0.08
0.1
0.07
0.22
0.08
0.04
0.04
0.08
0.05
0.36
0.05
0.72
0.07
3.77
0.05
0.09
0.18
0.14
0.48
0.05
0.06
0.14
0.21
2.87
0.32
0.05
2.03
0.08
0.06
0.04
0.06
0.53
0.04
0.15
0.04
0.09
0.27
0.24
0.06
0.63
0.07
0.15
0.86
0.06
0.14
0.05
0.38
0.12
0.2
0
0
0.05
0
0
-0.01
0
0.01
0
0.18
0
0
0
0
0
0
0
0
0
0.12
0
0
0
0
0.06
0
-0.09
0.01
0
0.14
0
0
-0.13
0
0
0
0
0.01
0
0
0
0
0
0.09
0
0.09
0
0
0.16
0
0
0
0
0
-0.09
0.04
0
0.23
0
0
0.26
0
-0.1
0
0.11
0
0
0
0
0
0
0
1.09
0
0.09
0
0
0.05
0.01
0.07
0
0.14
0.05
-0.11
0.07
0
0
0.28
0
-0.13
0
0
0.14
0
0
0
0
0.1
0.07
0
0.04
0
0
0.13
0
-0
0
-0.17
-0.03
0.02
0.11
-0
0.01
0
0
0.07
0
0
0
0
0
0
0
0
0
0.07
0
0.48
0
0.07
0
0
0.04
0
0.33
0
0
0.02
0.04
0.02
0.22
0
0.12
0
0
0
0
-0.04
0
0.03
0
-0.1
0.07
0.1
0
0.07
-0.31
0
0.21
0
0.01
0
0.13
-0.05
-0.1
C-58
YOR165W
YOR166C
YOR167C
YOR168W
YOR172W
YOR173W
YOR174W
YOR175C
YOR176W
YOR178C
YOR179C
YOR180C
YOR181W
YOR182C
YOR184W
YOR185C
YOR187W
YOR189W
YOR191W
YOR194C
YOR196C
YOR197W
YOR198C
YOR200W
YOR201C
YOR202W
YOR203W
YOR204W
YOR205C
YOR206W
YOR207C
YOR208W
YOR209C
YOR210W
YOR212W
YOR213C
YOR215C
YOR217W
YOR218C
YOR219C
YOR220W
YOR222W
YOR223W
YOR224C
YOR226C
YOR227W
YOR228C
YOR229W
YOR230W
YOR231W
YOR232W
YOR233W
YOR234C
YOR236W
YOR238W
RPS28A
GLN4
MED4
HEM15
GAC1
EHD2
LAS17
RPS30B
SER1
GSP2
RIS1
TOA1
LIP5
BFR1
PET56
HIS3
DED1
RET1
PTP2
NPT1
RPB10
STE4
SAS5
RFC1
STE13
RPB8
WTM2
WTM1
MKK1
MGE1
KIN4
DFR1
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
20
21
36
21
20
20
21
20
21
20
21
20
20
20
20
20
21
20
20
20
20
20
20
20
20
20
20
21
20
20
20
20
21
20
21
21
20
20
21
21
20
20
20
21
20
20
21
21
21
20
20
20
64
21
21
0.12
0.11
2.32
0.11
0.11
0.11
0.11
0.11
0.69
0.11
0.11
0.11
0.11
7
0.17
0.7
1.03
0.11
0.11
0.11
0.11
0.17
0.18
0.11
0.11
0.23
0.12
0.34
0.11
0.11
0.11
0.11
0.24
0.17
0.11
0.11
0.18
0.11
0.11
0.11
0.32
0.24
0.11
1.35
0.19
0.11
0.39
0.17
3.27
0.11
0.16
0.11
1.87
0.11
0.11
0.08
0.08
2.43
0.15
0.08
0.08
0.08
0.19
0.73
0.08
0.08
0.08
0.1
11.26
0.22
0.54
0.97
0.11
0.08
0.08
0.09
0.26
0.18
0.08
0.09
0.27
0.21
0.32
0.08
0.09
0.1
0.08
0.21
0.2
0.14
0.08
0.1
0.09
0.08
0.08
0.22
0.29
0.08
1.63
0.23
0.08
0.34
0.13
3.1
0.11
0.24
0.08
2.69
0.11
0.1
0.1
0.04
3.4
0.14
0.04
0.14
0.08
0.16
0.89
0.22
0.17
0.07
0.07
9.27
0.24
0.8
1.26
0.09
0.06
0.09
0.24
0.27
0.55
0.04
0.16
0.69
0.23
0.5
0.08
0.06
0.1
0.08
0.53
0.51
0.23
0.16
0.24
0.04
0.04
0.07
0.75
0.42
0.05
1.3
0.31
0.06
0.45
0.26
3.33
0.07
0.19
0.04
2.54
0.13
0.08
0.08
0.06
2.6
0.15
0.07
0.17
0.06
0.14
0.72
0.08
0.11
0.05
0.09
5.75
0.31
1.74
1.51
0.07
0.04
0.15
0.16
0.24
0.32
0.05
0.2
0.67
0.19
0.43
0.05
0.05
0.14
0.11
0.46
0.37
0.17
0.12
0.16
0.07
0.05
0.07
0.54
0.2
0.1
1.36
0.26
0.11
0.33
0.18
5.06
0.13
0.22
0.06
2.07
0.06
0.07
0
0
0.15
-0.02
0
0
0
-0.02
-0.04
0
0
0
0
0.18
0.06
-0.1
-0.02
0
0
0
0
-0.06
-0.03
0
0
-0.01
0.09
0.01
0
0
0
0
0.06
-0.04
0
0
-0.2
0
0
0
0
0.06
0
0.07
-0.05
0
0
0
-0.08
0
0.12
0
0.06
0
0
-0.06
0
0.08
-0.09
0
0
0
-0
0.07
0.29
-0.01
0
0
0.15
0.03
0.06
0.09
0
0
0
0.18
0.09
0.01
0
0.09
0.33
0.21
0.11
0
0
0
0
0.26
0.21
0
0.09
-0.01
0
0
0
0.15
0.14
0
0.07
0.07
0
0.06
-0.01
-0.04
0
0.05
0
0.06
0.09
-0.11
0
0
-0.14
0.02
0
0.13
0
-0.02
-0.07
-0.14
-0.08
0
0
-0.08
0.16
0.34
0.13
0
0
0
0.06
0.05
0
0
0.08
0.32
0.18
0.12
0
0
0
-0.2
0.2
0.1
0.02
-0.01
0.02
0
0
-0.2
0.17
-0.1
0
0.12
0.06
0
-0.07
0.02
0.2
0
0.03
0
-0.01
0
-0.17
C-59
YOR239W
YOR240W
YOR241W
YOR243C
YOR244W
YOR245C
YOR246C
YOR247W
YOR248W
YOR249C
YOR250C
YOR251C
YOR253W
YOR254C
YOR257W
YOR258W
YOR259C
YOR260W
YOR261C
YOR262W
YOR264W
YOR265W
YOR266W
YOR267C
YOR269W
YOR270C
YOR271C
YOR272W
YOR273C
YOR275C
YOR276W
YOR278W
YOR280C
YOR281C
YOR283W
YOR284W
YOR285W
YOR286W
YOR288C
YOR289W
YOR290C
YOR291W
YOR292C
YOR293W
YOR294W
YOR297C
YOR299W
YOR301W
YOR302W
YOR303W
YOR304C-A
YOR304W
YOR305W
YOR306C
YOR307C
ESA1
APC5
CLP1
SEC63
CDC31
RPT4
GCD1
RPN8
RBL2
PNT1
PAC1
VPH1
YTM1
CAF20
HEM4
MPD1
SNF2
RPS10A
BUD7
CPA1
ISW2
SLY41
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
20
21
20
20
21
20
20
20
22
20
21
20
20
20
21
21
20
20
20
20
21
20
20
20
21
21
20
20
21
20
20
21
20
20
20
21
20
20
21
20
21
20
20
50
20
20
20
21
20
20
20
20
20
21
20
0.11
0.11
0.11
0.11
0.11
0.11
0.27
3.99
1.59
0.11
0.11
0.14
0.22
0.11
0.11
0.11
0.22
0.29
0.11
0.11
0.11
0.21
0.11
0.61
0.11
1.73
0.48
0.11
0.42
0.11
0.65
0.11
0.17
0.11
0.11
0.11
3.41
0.52
0.18
0.11
0.11
0.14
0.11
3.03
0.11
0.19
0.11
0.11
0.54
0.67
0.11
0.11
0.13
0.11
0.11
0.14
0.1
0.11
0.08
0.08
0.11
0.42
5.53
2.18
0.08
0.08
0.17
0.27
0.2
0.14
0.08
0.26
0.4
0.09
0.09
0.08
0.18
0.08
0.55
0.08
2.15
0.67
0.09
0.4
0.08
0.75
0.08
0.1
0.08
0.12
0.08
1.68
0.58
0.18
0.14
0.1
0.09
0.08
3.22
0.08
0.17
0.08
0.13
0.39
0.68
0.08
0.08
0.08
0.08
0.1
0.12
0.18
0.11
0.04
0.08
0.19
0.32
4.21
2.03
0.04
0.16
0.24
0.39
0.23
0.23
0.05
0.35
0.33
0.1
0.12
0.07
0.31
0.08
0.8
0.07
1.38
0.62
0.08
0.86
0.05
0.74
0.07
0.28
0.08
0.21
0.09
4.63
0.8
0.53
0.23
0.07
0.08
0.07
3.27
0.06
0.27
0.06
0.12
0.83
1.58
0.06
0.05
0.11
0.06
0.09
0.14
0.1
0.14
0.08
0.09
0.24
0.32
3.89
1.14
0.05
0.11
0.17
0.21
0.23
0.23
0.04
0.53
0.49
0.12
0.17
0.09
0.22
0.06
1.16
0.07
2.54
0.73
0.04
0.35
0.07
0.58
0.1
0.23
0.08
0.2
0.04
6.73
0.69
0.25
0.24
0.06
0.08
0.09
2.24
0.06
0.2
0.08
0.12
0.83
1.35
0.04
0.04
0.15
0.14
0.12
0
0
0
0
0
0
0.1
0.21
0.11
0
0
0.02
0
0
0.03
0
0.05
0.15
0
0
0
-0.06
0
0
0
0.1
0.14
0
-0.07
0
0.13
0
0
0
0.04
0
-0.07
0.08
-0.03
0
-0.07
0
0
0.09
0
0
0
-0.08
-0.09
-0.02
0
0
0
0
0
0
0.13
0
0
0
0.04
-0.06
0.08
0.11
0
0.13
0.12
0.14
0.14
0.07
0
0.19
0.1
0
0
0
0.13
0
0
0
-0.03
0.03
0
0.16
0
0.08
0
0.09
0
0.08
-0.12
0.17
0.12
0.36
0.04
-0.27
0
0
0.02
0
-0.04
0
-0.19
0.14
0.28
0
0
0
-0.24
0
-0.01
0
-0.04
0
-0.19
0.15
-0.02
0.05
-0.02
0
-0.15
0.02
0
0.05
-0.05
0
0.34
0.22
0
0.01
0
0.02
0
0.15
0
0.14
-0.02
0
-0.05
0
-0.09
-0.05
0.11
0
0.16
0
0.22
0.04
0.21
0.19
-0.27
0
0
-0.2
0
0
0
-0.2
0.16
0.23
0
0
0
0.13
-0.11
C-60
YOR309C
YOR310C
YOR311C
YOR312C
YOR315W
YOR316C
YOR317W
YOR318C
YOR319W
YOR320C
YOR321W
YOR322C
YOR323C
YOR326W
YOR327C
YOR328W
YOR329C
YOR331C
YOR332W
YOR335C
YOR336W
YOR337W
YOR338W
YOR340C
YOR341W
YOR342C
YOR343C
YOR344C
YOR346W
YOR347C
YOR348C
YOR349W
YOR352W
YOR354C
YOR355W
YOR356W
YOR357C
YOR358W
YOR359W
YOR360C
YOR361C
YOR362C
YOR363C
YOR367W
YOR369C
YOR370C
YOR373W
YOR374W
YOR375C
YOR377W
YOR380W
YOR382W
YOR383C
YOR385W
YOR388C
NOP5
RPL20B
COT1
FAA1
HSH49
PMT3
PRO2
MYO2
SNC2
PDR10
SCD5
VMA4
ALA1
KRE5
TEA1
RPA43
RPA190
TYE7
REV1
PYK2
PUT4
CIN1
GDS1
GRD19
HAP5
PDE2
PRT1
PRE10
PIP2
SCP1
RPS12
MRS6
NUD1
ALD7
GDH1
ATF1
FDH1
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
34
20
20
66
20
21
20
21
20
21
20
20
20
20
21
20
20
21
20
20
21
21
20
20
21
21
20
20
21
21
20
21
21
20
20
20
20
21
20
20
20
20
21
20
21
20
21
20
20
20
20
20
21
20
27
0.41
0.42
0.38
1.2
0.11
0.11
0.46
0.11
0.11
0.11
0.11
0.11
0.2
0.13
0.27
0.11
0.11
0.11
0.91
0.35
0.11
0.11
0.11
0.11
0.11
0.11
0.11
0.21
0.11
0.13
0.11
0.11
0.11
0.11
0.15
0.11
0.11
0.11
0.12
0.15
0.24
0.23
0.11
0.11
3.54
0.12
0.11
0.88
1.18
0.11
0.11
0.14
1.18
0.12
0.11
0.93
0.76
0.38
1.65
0.08
0.15
0.38
0.08
0.08
0.11
0.09
0.08
0.17
0.1
0.35
0.08
0.1
0.08
0.49
0.43
0.12
0.08
0.08
0.08
0.08
0.08
0.08
0.17
0.08
0.11
0.08
0.08
0.08
0.1
0.2
0.13
0.1
0.08
0.21
0.11
0.3
0.26
0.11
0.1
3.26
0.15
0.08
0.48
1.05
0.08
0.08
0.15
1.37
0.14
0.08
0.99
0.87
0.53
1.14
0.11
0.19
0.44
0.05
0.06
0.07
0.16
0.08
0.25
0.1
0.44
0.04
0.09
0.05
1.03
0.56
0.13
0.06
0.06
0.1
0.06
0.07
0.08
0.53
0.04
0.25
0.06
0.05
0.08
0.08
0.2
0.14
0.12
0.05
0.16
0.16
0.34
0.56
0.06
0.12
5.34
0.17
0.04
1.58
2.05
0.05
0.11
0.28
1.37
0.18
0.07
0.62
0.66
0.41
1.08
0.04
0.26
0.76
0.04
0.06
0.08
0.19
0.08
0.27
0.1
0.46
0.1
0.1
0.04
0.95
0.41
0.1
0.04
0.12
0.07
0.11
0.1
0.09
0.38
0.05
0.21
0.04
0.05
0.09
0.07
0.32
0.11
0.13
0.11
0.21
0.23
0.37
0.66
0.11
0.21
4.02
0.25
0.07
1.55
0.93
0.06
0.1
0.41
1.72
0.12
0.04
0.29
0.21
0
0.11
0
-0.07
-0.13
0
0
0
0
0
-0.07
-0.1
-0.04
0
0
0
0
0.01
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0.15
0
0
0
-0.03
0
0.02
0.07
0
0
0.05
0
0
-0.21
0.01
0
0
0.02
0.04
0
0
0.31
0.22
0.09
-0.11
-0.1
-0.07
-0.06
0
0
0
0.01
0
0.03
0
0.12
0
0
0
0.04
0.17
-0.1
0
0
0
0
0
0
0.13
0
0.13
0
0
-0.36
0
0.15
0.08
0
0
0.02
-0
0.02
0.14
0
0
0.06
0
0
0.23
0.28
-0.35
0
0.14
0.06
0.02
0
0.12
0.11
0.01
-0.16
0
0.21
0.04
0
0
0
-0.07
0
0.11
0
0.13
0
0
0
0.02
0.05
0
0
0
0
-0.09
-0.07
0
0.07
0
0.08
0
0
0
0
0.23
0
0
0
0.07
0.1
0.03
0.24
-0.02
0.05
-0.17
0.12
0
0.23
-0.1
0
0
0.24
0.02
-0.11
0
C-61
YOR389W
YOR390W
YOR391C
YOR393W
YOR394W
YPL001W
YPL002C
YPL003W
YPL004C
YPL006W
YPL007C
YPL009C
YPL010W
YPL011C
YPL012W
YPL013C
YPL014W
YPL015C
YPL017C
YPL018W
YPL019C
YPL020C
YPL023C
YPL024W
YPL026C
YPL028W
YPL030W
YPL031C
YPL032C
YPL034W
YPL036W
YPL037C
YPL039W
YPL042C
YPL046C
YPL047W
YPL048W
YPL049C
YPL050C
YPL051W
YPL052W
YPL053C
YPL054W
YPL055C
YPL056C
YPL057C
YPL058C
YPL059W
YPL061W
YPL063W
YPL064C
YPL065W
YPL066W
YPL067C
YPL068C
ERR1
HAT1
SNF8
ULA1
NCR1
RET3
TAF47
HST2
CTF19
MET12
NCE4
SKS1
ERG10
PHO85
SVL3
PMA2
EGD1
MET31
SSN3
ELC1
CAM1
DIG1
MNN9
KTR6
LEE1
SUR1
PDR12
ALD6
VPS28
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
20
20
20
20
20
20
21
20
21
21
21
20
20
20
20
20
20
20
21
21
20
20
20
20
20
21
20
21
20
21
21
21
20
20
21
20
20
21
20
20
20
20
21
20
20
20
20
20
20
20
20
20
20
21
21
0.11
0.12
0.11
0.11
0.11
0.11
0.11
0.12
1.47
0.12
0.11
0.11
0.72
0.11
0.11
0.21
0.26
0.27
0.11
0.11
0.11
0.11
0.14
0.11
0.11
2.49
0.11
0.52
0.11
0.11
0.11
3.31
0.11
0.11
0.11
0.12
1.6
0.11
0.11
0.11
0.11
0.11
0.11
0.11
0.11
0.25
0.12
0.37
1.33
0.12
0.11
0.11
0.11
0.21
0.11
0.08
0.08
0.08
0.08
0.08
0.08
0.08
0.11
1.1
0.12
0.08
0.09
0.8
0.09
0.13
0.28
0.33
0.18
0.08
0.08
0.09
0.08
0.12
0.08
0.14
2.75
0.12
0.41
0.21
0.08
0.08
1.77
0.08
0.09
0.08
0.12
0.88
0.08
0.1
0.08
0.08
0.16
0.08
0.09
0.08
0.32
0.24
0.32
0.86
0.08
0.08
0.08
0.08
0.49
0.08
0.06
0.09
0.05
0.04
0.11
0.04
0.08
0.12
1.71
0.22
0.05
0.12
1.2
0.11
0.1
0.31
0.57
0.4
0.04
0.04
0.2
0.06
0.1
0.05
0.08
3.82
0.12
0.56
0.14
0.1
0.04
3.26
0.11
0.05
0.07
0.09
1.02
0.05
0.11
0.07
0.05
0.11
0.06
0.11
0.13
0.49
0.22
0.66
1.36
0.09
0.05
0.05
0.76
1.76
0.09
0.05
0.1
0.09
0.07
0.11
0.07
0.1
0.11
1.76
0.38
0.06
0.12
0.75
0.12
0.09
0.29
0.65
0.27
0.06
0.06
0.19
0.1
0.11
0.12
0.13
2.35
0.15
0.66
0.25
0.08
0.11
3.13
0.08
0.04
0.07
0.14
1.28
0.16
0.21
0.04
0.05
0.13
0.11
0.12
0.1
0.44
0.29
0.62
1.59
0.15
0.05
0.1
0.08
0.52
0.04
0
0
0
0
0
0
0
0
-0.04
-0.09
0
0
0
0
0.06
0.02
0.04
-0.04
0
0
0
0
0
0
0
0.04
0
0.01
0.07
0
0
0.01
0
0
0
0
-0.06
0
0
0
0
0.07
0
0
0
-0.05
0.11
0.01
0.01
0
0
0
0
0.01
0
0
-0.18
0
0
0
0
0
-0.05
0.15
0.13
0
0
0.13
0
0
0.13
0.17
0.09
0
0
0.07
0
0
0
-0.19
0.16
0
0.08
0
-0.1
0
0.01
0
0
0
0
0
0
0
0
0
0
-0.24
0
-0.09
0.2
0.13
0.22
0.05
0
0
0
0.8
0.77
-0.12
0
-0.23
0
0
-0.09
0
0
0
0.09
0.3
0
0
-0.02
0
-0.11
0.08
0.22
-0.07
0
0
0
0
0
0
-0.01
-0.06
0.06
0.14
0.11
-0.24
-0.1
-0.06
0
0
-0.27
0.02
-0.08
0
0.02
0
0
0.06
-0.19
0
0
0.08
0.12
0.24
0.09
0
0
0
0
0.02
0
C-62
YPL069C
YPL071C
YPL075W
YPL076W
YPL077C
YPL078C
YPL079W
YPL080C
YPL081W
YPL084W
YPL085W
YPL086C
YPL087W
YPL088W
YPL089C
YPL090C
YPL091W
YPL092W
YPL093W
YPL094C
YPL095C
YPL097W
YPL098C
YPL100W
YPL101W
YPL104W
YPL105C
YPL106C
YPL107W
YPL111W
YPL112C
YPL113C
YPL115C
YPL117C
YPL118W
YPL122C
YPL123C
YPL125W
YPL127C
YPL128C
YPL129W
YPL131W
YPL132W
YPL134C
YPL135W
YPL138C
YPL139C
YPL142C
YPL143W
YPL144W
YPL145C
YPL148C
YPL149W
YPL152W
YPL154C
BTS1
GCR1
GPI2
ATP4
RPL21B
RPS9A
BRO1
SEC16
HPA1
RLM1
RPS6A
GLR1
SSU1
SEC62
MSY1
MSD1
SSE1
CAR1
BEM3
IDI1
TFB2
HHO1
TBF1
RPL5
COX11
UME1
RPL33A
SNR17B
KES1
PPT2
APG5
RRD2
PEP4
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
21
20
21
21
20
20
20
20
21
21
20
21
20
20
20
20
20
21
20
20
20
20
20
20
20
20
20
20
20
20
21
20
21
20
20
20
20
21
20
21
20
21
20
20
20
20
20
21
18
20
20
20
21
21
20
0.11
0.11
0.11
0.11
0.11
0.65
17.13
0.11
0.25
0.11
0.11
0.11
1.01
0.11
0.11
2.44
0.24
0.11
0.11
0.7
0.32
0.11
0.94
0.11
0.11
0.11
0.11
0.83
0.11
0.11
0.11
0.11
0.11
0.12
0.11
0.11
0.11
0.11
0.34
0.16
0.16
9.79
0.11
0.24
0.76
0.11
0.11
0.13
12.45
0.32
0.17
0.13
0.42
0.11
1.94
0.08
0.08
0.08
0.08
0.09
0.53
10.75
0.08
0.33
0.08
0.19
0.11
0.52
0.08
0.12
3.1
0.15
0.08
0.08
0.61
0.31
0.1
1.46
0.08
0.08
0.08
0.08
0.49
0.08
0.09
0.1
0.08
0.08
0.15
0.09
0.08
0.08
0.08
0.24
0.2
0.16
15.07
0.08
0.2
0.47
0.08
0.17
0.1
7.79
0.24
0.15
0.11
0.42
0.08
1.3
0.04
0.06
0.12
0.16
0.04
1.32
16
0.04
0.4
0.08
0.14
0.07
0.7
0.04
0.17
2.6
0.27
0.24
0.05
1.46
0.52
0.11
1.19
0.05
0.08
0.04
0.16
0.97
0.06
0.1
0.08
0.05
0.04
0.18
0.13
0.07
0.04
0.07
0.22
0.11
0.15
11.54
0.06
0.77
0.67
0.04
0.14
0.06
8.49
0.23
0.12
0.08
0.5
0.04
1.85
0.05
0.06
0.12
0.11
0.04
0.65
9.9
0.06
0.53
0.06
0.14
0.06
1.46
0.12
0.27
2.14
0.25
0.13
0.1
0.78
0.18
0.13
1.28
0.1
0.1
0.07
0.07
1.72
0.04
0.12
0.08
0.04
0.08
0.25
0.1
0.09
0.08
0.04
0.12
0.23
0.18
9.28
0.13
0.22
1.16
0.1
0.08
0.13
7.04
0.22
0.1
0.13
0.49
0.09
3.12
0
0
0
0
0
0
-0.06
0
0.04
0
0
0
0
0
-0.03
0.05
0
0
0
0.02
0.02
0
0.12
0
0
0
0
-0.06
0
0
0
0
0
0
0
0
0
0
-0.06
0.06
0
0.1
0
0
0.04
0
0
0
-0.07
-0.02
0
0
0.02
0
-0.11
0
0
-0.08
0
0
0.31
-0.05
0
0.01
0
0
-0.26
0.03
0
0.05
0.04
0.07
0.24
0
0.24
0.17
0
0.15
0
0
0
-0.07
0.09
0
0
0
0
0
0
0
0
0
-0.24
-0.2
-0.22
-0.13
-0.05
0
0.36
-0.02
0
-0.05
0
0
-0.07
0
0
0.11
0
-0.04
0
0
0.05
-0.05
0
-0.05
-0.15
0
0.25
0
0
0
0.2
0
0.24
-0.14
0
0.03
0
0.17
-0.13
0
0.1
0
0
0
0
0.32
0
0
0
0
-0.11
0.08
0
0
0
0
-0.34
-0.04
-0.06
-0.11
-0.12
-0.14
0.31
0
-0.25
0
-0.11
-0.15
0
0.02
0.09
0
0.18
C-63
YPL156C
YPL157W
YPL159C
YPL160W
YPL162C
YPL163C
YPL168W
YPL169C
YPL170W
YPL171C
YPL172C
YPL173W
YPL175W
YPL176C
YPL177C
YPL178W
YPL179W
YPL180W
YPL182C
YPL183C
YPL184C
YPL186C
YPL187W
YPL188W
YPL190C
YPL195W
YPL196W
YPL197C
YPL198W
YPL199C
YPL203W
YPL204W
YPL206C
YPL207W
YPL208W
YPL210C
YPL211W
YPL212C
YPL214C
YPL215W
YPL218W
YPL219W
YPL220W
YPL221W
YPL222W
YPL223C
YPL224C
YPL225W
YPL226W
YPL227C
YPL229W
YPL230W
YPL231W
YPL232W
YPL234C
CDC60
SVS1
MEX67
OYE3
COX10
MRPL40
CUP9
MUD13
PPQ1
MFα1
POS5
APL5
RPL7B
PKA3
HRR25
SRP72
NIP7
PUS1
THI6
CBP3
SAR1
PCL8
RPL1A
GRE1
MMT2
ALG5
FAS2
SSO1
TFP3
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
20
20
20
20
21
20
20
20
21
20
20
20
20
20
21
21
20
21
20
20
20
21
20
20
20
21
21
21
39
20
21
21
20
20
20
20
21
21
20
21
20
20
20
21
21
21
21
21
21
20
21
20
20
20
21
0.11
0.11
0.11
0.12
0.11
0.48
0.11
0.16
0.42
0.11
0.11
0.11
0.11
0.16
0.2
0.16
0.11
0.11
0.11
0.11
0.12
0.11
0.11
0.11
0.11
0.11
0.11
0.11
0.81
0.23
0.18
0.31
0.44
0.11
0.11
0.11
0.11
0.11
0.11
0.11
2.18
0.11
9.9
0.26
0.11
0.11
0.15
0.24
0.11
0.11
0.3
0.11
1.52
0.14
2.78
0.08
0.08
0.08
0.16
0.08
0.82
0.08
0.11
0.26
0.08
0.08
0.09
0.08
0.12
0.25
0.2
0.11
0.08
0.09
0.08
0.2
0.08
2.88
0.08
0.08
0.08
0.08
0.08
0.76
0.21
0.14
0.13
0.14
0.18
0.08
0.11
0.15
0.08
0.08
0.1
1.36
0.08
5.87
0.14
0.08
0.08
0.09
0.18
0.13
0.08
0.22
0.08
0.83
0.21
1.14
0.05
0.05
0.11
0.21
0.08
0.87
0.04
0.15
0.51
0.07
0.06
0.12
0.09
0.13
0.27
0.17
0.13
0.04
0.05
0.04
0.15
0.07
0.07
0.13
0.06
0.08
0.06
0.04
1.02
0.29
0.18
0.21
0.36
0.18
0.07
0.05
0.17
0.08
0.1
0.16
3.16
0.05
10.04
0.48
0.04
0.06
0.11
0.64
0.07
0.07
0.32
0.09
2.07
0.23
2.44
0.06
0.04
0.1
0.21
0.06
0.61
0.06
0.25
0.75
0.04
0.1
0.12
0.09
0.18
0.32
0.19
0.14
0.04
0.04
0.09
0.12
0.09
0.04
0.09
0.06
0.06
0.08
0.07
1.97
0.21
0.34
0.41
0.45
0.22
0.06
0.1
0.11
0.06
0.04
0.11
2.2
0.04
5.6
0.52
0.08
1.04
0.16
0.57
0.09
0.1
0.48
0.11
1.08
0.29
1.56
0
0
0
0.08
0
0.18
0
0
0
0
0
0
0
0
-0.08
0
0
0
0
0
0.02
0
1.28
0
0
0
0
0
0
0
0
0
-0.25
-0.05
0
0
0.08
0
0
0
-0.08
0
-0.39
-0.22
0
0
0
0
0
0
0
0
0
0
-0.19
0
0
0
0.12
0
0.09
0
-0.22
0.16
0
0
0
0
-0.13
0.04
-0.12
0
0
0
0
-0.05
0
0
0.03
0
0
0
0
-0.05
-0.03
-0.01
-0.15
-0.05
0.03
-0.28
0
0.03
-0.23
0
0.15
0.1
0
-0.03
0.18
0
0
-0.28
0.23
-0.19
0
-0.01
0
0.04
0
-0.04
0
0
0
0.08
0
0
0
0.07
0.24
0
-0.21
-0.11
0
-0.1
0.01
0
0
0
0
0
0
-0.13
0
0
0
-0.33
-0.12
0
-0.04
-0.06
0.1
0.02
0.1
0.03
0
0
-0.08
0
0
-0.17
-0.06
0
-0.21
0.19
0
0.83
0
0.2
0
0
-0.01
0
-0.12
0.13
-0.12
C-64
YPL235W
YPL236C
YPL237W
YPL238C
YPL239W
YPL240C
YPL244C
YPL245W
YPL246C
YPL247C
YPL250C
YPL252C
YPL256C
YPL258C
YPL259C
YPL260W
YPL262W
YPL263C
YPL264C
YPL265W
YPL266W
YPL268W
YPL270W
YPL271W
YPL273W
YPL274W
YPL275W
YPL276W
YPL278C
YPL279C
YPL280W
YPL282C
YPL283C
YPR004C
YPR005C
YPR006C
YPR008W
YPR009W
YPR010C
YPR011C
YPR012W
YPR013C
YPR016C
YPR017C
YPR019W
YPR020W
YPR021C
YPR022C
YPR023C
YPR024W
YPR028W
YPR029C
YPR030W
YPR033C
YPR034W
SUI3
YAR1
HSP82
CLN2
APM1
FUM1
KEL3
DIP5
DIM1
PLC1
MDL2
ATP15
HAL1
ICL2
CDC95
DSS4
CDC54
YME1
APL4
HTS1
ARP7
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
21
21
20
20
20
20
21
20
20
20
21
20
21
21
20
21
21
20
20
20
20
20
21
20
20
20
24
20
20
20
20
20
20
20
21
20
21
21
20
20
21
20
21
20
21
20
21
21
20
21
41
20
20
20
21
0.18
0.11
0.18
0.11
0.11
0.15
0.21
0.11
0.96
0.43
1.05
0.88
0.21
0.11
0.11
0.11
0.97
0.11
0.11
0.2
0.11
0.11
0.11
2.42
0.25
0.17
0.11
0.11
0.11
0.11
0.11
0.11
0.72
0.42
0.11
0.11
0.11
0.11
0.27
0.11
0.12
0.11
0.99
0.11
0.11
0.32
0.11
0.11
0.24
0.11
4.33
0.11
0.11
0.33
0.11
0.12
0.08
0.22
0.08
0.08
0.14
0.17
0.14
0.72
0.09
0.53
0.78
0.15
0.08
0.11
0.08
0.64
0.08
0.09
0.22
0.08
0.08
0.09
0.58
0.18
0.22
0.08
0.08
0.11
0.15
0.08
0.08
0.33
0.55
0.08
0.08
0.08
0.15
0.41
0.08
0.08
0.08
1.06
0.08
0.08
0.15
0.08
0.08
0.32
0.08
1.52
0.08
0.08
0.31
0.11
0.2
0.06
0.28
0.04
0.11
0.21
0.27
0.08
0.81
0.55
0.73
0.97
0.17
0.05
0.09
0.04
3.11
0.05
0.08
0.17
0.09
0.04
0.07
3.99
0.43
0.22
0.07
0.06
0.12
0.11
0.05
0.08
0.63
0.61
0.09
0.05
0.07
0.14
0.36
0.08
0.14
0.08
0.93
0.08
0.06
0.61
0.11
0.08
0.23
0.05
3.02
0.05
0.09
0.6
0.06
0.27
0.09
0.28
0.08
0.11
0.67
0.22
0.13
0.68
0.38
0.48
1.09
0.2
0.05
0.06
0.1
1.42
0.04
0.08
0.26
0.06
0.1
0.11
2.87
0.16
0.35
0.04
0.04
0.14
0.16
0.1
0.06
0.78
0.67
0.05
0.04
0.09
0.14
0.37
0.09
0.12
0.05
0.67
0.05
0.04
0.16
0.13
0.09
0.36
0.09
3.43
0.08
0.04
0.47
0.07
-0.06
0
0.12
0
0
0
0
-0.01
0
-0.3
-0.12
0.02
0
0
0
0
-0.28
0
0
-0.08
0
0
0
-0.4
0
0.04
0
0
-0.06
0
0
0
-0.22
-0.03
0
0
0
0
0.1
0
0
0
0.07
0
0
0
0
0
0.04
0
-0.15
0
0
0.07
-0.01
-0.07
0
0.08
0
-0.09
-0.12
0.06
0
-0.09
0.14
-0.17
0.01
0
0
0
0
0.4
0
0
-0.12
0
0
-0.25
0.16
0.24
0.05
0
0
0.03
0
0
0
-0.12
0.01
-0.16
0
-0.19
0
0.02
0
-0.13
0
-0.02
-0.16
0
0.35
0
0
0.08
0
-0.1
0
0
0.18
-0.28
0.05
-0.07
0.13
-0.22
0
0.39
0
-0.08
-0.13
-0.09
0
0.1
-0.02
0
0
-0.25
0.14
0
0
0.07
0
-0.19
0.02
-0.08
0
0.22
0
0
-0
0.07
0
0
0
0
0
0
-0.1
-0.01
0.05
0
-0.2
0
-0.03
0
0
-0.21
-0.11
0
0.13
0
0.01
-0.2
0
0
0
C-65
YPR035W
YPR036W
YPR037C
YPR040W
YPR041W
YPR042C
YPR043W
YPR044C
YPR047W
YPR048W
YPR051W
YPR052C
YPR053C
YPR057W
YPR058W
YPR060C
YPR061C
YPR062W
YPR063C
YPR065W
YPR066W
YPR067W
YPR069C
YPR072W
YPR073C
YPR074C
YPR075C
YPR079W
YPR080W
YPR081C
YPR082C
YPR084W
YPR085C
YPR086W
YPR088C
YPR091C
YPR093C
YPR094W
YPR098C
YPR100W
YPR101W
YPR102C
YPR103W
YPR106W
YPR107C
YPR108W
YPR109W
YPR110C
YPR113W
YPR114W
YPR115W
YPR117W
YPR118W
YPR119W
YPR120C
GLN1
VMA13
TIF5
RPL43A
MSF1
MAK3
NHP6A
BRR1
YMC1
ARO7
FCY1
ROX1
UBA3
SPE3
LTP1
TKL1
OPY2
TEF1
SUA7
SNT309
RPL11A
PRE2
ISR1
YTH1
RPN7
RPC40
PIS1
CLB2
CLB5
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
20
21
20
20
20
21
20
20
21
21
21
21
20
20
21
20
21
20
22
20
21
20
20
20
20
20
20
21
20
21
21
20
20
20
20
21
21
20
20
20
20
28
20
20
20
21
20
20
20
20
21
20
20
20
21
1.04
1.16
0.46
0.11
0.2
0.11
15.59
0.13
0.11
0.11
0.11
1.5
0.12
0.11
0.36
0.11
0.11
0.62
1.37
0.11
0.11
0.2
0.29
0.12
0.11
1.97
0.11
0.11
11.68
0.11
0.13
0.11
0.11
0.12
0.25
0.11
0.11
0.11
0.94
0.13
0.11
4.58
1.33
0.28
0.11
0.26
0.18
0.16
2.51
0.69
0.11
0.11
0.17
0.11
0.11
0.63
1.1
0.39
0.08
0.27
0.09
9.63
0.14
0.08
0.08
0.08
0.49
0.15
0.08
0.22
0.12
0.08
0.55
0.72
0.08
0.08
0.16
0.24
0.11
0.08
1.53
0.16
0.08
4.82
0.08
0.17
0.08
0.08
0.17
0.22
0.08
0.08
0.08
0.77
0.2
0.08
1.3
0.57
0.29
0.08
0.18
0.09
0.19
1.89
0.4
0.08
0.08
0.17
0.08
0.08
1.73
1.57
0.46
0.06
0.2
0.05
9.66
0.14
0.04
0.05
0.11
1.39
0.12
0.06
0.61
0.06
0.07
0.79
1.4
0.06
0.05
0.2
0.49
0.14
0.08
2.79
0.2
0.14
10.21
0.04
0.48
0.06
0.07
0.25
0.32
0.05
0.07
0.06
1.35
0.27
0.04
3.45
1.21
0.19
0.08
0.27
0.24
0.22
1.65
0.59
0.21
0.04
0.16
0.08
0.07
2.74
1.97
0.41
0.08
0.29
0.09
7.48
0.06
0.05
0.05
0.07
1.2
0.14
0.11
0.3
0.11
0.04
0.7
1.46
0.06
0.05
0.3
0.39
0.09
0.04
2.72
0.21
0.16
8.14
0.1
0.2
0.08
0.05
0.14
0.4
0.07
0.05
0.09
1.39
0.2
0.05
3.44
1.25
0.31
0.09
0.31
0.24
0.19
1.64
0.81
0.1
0.07
0.21
0.06
0.13
-0.02
-0.1
-0.07
0
0
0
-0.18
0
0
0
0
-0.21
0
0
0.05
0
0
-0.01
0
0
0
0
-0.03
0
0
-0.06
0
0
-0.13
0
0
0
0
-0.06
0
0
0
0
-0.1
0
0
-0.28
0
0
0
0
0
-0.01
-0.12
-0.2
0
0
0
0
0
0.19
-0.02
0.01
0
0
0
-0.13
-0.1
0
0
0
-0.08
-0.15
0
0.25
0
-0.31
0.07
-0.02
0
0
0
0.09
0
0
0.02
0.04
0.05
-0.1
0
0.21
0
0
0.22
0.03
-0.3
0
0
0.06
0.07
0
-0.01
-0.12
0
0
0.04
0
0.09
-0.09
0.03
-0.14
0
0
0
0
0.43
0.2
-0.1
0
0.01
-0.16
-0.22
0
0
0
0
-0.11
0
0
-0.09
0
0
0
0
0
0
0.07
0
0
0
0.03
0.13
0.12
-0.14
0
0
-0.17
0
0.03
0.05
0
0
-0.12
0.05
-0.01
0
-0.08
0.06
-0.04
0
0.1
0.17
0.04
-0.14
0.05
-0.13
0
-0.07
0
-0.21
C-66
YPR121W
YPR124W
YPR125W
YPR126C
YPR127W
YPR128C
YPR129W
YPR131C
YPR132W
YPR133C
YPR134W
YPR135W
YPR138C
YPR139C
YPR140W
YPR143W
YPR144C
YPR145W
YPR146C
YPR147C
YPR148C
YPR149W
YPR151C
YPR153W
YPR154W
YPR155C
YPR156C
YPR157W
YPR158W
YPR159W
YPR160W
YPR161C
YPR162C
YPR163C
YPR165W
YPR166C
YPR167C
YPR169W
YPR172W
YPR173C
YPR174C
YPR176C
YPR178W
YPR181C
YPR182W
YPR183W
YPR184W
YPR185W
YPR187W
YPR188C
YPR191W
YPR194C
YPR198W
YPR199C
YPR204W
CTR1
SCD6
RPS23B
MSS18
CTF4
MEP3
ASN1
NCE102
NCA2
KRE6
GPH1
SGV1
ORC4
TIF3
RHO1
MRP2
MET16
VPS4
BET2
PRP4
SEC23
SMX3
DPM1
APG13
RPO26
QCR2
SGE1
ARR1
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
20
20
21
20
20
21
20
21
40
20
21
20
21
20
20
21
21
20
20
20
20
20
20
21
20
20
20
21
20
20
21
20
21
20
20
20
20
20
20
20
21
20
21
21
21
20
21
20
20
21
21
21
20
20
20
0.11
0.11
0.11
0.11
0.16
0.17
0.11
0.11
3.53
0.11
0.11
0.11
0.27
0.13
0.17
0.11
0.11
0.46
0.17
0.24
0.14
5.06
0.11
0.11
0.27
0.11
0.41
0.11
0.11
0.37
0.55
0.11
0.11
0.29
1.57
0.16
0.11
0.11
0.22
0.11
0.11
0.29
0.11
0.33
0.22
0.75
0.11
0.11
0.23
0.14
0.51
0.11
0.14
0.14
0.48
0.08
0.08
0.09
0.09
0.18
0.13
0.08
0.08
4.34
0.09
0.08
0.08
0.26
0.08
0.19
0.08
0.11
0.39
0.16
0.25
0.08
1.28
0.08
0.08
0.28
0.08
0.3
0.12
0.08
0.46
0.28
0.08
0.08
0.24
0.41
0.09
0.08
0.08
0.21
0.08
0.08
0.18
0.08
0.2
0.24
0.43
0.08
0.08
0.15
0.08
0.22
0.08
0.11
0.1
0.36
0.06
0.06
0.2
0.07
0.16
0.13
0.08
0.06
5.31
0.1
0.05
0.06
0.38
0.14
0.14
0.05
0.11
0.96
0.33
0.45
0.23
3.75
0.04
0.06
0.42
0.06
0.54
0.12
0.05
0.84
0.68
0.04
0.07
0.21
1.85
0.25
0.06
0.05
0.27
0.09
0.07
0.29
0.07
0.39
0.46
1.23
0.04
0.04
0.26
0.1
0.46
0.22
0.16
0.14
0.72
0.08
0.04
0.15
0.04
0.79
0.22
0.11
0.07
2.72
0.13
0.09
0.07
0.27
0.1
0.26
0.07
0.08
0.47
0.39
0.38
0.23
4.37
0.06
0.06
0.52
0.06
0.95
0.53
0.05
0.69
0.65
0.13
0.09
0.27
1.32
0.18
0.05
0.09
0.58
0.16
0.04
0.23
0.07
0.37
0.36
0.7
0.11
0.08
0.19
0.07
0.35
0.08
0.28
0.15
0.81
0
0
0
0
0
0
0
0
0.01
0
0
0
0
0
0
0
-0.07
0
0
0.03
0
-0.44
0
0
0
0
0
0
0
0
-0.13
0
0
0
-0.4
0
0
0
0
0
0
0
0
-0.1
-0.04
-0.16
0
0
0
-0.11
-0.22
0
0
0
0
0
0
0.08
0
-0.03
-0.22
0
0
0.05
0
0
0
0
-0.01
-0.15
0
-0.04
0.35
0.11
0.28
0.02
-0.09
0
-0.28
0.07
0
0
0
0
0.26
0.21
0
-0.26
-0.19
0.06
-0.03
0
0
0.01
0
-0.33
-0.06
0
0
0.13
0.18
0
0
0.04
-0.19
0.24
0
-0.02
-0.19
0.05
0
0
0.13
0
0.47
-0.08
0
-0.2
-0.14
0
-0.08
0
-0.05
0
0.16
-0.26
0
0.06
0.17
0.18
0.12
0.03
0
0
0.22
0
0.24
0.47
0
0.12
0.09
-0.03
0
-0.1
-0.08
0
0
-0.19
0.26
0.09
0
-0.11
0
0
0.1
-0.01
0
0
-0.11
-0.34
-0.13
0
0.14
0
0.1
C-67
References
1.
Wenzel, T.J., Teunissen, A.W. and de Steensma, H.Y., PDA1 mRNA: a
standard for quantitation of mRNA in Saccharomyces cerevisiae superior to ACT1
mRNA, Nucleic Acids Research, 23(5), 883-884, 1995.
2.
Iyer, V. and Struhl, K., Absolute mRNA levels and transcription initiation rates
in Saccharomyces cerevisiae., Proceedings of the National Academy of Sciences of the
United States of America, 93, 5208-5212, 1996.
C-68
Appendix D
Transcripts Not Detected
in Four Saccharomyces cerevisiae Cultures
A number of ORFs were not detected, for one of two reasons. The first possibility
is that probe pairs corresponding to the undetected ORF were simply not on the
microarray. Since the list of ORFs in S. cerevisiae, as represented by the Saccharomyces
Genome Database (SGD) has changed over time, since the design of the Affymetrix
microarrays. The following ORFs were not detected for this reason.
ORFs Not Represented on the Affymetrix Yeast Microarrays Used
ORF ID
YAL064C-A
YAL064W-B
YDL045W-A
YDL134C-A
YDL184C
YFL002W-A
YGL226C-A
YHR005C-A
YHR021W-A
YIL009C-A
YIL017C
YIL071C
YIL174W
YKR035W-A
YLR312W-A
YLR337C
YLR391W-A
YLR438C-A
YMR307W
YNL338W
YOR008C-A
YPR133W-A
Gene Name
MRP10
RPL47B
RPL41A
OST5
MRS11
ECM12
EST3
FTI1
MRPL15
VRP1
SSR1
SMX4
GAS1
KIM1
TOM5
Detection thresholds were calculated as described in Chapter 3. The following
table shows the detection thresholds applied for each microarray assay.
Detection Thresholds for each Microarray Assay
D-2
a
α
gal
heat
microarray “A”
0.086
0.039
0.069
0.091
microarray “B”
0.069
0.072
0.066
0.046
microarray “C”
0.347
0.089
0.260
0.236
microarray “D”
0.105
0.082
0.044
0.045
These detection thresholds range from 0.2 to greater than 1 transcript per cell,
based on the rough correspondence of absolute abundance units to number of transcripts
per cell described in Appendix C.
Listed below are those ORFs with absolute abundance measures that were below
detection thresholds in all four conditions, and which were undetectably changed between
conditions. These ORFs have been split into four lists, one for each microarray type.
D-3
ORFs not detected in any of four cultures on microarray ‘A’.
YAL001C
YAL002W
YAL004W
YAL010C
YAL011W
YAL013W
YAL015C
YAL018C
YAL020C
YAL024C
YAL025C
YAL026C
YAL028W
YAL029C
YAL031C
YAL032C
YAL034C
YAL034W-A
YAL035C-A
YAL037W
YAL041W
YAL043C-A
YAL047C
YAL048C
YAL058C-A
YAL058W
YAL059W
YAL064W
YAL065C
YAL065C-A
YAL066W
YAL067C
YAL069W
YAR002W
YAR008W
YAR014C
YAR018C
YAR019C
YAR029W
YAR030C
YAR031W
YAR037W
YAR040C
YAR043C
YAR044W
YAR047C
YAR050W
TFC3
VPS8
MDM10
DEP1
NTG1
ATS1
LTE1
MAK16
DRS2
MYO4
FUN21
FUN20
FUN19
CDC24
SPI6
CNE1
ECM1
FLO9
SEO1
SEN34
KIN3
CDC15
OSH1
FLO1
YBR184W
YBR186W
YBR190W
YBR192W
YBR193C
YBR194W
YBR195C
YBR197C
YBR200W
YBR202W
YBR203W
YBR204C
YBR208C
YBR209W
YBR215W
YBR216C
YBR217W
YBR219C
YBR223C
YBR224W
YBR225W
YBR226C
YBR228W
YBR229C
YBR232C
YBR233W
YBR236C
YBR237W
YBR238C
YBR240C
YBR245C
YBR247C
YBR250W
YBR251W
YBR255W
YBR257W
YBR259W
YBR266C
YBR267W
YBR270C
YBR271W
YBR272C
YBR273C
YBR275C
YBR277C
YBR278W
YBR281C
MEL1
PCH2
RIM2
MED8
MSI1
BEM1
CDC47
DUR1,2
HPC2
ROT2
ABD1
PRP5
THI2
ISW1
ENP1
MRPS5
POP4
RIF1
DPB3
YDL017W
YDL019C
YDL020C
YDL021W
YDL023C
YDL025C
YDL026W
YDL027C
YDL028C
YDL030W
YDL031W
YDL032W
YDL034W
YDL035C
YDL036C
YDL037C
YDL041W
YDL043C
YDL044C
YDL045C
YDL050C
YDL056W
YDL058W
YDL060W
YDL062W
YDL063C
YDL065C
YDL068W
YDL069C
YDL070W
YDL071C
YDL073W
YDL074C
YDL077C
YDL079C
YDL087C
YDL088C
YDL089W
YDL090C
YDL091C
YDL094C
YDL096C
YDL098C
YDL099W
YDL101C
YDL104C
YDL105W
CDC7
RPN4
GPM2
MPS1
PRP9
PRP11
MTF2
FAD1
MBP1
USO1
PEX19
CBS1
BDF2
VAM6
MRK1
EXM2
ASM4
RAM1
DUN1
QRI7
QRI2
YDR159W
YDR162C
YDR164C
YDR168W
YDR169C
YDR173C
YDR175C
YDR176W
YDR179C
YDR179W-A
YDR180W
YDR181C
YDR183W
YDR184C
YDR186C
YDR189W
YDR191W
YDR192C
YDR193W
YDR195W
YDR197W
YDR198C
YDR199W
YDR200C
YDR201W
YDR202C
YDR203W
YDR206W
YDR207C
YDR211W
YDR213W
YDR215C
YDR217C
YDR218C
YDR219C
YDR221W
YDR223W
YDR227W
YDR228C
YDR229W
YDR230W
YDR237W
YDR240C
YDR241W
YDR243C
YDR244W
YDR246W
SAC3
NBP2
SEC1
CDC37
STB3
ARG82
NGG1
SCC2
SAS4
ATC1
SLY1
HST4
NUP42
REF2
CBS2
UME6
GCD6
RAD9
SPR28
SIR4
PCF11
MRPL7
SNU56
PRP28
PEX5
D-4
YAR052C
YAR053W
YAR060C
YAR061W
YAR062W
YAR064W
YAR068W
YAR069C
YAR070C
YAR074C
YBL004W
YBL005W-A
YBL005W-B
YBL008W
YBL009W
YBL010C
YBL012C
YBL013W
YBL014C
YBL018C
YBL019W
YBL020W
YBL023C
YBL028C
YBL029W
YBL031W
YBL035C
YBL036C
YBL037W
YBL044W
YBL046W
YBL052C
YBL054W
YBL059W
YBL060W
YBL061C
YBL062W
YBL065W
YBL066C
YBL067C
YBL070C
YBL073W
YBL074C
YBL075C
YBL079W
YBL080C
YBL086C
YBL088C
YBL090W
YBL093C
HIR1
RRN6
ETH1
RFT1
MCM2
SHE1
POL12
SAS3
SKT5
SEF1
UBP13
AAR2
SSA3
NUP170
PET112
TEL1
MRP21
ROX3
YBR284W
YBR285W
YBR289W
YBR292C
YBR294W
YBR295W
YBR296C
YBR298C
YBR299W
YBR300C
YCL003W
YCL004W
YCL005W
YCL006C
YCL007C
YCL010C
YCL012W
YCL013W
YCL014W
YCL020W
YCL021W
YCL022C
YCL023C
YCL024W
YCL026C
YCL031C
YCL032W
YCL041C
YCL046W
YCL048W
YCL051W
YCL052C
YCL053C
YCL054W
YCL055W
YCL058C
YCL059C
YCL060C
YCL061C
YCL062W
YCL063W
YCL065W
YCL068C
YCL069W
YCL074W
YCL075W
YCL076W
YCLX01W
YCLX02C
YCLX03C
SNF5
SUL1
PCA1
MAL31
MAL32
PEL1
PEL1
CWH36
BUD3
RRP7
STE50
LRE1
PBN1
KAR4
KRR1
YDL106C
YDL107W
YDL108W
YDL113C
YDL114W
YDL115C
YDL116W
YDL117W
YDL118W
YDL119C
YDL121C
YDL127W
YDL129W
YDL138W
YDL139C
YDL146W
YDL148C
YDL149W
YDL150W
YDL151C
YDL152W
YDL154W
YDL156W
YDL159W
YDL161W
YDL162C
YDL163W
YDL164C
YDL166C
YDL167C
YDL169C
YDL170W
YDL172C
YDL175C
YDL176W
YDL177C
YDL183C
YDL186W
YDL187C
YDL189W
YDL194W
YDL196W
YDL197C
YDL199C
YDL203C
YDL206W
YDL207W
YDL209C
YDL210W
YDL211C
GRF10
MSS2
KIN28
NUP84
PCL2
RGT2
RPC53
MSH5
STE7
CDC9
NRP1
UGX2
UGA3
SNF3
ASF2
GLE1
UGA4
YDR249C
YDR250C
YDR251W
YDR253C
YDR254W
YDR255C
YDR256C
YDR257C
YDR259C
YDR263C
YDR265W
YDR268W
YDR269C
YDR270W
YDR273W
YDR274C
YDR277C
YDR278C
YDR279W
YDR281C
YDR282C
YDR283C
YDR285W
YDR288W
YDR289C
YDR290W
YDR295C
YDR299W
YDR305C
YDR310C
YDR311W
YDR312W
YDR313C
YDR314C
YDR316W
YDR317W
YDR324C
YDR325W
YDR326C
YDR327W
YDR330W
YDR331W
YDR332W
YDR333C
YDR334W
YDR336W
YDR340W
YDR344C
YDR351W
YDR355C
PAM1
MET32
CHL4
CTA1
RMS1
YAP6
DIN7
PEX10
MSW1
CCC2
MTH1
GCN2
ZIP1
BFR2
HNT2
SUM1
TFB1
SSF2
GPI8
SBE2
D-5
YBL094C
YBL095W
YBL096C
YBL097W
YBL098W
YBL100C
YBL101W-B
YBL104C
YBL105C
YBL107C
YBL108W
YBL109W
YBL111C
YBR002C
YBR003W
YBR007C
YBR012C
YBR017C
YBR021W
YBR027C
YBR030W
YBR032W
YBR033W
YBR040W
YBR044C
YBR045C
YBR047W
YBR051W
YBR055C
YBR057C
YBR059C
YBR060C
YBR064W
YBR065C
YBR074W
YBR075W
YBR076W
YBR081C
YBR089W
YBR094W
YBR095C
YBR097W
YBR098W
YBR099C
YBR100W
YBR102C
YBR103W
YBR104W
YBR110W
YBR112C
BRN1
PKC1
COQ1
KAP104
FUR4
FIG1
GIP1
PRP6
MUM2
RRR1
ECM2
ECM8
SPT7
VPS15
YMC2
ALG1
CYC8
YCLX04W
YCLX05C
YCLX07W
YCLX08C
YCLX09W
YCLX10C
YCLX11W
YCR001W
YCR003W
YCR006C
YCR007C
YCR010C
YCR014C
YCR015C
YCR016W
YCR019W
YCR022C
YCR024C
YCR025C
YCR026C
YCR027C
YCR028C
YCR032W
YCR033W
YCR038C
YCR041W
YCR042C
YCR045C
YCR049C
YCR050C
YCR054C
YCR055C
YCR056W
YCR058C
YCR063W
YCR064C
YCR066W
YCR068W
YCR073C
YCR074C
YCR081W
YCR085W
YCR086W
YCR089W
YCR091W
YCR092C
YCR093W
YCR094W
YCR095C
YCR097WA
FRM2
MRPL32
POL4
MAK32
FEN2
BPH1
BUD5
TSM1
CTR86
PWP2
PWP2
RAD18
SSK22
SRB8
FIG2
KIN82
MSH3
CDC39
CDC50
A1
YDL214C
YDL216C
YDL218W
YDL219W
YDL221W
YDL225W
YDL227C
YDL231C
YDL233W
YDL238C
YDL239C
YDL240W
YDL242W
YDL243C
YDL244W
YDL245C
YDL247W
YDL248W
YDR004W
YDR008C
YDR010C
YDR013W
YDR014W
YDR015C
YDR018C
YDR021W
YDR022C
YDR026C
YDR028C
YDR029W
YDR030C
YDR034C
YDR040C
YDR042C
YDR048C
YDR049W
YDR052C
YDR053W
YDR054C
YDR057W
YDR058C
YDR060W
YDR061W
YDR065W
YDR066C
YDR068W
YDR069C
YDR075W
YDR076W
YDR078C
HO
LRG1
HXT15
COS7
RAD57
FAL1
CIS1
REG1
RAD28
LYS14
ENA1
DBF4
CDC34
TGL2
DOS2
DOA4
PPH3
RAD55
YDR356W
YDR359C
YDR360W
YDR361C
YDR363W
YDR366C
YDR369C
YDR370C
YDR371W
YDR372C
YDR374C
YDR379W
YDR380W
YDR383C
YDR386W
YDR393W
YDR396W
YDR401W
YDR402C
YDR403W
YDR405W
YDR406W
YDR412W
YDR413C
YDR414C
YDR416W
YDR417C
YDR419W
YDR420W
YDR421W
YDR425W
YDR426C
YDR428C
YDR430C
YDR431W
YDR437W
YDR438W
YDR439W
YDR440W
YDR442W
YDR443C
YDR444W
YDR445C
YDR446W
YDR448W
YDR449C
YDR455C
YDR458C
YDR460W
YDR467C
NUF1
ESC2
XRS2
RGA2
DIT1
MRP20
PDR15
ERD1
SYF1
RAD30
HKR1
LRS4
PCH1
SSN2
ECM11
ADA2
TFB3
D-6
YBR113W
YBR114W
YBR119W
YBR120C
YBR124W
YBR128C
YBR130C
YBR131W
YBR134W
YBR136W
YBR138C
YBR141C
YBR142W
YBR144C
YBR148W
YBR150C
YBR152W
YBR153W
YBR155W
YBR156C
YBR161W
YBR167C
YBR168W
YBR170C
YBR172C
YBR174C
YBR176W
YBR178W
YBR179C
YBR180W
YBR182C
RAD16
MUD1
CBP6
ESR1
HDR1
MAK5
YSW1
RIB7
CNS1
RPP2
NPL4
SMY2
ECM31
FZO1
SMP1
YCR097WB
YCR098C
YCR099C
YCR100C
YCR101C
YCR102C
YCR103C
YCR105W
YCR106W
YCR107W
YCRX01W
YCRX02C
YCRX03C
YCRX04W
YCRX05W
YCRX06W
YCRX09C
YCRX10W
YCRX11W
YCRX12W
YCRX14W
YCRX15W
YCRX16C
YCRX18C
YCRX20C
YDL002C
YDL003W
YDL006W
YDL011C
YDL013W
YDL016C
A1
GIT1
NHP10
MCD1
PTC1
HEX3
YDR080W
YDR081C
YDR083W
YDR085C
YDR087C
YDR088C
YDR089W
YDR095C
YDR096W
YDR102C
YDR104C
YDR106W
YDR108W
YDR109C
YDR110W
YDR112W
YDR113C
YDR114C
YDR118W
YDR122W
YDR124W
YDR125C
YDR131C
YDR132C
YDR135C
YDR136C
YDR137W
YDR145W
YDR149C
YDR150W
YDR157W
VPS41
PDC2
AFR1
RRP1
SLU7
GIS1
ARP10
GSG1
FOB1
PDS1
APC4
KIN1
ECM18
YCF1
RGP1
TAF61
NUM1
YDR469W
YDR473C
YDR475C
YDR478W
YDR480W
YDR484W
YDR485C
YDR488C
YDR491C
YDR495C
YDR496C
YDR499W
YDR501W
YDR507C
YDR509W
YDR515W
YDR521W
YDR522C
YDR523C
YDR524C
YDR525W
YDR526C
YDR527W
YDR528W
YDR530C
YDR532C
YDR535C
YDR536W
YDR537C
YDR540C
YDR544C
SNM1
DIG2
SAC2
PAC11
VPS3
GIN4
SLF1
SPS2
SPS1
APA2
STL1
D-7
ORFs not detected in any of four cultures on microarray ‘B’.
YEL003W
YEL004W
YEL005C
YEL008W
YEL010W
YEL014C
YEL016C
YEL018W
YEL019C
YEL022W
YEL023C
YEL025C
YEL028W
YEL029C
YEL030W
YEL032W
YEL033W
YEL035C
YEL039C
YEL041W
YEL044W
YEL045C
YEL048C
YEL053C
YEL055C
YEL061C
YEL062W
YEL064C
YEL065W
YEL067C
YEL068C
YEL069C
YEL070W
YEL072W
YEL076C
YEL076C-A
YEL076W-C
YER002W
YER006W
YER007W
YER008C
YER013W
YER015W
YER018C
YER032W
YER033C
PFD2
YEA4
MMS21
ECM10
MCM3
UTR5
CYC7
MAK10
POL5
CIN8
NPR2
HXT13
PAC2
SEC3
PRP22
FAA2
FIR1
YGL033W
YGL034C
YGL041C
YGL042C
YGL043W
YGL046W
YGL049C
YGL050W
YGL052W
YGL059W
YGL060W
YGL061C
YGL063W
YGL064C
YGL065C
YGL066W
YGL069C
YGL071W
YGL072C
YGL073W
YGL074C
YGL075C
YGL083W
YGL085W
YGL086W
YGL090W
YGL092W
YGL093W
YGL094C
YGL095C
YGL098W
YGL108C
YGL109W
YGL110C
YGL113W
YGL116W
YGL118C
YGL120C
YGL129C
YGL131C
YGL132W
YGL133W
YGL136C
YGL138C
YGL139W
YGL140C
HOP2
DST1
TIF4632
DUO1
PUS2
ALG2
RCS1
HSF1
SCY1
MAD1
NUP145
PAN2
VPS45
CDC20
PRP43
YGR140W
YGR142W
YGR145W
YGR150C
YGR151C
YGR152C
YGR153W
YGR154C
YGR156W
YGR158C
YGR160W
YGR164W
YGR166W
YGR168C
YGR170W
YGR171C
YGR176W
YGR177C
YGR179C
YGR186W
YGR187C
YGR188C
YGR190C
YGR196C
YGR198W
YGR202C
YGR205W
YGR208W
YGR212W
YGR213C
YGR219W
YGR221C
YGR223C
YGR225W
YGR226C
YGR228W
YGR230W
YGR233C
YGR236C
YGR237C
YGR238C
YGR239C
YGR242W
YGR245C
YGR247W
YGR249W
CBF2
RSR1
MTR3
KRE11
PSD2
MSM1
ATF2
TFG1
HGH1
BUB1
PCT1
SER2
RTA1
PHO81
KEL2
MGA1
YHR177W
YHR178W STB5
YHR182W
YHR184W SSP1
YHR185C
YHR186C
YHR189W
YHR196W
YHR197W
YHR204W
YHR207C
YHR209W
YHR210C
YHR211W
YHR212C
YHR213W
YHR214W
YHR214W-A
YHR216W
YHR218W
YIL002C
INP51
YIL003W
YIL004C
BET1
YIL005W
YIL006W
YIL012W
YIL013C
PDR11
YIL016W SNL1
YIL017W
YIL019W
YIL024C
YIL025C
YIL026C
IRR1
YIL028W
YIL029C
YIL031W SMT4
YIL032C
YIL035C
CKA1
YIL037C
YIL054W
YIL055C
YIL057C
YIL058W
YIL060W
YIL061C
SNP1
YIL063C
YRB2
D-8
YER038C
YER040W
YER041W
YER044C-A
YER047C
YER051W
YER054C
YER059W
YER065C
YER066C-A
YER070W
YER071C
YER075C
YER077C
YER085C
YER093C
YER096W
YER097W
YER098W
YER101C
YER104W
YER105C
YER108C
YER109C
YER110C
YER111C
YER116C
YER119C-A
YER123W
YER128W
YER129W
YER132C
YER135C
YER137C
YER139C
YER140W
YER142C
YER144C
YER147C
YER149C
YER153C
YER161C
YER162C
YER168C
YER169W
YER171W
YER172C
YER173W
YER179W
YER180C
GLN3
MEI4
SAP1
GIP2
PCL6
ICL1
RNR1
PTP3
UBP9
AST2
NUP157
FLO8
FLO8
KAP123
SWI4
YCK3
PAK1
PMD1
MAG1
UBP5
PEA2
PET122
SPT2
RAD4
CCA1
RPH1
RAD3
BRR2
RAD24
DMC1
ISC10
YGL144C
YGL145W
YGL146C
YGL149W
YGL150C
YGL152C
YGL158W
YGL163C
YGL164C
YGL165C
YGL168W
YGL169W
YGL170C
YGL171W
YGL174W
YGL175C
YGL176C
YGL177W
YGL180W
YGL182C
YGL183C
YGL185C
YGL190C
YGL192W
YGL194C
YGL201C
YGL204C
YGL205W
YGL211W
YGL212W
YGL214W
YGL217C
YGL218W
YGL222C
YGL226W
YGL227W
YGL228W
YGL229C
YGL230C
YGL232W
YGL233W
YGL235W
YGL237C
YGL239C
YGL240W
YGL241W
YGL243W
YGL246C
YGL249W
YGL250W
TIP20
RCK1
RAD54
SUA5
ROK1
SAE2
APG1
CDC55
IME4
HOS2
MCM6
POX1
VAM7
TIN1
SAP4
SEC15
HAP2
DOC1
ZIP2
YGR251W
YGR259C
YGR261C
YGR265W
YGR266W
YGR269W
YGR271W
YGR272C
YGR273C
YGR274C
YGR276C
YGR278W
YGR280C
YGR283C
YGR287C
YGR288W
YGR289C
YGR290W
YGR291C
YGR292W
YGR293C
YHL005C
YHL007C
YHL009C
YHL010C
YHL012W
YHL013C
YHL014C
YHL016C
YHL018W
YHL022C
YHL023C
YHL030W
YHL036W
YHL037C
YHL038C
YHL041W
YHL042W
YHL043W
YHL045W
YHL047C
YHR002W
YHR006W
YHR011W
YHR014W
YHR015W
YHR023W
YHR029C
YHR031C
YHR035W
APL6
TAF145
RNH70
AGT1
MAL1
STE20
YAP3
YLF2
DUR3
SPO11
ECM29
MUP3
CBP2
ECM34
STP2
SPO13
MIP6
MYO1
YIL068C
YIL071W
YIL072W
YIL073C
YIL079C
YIL080W
YIL082W
YIL082W-A
YIL084C
YIL086C
YIL089W
YIL091C
YIL092W
YIL095W
YIL096C
YIL097W
YIL100W
YIL102C
YIL103W
YIL105C
YIL107C
YIL110W
YIL112W
YIL120W
YIL122W
YIL126W
YIL127C
YIL128W
YIL130W
YIL132C
YIL138C
YIL139C
YIL141W
YIL143C
YIL144W
YIL146C
YIL147C
YIL149C
YIL150C
YIL151C
YIL153W
YIL159W
YIL161W
YIL163C
YIL166C
YIL167W
YIL168W
YIL171W
YIL172C
YIL173W
SEC6
HOP1
SDS3
PRK1
PFK26
STH1
MET18
TPM2
REV7
SSL2
TID3
ECM37
SLN1
DNA43
RRD1
BNR1
SDL1
HXT12
D-9
YER181C
YER182W
YER184C
YER187W
YER188W
YER189W
YFL001W
YFL003C
YFL004W
YFL008W
YFL011W
YFL012W
YFL013W-A
YFL015C
YFL023W
YFL024C
YFL025C
YFL029C
YFL032W
YFL033C
YFL035C
YFL036W
YFL040W
YFL042C
YFL046W
YFL047W
YFL049W
YFL050C
YFL051C
YFL052W
YFL053W
YFL055W
YFL056C
YFL060C
YFL061W
YFL063W
YFL064C
YFL065C
YFL067W
YFL068W
YFR002W
YFR005C
YFR008W
YFR012W
YFR013W
YFR014C
YFR016C
YFR019W
YFR023W
YFR027W
DEG1
MSH4
SMC1
HXT10
BST1
CAK1
RIM15
MOB2
RPO41
ALR2
DAK2
AGP3
SNO3
NIC96
CMK1
FAB1
PES4
YGL251C
YGL254W
YGL257C
YGL258W
YGL259W
YGL260W
YGL262W
YGL263W
YGR002C
YGR003W
YGR005C
YGR006W
YGR012W
YGR013W
YGR016W
YGR018C
YGR022C
YGR025W
YGR030C
YGR035C
YGR039W
YGR040W
YGR042W
YGR045C
YGR046W
YGR047C
YGR048W
YGR051C
YGR053C
YGR056W
YGR057C
YGR058W
YGR059W
YGR064W
YGR066C
YGR067C
YGR068C
YGR070W
YGR071C
YGR072W
YGR081C
YGR087C
YGR089W
YGR091W
YGR092W
YGR093W
YGR096W
YGR098C
YGR099W
YGR100W
HFM1
FZF1
YPS5
COS12
TFG2
PRP18
SNU71
KSS1
TFC4
UFD1
RSC1
LST7
SPR3
ROM1
UPF3
PDC6
PRP31
DBF2
ESP1
TEL2
MDR1
YHR036W
YHR038W KIM4
YHR040W
YHR044C DOG1
YHR047C AAP1'
YHR048W
YHR049C-A
YHR058C MED6
YHR059W
YHR060W VMA22
YHR061C GIC1
YHR066W SSF1
YHR073W
YHR075C
YHR077C NMD2
YHR079BC SAE3
YHR079C IRE1
YHR080C
YHR081W
YHR085W
YHR088W
YHR090C NBN1
YHR093W AHT1
YHR095W
YHR099W TRA1
YHR101C BIG1
YHR102W NRK1
YHR103W SBE22
YHR105W
YHR109W
YHR111W
YHR117W TOM71
YHR118C ORC6
YHR119W SET1
YHR120W MSH1
YHR121W
YHR122W
YHR124W NDT80
YHR125W
YHR126C
YHR127W HSN1
YHR129C ARP1
YHR130C
YHR131C
YHR134W
YHR136C SPL2
YHR137W ARO9
YHR139C-A
YHR144C DCD1
YHR148W
YIL175W
YIR001C
YIR002C
YIR004W
YIR005W
YIR008C
YIR009W
YIR010W
YIR014W
YIR015W
YIR017C
YIR020C
YIR023W
YIR025W
YIR027C
YIR029W
YIR030C
YIR031C
YIR032C
YIR033W
YIR039C
YIR040C
YIR042C
YJL003W
YJL005W
YJL006C
YJL007C
YJL009W
YJL010C
YJL013C
YJL018W
YJL019W
YJL022W
YJL023C
YJL024C
YJL025W
YJL028W
YJL029C
YJL031C
YJL033W
YJL035C
YJL036W
YJL037W
YJL038C
YJL039C
YJL043W
YJL046W
YJL047C
YJL049W
YJL050W
DJP1
PRI1
MSL1
MET28
DAL81
DAL1
DAL2
DCG1
DAL7
DAL3
MGA2
YPS6
CYR1
CTK2
MAD3
PET130
APS3
RRN7
BET4
HCA4
MTR4
D-10
YFR029W
YFR032C
YFR035C
YFR038W
YFR039C
YFR040W
YFR043C
YFR046C
YFR054C
YFR055W
YFR056C
YFR057W
YGL005C
YGL007W
YGL014W
YGL015C
YGL016W
YGL017W
YGL018C
YGL025C
YGL027C
PTR3
SAP155
PDR6
ATE1
JAC1
PGD1
CWH41
YGR103W
YGR104C
YGR107W
YGR109C
YGR112W
YGR113W
YGR114C
YGR115C
YGR116W
YGR117C
YGR119C
YGR120C
YGR122W
YGR123C
YGR128C
YGR129W
YGR130C
YGR131W
YGR134W
YGR139W
SRB5
CLB6
SHY1
DIF1
SPT6
NUP57
PPT1
SYF2
YHR149C
YHR150W
YHR151C
YHR152W
YHR153C
YHR154W
YHR155W
YHR156C
YHR157W
YHR158C
YHR159W
YHR160C
YHR164C
YHR165C
YHR166C
YHR167W
YHR168W
YHR169W
YHR172W
YHR173C
SPO12
SPO16
ESC4
REC104
KEL1
DNA2
PRP8
CDC23
DBP8
SPC97
YJL051W
YJL054W
YJL056C
YJL058C
YJL059W
YJL064W
YJL067W
YJL069C
YJL070C
YJL071W
YJL072C
YJL073W
YJL074C
YJL075C
YJL076W
YJL077C
YJL084C
YJL085W
YJL086C
YJL087C
TIM54
ZAP1
YHC3
ARG2
JEM1
SMC3
ESC5
EXO70
TRL1
D-11
ORFs not detected in any of four cultures on microarray ‘C’.
YJL089W
YJL090C
YJL092W
YJL093C
YJL094C
YJL095W
YJL096W
YJL098W
YJL099W
YJL100W
YJL101C
YJL102W
YJL103C
YJL104W
YJL105W
YJL106W
YJL107C
YJL108C
YJL109C
YJL110C
YJL112W
YJL113W
YJL114W
YJL115W
YJL118W
YJL119C
YJL120W
YJL122W
YJL123C
YJL125C
YJL126W
YJL127C
YJL128C
YJL129C
YJL131C
YJL132W
YJL135W
YJL137C
YJL139C
YJL140W
YJL141C
YJL142C
YJL144W
YJL145W
YJL146W
YJL147C
YJL148W
SIP4
DPB11
HPR5
TOK1
BCK1
CHS6
GSH1
MEF2
IME2
GZF3
ASF1
GCD14
NIT2
SPT10
PBS2
TRK1
GLG2
YUR1
RPB4
YAK1
IDS2
RPA34
YKL070W
YKL071W
YKL072W
YKL073W
YKL074C
YKL075C
YKL076C
YKL078W
YKL079W
YKL082C
YKL083W
YKL088W
YKL089W
YKL090W
YKL092C
YKL093W
YKL095W
YKL097C
YKL098W
YKL099C
YKL101W
YKL102C
YKL105C
YKL106W
YKL107W
YKL108W
YKL109W
YKL110C
YKL111C
YKL112W
YKL113C
YKL114C
YKL115C
YKL116C
YKL118W
YKL119C
YKL121W
YKL123W
YKL124W
YKL125W
YKL129C
YKL130C
YKL131W
YKL132C
YKL133C
YKL134C
YKL135C
STB6
LHS1
MUD2
SMY1
MIF2
BUD2
MBR1
YJU2
HSL1
AAT1
HAP4
KTI12
ABF1
RAD27
APN1
VPH2
SSH4
RRN3
MYO3
APL2
YLR055C
YLR057W
YLR062C
YLR063W
YLR067C
YLR068W
YLR070C
YLR071C
YLR072W
YLR077W
YLR080W
YLR082C
YLR084C
YLR085C
YLR086W
YLR087C
YLR090W
YLR091W
YLR092W
YLR094C
YLR096W
YLR097C
YLR098C
YLR101C
YLR102C
YLR103C
YLR105C
YLR106C
YLR107W
YLR108C
YLR111W
YLR114C
YLR115W
YLR116W
YLR117C
YLR119W
YLR122C
YLR123C
YLR124W
YLR125W
YLR126C
YLR127C
YLR128W
YLR131C
YLR135W
YLR136C
YLR137W
SPT8
PET309
RGR1
ARP6
SMC4
XDJ1
SUL2
KIN2
CHA4
APC9
CDC45
SEN2
CFT2
MSL5
SRN2
APC2
ACE2
TIS11
YLR444C
YLR445W
YLR446W
YLR450W
YLR451W
YLR452C
YLR453C
YLR454W
YLR455W
YLR456W
YLR457C
YLR458W
YLR460C
YLR462W
YLR463C
YLR464W
YLR465C
YML002W
YML003W
YML005W
YML006C
YML007W
YML011C
YML013C-A
YML013W
YML015C
YML016C
YML017W
YML020W
YML021C
YML023C
YML032C
YML032C-A
YML033W
YML034W
YML035C
YML035C-A
YML036W
YML037C
YML038C
YML041C
YML042W
YML043C
YML046W
YML047C
YML048W-A
YML049C
HMG2
LEU3
SST2
RIF2
NBP1
YAP1
TAF40
PPZ1
PSP2
UNG1
RAD52
AMD1
CAT2
RRN11
PRP39
RSE1
D-12
YJL149W
YJL150W
YJL154C
YJL155C
YJL156C
YJL160C
YJL161W
YJL162C
YJL163C
YJL165C
YJL168C
YJL169W
YJL170C
YJL172W
YJL175W
YJL176C
YJL179W
YJL180C
YJL181W
YJL182C
YJL183W
YJL184W
YJL185C
YJL186W
YJL187C
YJL188C
YJL193W
YJL194W
YJL195C
YJL197W
YJL198W
YJL200C
YJL201W
YJL202C
YJL203W
YJL204C
YJL206C
YJL207C
YJL208C
YJL209W
YJL211C
YJL212C
YJL213W
YJL214W
YJL215C
YJL216C
YJL218W
YJL219W
YJL220W
YJL221C
VPS35
FBP26
SSY5
HAL5
SET2
ASG7
CPS1
SWI3
PFD1
ATP12
MNN11
SWE1
CDC6
UBP12
ECM25
PRP21
NUC1
CBP1
HXT8
HXT9
FSP2
YKL136W
YKL137W
YKL138C
YKL139W
YKL143W
YKL147C
YKL149C
YKL153W
YKL154W
YKL155C
YKL158W
YKL159C
YKL161C
YKL162C
YKL166C
YKL168C
YKL169C
YKL171W
YKL173W
YKL176C
YKL177W
YKL179C
YKL183W
YKL187C
YKL188C
YKL189W
YKL193C
YKL194C
YKL195W
YKL197C
YKL198C
YKL200C
YKL201C
YKL202W
YKL203C
YKL204W
YKL205W
YKL206C
YKL208W
YKL209C
YKL215C
YKL217W
YKL218C
YKL219W
YKL220C
YKL221W
YKL222C
YKL223W
YKL224C
YKL225W
MRPL31
CTK1
LTV1
DBR1
TPK3
KKQ8
SNU114
PXA2
HYM1
SDS22
MST1
PEX1
PTK1
TOR2
LOS1
CBT1
STE6
JEN1
COS9
FRE2
YLR138W
YLR139C
YLR140W
YLR141W
YLR142W
YLR143W
YLR144C
YLR145W
YLR147C
YLR148W
YLR149C
YLR151C
YLR152C
YLR156W
YLR158C
YLR159W
YLR161W
YLR162W
YLR163C
YLR164W
YLR165C
YLR166C
YLR168C
YLR169W
YLR170C
YLR171W
YLR173W
YLR174W
YLR176C
YLR181C
YLR182W
YLR183C
YLR184W
YLR187W
YLR188W
YLR189C
YLR190W
YLR191W
YLR193C
YLR196W
YLR198C
YLR200W
YLR205C
YLR207W
YLR210W
YLR211C
YLR213C
YLR214W
YLR215C
YLR217W
NHA1
SLS1
RRN5
PUT1
ACF2
SMD3
PEP3
ASP3
MAS1
SEC10
MSF1'
APS1
IDP2
RFX1
SWI6
MDL1
PEX13
PWP1
YKE2
HRD3
CLB4
FRE1
YML050W
YML053C
YML054C
YML058C-A
YML059C
YML060W
YML061C
YML062C
YML065W
YML066C
YML068W
YML069W
YML071C
YML076C
YML077W
YML080W
YML081W
YML082W
YML083C
YML084W
YML087C
YML088W
YML089C
YML090W
YML091C
YML093W
YML094W
YML095C
YML095C-A
YML096W
YML097C
YML098W
YML099C
YML100W-A
YML102C-A
YML102W
YML103C
YML104C
YML107C
YML108W
YML109W
YML111W
YML115C
YML117W
YML118W
YML119W
YML120C
YML122C
YMR001C
YMR004W
CYB2
OGG1
PIF1
MFT1
ORC1
POB3
RPM2
PFD5
RAD10
VPS9
TAF19
ARG81
CAC2
NUP188
MDM1
ZDS2
VAN1
NDI1
CDC5
MVP1
D-13
YJL222W
YJL223C
YJL225C
YJR002W
YJR003C
YJR005W
YJR006W
YJR010W
YJR011C
YJR012C
YJR013W
YJR018W
YJR020W
YJR021C
YJR022W
YJR023C
YJR030C
YJR031C
YJR032W
YJR033C
YJR034W
YJR035W
YJR036C
YJR037W
YJR038C
YJR039W
YJR040W
YJR041C
YJR042W
YJR043C
YJR046W
YJR047C
YJR049C
YJR050W
YJR051W
YJR052W
YJR053W
YJR054W
YJR055W
YJR056C
YJR057W
YJR060W
YJR061W
YJR062C
YJR066W
YJR067C
YJR068W
YJR071W
YJR072C
YJR078W
MPP10
APL1
MET3
REC107
GEA1
CPR7
PET191
RAD26
GEF1
NUP85
POL32
ANB1
UTR1
UTR3
OSM1
RAD7
HIT1
CDC8
CBF1
NTA1
TOR1
YAE1
RFC2
YKR001C
YKR002W
YKR003W
YKR005C
YKR007W
YKR008W
YKR009C
YKR010C
YKR011C
YKR012C
YKR014C
YKR015C
YKR016W
YKR017C
YKR019C
YKR020W
YKR021W
YKR022C
YKR023W
YKR024C
YKR027W
YKR028W
YKR029C
YKR031C
YKR032W
YKR033C
YKR034W
YKR035C
YKR036C
YKR037C
YKR040C
YKR041W
YKR044W
YKR045C
YKR047W
YKR050W
YKR051W
YKR052C
YKR053C
YKR054C
YKR055W
YKR058W
YKR060W
YKR061W
YKR063C
YKR064W
YKR069W
YKR072C
YKR073C
YKR075C
VPS1
PAP1
RSC4
FOX2
TOF2
YPT52
IRS4
DBP7
SAP190
SPO14
DAL80
CAF4
TRK2
MRS4
YSR3
DYN1
RHO4
GLG1
KTR2
LAS1
MET1
SIS2
YLR218C
YLR219W
YLR221C
YLR223C
YLR225C
YLR226W
YLR227C
YLR228C
YLR230W
YLR232W
YLR233C
YLR234W
YLR235C
YLR236C
YLR238W
YLR239C
YLR240W
YLR242C
YLR243W
YLR245C
YLR246W
YLR247C
YLR254C
YLR255C
YLR260W
YLR261C
YLR262C
YLR263W
YLR265C
YLR266C
YLR267W
YLR269C
YLR271W
YLR272C
YLR273C
YLR274W
YLR275W
YLR276C
YLR277C
YLR278C
YLR279W
YLR280C
YLR281C
YLR282C
YLR283W
YLR284C
YLR287C
YLR288C
YLR289W
YLR296W
IFH1
ECM22
EST1
TOP3
VPS34
ARV1
LCB5
YPT6
RED1
PIG1
CDC46
SMD2
DBP9
YSH1
EHD1
MEC3
GUF1
YMR007W
YMR013C
YMR014W
YMR016C
YMR017W
YMR018W
YMR019W
YMR020W
YMR021C
YMR023C
YMR025W
YMR026C
YMR028W
YMR029C
YMR030W
YMR031C
YMR031W-A
YMR032W
YMR033W
YMR034C
YMR036C
YMR037C
YMR039C
YMR040W
YMR041C
YMR044W
YMR045C
YMR046C
YMR048W
YMR052C-A
YMR052W
YMR053C
YMR057C
YMR059W
YMR060C
YMR061W
YMR063W
YMR064W
YMR065W
YMR066W
YMR068W
YMR069W
YMR070W
YMR075C-A
YMR075W
YMR076C
YMR077C
YMR078C
YMR080C
YMR082C
SEC59
SOK2
DBI9
STB4
FMS1
MAC1
MSS1
PEX12
TAP42
CYK2
ARP9
MIH1
MSN2
SUB1
FAR3
STB2
SEN15
TOM37
RNA14
RIM9
AEP1
KAR5
MOT3
PDS5
CTF18
NAM7
D-14
YJR079W
YJR082C
YJR083C
YJR087W
YJR088C
YJR089W
YJR090C
YJR091C
YJR092W
YJR093C
YJR094C
YJR095W
YJR097W
YJR098C
YJR099W
YJR100C
YJR102C
YJR106W
YJR107W
YJR108W
YJR109C
YJR110W
YJR111C
YJR112W
YJR114W
YJR119C
YJR120W
YJR122W
YJR124C
YJR128W
YJR129C
YJR130C
YJR131W
YJR132W
YJR134C
YJR135C
YJR136C
YJR137C
YJR138W
YJR140C
YJR141W
YJR142W
YJR144W
YJR146W
YJR147W
YJR149W
YJR150C
YJR151C
YJR152W
YJR153W
GRR1
JSN1
BUD4
FIP1
IME1
ACR1
YUH1
ECM27
CPA2
NNF1
CAF17
MNS1
NMD5
MCM22
ECM17
HIR3
MGM101
HMS2
DAN1
DAL5
PGU1
YKR077W
YKR078W
YKR079C
YKR081C
YKR082W
YKR083C
YKR084C
YKR085C
YKR086W
YKR087C
YKR089C
YKR090W
YKR091W
YKR092C
YKR095W
YKR096W
YKR097W
YKR098C
YKR099W
YKR101W
YKR102W
YKR103W
YKR104W
YKR105C
YKR106W
YLL001W
YLL002W
YLL003W
YLL004W
YLL005C
YLL006W
YLL007C
YLL008W
YLL011W
YLL012W
YLL013C
YLL015W
YLL016W
YLL017W
YLL019C
YLL021W
YLL029W
YLL030C
YLL032C
YLL033W
YLL034C
YLL035W
YLL036C
YLL037W
YLL038C
NUP133
HBS1
MRPL20
PRP16
SRP40
MLP1
PCK1
UBP11
BAS1
SIR1
FLO10
DNM1
KIM2
SFI1
ORC3
MMM1
DRS1
SOF1
SDC25
KNS1
SPA2
PRP19
YLR298C
YLR299W
YLR302C
YLR305C
YLR306W
YLR307W
YLR308W
YLR309C
YLR310C
YLR311C
YLR312C
YLR313C
YLR314C
YLR315W
YLR316C
YLR318W
YLR319C
YLR320W
YLR321C
YLR322W
YLR323C
YLR324W
YLR326W
YLR329W
YLR331C
YLR332W
YLR334C
YLR336C
YLR337W
YLR338W
YLR339C
YLR341W
YLR343W
YLR345W
YLR346C
YLR349W
YLR352W
YLR353W
YLR357W
YLR358C
YLR360W
YLR361C
YLR362W
YLR363C
YLR365W
YLR366W
YLR368W
YLR369W
YLR371W
YLR373C
YHC1
ECM38
STT4
UBC12
CDA1
CDA2
IMH1
CDC25
SPH1
CDC3
EST2
BUD6
SFH1
REC102
MID2
SGD1
BUD8
RSC2
VPS38
STE11
NMD4
YMR084W
YMR085W
YMR086C-A
YMR086W
YMR093W
YMR094W
YMR095C
YMR096W
YMR097C
YMR098C
YMR100W
YMR101C
YMR102C
YMR103C
YMR104C
YMR106C
YMR107W
YMR109W
YMR111C
YMR112C
YMR114C
YMR115W
YMR117C
YMR118C
YMR122C
YMR124W
YMR125W
YMR126C
YMR127C
YMR129W
YMR130W
YMR132C
YMR133W
YMR134W
YMR135W-A
YMR137C
YMR138W
YMR139W
YMR140W
YMR141C
YMR144W
YMR147W
YMR151W
YMR153C-A
YMR153W
YMR154C
YMR155W
YMR156C
YMR158W
YMR158W-A
CTF13
SNO1
SNZ1
MUB1
YPK2
HDF2
MYO5
STO1
SAS2
POM152
REC114
SNM1
CIN4
RIM11
RIM13
D-15
YJR154W
YJR155W
YJR156C
YJR157W
YJR158W
YJR159W
YJR160C
YJR162C
YKL005C
YKL006C-A
YKL011C
YKL012W
YKL014C
YKL015W
YKL017C
YKL020C
YKL021C
YKL022C
YKL023W
YKL025C
YKL026C
YKL027W
YKL030W
YKL031W
YKL032C
YKL033W
YKL036C
YKL037W
YKL038W
YKL040C
YKL041W
YKL042W
YKL044W
YKL045W
YKL047W
YKL048C
YKL049C
YKL050C
YKL052C
YKL055C
YKL057C
YKL059C
YKL061W
YKL063C
YKL064W
YKL068W
YKL069W
THI11
HXT16
SOR1
SFT1
CCE1
PRP40
PUT3
HCS1
SPT23
MAK11
CDC16
PAN3
IXR1
RGT1
VPS24
SPC42
PRI2
ELM1
CSE4
NUP120
MNR2
NUP100
YLL042C
YLL046C
YLL047W
YLL052C
YLL054C
YLL055W
YLL057C
YLL059C
YLL060C
YLL061W
YLL062C
YLL063C
YLL065W
YLR002C
YLR003C
YLR004C
YLR006C
YLR007W
YLR009W
YLR010C
YLR011W
YLR012C
YLR013W
YLR014C
YLR015W
YLR016C
YLR020C
YLR021W
YLR022C
YLR024C
YLR026C
YLR030W
YLR031W
YLR032W
YLR033W
YLR035C
YLR036C
YLR039C
YLR041W
YLR045C
YLR046C
YLR047C
YLR049C
YLR051C
YLR052W
YLR053C
YLR054C
RNP1
GIN11
SSK1
PPR1
SED5
RAD5
RIC1
STU2
YLR374C
YLR376C
YLR377C
YLR379W
YLR381W
YLR382C
YLR383W
YLR385C
YLR386W
YLR387C
YLR389C
YLR392C
YLR393W
YLR394W
YLR396C
YLR397C
YLR398C
YLR399C
YLR400W
YLR401C
YLR402W
YLR403W
YLR407W
YLR408C
YLR409C
YLR410W
YLR411W
YLR415C
YLR416C
YLR417W
YLR418C
YLR419W
YLR422W
YLR423C
YLR424W
YLR425W
YLR427W
YLR428C
YLR430W
YLR431C
YLR433C
YLR434C
YLR435W
YLR436C
YLR440C
YLR442C
YLR443W
FBP1
NAM2
RHC18
STE23
ATP10
VPS33
AFG2
SKI2
BDF1
SFP1
CTR3
VPS36
CDC73
SEN1
CNA1
ECM30
SIR3
ECM7
YMR159C
YMR160W
YMR162C
YMR163C
YMR164C
YMR165C
YMR166C
YMR167W
YMR168C
YMR170C
YMR172C-A
YMR172W
YMR176W
YMR178W
YMR179W
YMR180C
YMR182C
YMR183C
YMR185W
YMR187C
YMR188C
YMR190C
YMR192W
YMR193C-A
YMR193W
YMR196W
YMR197C
YMR198W
YMR199W
YMR201C
YMR204C
YMR206W
YMR207C
YMR209C
YMR210W
YMR212C
YMR213W
YMR214W
YMR218C
YMR219W
YMR220W
YMR223W
YMR225C
YMR227C
YMR228W
YMR229C
SAP18
MSS11
SMP2
MLH1
CEP3
ALD2
ECM5
SPT21
RGM1
SSO2
SGS1
VTI1
CIK1
CLN1
RAD14
HFA1
CEF1
SCJ1
ESC1
ERG8
MRPL44
TAF67
MTF1
FMI1
D-16
ORFs not detected in any of four cultures on microarray ‘D’.
YMR231W
YMR232W
YMR233W
YMR251W
YMR254C
YMR265C
YMR268C
YMR270C
YMR273C
YMR277W
YMR279C
YMR280C
YMR282C
YMR284W
YMR285C
YMR287C
YMR288W
YMR294W
YMR306C-A
YMR306W
YMR313C
YMR316C-B
YMR317W
YMR320W
YMR324C
YMR326C
YNL012W
YNL014W
YNL017C
YNL018C
YNL019C
YNL020C
YNL024C
YNL027W
YNL028W
YNL033W
YNL034W
YNL041C
YNL047C
YNL049C
YNL057W
YNL059C
YNL068C
YNL077W
YNL082W
YNL083W
YNL089C
PEP5
FUS2
PRP24
RRN9
ZDS1
FCP1
CAT8
AEP2
HDF1
MSU1
JNM1
FKS3
SPO1
ARK1
CRZ1
ARP5
FKH2
PMS1
YNL318C
YNL319W
YNL324W
YNL325C
YNL335W
YNR003C
YNR004W
YNR005C
YNR008W
YNR023W
YNR024W
YNR042W
YNR045W
YNR056C
YNR059W
YNR060W
YNR062C
YNR063W
YNR064C
YNR066C
YNR069C
YNR070W
YNR072W
YNR073C
YNR077C
YOL006C
YOL015W
YOL017W
YOL018C
YOL023W
YOL024W
YOL025W
YOL028C
YOL029C
YOL034W
YOL037C
YOL041C
YOL044W
YOL045W
YOL046C
YOL047C
YOL050C
YOL054W
YOL067C
YOL069W
YOL076W
YOL078W
FIG4
RPC34
SNF12
PET494
BIO5
FRE4
HXT17
TOP1
TLG2
IFM1
LAG2
YAP7
PEX15
RTG1
NUF2
DEC1
YOR118W
YOR127W
YOR139C
YOR144C
YOR146W
YOR148C
YOR156C
YOR162C
YOR169C
YOR170W
YOR171C
YOR177C
YOR183W
YOR186W
YOR188W
YOR190W
YOR192C
YOR193W
YOR195W
YOR199W
YOR211C
YOR214C
YOR216C
YOR221C
YOR225W
YOR235W
YOR237W
YOR242C
YOR252W
YOR255W
YOR256C
YOR263C
YOR268C
YOR274W
YOR277C
YOR279C
YOR282W
YOR287C
YOR295W
YOR296W
YOR298W
YOR300W
YOR308C
YOR313C
YOR314W
YOR324C
YOR325W
YPL151C
YPL153C
YPL155C
YPL158C
YPL161C
SPP2
YPL164C
NFI1
YPL165C
YRR1
YPL166W
YPL167C
YPL174C
LCB4
YPL181W
YPL185W
YPL189W
YPL191C
MSB1
YPL192C
SPR1
YPL193W
YPL194W
YPL200W
SLK19
YPL201C
YPL202C
MGM1
YPL205C
YPL209C
RUD3
YPL213W
YPL216W
YPL217C
SNR17A YPL228W
HES1
YPL233W
YPL241C
YPL242C
YPL243W
YPL248C
YPL249C
YPL251W
MOD5
YPL253C
YPL254W
YPL255W
YPL257W
YPL261C
YPL267W
YPL269W
YPL272C
YPL277C
YPL281C
SPS4
YPR001W
YPR002W
YPR003C
YPR007C
RGA1
RAD53
KIP2
BEM4
REV3
NIP100
DDC1
IPL1
CET1
CIN2
IQG1
SRP68
GAL4
VIK1
HFI1
BBP1
KAR9
ERR2
CIT3
D-17
YNL095C
YNL102W
YNL105W
YNL106C
YNL109W
YNL119W
YNL120C
YNL126W
YNL127W
YNL128W
YNL139C
YNL140C
YNL143C
YNL146W
YNL148C
YNL152W
YNL161W
YNL164C
YNL171C
YNL172W
YNL179C
YNL182C
YNL187W
YNL188W
YNL196C
YNL197C
YNL198C
YNL203C
YNL204C
YNL205C
YNL207W
YNL210W
YNL212W
YNL214W
YNL215W
YNL218W
YNL224C
YNL225C
YNL226W
YNL227C
YNL228W
YNL233W
YNL235C
YNL242W
YNL250W
YNL253W
YNL254C
YNL257C
YNL258C
YNL260C
POL1
INP52
SPC98
TEP1
RLR1
ALF1
APC1
KAR1
SLZ1
WHI3
SPS18
MER1
PEX17
CNM67
BNI4
RAD50
SIP3
YOL079W
YOL085C
YOL089C
YOL091W
YOL093W
YOL095C
YOL099C
YOL100W
YOL104C
YOL105C
YOL113W
YOL114C
YOL115W
YOL116W
YOL117W
YOL118C
YOL131W
YOL132W
YOL134C
YOL138C
YOL141W
YOL144W
YOL145C
YOL150C
YOL152W
YOL156W
YOL157C
YOL160W
YOL161C
YOL163W
YOL166C
YOR003W
YOR005C
YOR011W
YOR012W
YOR017W
YOR019W
YOR024W
YOR025W
YOR026W
YOR028C
YOR029W
YOR030W
YOR032C
YOR033C
YOR037W
YOR038C
YOR041C
YOR048C
YOR049C
NDJ1
WSC3
SKM1
TRF4
MSN1
CTR9
FRE7
HXT11
YSP3
DNL4
PET127
HST3
BUB3
CIN5
DFG16
HMS1
DHS1
CYC2
HIR2
RAT1
YOR330C
YOR333C
YOR334W
YOR339C
YOR345C
YOR350C
YOR351C
YOR353C
YOR364W
YOR365C
YOR366W
YOR368W
YOR371C
YOR372C
YOR376W
YOR378W
YOR379C
YOR381W
YOR384W
YOR386W
YOR387C
YOR392W
YPL005W
YPL008W
YPL016W
YPL021W
YPL022W
YPL025C
YPL027W
YPL029W
YPL033C
YPL035C
YPL038W
YPL040C
YPL041C
YPL043W
YPL044C
YPL045W
YPL060W
YPL062W
YPL070W
YPL072W
YPL073C
YPL074W
YPL082C
YPL083C
YPL096W
YPL099C
YPL102C
YPL103C
MIP1
MRS2
MNE1
MEK1
RAD17
FRE3
FRE5
PHR1
CHL1
SWI1
ECM23
RAD1
SUV3
ISM1
NOP4
VPS16
MOT1
SEN54
YPR014C
YPR015C
YPR018W
YPR025C
YPR026W
YPR027C
YPR031W
YPR032W
YPR038W
YPR039W
YPR045C
YPR046W
YPR049C
YPR050C
YPR054W
YPR055W
YPR056W
YPR059C
YPR064W
YPR068C
YPR070W
YPR071W
YPR076W
YPR077C
YPR078C
YPR083W
YPR087W
YPR089W
YPR090W
YPR092W
YPR095C
YPR096C
YPR097W
YPR099C
YPR104C
YPR105C
YPR111W
YPR112C
YPR116W
YPR122W
YPR123C
YPR130C
YPR136C
YPR137W
YPR141C
YPR142C
YPR150W
YPR152C
YPR164W
YPR168W
RLF2
CCL1
ATH1
SRO7
MCM16
SMK1
SEC8
TFB4
HOS1
FHL1
DBF20
AXL1
KAR3
KIM3
NUT2
D-18
YNL266W
YNL267W
YNL269W
YNL270C
YNL272C
YNL273W
YNL275W
YNL276C
YNL279W
YNL282W
YNL285W
YNL286W
YNL295W
YNL296W
YNL297C
YNL298W
YNL299W
YNL309W
YNL311C
PIK1
ALP1
SEC2
TOF1
POP3
CUS2
CLA4
TRF5
STB1
YOR050C
YOR055W
YOR058C
YOR060C
YOR068C
YOR070C
YOR073W
YOR075W
YOR076C
YOR077W
YOR080W
YOR082C
YOR083W
YOR093C
YOR100C
YOR105W
YOR111W
YOR113W
YOR114W
ASE1
GYP1
UFE1
RTS2
AZF1
YPL108W
YPL109C
YPL110C
YPL114W
YPL116W
YPL119C
YPL120W
YPL121C
YPL124W
YPL126W
YPL130W
YPL133C
YPL136W
YPL137C
YPL140C
YPL141C
YPL146C
YPL147W
YPL150W
HOS3
DBP1
VPS30
MEI5
NIP29
MKK2
PXA1
YPR170C
YPR171W
YPR175W
YPR177C
YPR179C
YPR180W
YPR186C
YPR189W
YPR190C
YPR192W
YPR193C
YPR195C
YPR196W
YPR197C
YPR200C
YPR201W
YPR202W
YPR203W
DPB2
AOS1
PZF1
SKI3
RPC82
HPA2
ARR2
ARR3
D-19
Appendix E
Transcripts with the Highest Average Abundance
among Four Saccharomyces cerevisiae Cultures
This appendix contains a table of the 500 ORFs with the most abundant transcripts.
Ranking of abundance in this table is by the mean of absolute abundance across the four
cultures measured, with absolute abundance calculated as described in Chapter 2.
It was interesting to find that eleven of the one hundred most abundant transcripts
measured derive from ORFs which have not been assigned a gene name. A cursory
examination of these ORFs showed that YDR154C (rank 1) overlaps YDR155C (gene CPH1,
ranked 33), and the ORFs YDR134C (rank 16) and YDR133C (rank 44) overlap each other.
This effectively reduces the number of abundant unnamed transcripts to 9 of the top 100.
Unnamed transcripts in the 100 most abundant ORFs
Rank
1
ID
YDR154C
3
YLR110C
16
YDR134C
30
YMR173WA
37
YKL056C
44
YDR133C
52
55
YDR033W
YDR276C
69
YLR109W
76
96
YER150W
YNL208W
Notes
overlaps YDR155C
(CPH1; rank 33)
converegent with
YLR109W (rank 69)
overlaps YDR133C
(unnamed; rank 44)
overlaps YMR173W
(DDR48; rank 1362)
overlaps YDR134C
(unnamed; rank 16)
convergent with
YLR110C (rank 3)
Homology (BLAST GenEMBL)
CPH1, C. albicans CYP1,
S. Pombe ISP4
YAR050W (FLO1), YKR102W (FLO10), YNR044W
(AGA1)
YLR110C, YAR050W (FLO1), YKR102W (FLO10),
YNR044W (AGA1)
DDR48
translationally controlled tumor protein (TCTP)
conserved in animals and higher plants.
YLR110C
YBR054W (YRO2), YCR021C (YRO1/HSP30)
H. vulgare blt101, L. elongatum salt-stress induced
ESI3, YJL152W, YJL153C (APR1/INO1)
L. kononenkoae putative peroxisomal protein,
C.boidinii peroxisomal membrane protein A and B,
YDR077W (SED1)
-
Homology searches were performed using TBLASTN against the non-redundant
GenBank+EMBL+DDBJ+PDB databases (April 1997) using a web interface provided by the
Saccharomyces Genome Database [Altschul, 1990 #340].
E-2
Guide to abundance table. The columns labeled ‘R’ refer to the rank of the transcript
according to average abundance. ‘Avg’ is the average of four absolute abundances (which
can be found for each ORF in Appendix C). ‘ID’ refers to the ORF identifier as assigned by
the Saccharomyces Genome Database (SGD). An ORF identifier printed in italics indicates
that the sequence of some of the mismatch probes for this ORF were not unique in the
cerevisiae genome. In this case PM values were substituted for ∆ values in calculating
absolute and relative abundance, so that the quantitation for these ORFs should be viewed
more critically. The gene names were taken from the current (10 April 98) SGD table of
gene names.
E-3
ORFs with the highest average absolute abundance across four cultures assayed.
R
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
Avg
36.0
28.7
25.1
22.0
21.1
21.0
18.9
17.8
17.0
16.6
16.3
14.2
13.4
13.4
13.2
12.1
11.8
11.7
11.5
11.4
11.4
11.4
10.7
10.7
10.6
10.4
10.3
10.3
10.2
9.9
9.3
9.1
9.1
8.9
8.9
8.7
8.7
8.6
8.5
8.3
8.2
7.9
7.6
7.5
7.5
7.4
ID
Gene
YDR154C
YKL097WA CWP2
YLR110C
YGR192C TDH3
YDR382W RPP2B
YBR191W RPL21A
YHR174W ENO2
YDL130W RPP1B
YKL060C FBA1
YDR050C TPI1
YBL072C RPS8A
YBR031W RPL4A
YPL079W RPL21B
YGL189C RPS26A
YOL040C RPS15
YDR134C
YLR044C PDC1
YCR012W PGK1
YHR021C RPS27B
YIL018W
RPL2B
YPL131W RPL5
YHR053C CUP1
YOL039W RPP2A
YMR251WA HOR7
YPR043W RPL43A
YBR118W TEF2
YKL180W RPL17A
YJR073C
OPI3
YOL086C ADH1
YMR173WA
YJL190C
RPS22A
YGR254W ENO1
YDR155C CPH1
YPL143W RPL33A
YOL053CA DDR2
YPR080W TEF1
YKL056C
YHR055C CUP1
YGL135W RPL1B
YOR182C RPS30B
YJR009C
TDH2
YPL220W RPL1A
YKL152C GPM1
YDR133C
YOL120C RPL18A
YNL031C HHT2
R
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
Avg
2.9
2.9
2.8
2.8
2.8
2.7
2.7
2.7
2.7
2.7
2.6
2.6
2.6
2.6
2.6
2.6
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.4
2.4
2.4
2.4
2.4
2.4
2.4
2.4
2.4
2.3
2.3
2.3
2.3
2.3
2.3
2.3
2.3
2.3
2.2
2.2
2.2
2.2
ID
YPL037C
YPL028W
YDR447C
YBR067C
YDR178W
YML073C
YOR167C
YLR441C
YNR050C
YLL024C
YER091C
YNL302C
YDR055W
YPL090C
YBL092W
YNL134C
YDR353W
YNL209W
YJR145C
YMR083W
YJL151C
YEL026W
YJL138C
YPL271W
YDL137W
YER011W
YMR297W
YBR189W
YDR450W
YHR183W
YIL043C
YKL156W
YLL050C
YKR059W
YDR233C
YGL037C
YGR060W
YOL127W
YJL159W
YOR234C
YJL191W
YPR074C
YLR048W
YPL218W
YDR345C
YER117W
Gene
EGD1
ERG10
RPS17B
TIP1
SDH4
RPL6A
RPS28A
RPS1A
LYS9
SSA2
MET6
RPS19B
RPS6A
RPL32
TRR1
SSB2
RPS4A
ADH3
TIF2
ATP15
ARF2
TIR1
PRC1
RPS9B
RPS18A
GND1
CBR1
RPS27A
COF1
TIF1
ERG25
RPL25
RPS14B
TKL1
RPS0B
SAR1
HXT3
RPL23B
R
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
Avg
1.3
1.3
1.3
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
ID
YBR106W
YHR018C
YLR354C
YGL202W
YLR395C
YLL041C
YPR063C
YDR404C
YBR109C
YDR025W
YLR150W
YPL098C
YNL096C
YLR303W
YMR195W
YDR471W
YGL187C
YKL085W
YKR094C
YPL048W
YBR009C
YOR187W
YLR286C
YOL139C
YJR139C
YDL128W
YER009W
YIL094C
YDL232W
YGR285C
YLR229C
YBL099W
YLR375W
YDR304C
YPR052C
YPL198W
YOR374W
YLR178C
YFL045C
YPR098C
YFL010C
YKL080W
YLR179C
YMR256C
YIL062C
YCL035C
Gene
PHO88
ARG4
TAL1
ARO8
COX8
SDH2
RPB7
CMD1
RPS11A
MPT4
RPS7B
MET17
RPL27B
COX4
MDH1
RPL40B
CAM1
HHF1
CTS1
CDC33
HOM6
VCX1
NTF2
OST4
ZUO1
CDC42
ATP1
STP3
CYP5
NHP6A
RPL7B
ALD7
TFS1
SEC53
VMA5
COX7
ARC15
E-4
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
7.2
7.2
7.1
7.0
7.0
6.8
6.7
6.6
6.6
6.6
6.5
6.5
6.5
6.4
6.4
6.3
6.3
6.2
6.2
6.1
6.1
6.0
5.9
5.9
5.9
5.7
5.6
5.6
5.6
5.5
5.4
5.3
5.3
5.3
5.3
5.2
5.2
5.2
5.2
5.1
5.1
5.1
5.0
5.0
4.9
4.9
4.7
4.6
4.6
4.5
YMR116C
YNL055C
YNL135C
YGL008C
YNL178W
YDR033W
YCR031C
YLR061W
YDR276C
YDR500C
YEL027W
YDR077W
YLR340W
YDR012W
YHR203C
YHR026W
YGL123W
YML028W
YLR388W
YNL145W
YLR075W
YJL158C
YLR109W
YJL052W
YFL014W
YDR064W
YIL133C
YLR300W
YJL136C
YER150W
YGR085C
YAL038W
YDL081C
YKR042W
YOR063W
YGL030W
YER102W
YKL164C
YER177W
YDL125C
YKL096W
YKR057W
YNL069C
YJR104C
YDL192W
YLR167W
YMR194W
YNL160W
YLR185W
YNL208W
BEL1
POR1
FPR1
PMA1
RPS3
RPS14A
RPL22A
RPL37B
CUP5
SED1
RPP0
RPL4B
RPS4B
PPA1
RPS2
TSA1
RPS29A
MFA2
RPL10
CIS3
TDH1
HSP12
RPS13
RPL16A
EXG1
RPS21B
RPL11B
CDC19
RPP1A
UTH1
RPL3
RPL30
RPS8B
PIR1
RPL23B
HNT1
CWP1
RPS21A
RPL16B
SOD1
ARF1
RPS31
RPL36A
YGP1
RPL37A
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
2.2
2.2
2.2
2.2
2.2
2.1
2.1
2.1
2.1
2.1
2.1
2.1
2.1
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.9
1.9
1.9
1.9
1.9
1.9
1.9
1.9
1.9
1.9
1.9
1.9
1.9
1.9
1.8
1.8
1.8
1.8
1.8
1.8
1.8
1.8
1.8
1.8
1.8
1.7
YNL030W
YNR018W
YKL035W
YDR502C
YDR298C
YBL030C
YDL191W
YGR209C
YDR158W
YNL327W
YHR193C
YOL109W
YPL154C
YOR045W
YLR264W
YNL300W
YMR202W
YGR282C
YBL002W
YLR406C
YNL044W
YPL234C
YMR295C
YOR270C
YOR136W
YLR355C
YCL043C
YNL190W
YPR113W
YMR142C
YGL256W
YLL045C
YDR388W
YEL054C
YDR032C
YHR025W
YNL067W
YLR350W
YGL055W
YBR020W
YML012W
YER056CA
YBR082C
YHR141C
YBR249C
YGL200C
YJR085C
YNL015W
YNL301C
YBR196C
HHF2
SAM2
ATP5
PET9
RPL35A
TRX2
HOM2
EGT2
EGD2
ZEO1
PEP4
TOM6
RPS28B
ERG2
BGL2
HTB2
RPL31B
TFP3
VPH1
IDH2
ILV5
PDI1
PIS1
RPL13B
ADH4
RPL8B
RVS167
RPL12A
THR1
RPL9B
OLE1
GAL1
ERV25
RPL34A
UBC4
RPL42B
ARO4
EMP24
PBI2
RPL18B
PGI1
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
430
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
YLR056W ERG3
YKL067W YNK1
YPR103W PRE2
YGL026C TRP5
YIR022W SEC11
YLR027C AAT2
YDL131W LYS21
YOR303W CPA1
YBL003C HTA2
YNL268W LYP1
YCL018W LEU2
YHR001WA QCR10
YOR007C SGT2
YCR024CA PMP1
YOL030W
YFR044C
YOR120W GCY1
YKL182W FAS1
YMR241W
YML092C PRE8
YGR180C RNR4
YER072W
YDR328C SKP1
YBR115C LYS2
YHR051W COX6
YMR305C
YGL220W
YJR105W
YMR315W
YMR008C PLB1
YDL048C STP4
YNL305C
YHR064C PDR13
YLR208W SEC13
YPL106C SSE1
YER057C HIG1
YIL123W SIM1
YCL009C ILV6
YHR179W OYE2
YJR121W ATP2
YNL244C SUI1
YHR039BC VMA10
YBR029C CDS1
YIL041W
YML100W TSL1
YER023W PRO3
YDR519W FKB2
YGL089C MFα2
YIL078W THS1
YNR036C
E-5
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
4.5
4.4
4.4
4.4
4.4
4.4
4.4
4.4
4.4
4.3
4.3
4.2
4.2
4.1
4.1
4.1
4.1
4.1
4.1
4.0
4.0
4.0
4.0
4.0
3.9
3.9
3.8
3.8
3.8
3.8
3.8
3.7
3.7
3.7
3.7
3.7
3.6
3.6
3.6
3.6
3.6
3.5
3.5
3.5
3.5
3.5
3.4
3.4
3.3
3.3
YGL103W
YDR342C
YDL182W
YEL017CA
YOR247W
YFR053C
YDL083C
YJR123W
YDL229W
YLR448W
YDR497C
YDR343C
YCL040W
YJR094WA
YJL189W
YOR285W
YLR391W
YEL034W
YDR418W
YOR369C
YHL015W
YPR132W
YEL009C
YCR021C
YBR010W
YGL255W
YLR043C
YKL006W
YFR031CA
YOR122C
YGL076C
YJL177W
YDR533C
YOR230W
YFL039C
YKL192C
YOL121C
YPR149W
YIL148W
YDR461W
YLR287CA
YIR034C
YHR010W
YDL022W
YDR226W
YIL053W
YGR037C
YIL051C
YML024W
YIL052C
RPL28
HXT7
LYS20
PMP2
HXK1
RPS16B
RPS5
SSB1
RPL6B
ITR1
HXT6
GLK1
RPL43B
RPL39
HYP2
RPL12B
RPS12
RPS20
RPS23B
GCN4
HSP30
HHT1
ZRT1
TRX1
RPL14A
RPL2A
PFY1
RPL7A
RPL17B
WTM1
ACT1
RPS19A
NCE102
RPL40A
MFA1
RPS30A
LYS1
RPL27A
GPD1
ADK1
RHR2
ACB1
MMD1
RPS17A
RPL34B
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
1.7
1.7
1.7
1.7
1.7
1.7
1.7
1.7
1.7
1.7
1.7
1.7
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.4
1.4
1.4
1.4
1.4
1.4
1.4
YOR248W
YKR013W
YDL055C
YLR325C
YFL031W
YOL129W
YDR224C
YHR162W
YBL087C
YMR002W
YML058W
YLR333C
YGR214W
YMR143W
YER178W
YOR099W
YLR259C
YGR183C
YGL253W
YMR226C
YGR118W
YOR020C
YLR293C
YHL033C
YAL005C
YPR035W
YPL262W
YNL322C
YDL067C
YNL162W
YPL004C
YER120W
YKR066C
YDL181W
YML078W
YJL079C
YLR029C
YDL004W
YNL104C
YAL012W
YDL124W
YDL075W
YPR036W
YLR372W
YNL007C
YNL052W
YBR054W
YGL147C
YBR072W
YOR224C
PRY2
PSA1
RPL38
HAC1
HTB1
RPL23A
RPS25B
RPS0A
RPS16A
PDA1
KTR1
HSP60
QCR9
HXK2
RPS23A
HSP10
GSP1
RPL8A
SSA1
GLN1
FUM1
KRE1
COX9
RPL42A
SCS2
CCP1
INH1
CPR3
PRY1
RPL15A
ATP16
LEU4
CYS3
RPL31A
VMA13
SUR4
SIS1
COX5A
YRO2
RPL9A
HSP26
RPB8
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476
477
478
479
480
1.0
1.0
1.0
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
YHR094C HXT1
YBR018C GAL7
YGL077C HNM1
YDR513W TTR1
YLL023C
YOR185C GSP2
YDR368W YPR1
YMR318C
25SRRNAA
YPL252C
YBR086C
YBR126C TPS1
YER094C PUP3
YLL039C UBI4
YER062C HOR2
YPL087W
YFL038C YPT1
YBR181C RPS6B
YNL130C CPT1
YBR011C IPP1
YER056C FCY2
YLR294C
YPR016C CDC95
YIR038C
YKR065C
YCR053W THR4
YLR180W SAM1
YOL154W
YNL064C YDJ1
YLR378C SEC61
CONTROL2
YPL094C SEC62
YMR145C
YLR081W GAL2
YPL010W RET3
YBR019C GAL10
CONTROL10
YGR181W
YGR027C RPS25A
YBR159W
YML052W SUR7
YOR332W VMA4
YNL071W LAT1
YMR215W
YGL148W ARO2
YMR205C PFK2
YHR008C SOD2
YDL188C PPH22
YBR025C
YDR070C
E-6
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
3.3
3.3
3.3
3.2
3.2
3.2
3.2
3.2
3.2
3.1
3.1
3.1
3.1
3.1
3.0
3.0
2.9
2.9
2.9
2.9
2.9
YER043C
YGR279C
YIR037W
YLR058C
YHL001W
YKL163W
YPR102C
YOR133W
YBR286W
YOR096W
YDL061C
YDR225W
YDR385W
YPR028W
YJR077C
YML106W
YOR293W
YGR034W
YGL031C
YDR454C
YDL082W
SAH1
HYR1
SHM2
RPL14B
PIR3
RPL11A
EFT1
APE3
RPS7A
RPS29B
HTA1
EFT2
MIR1
URA5
RPS10A
RPL26B
RPL24A
GUK1
RPL13A
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
YOR383C
YHR007C
YPL231W
YNR001C
YML026C
YDR433W
YGL225W
YJL034W
YLR249W
YAL003W
YDR297W
YOR375C
YML126C
YOR010C
YGR148C
YPR165W
YDL136W
YPL061W
YDL072C
YGR008C
YOR312C
ERG11
FAS2
CIT1
RPS18B
GOG5
KAR2
YEF3
EFB1
SUR2
GDH1
HMGS
TIR2
RPL24B
RHO1
RPL35B
ALD6
STF2
RPL20B
481
482
483
484
485
486
487
488
489
490
491
492
493
494
495
496
497
498
499
500
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
YJR065C
YGR240C
YMR242C
YGR155W
YGR106C
YJL153C
YOL058W
YDR234W
YDR483W
YLL014W
YER055C
YGR295C
YAL044C
YFR047C
YPL246C
YML132W
YBR127C
YGL012W
YLR367W
YMR272C
ARP3
PFK1
RPL20A
CYS4
INO1
ARG1
LYS4
KRE2
HIS1
COS6
GCV3
COS3
VMA2
ERG4
RPS22B
SCS7
E-7
References
E-8
Appendix F
Transcripts Most Changed in Abundance
among Four Cultures Assayed
The four cultures examined in Chapter 3 consisted of a ‘baseline’ condition, and
three ‘experimental’ condtions, where only one variable (either genotypic or
environmental) was changed relative to baseline. This allows for three whole-genome
scale comparisons of transcript abundance. The following table contains those genes
most changed in these comparisons. Since there are three comparisons, there are six sets
of extremaa set of ORFs most increased and most decreased for each comparison.
glucose
30oC
Mating type a
galactose
30oC
Mating type a
glucose
30oC
Mating type α
glucose
-> 39o C shock
Mating type a
30o C
Guide to relative abundance table. The first column (“ID”) contains the ORF
identifier as issued by the Saccharomyces Genome Database. An ORF identifier printed
in italics indicates that the sequence of some of the mismatch probes for this ORF were
not unique in the cerevisiae genome. In this case PM values were substituted for ∆ values
in calculating absolute and relative abundance, so that the quantitation for these ORFs
should be viewed more critically.
The second column (“Gene”) contains the common gene names corresponding to
each ORF identifier. The gene names were taken from the current (10 April 98) SGD
table of gene names.
F-2
The fourth and fifth columns contain absolute abundances of the ORF’s transcript
in the two conditions being compared. Transcripts which fell below the detection
threshold of the corresponding hybridization experiment are indicated by abundance
values in italics. In this case, ∆ values used to calculate the abundance value were
adjusted to the detection threshold if they fell below it. The sixth column contains the
logarithm (base 10) of the median ∆-ratio value for this comparison. Transcripts
considered below detection threshold in one or both conditions being compared are
indicated by median log ∆-ratio values in italics. If a transcript is below detection
threshold in both conditions being compared, the median log ∆-ratio is set to zero. For
each of the relative abundance values, a measure of significance is calculated by dividing
the median log ∆-ratio by the median deviation of log ∆-ratios. If this measure of
significance is one or greater, and the median log ∆-ratio is 0.2 or greater, the median log
∆-ratio value is in bold type. Absolute and relative abundance calculations are described
in Chapters 2 and 3.
F-3
ORFs most abundant in mating type α relative to mating type a culture.
R
ID
Gene
a
alpha
1
2
3
YPL187W
YGL089C
YCL066W
MF(α)1
MF(α)2
α1
0.11
0.07
0.09
2.88
3.67
0.51
log
α/a
1.28
1.22
0.67
4
YCR040W
α1
0.09
0.37
0.63
5
6
7
8
9
10
11
12
13
14
YJR004C
YLR040C
YHR053C
YHR128W
YHR141C
YGL106W
YGR038W
YLR355C
YLR029C
YGL030W
SAG1
0.35
0.35
5.96
0.44
1.03
0.16
0.17
1.09
0.97
4.86
1.74
1
17
1.09
1.98
0.51
0.3
2.59
2.84
9.72
0.48
0.42
0.4
0.38
0.35
0.35
0.35
0.33
0.32
0.32
15
16
17
18
19
YGR159C
YOR309C
YIL052C
YLR056W
YNL112W
RPL34B
ERG3
DBP2
0.21
0.41
2.34
0.65
0.16
0.48
0.93
4.11
1.53
0.33
0.31
0.29
0.28
0.28
0.27
RPL16A
CDC42
0.19
4.77
0.72
0.54
8.84
1.6
0.26
0.26
0.26
2.08
0.77
1.59
10.86
3.91
1.74
2.96
20.6
0.26
0.25
0.24
0.24
1.16
0.48
0.65
0.35
0.25
2.22
0.82
0.42
0.13
0.11
3.99
1.82
0.54
1.58
2.37
0.86
1.19
1.25
0.51
5.11
1.28
0.76
0.36
0.21
5.53
3.53
0.64
2.59
0.24
0.23
0.22
0.22
0.22
0.22
0.21
0.21
0.21
0.21
0.21
0.21
0.21
0.21
20 YGR232W
21 YIL133C
22 YLR229C
CUP1
FUR1
RPL42B
MLC1
ORM1
ILV5
RPL15A
RPL30
NSR1
23
24
25
26
YJR145C
YLR150W
YEL026W
YOL040C
RPS4A
MPT4
27
28
29
30
31
32
33
34
35
36
37
38
39
40
YLR293C
YMR292W
YGL055W
YJL153C
YNL255C
YFR031C-A
YDR471W
YOR310C
YER086W
YOL021C
YOR247W
YER117W
YMR276W
YLR333C
GSP1
RPS15
OLE1
INO1
RPL2A
RPL27B
NOP5
ILV1
DIS3
RPL23B
DSK2
RPS25B
Brief SGD Gene Description
mating factor α
α mating factor
transcripton factor involved in the regulation of
the alpha-specific genes
transcripton factor involved in the regulation of
the alpha-specific genes
α-agglutinin
copper-binding metallothionein
UPRTase
Ribosomal protein L42B (YL27) (L41) (YP44)
myosin light chain
acetohydroxyacid reductoisomerase
Ribosomal protein L15A (YL10) (rp15R) (L13)
Large ribosomal subunit protein L30 (L32)
(rp72) (YL38)
nuclear localization sequence binding protein
Ribosomal protein L34B
C-5 sterol desaturase
ATP-dependent RNA helicase of DEAD box
family
Ribosomal protein L16A (L21) (rp22) (YL15)
member of the Rho subfamily of Ras-like
proteins
Ribosomal protein S4A (YS6) (rp5) (S7)
40S ribosomal protein S15 (S21) (rp52) (RIG
protein)
GTP-binding protein
delta-9-fatty acid desaturase
L-myo-inositol-1-phosphate synthase
Ribosomal protein L2A (L5) (rp8) (YL6)
60S ribosomal protein L27, identical to Yhr010p
nucleolar protein
threonine deaminase
Ribosomal protein L23B (L17a) (YL32)
ubiquitin-like protein
Ribosomal protein S25B (S31) (rp45) (YS23)
F-4
41
42
43
44
45
46
47
48
49
YDR450W
YOR021C
YMR321C
YIL069C
YIL018W
YGR124W
YGL198W
YEL040W
YHR193C
50 YLR286C
RPS18A
UTR2
EGD2
1.45
0.11
0.46
0.45
8.69
0.25
0.21
0.36
1.12
3.12
0.23
0.63
0.93
15.9
0.25
0.82
0.75
2.16
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.19
CTS1
1.1
1.61
0.19
RPS24B
RPL2B
ASN2
Ribosomal protein S18A
40S ribosomal protein S24B
Ribosomal protein L2B (L5) (rp8) (YL6)
asparagine synthetase
GAL4 enhancer protein, homolog of human
alpha NAC subunit of the nascent-polypeptideassociated complex
Endochitinase
F-5
ORFs most abundant in mating type a relative to mating type α culture.
R
ID
GENE
a
alpha
1
2
3
4
YDR461W
YNL145W
YGL032C
YFL026W
MFA1
MFA2
AGA2
STE2
4.42
7.14
0.6
0.57
0.04
0.09
0.07
0.07
5
6
YIL015W
YCR024C-A
BAR1
PMP1
0.45
1.83
0.07
0.54
7
YJL164C
SRA3
0.47
0.15
8
9
10
11
YLL040C
YKR071C
YBR147W
YJR086W
VPS13
STE18
0.35
0.35
0.39
0.35
0.11
0.11
0.11
0.11
12 YML027W
13 YMR042W
YOX1
ARG80
0.35
0.35
0.15
0.14
14 YMR047C
NUP116
0.35
0.15
15
16
17
18
19
20
21
YKR018C
YLL031C
YKL214C
YKL170W MRPL38
YMR119W
YBR011C
IPP1
YBR106W
PHO88
0.35
0.35
0.35
0.35
0.35
1.17
2.11
0.19
0.17
0.14
0.12
0.14
0.63
0.76
22
23
24
25
26
YAL061W
YBL015W
YKL128C
YMR003W
YPR149W
0.46
0.46
0.35
0.35
5.06
0.16
0.11
0.15
0.13
1.28
27
28
29
30
31
YCR012W
YKL066W
YBR268W
YDR343C
YPR165W
23.1
0.35
0.26
6
1.57
5.85
0.13
0.05
2.42
0.41
0.24
0.21
5.87
0.17
ACH1
PMU1
NCE102
PGK1
MRPL37
HXT6
RHO1
32 YBR072W
33 YMR090W
34 YPL220W
HSP26
RPL1A
0.68
0.35
9.9
35 YML075C
HMG1
0.35
log
a/α
1.98
1.64
0.9
0.8
Brief SGD Gene Description
a-factor mating pheromone precursor
mating a-factor pheromone precursor
adhesion subunit of a-agglutinin
alpha-factor pheromone receptor\; seventransmembrane domain protein
0.68 encodes a-cell barrier activity on alpha factor
0.6 Proteolipid associated with plasma membrane H(+)ATPase (Pma1p)
0.56 putative catalytic subunit of cAMP-dependent protein
kinase
0.55
0.53
0.52
0.51 gamma subunit of G protein coupled to mating factor
receptors
0.5 Homeobox-domain containing protein
0.5 Regulator of arginine-responsive genes with ARG81
and ARG82
0.5 Nuclear pore complex protein that is member of
GLFG repeat-containing family of nucleoporins and is
highly homologous to Nup100p
0.49
0.49
0.48
0.47 mitochondrial ribosomal protein L14
0.47
0.46 Inorganic pyrophosphatase
0.46 May be a membrane protein involved in inorganic
phosphate transport and regulation of Pho81p
function
0.45
0.44 acetyl CoA hydrolase
0.44 Phospo-mutase homolog
0.44
0.44 involved in secretion of proteins that lack classical
secretory signal sequences
0.44 3-phosphoglycerate kinase
0.43
0.42 Probable mitochondrial protein L37
0.42 Hexose transporter
0.4 GTP-binding protein of the rho subfamily of ras-like
proteins
0.4 heat shock protein 26
0.39
0.39 Ribosomal protein L1A, forms part of the 60S
ribosomal subunit
0.38 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase isozyme
F-6
36 YJL210W
PEX2
0.6
0.26
37 YBL045C
COR1
0.4
0.17
38
39
40
41
42
YJR103W
YOL058W
YPL271W
YKL196C
YLR028C
URA8
ARG1
ATP15
YKT6
ADE16
0.35
0.65
2.42
0.35
0.35
0.17
0.22
0.58
0.16
0.23
43
44
45
46
47
48
49
50
YMR038C
YMR184W
YDL047W
YDR490C
YDR506C
YDR342C
YBR107C
YEL031W
LYS7
0.35
0.35
0.09
0.12
0.09
6.13
0.09
0.21
0.22
0.2
0.05
0.05
0.07
3.01
0.06
0.07
SIT4
HXT7
SPF1
0.38 CH3HC4 zinc-binding integral peroxisomal
membrane protein
0.37 44 kDa core protein of yeast coenzyme QH2
cytochrome c reductase
0.36 CTP synthase
0.35 arginosuccinate synthetase
0.35 nuclear gene for ATP synthase epsilon subunit
0.34 v-SNARE
0.34 5-aminoimidazole-4-carboxamide ribonucleotide
(AICAR) transformylase\/IMP cyclohydrolase
0.34
0.34
0.33 SIT4 suppress mutations in DBF2
0.33
0.33
0.33 Hexose transporter
0.32
0.32 P-type ATPase
F-7
ORFs most abundant in galactose vs. glucose-fed culture.
R
ID
Gene
glu
gal
1
2
3
4
5
6
7
8
9
YBR020W
YBR018C
YBR019C
YOR120W
YLR081W
YPL066W
YPL067C
YMR318C
YNL015W
GAL1
GAL7
GAL10
GCY1
GAL2
0.09
0.09
0.09
0.11
0.35
0.11
0.21
0.37
0.95
7.12
3.59
3.24
3.21
2.84
0.76
1.76
1.89
3.03
log
gal/glu
1.81
1.62
1.57
1.09
0.91
0.8
0.77
0.6
0.59
10
11
12
13
14
15
16
17
18
19
20
21
22
YOL058W
YGL055W
YHR033W
YDR009W
YGR244C
YNL052W
YMR256C
YOL031C
YGL121C
YGR232W
YGR234W
YNL239W
YPL262W
ARG1
OLE1
YHB1
LAP3
FUM1
0.65
0.65
0.21
0.09
0.17
1.09
0.54
0.11
0.15
0.19
0.37
0.26
0.97
1.99
2.44
0.65
0.29
0.53
2.69
2.43
0.43
0.43
0.56
1.38
0.88
3.11
0.53
0.51
0.5
0.49
0.48
0.47
0.45
0.45
0.44
0.42
0.41
0.41
0.4
23 YGL126W
24 YHR193C
SCS3
EGD2
0.31
1.12
0.81
2.79
0.39
0.38
25 YER069W
ARG5,6
0.27
0.5
0.37
0.88
0.35
MPD1 0.18
0.24
QCR10 0.81
1.94
1.03
0.53
0.77
2.1
0.37
0.36
0.36
0.36
0.35
31
32
33
34
YGL187C
YER067W
YOR288C
YPL134C
YHR001WA
YHR018C
YHR057C
YHR179W
YNL104C
ARG4
CYP2
OYE2
LEU4
1.11
0.11
0.78
1.2
2.01
0.51
1.1
1.98
0.35
0.35
0.35
0.35
35
36
37
38
39
YNL112W
YPR020W
YPR145W
YGL117W
YGR183C
DBP2
QCR9
0.16
0.32
0.46
0.08
1.45
0.44
0.61
0.96
0.28
3.17
0.35
0.35
0.35
0.34
0.34
40 YHR008C
SOD2
0.62
1.24
0.34
26
27
28
29
30
PBI2
GAL3
COX5A
COX7
COX4
ASN1
Brief SGD Gene Description
galactokinase
galactose-1-phosphate uridyl transferase
UDP-glucose 4-epimerase
Similar to mammalian aldo\/keto reductases
galactose permease
Proteinase inhibitor I2B (PBI2), that inhibits protease
Prb1p (yscB)
arginosuccinate synthetase
delta-9-fatty acid desaturase
galactokinase
Cytochrome-c oxidase chain Va
subunit VII of cytochrome c oxidase
Flavohemoglobin
Aminopeptidase of cysteine protease family
mitochondrial and cytoplasmic fumarase (fumarate
hydralase)
GAL4 enhancer protein, homolog of human alpha NAC
subunit of the nascent-polypeptide-associated complex
N-acetyl-gamma-glutamyl-phosphate reductase and
acetylglutamate kinase
subunit IV of cytochrome c oxidase
Disulfide isomerase related protein
8.5 kDa subunit of the ubiqunol-cytochrome c
oxidoreductase complex
argininosuccinate lyase
Peptidylprolyl isomerase (cyclophilin) ER or secreted
NAPDH dehydrogenase (old yellow enzyme), isoform 2
alpha-isopropylmalate synthase (2-Isopropylmalate
Synthase)
ATP-dependent RNA helicase of DEAD box family
asparagine synthetase
7.3 kDa subunit 9 of the ubiquinol cytochrome c
oxidoreductase complex
Manganese-containing superoxide dismutase
F-8
41 YIL050W
42 YOL143C
PCL7
RIB4
0.1
0.32
0.29
0.66
0.34
0.34
43 YGR008C
44 YGR037C
STF2
ACB1
1.26
2.26
1.79
6.31
0.33
0.33
YHR051W COX6 0.56
YHR141C RPL42B 1.03
YOR202W
HIS3
0.23
YFL030W
0.14
YHR071W
PCL5
0.07
YNL259C
ATX1 0.22
2.02
2.78
0.69
0.69
0.18
0.35
0.33
0.33
0.33
0.32
0.32
0.32
45
46
47
48
49
50
6,7-dimethyl-8-ribityllumazine synthase (DMRL
synthase)
Acyl-CoA-binding protein (ACBP)\/Diazepam binding
inhibitor (DBI)\/endozepine (EP)
subunit VI of cytochrome c oxidase
Ribosomal protein L42B (YL27) (L41) (YP44)
imidazoleglycerol-phosphate dehydratase
PHO85 cyclin
Antioxidant protein and metal homeostasis factor,
protects against oxygen toxicity
F-9
ORFs most abundant in glucose- vs. galactose-fed culture.
R
1
2
3
4
5
ID
YDR345C
YGL189C
YHR094C
YOL154W
YGL030W
6 YFL045C
7 YBR106W
8
9
10
11
12
13
14
15
YER190W
YBR011C
YER178W
YCR005C
25srRnaa
YHR092C
YFR024C
YJR073C
16
17
18
19
20
21
22
23
24
YKL096W
YLL024C
YJL190C
YFR051C
YKL035W
YBR072W
YJL191W
YGL256W
YCR024C-A
25 YBL087C
26 YNL054W
27 YJL158C
Gene
HXT3
3.77
RPS26A 14.83
HXT1
0.84
1.89
RPL30 4.86
0.09
1.19
0.07
0.17
0.89
log
glu/gal
1.4
0.89
0.8
0.78
0.73
SEC53
PHO88
1.25
2.11
0.29
0.34
0.71
0.7
0.73
1.17
1.88
1.05
1.54
0.76
0.27
14.51
0.1
0.41
0.32
0.19
0.32
0.12
0.07
4.73
0.69
0.58
0.54
0.52
0.51
0.51
0.51
0.47
CWP1 4.38
SSA2
2.07
RPS22A 19.08
RET2
0.55
2.32
HSP26 0.68
RPS14B 2.33
ADH4 2.66
PMP1
1.83
1.36
0.76
3.19
0.16
0.81
0.18
0.94
0.52
0.8
0.47
0.46
0.44
0.43
0.42
0.39
0.39
0.39
0.38
RPL23A
VAC7
CIS3
2.07
0.11
9.57
1.01
0.05
3.2
0.38
0.37
0.36
0.08
9.14
3.96
0.05
1.66
0.74
0.08
0.36
0.35
0.35
0.35
0.35
0.34
0.33
0.05
0.07
1.9
0.11
0.07
0.27
0.33
0.33
0.33
0.32
0.32
0.31
IPP1
PDA1
CIT2
HXT4
OPI3
glu
28
29
30
31
32
33
34
YOR352W
YCR012W
YJR009C
YOR377W
YML073C
YLL045C
YGL209W
PGK1
TDH2
ATF1
RPL6A
RPL8B
MIG2
0.11
23.1
7.93
0.11
3.12
1.68
0.21
35
36
37
38
39
40
YOL158C
YPR174C
YJR094W-A RPL43B
YBR101C
YGL157W
YDR171W
HSP42
0.11
0.11
3.91
0.29
0.26
0.5
gal
Brief SGD Gene Description
High-affinity glucose transporter
High-affinity hexose (glucose) transporter
Large ribosomal subunit protein L30 (L32) (rp72)
(YL38)
phosphomannomutase
May be a membrane protein involved in inorganic
phosphate transport and regulation of Pho81p function
Inorganic pyrophosphatase
alpha subunit of pyruvate dehydrogenase (E1 alpha)
non-mitochondrial citrate synthase
High-affinity glucose transporter
Methylene-fatty-acyl-phospholipid synthase
(unsaturated phospholipid N-methyltransferase)
cell wall mannoprotein
member of 70 kDa heat shock protein family
Ribosomal protein S22A (S24) (rp50) (YS22)
heat shock protein 26
Ribosomal protein S14B (rp59)
alcohol dehydrogenase isoenzyme IV
Proteolipid associated with plasma membrane H(+)ATPase (Pma1p)
Ribosomal protein L23A (L17a) (YL32)
Protein with homology to Hsp150p and Pir1p, Pir2p,
and Pir3p
3-phosphoglycerate kinase
glyceraldehyde 3-phosphate dehydrogenase
Alcohol acetyltransferase
Ribosomal protein L6A (L17) (rp18) (YL16)
Ribosomal protein L8B (L4) (rp6) (YL5)
Protein containing zinc fingers very similar to zinc
fingers in Mig1p
Ribosomal protein L43B
Similar to HSP26\; expression is regulated by stress
conditions
F-10
41 YNL084C
END3
0.11
0.07
0.31
RPS5
0.11
3.58
0.11
5.23
0.07
1.96
0.05
1.26
0.31
0.31
0.3
0.3
46 YLR043C
TRX1
2.64
47 YKL097W-A CWP2 40.86
48 YFL021W
GAT1
0.17
2.07
15.05
0.07
0.3
0.29
0.29
49 YMR116C
50 YLR264W
3.58
0.52
0.29
0.29
42
43
44
45
YPR061C
YLR109W
YPR091C
YJR123W
BEL1
RPS28B
9.06
2.16
Protein necessary for internalization of alpha-factor
receptor when bound to ligand
ribosomal protein RPS5 (mammalian S5) (previously
called rp14, S2 or YS8)
thioredoxin
cell wall mannoprotein
transcriptional activator with GATA-1-type Zn finger
DNA-binding motif
Ribosomal protein S28B (S33) (YS27)
F-11
ORFs most abundant in heat-shocked vs. 30 °C culture.
R
ID
1
2
3
4
5
6
7
8
9
10
YFL014W
YDR453C
YPL223C
YGL121C
YLR303W
YBR072W
YGR256W
YLR178C
YDR533C
YDR019C
2.53
0.2
GRE1 0.11
0.15
MET17 0.39
HSP26 0.68
GND2 0.08
TFS1 0.39
1.53
GCV1 0.16
16.82
1.66
1.04
1.53
3.15
4.62
0.53
3.31
9.8
1
log
heat/30°C
0.89
0.88
0.83
0.82
0.77
0.75
0.75
0.65
0.65
0.64
11
12
13
14
15
16
YGL055W
YLR058C
YGR250C
YLL039C
YDR055W
YHR104W
OLE1
SHM2
GRE3
0.65
1.52
0.07
0.35
1.54
0.43
3.08
6.78
0.52
2.2
5.63
1.63
0.62
0.59
0.59
0.57
0.57
0.57
CPR6
0.27
0.35
1.09
1.4
0.53
0.53
0.51
0.35
0.16
0.26
0.59
0.35
1.28
0.31
0.11
0.16
1.02
0.35
0.11
0.2
0.23
0.09
0.11
5.4
6.8
0.54
1.04
1.22
0.07
0.07
0.66
2.18
1.45
0.69
0.84
2.05
1.33
9.38
0.96
0.72
0.79
2.6
1.06
0.53
0.65
0.97
0.3
0.67
16.53
15.95
1.2
2.74
2.71
0.29
0.37
1.67
0.52
0.51
0.51
0.5
0.5
0.5
0.49
0.48
0.48
0.47
0.47
0.47
0.47
0.47
0.45
0.44
0.44
0.44
0.43
0.43
0.43
0.42
0.41
0.41
0.41
17 YDR214W
18 YLR216C
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
YDR070C
YMR174C
YNL281W
YER103W
YER062C
YMR175W
YKL163W
YGL196W
YOR120W
YPR127W
YHR007C
YML128C
YPR157W
YMR246W
YDL222C
YBR117C
YGR088W
YOL053C-A
YHR055C
YMR276W
YPR035W
YOR020C
YER042W
YGR043C
YIR038C
Gene
30°C
HSP12
UBI4
PAI3
SSA4
HOR2
SIP18
PIR3
GCY1
ERG11
FAA4
TKL2
CTT1
DDR2
CUP1
DSK2
GLN1
HSP10
heat
Brief SGD Gene Description
12 kDa heat shock protein
Induced by osmotic stress
O-Acetylhomoserine-O-Acetylserine Sulfhydralase
heat shock protein 26
6-phosphogluconate dehydrogenase
suppressor of cdc25
glycine cleavage T protein (T subunit of glycine
decarboxylase complex
delta-9-fatty acid desaturase
serine hydroxymethyltransferase
ubiquitin
Induced by osmotic stress\; similar to xylose
reductase from other fungi
a cyclophilin related to the mammalian CyP-40\;
physically interacts with RPD3 gene product
Cytoplasmic inhibitor of proteinase Pep4p
member of 70 kDa heat shock protein family
DL-glycerol-3-phosphatase
Protein containing tandem internal repeats
Similar to mammalian aldo\/keto reductases
cytochrome P450 lanosterol 14a-demethylase
long-chain fatty acid--CoA ligase and synthetase 4
transketolase, homologous to tkl1
cytoplasmic catalase T
copper-binding metallothionein
ubiquitin-like protein
glutamine synthetase
10 kDa mitochondrial heat shock protein
F-12
44 YOR007C
SGT2
0.71
1.86
0.41
45
46
47
48
49
50
PRE8
YRO2
HSP82
0.56
1.05
0.15
0.11
0.12
0.76
2.15
2.94
0.67
0.42
0.39
2.35
0.39
0.39
0.39
0.39
0.39
0.39
YML092C
YBR054W
YPL240C
YDL223C
YER160C
YLR375W
STP3
small glutamine-rich tetratricopeptide repeat
containing protein
proteasome component Y7
Homolog to HSP30 heat shock protein Yro1p
heat shock protein
Involved in pre-tRNA splicing and in uptake of
branched-chain amino acids
F-13
ORFs most abundant in 30 °C vs. heat-shocked culture.
R
ID
Gene
30°C
heat
1
2
3
4
YJL052W
YOL154W
YGR234W
YBR010W
TDH1
9.02
1.89
0.37
5.04
0.05
0.08
0.11
1.29
log
heat/30°
C
-1.69
-0.99
-0.62
-0.53
5 YBL072C
6 YBL002W
RPS8A 23.04
HTB2 2.74
7.03
0.73
-0.49
-0.48
7 YBL003C
HTA2
1.31
0.47
-0.48
8 YFR015C
GSY1
0.16
0.05
-0.46
9 YBR009C
HHF1
1.7
0.55
-0.41
10 YIR034C
11 YNL030W
LYS1
HHF2
4.01
2.55
2.33
1.03
-0.4
-0.39
12 YGL256W
13 YCR034W
ADH4
FEN1
2.66
0.75
0.99
0.22
-0.38
-0.37
14 YNL117W
15 YNL199C
MLS1
GCR2
0.11
0.11
0.05
0.08
-0.36
-0.35
16 YPL127C
17 YPR188C
18 YMR283C
HHO1
RIT1
0.34
0.14
0.11
0.12
0.07
0.06
-0.34
-0.34
-0.34
19 YGL255W
20 YJL158C
ZRT1
CIS3
4.53
9.57
1.99
4.62
-0.34
-0.33
21 YDR382W
22 YPL195W
RPP2B 30.31
APL5
0.11
13.72
0.06
-0.33
-0.33
0.46
1.83
0.14
1.02
-0.33
-0.32
YBL092W RPL32 3.47
YDL081C RPP1A 7.2
YDR516C
0.54
YOR081C
0.11
YOR154W
0.11
YOL053W
0.11
YJL190C RPS22A 19.08
YJL088W
ARG3 0.28
YMR240C CUS1
0.11
1.7
2.72
0.26
0.11
0.07
0.06
6.52
0.1
0.06
-0.32
-0.31
-0.31
-0.31
-0.31
-0.3
-0.29
-0.29
-0.29
YHB1
HHT1
23 YBL015W ACH1
24 YCR024C-A PMP1
25
26
27
28
29
30
31
32
33
Brief SGD Gene Description
Glyceraldehyde-3-phosphate dehydrogenase 1
Flavohemoglobin
Histone H3 (HHT1 and HHT2 code for identical
proteins)
Ribosomal protein rp19 (YS9) (Mammalian S8)
Histone H2B (HTB1 and HTB2 code for nearly
identical proteins)
Histone H2A (HTA1 and HTA2 code for nearly
identical proteins)
Glycogen synthase (UDP-gluocse--starch
glucosyltransferase)
Histone H4 (HHF1 and HHF2 code for identical
proteins)
saccharopine dehydrogenase
Histone H4 (HHF1 and HHF2 code for identical
proteins)
alcohol dehydrogenase isoenzyme IV
Probable subunit of 1,3-beta-glucan synthase\;
homolog of ELO1
carbon-catabolite sensitive malate synthase
Activates transcription of glycolytic genes\;
homologous to GCR1\; may function in complex
with Gcr2p
histone H1
Initiator methionine tRNA 2'-O-ribosyl phosphate
transferase
Protein with homology to Hsp150p and Pir1p, Pir2p,
and Pir3p
Ribosomal protein P2B (YP2b) (L45)
delta-like subunit of the yeast AP-3 adaptin
component of the membrane-associated clathrin
assembly complex
acetyl CoA hydrolase
Proteolipid associated with plasma membrane H(+)ATPase (Pma1p)
Ribosomal protein L32
Acidic ribosomal protein P1A (YP1a) (A1)
Ribosomal protein S22A (S24) (rp50) (YS22)
Ornithine carbamoyltransferase
U2 snRNP protein
F-14
34
35
36
37
YBR115C
LYS2
1.82
YBL027W RPL19B 0.64
YOR290C
SNF2
0.11
YDL182W LYS20 6.35
0.66
0.23
0.06
3.4
-0.28
-0.28
-0.27
-0.27
0.11
14.51
0.07
9.55
-0.27
-0.26
YDR064W RPS13 7.08
YPR143W
0.11
YML073C RPL6A 3.12
YDL130W RPP1B 20.92
YPL139C
UME1 0.11
YPL260W
0.11
YHL015W RPS20 3.39
YIL052C RPL34B 2.34
YCR005C
CIT2
1.05
YDR133C
10.29
YBR268W MRPL37 0.26
4.32
0.07
1.81
13.86
0.08
0.1
3.35
1.76
0.48
5.16
0.11
-0.26
-0.26
-0.25
-0.25
-0.25
-0.25
-0.25
-0.25
-0.24
-0.24
-0.24
38 YPL046C
39 YJR073C
40
41
42
43
44
45
46
47
48
49
50
ELC1
OPI3
alpha aminoadipate reductase
Ribosomal protein L19B (YL14) (L23) (rpl5L)
transcriptional regulator
homocitrate synthase, highly homologous to
YDL131W
Elongin C transcription elongation factor
Methylene-fatty-acyl-phospholipid synthase
(unsaturated phospholipid N-methyltransferase)
Ribosomal protein S13 (S27a) (YS15)
Ribosomal protein L6A (L17) (rp18) (YL16)
Ribosomal protein P1B (L44') (YP1b) (Ax)
Transcriptional modulator
Ribosomal protein S20
Ribosomal protein L34B
non-mitochondrial citrate synthase
Probable mitochondrial protein L37
F-15
Appendix G
Sizes of Intergenic Regions in S. cerevisiae,
E. coli and H. influenzae
This appendix contains the size distribution of intergenic regions for three
organismsSaccharomyces cerevisiae, Eschericia coli, and Haemophilus influenzae.
The size of intergenic regions in S. cerevisiae is relevant to Chapter 3, in which a choice
was made about how much upstream non-coding sequence to examine, i.e., at what
distance from translation start are we unlikely to find regulatory sequences? The size of
intergenic regions for prokaryotes E. coli and H. influenzae is not relevant to any other
work in this thesis, but I include it here as a reference.
For each organism, each intergenic region was classified as being one of three
types: divergent, convergent or tandem. A divergent region is a region between two
flanking genes which have opposite directions of translation. A divergent intergenic
region must then contain transcription regulation signals for two genes. A convergent
region is defined as having two flanking genes, both having directions of translation
oriented towards the intergenic region. Therefore, a convergent intergenic region
presumably contains no transcription regulation signals. A tandem intergenic region is
flanked by two genes, one oriented away from and one towards the intergenic region, so
that a tandem intergenic region contains the transcription signals for one gene (or
possibly none if the intergenic region is within an operon). In addition to these three
types, we might also consider the intron to be a type of intergenic region.
Convergent intergenic regions have the shortest length distribution in all three of
the organisms examined, which was to be expected since these regions will in general not
contain any transcriptional control sequences. Tandem intergenic regions were the next
highest length distribution in all three organisms, consistent with the expectation that
these regions will, in general, contain the transcriptional control elements of one gene.
G-2
The largest intergenic regions are divergent regions, which is to be expected since these
will often contain transcriptional control elements for two genes.
In Chapter 3, AlignACE was used to find conserved upstream DNA elements. It
was important to have an estimate of how great a distance upstream of translation start
one might expect to find transcriptional regulatory elements. It is instructive to look at
the size distribution of tandem intergenic regions, since these should in general contain a
set of transcriptional elements for one (and only one) gene. Setting an upper length
bound of 600 base pairs seemed reasonble, since more than 75% of tandem intergenic
regions that are greater than zero in length are less than 600 base pairs long. Un upper
limit of 975 base pairs would be required to include the full width of 90% of the
intergenic regions with non-negative length.
It is also worth noting that the distribution of tandem regions in the two
eubacterial genomes appeared bimodal. Presumably this is due to the fact that operon
structure is found in these organisms, with shorter intergenic regions corresponding to
genes within operons.
It is intriguing to find that intron lengths in S. cerevisiae also form a bimodal
distribution. This may be an artifact due to the software used to predict intron positions,
or it reflect distinct types of introns (perhaps the difference is in length is due to introns
containing genes). This observation bears further investigation.
For the purpose of this appendix, the collection of regions between open reading
frames (ORFs) was taken as a surrogate for intergenic regions, i.e., non-protein-coding
regions such as tRNAs and rRNAs were not included as genes. This decision was made
for the sake of convenience and excluded roughly 400 genes from S. cerevisiae, and
G-3
roughly 100 E. coli & H. influenzae genes. Thus, the distributions presented here are
slightly biased towards larger intergenic regions.
The positions of start and stop codons for each ORF in S. cerevisiae were
obtained from SGD, and are current as of August 1997. The positions of start and stop
codons in E. coli were derived from the M52 version of the E. coli K-12 sequence
(September 1997) and were obtained from NCBI at
ftp://ncbi.nlm.nih.gov/genbank/genomes/bacteria/Ecoli/. The positions of start and stop
codons for H. influenzae are current as of February 1998 and were obtained from the
Institute for Genomic Research (TIGR) Microbial Database at
http://www.tigr.org/tdb/mdb/hidb/hidb.html.
G-4
Size Distribution of Convergent Intergenic Regions in S. cerevisiae.
120
100
80
60
40
20
1500
1250
1000
750
500
250
0
-250
-500
-750
-1000
0
Length (bp)
Size Distribution of Divergent Intergenic Regions in S. cerevisiae.
80
70
60
50
40
30
20
10
1500
1250
1000
750
500
250
0
-250
-500
-750
-1000
0
Length (bp)
G-5
Size Distribution of Tandem Intergenic Regions in S. cerevisiae.
160
140
120
100
80
60
40
20
1500
1250
1000
750
500
250
0
-250
-500
-750
-1000
0
Length (bp)
Size Distribution of Introns in S. cerevisiae.
45
40
35
30
25
20
15
10
5
1000
750
500
250
0
0
Length (bp)
G-6
Size Distribution of Convergent Intergenic Regions in E. coli.
90
80
70
580
530
480
430
380
330
280
230
180
130
80
30
-20
-70
-2500
60
50
40
30
20
10
0
Length (bp)
Size Distribution of Divergent Intergenic Regions in E. coli.
30
25
20
15
10
5
580
530
480
430
380
330
280
230
180
130
80
30
-20
-70
-2500
0
Length (bp)
G-7
Size Distribution of Tandem Intergenic Regions in E. coli.
450
400
350
300
250
200
150
100
50
580
530
480
430
380
330
280
230
180
130
80
30
-20
-70
-2500
0
Length (bp)
G-8
Size Distribution of Convergent Intergenic Regions in H. influenzae.
25
20
15
10
5
580
530
480
430
380
330
280
230
180
130
80
30
-20
-70
-2500
0
Length (bp)
Size Distribution of Divergent Intergenic Regions in H. influenzae.
12
10
8
6
4
2
580
530
480
430
380
330
280
230
180
130
80
30
-20
-70
-2500
0
Length (bp)
G-9
Size Distribution of Tandem Intergenic Regions in H. influenzae.
250
200
150
100
50
580
530
480
430
380
330
280
230
180
130
80
30
-20
-70
-2500
0
Length (bp)
G-10