A Gene Group Database
for Systematic Analysis of Microarray Data
Madelaine Marchin and Chris Seidel
Stowers Institute for Medical Research, Kansas City, Missouri, USA
Other databases
Introduction
Gene Group Database
Often when analysing microarray data, it is easy to focus only on the genes that show
the most difference between two samples. This artificially crops the center out of the
data, in effect ignoring small changes that could offer valuable insight.
Other gene group databases have been created. GSEA has MSigDB (Molecular
signatures database), which contains groups of genes, including groups based on
chromosomal position, signaling pathways, and experimental gene expression res
from literature. MSigDB does not currently allow users to upload new groups or
We do not limit the type of group users can upload. We encourage users to upload any
groups they have developed. Groups might show enrichment in someone else’s data redistribute the database.
set, which could be meaningful to both parties.
We originally populated the database
L2L is another gene list database.
All lists represent experimental gene expression
with groups from Gene Ontology and L2L (1,2). Here is a screenshot of the download
results. Users can contribute their own experimental results.
This database has been
page.
included in our Gene Group Database.
Microarray Data
Up Genes
Data Analysis
Up Genes
Down Genes
Gene group analysis does not work without groups of genes. We built a web database
(http://research.stowers-institute.org/microarray/gene_groups) for people to use with
group analysis.
Our database imposes no limitation on groups, is generally extensible, encourage
sharing, and serves multiple group analysis platforms.
Down Genes
Instead, gene group analysis (also known as gene set enrichment or iterative group
analysis) aims to take predefined groups of genes and check their overall values in the
microarray data. If a group’s member genes are showing a change in expression, that
group is suddenly very interesting.
Visualization
• Gene Ontology groups
• Chromosomal locations
• Pathways
• Groups from experimental results
• genes targeted by a specific microRNA
chromatin remodeling
If you take every group of genes that you and other people can think of and examine
the behavior of the groups in your data, the results are an easy to analyze list of groups
changing in your experiment that can offer surprising insights.
Group Analysis
wt
mut
012345
012345
500 Random groups of 6
Tag cloud
Search options
Users can upload and download groups without registering. Users who would like
to keep track of private gene groups may register with a password. Groups can
be downloaded in your chosen file format (currently three formats are offered to
correspond with iGA, Catmap, and GSEA). A help page explains how to use iGA,
Catmap, and Gene Group Database to analyze data.
YKL067W
YMR271C
YGR061C
The database back-end is a MySQL database with 7 tables to hold information about
groups, users, tags, and genes.
The website is written in HTML, PHP
and javascript.
0.00
YGL234W
0.10
YML106W
Density
YMR120C
YJL130C
YIL116W
0
10
20
30
40
50
user
id
email
password
N = 500 Bandwidth = 0.7609
RPI1
SNO1
SNZ1
GO groups of 6
SNZ2
SNZ3
ER lumen
THI2
THI20
THI21
THI22
THI4
THI5
THI80
Two groups of genes are shown above,
as measured in a time course of yeast
induced for expression of either a wt
protein, or a misfolded mutant protein,
which causes ER stress. Genes in group
A are roughly the same under the two
conditions, whereas genes in group B
show diff
erential expression in the wt
cells relative to the mutant cells.
Enrichment Factor
Contact Information
Entity-Relationship Diagram for Gene Groups
Database. Each shape is a table in the database, and terms in red are keys.
1
20
Summary
-We created a public web database to store gene groups for
microarray data analysis.
-We used our gene groups to run group analysis on a data set.
1
10
DNA replication initiation
ribosome biogenesis
signal transduction during conjugation with cellular fusion
microtubule motor activity
tRNA modification
spindle pole body
thiamin biosynthesis
cation homeostasis
arginine biosynthesis
pyrimidine salvage
fatty acid biosynthesis
m
group_user
group_id
user_id
0
35S primary transcript processing
DNA replication checkpoint
regulation of transcription, DNA−dependent
alpha−amylase activity
alpha DNA polymerase:primase complex
ribosome biogenesis and assembly
rRNA processing
prospore formation
1,6−beta−glucan biosynthesis
cytokinesis
centric heterochromatin
alpha−glucan biosynthesis
ATPase activity, coupled to transmembrane movement of substances
1,3−beta−glucan biosynthesis
glutamate catabolism
glycolysis
cell separation during cytokinesis
vacuolar protein catabolism
0.10
THI13
0.00
THI12
Density
THI11
B
1
nucleus
transcription factor TFIID complex
DASH complex
mismatch repair
nuclear chromatin
telomere maintenance
cytosol
mRNA cleavage
cell wall (sensu Fungi)
SNARE binding
nucleotide−excision repair
RNA binding
mediator complex
endonuclease activity
mitochondrial intermembrane space
riboflavin biosynthesis
transcription from RNA polymerase II promoter
cell surface
mitochondrial protein processing
histone acetylation
cell wall organization and biogenesis
sporulation (sensu Fungi)
prefoldin complex
vacuolar membrane
double−strand break repair via homologous recombination
mRNA export from nucleus
ER−associated protein catabolism
Ctf18 RFC−like complex
cell wall mannoprotein biosynthesis
ESCRT III complex
GTP binding
exocyst
phosphoprotein phosphatase activity
cytoplasmic mRNA processing body
SNAP receptor activity
intracellular protein transport
late endosome to vacuole transport
de novo pyrimidine base biosynthesis
chromosome condensation
chromatin silencing at telomere
cytosolic large ribosomal subunit (sensu Eukaryota)
ergosterol biosynthesis
Golgi membrane
metallopeptidase activity
heme biosynthesis
DNA repair
signal recognition particle (sensu Eukaryota)
mitochondrial outer membrane
kinetochore
Golgi apparatus
iron−sulfur cluster assembly
cell septum
conjugation with cellular fusion
mitochondrial small ribosomal subunit
proteolysis
chromosome segregation
translation elongation factor activity
barrier septum
mRNA catabolism
DNA replication, removal of RNA primer
polynucleotide adenylyltransferase activity
mRNA processing
DNA−dependent ATPase activity
protein folding
COPII vesicle coat
response to cadmium ion
cyclin−dependent protein kinase regulator activity
cytosolic ribosome (sensu Eukaryota)
protein amino acid acetylation
nucleolar ribonuclease P complex
DNA−directed RNA polymerase III complex
histone methylation
attachment of spindle microtubules to kinetochore
glutathione transferase activity
actin cortical patch distribution
cell wall chitin biosynthesis
mRNA cleavage and polyadenylation specificity factor complex
chromatin silencing at silent mating−type cassette
mRNA binding
RNA elongation from RNA polymerase II promoter
DNA binding
chromosome, telomeric region
chromatin silencing
homologous chromosome segregation
DNA recombination
commitment complex
cellular response to nitrogen starvation
attachment of spindle microtubules to kinetochore during meiosis I
nuclear pore
posttranslational protein targeting to membrane
centromeric DNA binding
cellular morphogenesis
establishment and/or maintenance of cell polarity (sensu Fungi)
ATPase activity
transcription initiation from RNA polymerase III promoter
histidine biosynthesis
nucleolus
anaphase−promoting complex−dependent proteasomal ubiquitin−dependent protein catabolism
medial ring
Rho guanyl−nucleotide exchange factor activity
RNA splicing factor activity, transesterification mechanism
spore wall (sensu Fungi)
DNA−directed RNA polymerase II, holoenzyme
chromatin silencing at centromere
protein sumoylation
collapsed replication fork processing
microtubule cytoskeleton organization and biogenesis
barrier septum formation
regulation of progression through cell cycle
methionine metabolism
sphingolipid biosynthesis
GTPase activator activity
endocytosis
horsetail nuclear movement
alpha−1,2−galactosyltransferase activity
isoleucine biosynthesis
endoplasmic reticulum membrane
mannosyltransferase activity
DNA replication
bipolar cell growth
exocytosis
acetyl−CoA biosynthesis from pyruvate
calcium ion transport
nitrogen compound metabolism
DNA−directed RNA polymerase activity
cell cortex
chromatin assembly or disassembly
chromatin
S−adenosylmethionine−dependent methyltransferase activity
cytokinesis, site selection
chaperonin−containing T−complex
de novo IMP biosynthesis
intra−Golgi vesicle−mediated transport
GPI anchor biosynthesis
histone acetyltransferase complex
GTPase activity
guanyl−nucleotide exchange factor activity
induction of conjugation upon nitrogen starvation
potassium ion homeostasis
equatorial microtubule organizing center
ATP−dependent DNA helicase activity
ATP−dependent RNA helicase activity
mating type switching
3−5 exonuclease activity
DNA clamp loader activity
processing of 20S pre−rRNA
Shown here are results using groups from our database and iGA on data from Elena
Hidalgo, S. pombe untreated vs. Osmotic shock. Shown are the groups that most
changed from untreated to osmotic shock.
Behind the scenes
YMR217W
A
membrane
actin binding
iron ion homeostasis
protein targeting to vacuole
Golgi to endosome transport
cytokinesis, contractile ring formation
calcium ion binding
hexose transporter activity
mitochondrial large ribosomal subunit
Hsp70 protein binding
mitochondrion
cell cortex of cell tip
integral to endoplasmic reticulum membrane
meiotic recombination
cytosolic small ribosomal subunit (sensu Eukaryota)
cell tip
vesicle−mediated transport
double−strand break repair
response to oxidative stress
actin cytoskeleton organization and biogenesis
integral to plasma membrane
endosome
cell wall biosynthesis (sensu Fungi)
translation initiation factor activity
protein amino acid phosphorylation
ribosome
meiotic chromosome segregation
mitotic spindle checkpoint
anaphase−promoting complex
calcium ion homeostasis
tricarboxylic acid cycle
DNA damage checkpoint
transcription factor activity
protein complex assembly
oligosaccharyl transferase complex
ubiquitin binding
negative regulation of transcription by glucose
nuclear membrane
plasma membrane
protein ubiquitination
G2/M transition of mitotic cell cycle
protein binding
hydrolase activity
endoplasmic reticulum
mitochondrial outer membrane translocase complex
COPI vesicle coat
dolichol−linked oligosaccharide biosynthesis
0.8
Groups of genes can be created for a number of different reasons. Groups of genes
are limited only by the imagination, and could include:
You can search groups to find all groups containing genes of interest. When users
upload groups, they are asked to “tag” them with various category terms for easy usergenerated categories. On the download page, a tag cloud shows the tags that have the
most member groups and allows for easy navigation.
0.6
Group 5
0.4
Group 4
Group 3
untreated / osmotic shock groups
electron transport
extracellular region
mitochondrial electron transport, ubiquinol to cytochrome c
cAMP−mediated signaling
proteasomal ubiquitin−dependent protein catabolism
ATP synthesis coupled proton transport (sensu Eukaryota)
phosphoinositide binding
mitochondrial matrix
signal transduction
proteasome regulatory particle, base subcomplex (sensu Eukaryota)
endopeptidase activity
damaged DNA binding
external side of plasma membrane
mitochondrial genome maintenance
protein amino acid dephosphorylation
aerobic respiration
clathrin binding
autophagy
oxysterol binding
general RNA polymerase II transcription factor activity
meiosis
response to stress
cytochrome c oxidase complex assembly
chromatin remodeling
membrane
actin binding
iron ion homeostasis
protein targeting to vacuole
Golgi to endosome transport
cytokinesis, contractile ring formation
calcium ion binding
hexose transporter activity
mitochondrial large ribosomal subunit
Hsp70 protein binding
integral to membrane
nuclear mRNA splicing, via spliceosome
peroxisomal membrane
ER to Golgi transport vesicle
Golgi to vacuole transport
condensed nuclear chromosome kinetochore
FAD binding
lipid metabolism
peptide alpha−N−acetyltransferase activity
chromosome organization and biogenesis (sensu Eukaryota)
mitochondrial inner membrane
ER to Golgi vesicle−mediated transport
sulfur metabolism
protein ubiquitination during ubiquitin−dependent protein catabolism
actin cortical patch
nuclear envelope−endoplasmic reticulum network
carrier activity
3−5−exoribonuclease activity
protein binding, bridging
vacuolar membrane (sensu Fungi)
mitochondrial nucleoid
G1/S transition of mitotic cell cycle
eukaryotic translation initiation factor 3 complex
response to DNA damage stimulus
0.2
Group 1
electron transport
extracellular region
mitochondrial electron transport, ubiquinol to cytochrome c
cAMP−mediated signaling
proteasomal ubiquitin−dependent protein catabolism
ATP synthesis coupled proton transport (sensu Eukaryota)
phosphoinositide binding
mitochondrial matrix
signal transduction
proteasome regulatory particle, base subcomplex (sensu Eukaryota)
endopeptidase activity
damaged DNA binding
external side of plasma membrane
mitochondrial genome maintenance
protein amino acid dephosphorylation
aerobic respiration
clathrin binding
autophagy
oxysterol binding
general RNA polymerase II transcription factor activity
meiosis
response to stress
cytochrome c oxidase complex assembly
0.0
Group 2
30
40
50
N = 111 Bandwidth = 0.8769
For any given group of genes, a distance based
on expression values can be calculated between
two conditions, such as wt and mutant. For the
example above, distances between wt ant mutant
were calculated for groups containing randomly
chosen genes. One can see that groups with random
members give a distribution of distances. However
when distances are calculated for groups of genes
based on Gene Ontology terms, some groups partition
themselves far away from the mean. In this case,
groups relevant to ER stress distinguish themselves.
Alternative methods of group analysis exist but all
require a source of groups.
m
1
group
id
description
group_name
date
creator
visibility
downloads
Chris Seidel, Managing Director of Microarray, Stowers Institute
cws@stowers-institute.org
http://research.stowers-institute.org/microarray/gene_groups
Acknowledgements
m
Thanks to Elena Hidalgo for the S. pombe untreated vs. osmotic shock data and
Antony Cooper for the ER stress data.
1
References
group_tag
group_id
tag_id
group_gene
group_id
gene_id
1
1
Breitling, R., Amtmann, A., & Herzyk, P. (2004). BMC Bioinformatics, 5.
m
m
tag
id
tag
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., & Cherry, J. M. et al. (2000). Nature Genetics,
25(1), 25-29.
gene
id
gene_name
Breslin, T., Ede´n, P., & Krogh, M. (2004). BMC Bioinformatics, 5.
Newman, J. C., & Weiner, A. M. (2005). Genome biology, 6
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., & Gillette, M. A. et al. (2005).