http://pastime.cgu.edu.tw/petang/index.htm
Bioinformatics 95
Lecture 1 – Introduction to
Bioinformtics
Petrus Tang, Ph.D. (鄧致剛)
Graduate Institute of Basic Medical Sciences
and
Bioinformatics Center, Chang Gung University.
petang@mail.cgu.edu.tw
EXT: 5136
助教：
葉元鳴 (分機)
曾詩涵 (分機5690)
Bioinformatics: A Practical Guide to the Analysis of
Genes & Proteins
Contents
Bioinformatics and the Internet
The NCBI Data Model
The GenBank Sequence Database
Structure Databases
Genomic Mapping and Mapping Databases
Information Retrieval from Biological
Databases
Sequence Alignment and Database
Searches
Multiple Sequence Alignment
Predictive Methods using DNA Sequences
Predictive Methods using Protein
Sequences Expressed Sequence Tags
Sequence Assembly and Finishing
Methods Phylogenetic Analysis
Comparative Genome Analysis
Using Perl to Facilitate Biological Analysis
432 pages (2001) Wiley-Liss; ISBN: 0471383910
WHAT IS
BIOINFORMATICS?
?
AGCTAGCTAGCTAGCTAGCTAGCTAGCTAGCTAGCTAGCT
AGCTAGCTAGCTAGCTAGCTAGCTATCGATGCATGCATGCATGCA
TGCATGCATGCATGCACTAGCTAGCTAGTGCATGCATGCATG
AGGTTGACCAATGTGAAATGGCCAATTGATGACCAGAGATTTAGGCCAATTAA
AGGTTGACCAATGTGAAATGGCCAATTGATGACCAGAGA
What is Bioinformatics?
The answer to this question depends on whether you are talking to
A computer scientist who 'does' biology, or
A molecular biologist who 'does' computing.
Bioinformatics is the application of computer technology to the management
of biological information. Computers are used to gather, store, analyze and
integrate biological and genetic information which can then be applied to
gene-based drug discovery and development.
結合生物學、計算機科學與資訊學的技術,應用於生物化學資料的處理，
將繁瑣無意的資料轉化成有意義、有價值的訊息。
Biology
Technology
Mathematics
Chemistry
Physics
Information
Protein coding sequence
3‘UTR
5‘UTR
promotor
exon 1
exon 2
exon n-1
exon n
Gene prediction
Codon usage (single exon)
coding
Frame 1
non-coding
Frame 2
coding sequence
Frame 3
correct start
Gene prediction
Codon usage (multiple exons)
coding
Frame 1
non-coding
Frame 2
Frame 3
Splice sites
Exons:
208. .295
1029. .1349
1500. .1688
2686. .2934
3326. .3444
3573. .3680
4135. .4309
4708. .4846
4993. .5096
7301. .7389
7860. .8013
8124. .8405
8553. .8713
9089. .9225
13841. .14244
Drosophila
Nucleic Acid
Binding
Functional Assignment8%
using
Hypothetical
11%
Enzyme
Gene Ontology
18%
Signal
Transduction
4%
Transporter
4%
13,601 Genes
Structural Protein
2%
Unknown
48%
Ligand Binding or
Carrier
2%
Motor Protein
1%
Nucleic Acid Binding
Transporter
Cell Adhesion
Unknown
Enzyme
Structural Protein
Chaperone
Hypothetical
Chaperone
1%
Cell Adhesion
1%
Signal Transduction
Ligand Binding or Carrier
Motor Protein
Gene Number in the Human Genome
Number of genes
10 K
Known genes
20 K
30 K
Otto
4
3
2
40 K
1
50K
Confidence
Experiment
Driven
Hypothesis
Experiments
Results
Information
Driven
Experiments
Hypothesis
THE COMPONENTS OF
BIOINFORMATICS
TECHNOLOGY
ALGORITHM
ANALYSIS
TOOLS
DATABASE COMPUTING
POWER
DNA
Genome
RNA
protein
Transcriptome
Proteome
phenotype
DNA Sequencing
MegaBRACE 1000
96 DNA sequencing in 2 hrs, approximately 600-800 readable bps per run.
1,000,000 bps in 24 hrs.
Microarray
10,000
Clones
per
slide
Proteomics
2 Dimensional Electrophoresis gels,
differences that are characteristics of
the individual starting states
recognized by comparison of two
protein pattern
6,000
protein spots
per gel
MALDI-MS peptide mass
fingerprint, for identification of
proteins separated by 2D
electrophoresis
3D Modeling
DNA
Genome
Projects
RNA
Microarry
ESTs
SAGE
protein
phenotype
2D Electrophoresis
Protein Modeling
Protein-Protein Interaction
Genetic Sequence Data Bank Aug 15
2006, Release 155.0
65,369,091,950 bases, from
61,132,599 reported sequences
Homo sapiens
12,385,903,706 bases from
10,649,134 sequences
Expressed sequence tags
7,893,983
Recent years have seen an explosive growth in biological data. Large sequencing projects are producing
increasing quantities of nucleotide sequences. The contents of nucleotide databases are doubling in size
approximately every 14 months. The latest release of GenBank (V.139) exceeded two billion base pairs.
Not only the size of sequence data is rapidly increasing, but also the number of characterized genes from
many organisms and protein structures doubles about every two years. To cope with this great quantity of
data, a new scientific discipline has emerged: bioinformatics, biocomputing or computational biology
Entries
10649134
6753652
1267882
1663937
1287702
2499723
1149146
226213
1236899
1175934
1426915
655519
800633
1198209
209185
868038
397437
784170
69335
696319
Bases
12385903706
8049817803
5747965742
3566605068
2540551749
1998269811
1500985768
1251961979
1075752229
961525020
893771790
845341580
770627209
758043364
691252171
507883206
468939096
465881813
463195893
421330392
Species
Homo sapiens
Mus musculus
Rattus norvegicus
Bos taurus
Danio rerio
Zea mays
Oryza sativa
Strongylocentrotus purpuratus
Sus scrofa
Xenopus tropicalis
Canis familiaris
Drosophila melanogaster
Gallus gallus
Arabidopsis thaliana
Pan troglodytes
Triticum aestivum
Medicago truncatula
Sorghum bicolor
Macaca mulatta
Ciona intestinalis
THE COMPONENTS OF
BIOINFORMATICS
TECHNOLOGY
ALGORITHM
ANALYSIS
TOOLS
DATABASE COMPUTING
POWER
The International Nucleotide
Sequence Database Collaboration
GenBank: http://www.ncbi.nlm.nih.gov/
National Center for Biotechnology Information (NCBI)
DDBJ: http://www.ddbj.nig.ac.jp/
National Institute of Genetics (NIG)
EMBL: http://www.ebi.ac.uk
European Bioinformatics Institute (EBI)
ExPASy: http://tw.expasy.org
Expert Protein Analysis System
GenBank/EMBL/DDBJ
International
Nucleotide Sequence Database
DDBJ: DNA Data Bank of Japan
CIB: Center for Information Biology and
DNA Data Bank of Japan
NIG: National Institute of Genetics
IAM: International Advisory Meeting
ICM: International Collaborative Meeting
NCBI:
National Center for Biotechnology Information
NLM:
National Library of Medicine
EMBL:
European Molecular Biology
Laboratory
EBI:
European Bioinformatics
Institute
Protein Databases
Protein Information Resources (PIR)
http://pir.georgetown.edu/
In 1988, The Protein Information Resource (PIR), established a cooperative effort with
the Munich Information Center for Protein Sequences (MIPS) and the Japan
International Protein Information Database (JIPID) , produces the PIR-International .
Protein Sequence Database (PIR-PSD) -- a comprehensive, non-redundant, expertly
annotated, fully classified and extensively cross-referenced protein sequence database
in the public domain. The PIR-PSD, PIR-NREF, iProClass and other PIR auxiliary
databases provide an integration of sequences, functional, and structural information to
support genomics and proteomics research
The PIR-PSD, Current Release 71.04, March 01, 2002, Contains 283153 Entries
SWISSPROT
http://www.ebi.ac.uk/swissprot/
The SWISS-PROT Protein Knowledgebase is an annotated protein sequence database
established in 1986. It is maintained collaboratively by the Swiss Institute for Bioinformatics
(SIB) and the European Bioinformatics Institute (EBI).
Protein Databases
ExPASY Molecular Biology Server
http://tw.expasy.org
The ExPASy (Expert Protein Analysis System) proteomics server of the Swiss Institute
of Bioinformatics (SIB) is dedicated to the analysis of protein sequences and structures
as well as 2-D PAGE
Protein Data Bank
http://www.rcsb.org
The Protein Data Bank (PDB) is operated by Rutgers, The State University of
New Jersey; the San Diego Supercomputer Center at the University of
California, San Diego; and the National Institute of Standards and
Technology -- three members of the Research Collaboratory for Structural
Bioinformatics (RCSB). The PDB is supported by funds from the National
Science Foundation, the Department of Energy, and two units of the
National Institutes of Health: the National Institute of General Medical
Sciences and the National Library of Medicine.
Metabolic & Signalling Pathways
Biocarta
( http://biocarta.com)
Kyto Encyclopedia of Genes &Genomes
http://www.genome.ad.jp/kegg/
The Cancer Genome Anatomy Project
(CGAP) http://cgap.nci.nih.gov/
THE COMPONENTS OF
BIOINFORMATICS
TECHNOLOGY
ALGORITHM
ANALYSIS
TOOLS
DATABASE COMPUTING
POWER
BIOINFORMATICS ANALYSIS TOOLS
$ Vector NTI suite, Omiga, DNAsis
$ Staden Package, EMBOSIS, BLAST, FASTA
On line analysis tools
http://bioinfo.nhri.org.tw/
國家衛生研究院巨分子序列分析服務
巨 分 子 序 列 分 析 服 務 GCG
在 Unix 系 統 下 以 Command Mode 進 行 核 酸 或 蛋 白 質 的 序 列 分 析 。
( telnet://bioinfo.nhri.org.tw )
巨 分 子 序 列 分 析 服 務 SeqWeb
連 線 至 SeqWEB 以 瀏 覽 器 進 行 核 酸 或 蛋 白 質 的 序 列 分 析 。
(http://bioinfo.nhri.org.tw/)
EMBOSS
連 線 至 SeqWEB 以 瀏 覽 器 進 行 核 酸 或 蛋 白 質 的 序 列 分 析
(http://srs.nchc.org.tw/EMBOSS/)
Smith-Waterman 快 速 序 列 搜 尋 系 統 GenWEB
直 接 連 線 至 GenWeb 以 瀏 覽 器 進 行 核 酸 或 蛋 白 質 的 快 速 序 列 搜 尋 。
以 特 殊 設 計 的 硬 體 加 速 序 列 搜 尋 的 速 度 , 可 進 行 Smith-Waterman 及
FrameSearch 等 搜 尋 功 能 。
(http://sw.nhri.org.tw/cgi-bin/genweb/bin/login.cgi)
ExPASy (Expert Protein Analysis System)
連 線 至 ExPASy 以 瀏 覽 器 進 行 蛋 白 質 的 序 列 分 析 。
(http://tw.expasy.org)
THE COMPONENTS OF
BIOINFORMATICS
TECHNOLOGY
ALGORITHM
ANALYSIS
TOOLS
DATABASE COMPUTING
POWER
設備
醫學大樓9樓0917
SunFire 6800
16 CPU
設備
COMPUTER
SunFire 6800
Sun V60 Cluster
IBM X336 Cluster
IBM X225 Cluster
HP DL580G3 Cluster
LunuxWorX Cluster
IBM Z-pro Graphic Station
教學電腦
教學電腦
CPU
Sparc 750 MHz
Xeon 2.8 GHz
Xeon 3.2 GHz
Xeon 2.4 GHz
Xeon 3.0 GHz
Xeon 2.4 GHz
Xeon 3.2 GB x 2
P4 2.4 GHz
P4 3.2 GHz
ITEMS
Proware RAID System
Petastor Fibre RAID System
Proware NAS System
Brocad silkworm 2G Fibre switch
UPS
UPS
Video Conference System
Telephone Conference System
NO.
24
20
14
2
16
8
2
15
15
MEMMORY
48 GB
20 GB
14 GB
1.5GB
16 GB
8 GB
3 GB
512 MB
1 GB
SPECIFICATION
250 GB x 16 (4 TB)
400 GB x 16 (6.4 TB x 4)
80 GB x 8 (640 GB)
12 ports
10 KVA
30 KVA
Centura
Polycom sound station
NO
1
4
1
1
1
2
50
1
設備
[Vector NTI Advanced Server]
[GENOMAX High-Throughout Sequence Analysis System]
[Paracel BLAST] [Paracel TranscriptAssembler]
[Bioinformatics Linux Cluster]
[Expression Sequence Tag Analysis Pipeline]
[Protein Sequence Analysis Pipeline]
[Protein Modeling & Docking System]
[Lead Compound Database]
[ The European Molecular Biology
Open Software Suite ]
[Sequence Retrieval System]
[MetaCore:
PPI Network]
[Expressionist]
Steps to Identify a Gene
Gene-Search
Protein-Search
Annotation
Full length ORF of TvEST-14G2
-2
101
201
301
401
501
601
701
801
901
1001
1101
1201
1301
1401
1501
1601
…AGATGCGAAAAA
AAGTTTCGGA
TTGCTCTCAA
GAAGCCAAGC
TGTAGAACCA
AGACAACTAA
TTAGTTTCAT
CGGACAAATG
ACCGCGACAT
AACAAAATTT
AAATAATCGT
CAAGATATTC
GATGACATGG
TCTTCCTTGG
TTTTAATGAA
AATAGTTTCT
AGAAGAACCA
TTGCTGATCA
ATTGTTCGCC
AGGAAAATGT
GATATTCTTC
ATTAAGAACA
CCTTGATGAA
ATCAGAAACC
ATGAGATCAA
TTCGGCAGTT
CACATCCTGC
TCTTCTACAA
GGCTTCATCA
ACGGAATTCG
AGTAAGCCTC
GGCTCCTCTC
TTTTCTTTTT
TCTACGGCAA
GAGGTTTGGG
ATTAGAGCCC
TATACTCAAT
TGCAACAACA
CTACATGGCC
CGGTCCCTAG
ATTTCCTGTG
CAAGCCAGAT
ATATTATCGA
CATATTAGAA
ATCAATTAAT
AATCTTTGGT
ATGAGCTTAC
GAAGAGATCA
TTGTAAACTA
AATTACGCGA
AATTCCTTTT
CACAACGTGA
CCAAACTCAG
GCACAGACAA
GTAGTTCAAG
TCATCTCAAG
ATATACACCG
AGACTACAAT
AAGAAAGAAT
AACTACAAAA
CGAAACCGGC
AGACGTACAT
CCCTGCAAAG
CGGTATCTTA
ACATCTCGTC
CTATCTGTAT
TTACATTACG
AAGCTGTCAG
CGAAACTCTA
GTTTCAGGCT
TTCCAGTTGT
ATGGAATTAC
ATTTTCCCAA
TTGAATTCGT
AATTTTGCGA
TTTTGGACTT
ATTGCACAGG
GCGCTCGAAG
ATATGTCTGG
CTACAACAGG
ACGAAACCCG
CTTAATAGCA
TGTACAGGAA
GATTATCGCT
AAACCAATCA
CTGAGTTTGA
GTACAAAGCC
TCCATCAAAG
ATAAAAAGCC
CCACGTACAA
CAATACTGCA
CGTCAGCAAC
ACAACAAAAA
AACTACGAGC
CAACTCTACG
GAAAGAACTG
CCGTACTGGA
GCTGAAATAT
ATTAAATGTA
CAGAAGCGTC
TCATTCGACC
GTGTTCCACA
TCAAAATCCA
TTATGCGACT
TTGGCAAGTC
AAGACAATAT
TCACAAACAT
TGGGAGTCAG
TCCAAGAAGT
AAAATCACTT
GAAAGGAACA
GTTTATTTAC
CCGCAAGAAG
AAGAATTATG
GTTCGCTCAT
AATGATATAC
ATGATTGGGT
CAGTTGTCCG
TGGTTTCTCC
CCGTTTCATC
GATATTTTGC
AATCAAAGCT
TTAATACTAC
AGAACAACAG
AAGGACTGTT
CTGTAAATAG
TCTCACAAAG
TTCAAGTCGC
CGCTTTTCAC
ATGCTTCCGA
ATTTTTTATA
TTTCTATATT
TCGGTTCAGG
GGACAAAAGG
ATTATTTTTC
CAAATAATAG
GGTCAAACAG
TCTGGAAGAT
TAATGCTTGC
AATTTTATTC
TGAGAACTCA
ACATTGACCA
ACCGGAACCG
GTCTATAAGA
TTCATGGACG
TATGAGGCCA
TTTAGGACTT
TGAAATTTGA
GACGCAATGA
CAAAACGAGA
AACGTCAAGA
TCCATCAAAG
TAGAGATGTC
AATCATCAAC
GTCGAATCGA
CGAAACAAGA
CAAAGAACTC
AAGAAAGAAA
ACAATTGAAC
ACTCAGAACC
CGCCAAAATG
AGCTACAGCC
AATGGATGAT
TTATTTATTT
ATTAAAAAAA
Amino Acid Sequence Comparison
(1)
01B1 (1)
1B1(final)
04E12 (1)
CK1-1_full
14G2 (1)
CK1-2_full
ciparum
) (1)
PFCK
s pombe)
Yeast (1)
sapiens
) (1)
Human
musculus
) (1)
Mouse
oma
cruzi) (1)
TcCK1.1
ma cruzi ) (1)
TcCK1.2
onsensus (1)
1
(151)
01B1 (131)
1B1(final)
04E12(139)
CK1-1_full
CK1-2_full
14G2 (147)
ciparum
) (139)
PFCK
s pombe)
Yeast(141)
sapiens
) (139)
Human
usculus
) (139)
Mouse
maTcCK1.1
cruzi) (142)
maTcCK1.2
cruzi ) (144)
onsensus (151)
151
(301)
1B1(final)
01B1 (273)
CK1-1_full (289)
04E12
CK1-2_full (295)
14G2
ciparum ) (289)
PFCK
s pombe) (291)
Yeast
sapiens ) (289)
Human
musculus ) (289)
Mouse
ma
cruzi) (292)
maTcCK1.1
cruzi ) (294)
TcCK1.2
onsensus
(301)
301
(451)
1B1(final)
01B1 (397)
K1-1_full
04E12(410)
K1-2_full
14G2 (445)
ciparum
) (325)
PFCK
s pombe)
Yeast (366)
Human
sapiens
) (410)
Mouse
usculus
) (410)
maTcCK1.1
cruzi) (313)
maTcCK1.2
cruzi ) (331)
nsensus (451)
451
10
20
30
40
50
60
70
80
92 93
(93)
100
110
120
130
140
150
Translation of 01B1(final) (73) TMELLGDSLEKLFERCGRKFSLKTVLMLADQMIKCVQYIHTKSFIHRDIKPENFTIGTGPN
----------MKVGERIGGGSYGNIFYAYNTANKKELALKIESEKTKRSQIFNEYRALKCLAGY----------VGIPKVYFETCYGNQNAF
Translation of CK1-1_full (81) VIDLLGKSLEEHLNKVNRRMSLKTVLMLVDQMITAVEFFHSKNYIHRDIKPDNFVMGVNQN
--MEEICGGEYQIIKKIGQGSFGKIYIIKQVKTGLLFAAKLENSDAPIPQLLFESRLYQIMSGS----------TNVPRLHAHSFDSRYNTI
Translation of CK1-2_full (90) AMELLGKSLEDLVSSVP-RFSQKTILMLAGQMISCVEFVHKHNFIHRDIKPDNFAMGVSEN
---MRKIYGNYITQKRLGSGSFGEVWEAVSHSTGQKVALKLEPRNSSVPQLFFEAKLYSMFQASKSTNNSVEPCNNIPVVYATGQTETTNYM
Translation of CK1(Plasmodium falciparum ) (81) VLDLLGPSLEDLFTLCNRKFSLKTVRMTADQMLNRIEYVHSKNFIHRDIKPDNFLIGRGKK
--MEIRVANKYALGKKLGSGSFGDIYVAKDIVTMEEFAVKLESTRSKHPQLLYESKLYKILGGG----------IGVPKVYWYGIEGDFTIM
Translation of CK1(Schizosaccharomyces pombe) (83) VMDLLGPSLEDLFNFCNRKFSLKTVLLLADQLISRIEFIHSKSFLHRDIKPDNFLMGIGKR
MALDLRIGNKYRIGRKIGSGSFGDIYLGTNVVSGEEVAIKLESTRAKHPQLEYEYRVYRILSGG----------VGIPFVRWFGVECDYNAM
Translation of CK1(Homo sapiens ) (81) VMELLGPSLEDLFNFCSRKFSLKTVLLLADQMISRIEYIHSKNFIHRDVKPDNFLMGLGKK
--MELRVGNKYRLGRKIGSGSFGDIYLGANIASGEEVAIKLECVKTKHPQLHIESKFYKMMQGG----------VGIPSIKWCGAEGDYNVM
Translation of CK1(Mus musculus ) (81) VMELLGPSLEDLFNFCSRKFSLKTVLLLADQMISRIEYIHSKNFIHRDVKPDNFLMGLGKK
--MELRVGNKYRLGRKIGSGSFGDIYLGANIASGEEVAIKLECVKTKHPQLHIESKFYKMMQGG----------VGIPSIKWCGAEGDYNVM
Translation of CK1.1(Trypansoma cruzi) (84) VMDLLGPSLEDLFSFCGRKLSLKTTLMLAEQMIARIEFVHSKSVIHRDMKPDNFLMGTGKK
--MNLMIANRYCISQKIGAGSFGEIFRGTNMQTGETVAIKLEQAKTRHPQLAFEARFYRILNAGGGV-------VGIPNILFYGVEGEFNVM
Translation of CK1.2(Trypansoma cruzi ) (86) VMDLLGPSLEDLFSFCDRKLSLKTTLMLAEQMIARIEFVHSKSVIHRDMKPDNFLMGTGKK
MSLELRVGNRFRLGQKIGAGSFGEIFRGTNIQTGETVAIKLEQAKTRHPQLALEARFYRILNAGGGV-------VGIPNILFYGVEGEFNVM
(93) VMDLLGPSLEDLF FC RKFSLKTVLMLADQMISRIEFIHSKNFIHRDIKPDNFLMGLGKK
MELRVGNKYRLGKKIGSGSFGDIYLG NI TGEEVAIKLE KTKHPQL FESR YKILQGG
VGIP I WConsensus
G EGDYNVM
160
170
180
190
200
210
220
230
(243)
242243
250
260
270
280
290
300
Translation of 01B1(final) (215) IKLSTSVEELCEGLPVEFSIFLQDMRKLDFEEEPNYSKYLQLFRSLFLNSGFVYDDVYDWTL
GPNSNVIYIIDFGLAKRYINGQTLTHIPYREGRSFTGTTRYGSINDHLDIEQSRRDDMESLAYTLIYFLKGFLPWHGCKRETFQ-------Translation of CK1-1_full (231) CKRDTPLEKLCEGLPSEIITYIRKVRSLRFTERLHYASYRRLFRGLFRAMQFTFDYIYDWSP
NQNSNKLYIIDYGLAKKYRDVNTHEHIPYIEGKSLTGTARYASINALLGCEQSRRDDMEAIGYVIVYLLKGHLPWMGIDGATNQERYRRIAE
Translation of CK1-2_full (237) KKRSTKPEELCLGLNSFFVNYLIAVRSLKFEEEPNYAMYRKMIYDAMIADQIPFDYRYDWVK
SENSNKIYIIDFGLSKKYIDQ-NNRHIRNCTGKSLTGTARYSSINALEGKEQSIRDDMESLVYVWVYLLHGRLPWMSLPTTGRK-KYEAILM
Translation of CK1(Plasmodium falciparum ) (231) KKISTSVEVLCRNASFEFVTYLNYCRSLRFEDRPDYTYLRRLLKDLFIREGFTYDFLFDWTGKKVTLIHIIDFGLAKKYRDSRSHTSYPYKEGKNLTGTARYASINTHLGIEQSRRDDIEALGYVLMYFLRGSLPWQGLKAISKKDKYDKIME
Translation of CK1(Schizosaccharomyces pombe) (233) KKISTPTEVLCRGFPQEFSIYLNYTRSLRFDDKPDYAYLRKLFRDLFCRQSYEFDYMFDWTL
GKRGNQVNIIDFGLAKKYRDHKTHLHIPYRENKNLTGTARYASINTHLGIEQSRRDDLESLGYVLVYFCRGSLPWQGLKATTKKQKYEKIME
Translation of CK1(Homo sapiens ) (231) KKMSTPIEVLCKGYPSEFSTYLNFCRSLRFDDKPDYSYLRQLFRNLFHRQGFSYDYVFDWNM
GKKGNLVYIIDFGLAKKYRDARTHQHIPYRENKNLTGTARYASINTHLGIEQSRRDDLESLGYVLMYFNLGSLPWQGLKAATKRQKYERISE
Translation of CK1(Mus musculus ) (231) KKMSTPIEVLCKGYPSEFSTYLNFCRSLRFDDKPDYSYLRQLFRNLFHRQGFSYDYVFDWNM
GKKGNLVYIIDFGLAKKYRDARTHQHIPYRENKNLTGTARYASINTHLGIEQSRRDDLESLGYVLMYFNLGSLPWQGLKAATKRQKYERISE
Translation of CK1.1(Trypansoma cruzi) (234) CKMSLSLETLCKGFPAEFAAYLNYTRGLRFEDKPDYSYLKRLFRELFIREGYHVDYVFDWTL
GKKGHHVYVVDFGLAKKYRDPRTHQHIPYKEGKSLTGTARYCSINTHLGIEQSRRDDLEGIGYILMYFLRGSLPWQGLPAATKQEKYVAIAK
Translation of CK1.2(Trypansoma cruzi ) (236) RKQTTPVETLCKGFPAEFAAYLNYIRSLRFEDKPDYSYLKRLFRELFIREGYHVDYVFDWTL
GKKGHHVYVVDFGLAKKYRDPRTHQHIPYKEGKSLTGTARYCSINTHLGIEQSRRDDLEGIGYILMYFLRGSLPWQGLKAHTKQEKYSRISE
Consensus
(243) KKMSTPVE LCKGFPSEFS YLNY RSLRFEDKPDYSYLRRLFRDLFIR GF YDYVFDWTL
GKKGN VYIIDFGLAKKYRD RTH HIPYREGKSLTGTARYASINTHLGIEQSRRDDLESLGYVLMYFLRGSLPWQGLKA TKK
KYERISE
310
320
330
340
350
360
370
380
(393)
392393
400
410
420
430
440
450
Translation of 01B1(final) (344) PKRFSLETNQTLLSLFNK-SVNDYF-G-ILFLI-GFIFLSGKYGIVGKKKKKKKKKK--DWTLLPEEPPRPHFKQDVFNSKISN---------DDSSDSIIKTKQPHREKSAGTSRLSLISLPTQNVLAQSGIFLTK------------KP
Translation of CK1-1_full (352) VEVKQIELSSSSSQDKPKTKPNYMREIDAILNRVKPIQTPKIVSHLPPPPIEELPKKLRK
DWSPRKDNDVPPVRYTRRKGQMP-----------------VNERRPSIEAVFSGERRRRSEENMRTIDFENEEIPEPK------------KP
Translation of CK1-2_full (387) PYTPPRTINTTETRMRSKTTINTARTTAKNSSAVKKESSATRTVKKETHPATTKTTKTVN
DWVKTRIVRPQRENQSQLSERQEGKCPNSAEFDGFSSIKGYSSHRQVQSPVSSRDVIKNSSSSPSKDILQSSTLDESSQDKKPIKAVESNQK
Translation of CK1(Plasmodium falciparum ) (325) -----------------------------------------------------------DWT---------CVYASEKDKKK-----------------MLENKNRFDQTADQEGRDQRNN-----------------------------Translation of CK1(Schizosaccharomyces pombe) (343) INTTVPVINDPSATGAQYINRPN------------------------------------DWTLKRKTQQDQQH---------------------------QQQLQQQLSATPQAINPP-PERSSFRNYQKQNFDEKG------------GD
Translation of CK1(Homo sapiens ) (352) PASRIQPAGNTSPRAISRVDRERKVSMRLHRGAPANVSSSDLTGRQEVSRIPASQTSVPF
DWNMLKFGAARNPEDVDRERREH-----------------EREERMGQLRGSATRALPPGPPTGATANRLRSAAEPVA------------ST
Translation of CK1(Mus musculus ) (352) PASRIQQTGNTSPRAISRADRERKVSMRLHRGAPANVSSSDLTGRQEVSRLAASQTSVPF
DWNMLKFGAARNPEDVDRERREH-----------------EREERMGQLRGSATRALPPGPPTGATANRLRSAAEPVA------------ST
Translation of CK1.1(Trypansoma cruzi) (313) -----------------------------------------------------------DWTLKRIHESLQDE-----EKEL-----------------SNN------------------------------------------------Translation of CK1.2(Trypansoma cruzi ) (331) -----------------------------------------------------------DWTLKRIHENLKAEGSG--QQEQ-----------------KQQQQQQRERGDVEQA-----------------------------------Consensus (393)
T
K
DWTL R
R
RQ
SA
460
470
480
490
500
510
520
530
542
-------------------------------------------------------------------------------------------RKEEEKTHHHRKLSGHRTHHHESKRVVKKEKTKVEEEEEIIPKRFTKRKELEMPSDDEPLTSVDEFLIRRGLMKPRKPKI-Y-FFYCLYLFF
VNRQLNSSTTKPATTSSHKDSEPASSRRTSTLRSSRRQNDGIRPAKERTALFTATASKPPVSYRTGMLPKWMMAPLTSRR-NIFFILFIFFF
--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------PFDHLGK------------------------------------------------------------------------------------PFDHLGK---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
: kinesin homology domain
: casein kinase 1 specific motifs
PFCK : Plasmodium casein kinase 1
TcCK1.1: Trypansoma cruzi casein kinase 1.1
TcCK1.2: Trypansoma cruzi casein kinase 1.2
Similarity of Various CK1s from
Different Species
TvEST04E12
TvEST14G2
TvEST01B1
T. cruzi
CK1.1
T. cruzi
CK1.2
PFCK
Yeast
CK1
Mouse
CK1
Human
CK1
TvEST04E12
TvEST14G2
TvEST01B1
T. cruzi
CK1.1
T. cruzi
CK1.2
PFCK
Yeast
CK1
Mouse
CK1
Human
CK1
100
32
32
34
34
34
37
37
37
100
24
24
23
24
24
26
25
100
47
47
48
48
38
38
100
23
73
24
61
61
100
74
70
63
63
100
69
62
62
100
69
67
100
99
100
3-D Structure of TvEST-14G2
and other CK1s
TVEST-14G2
TcCK1.1
TcCK1.2
1
MRKIYGNYIT QKRLGSGSFG EVWEAVSHST GQKVALKLEP RNSSVPQLFF
51
EAKLYSMFQA SKSTNNSVEP CNNIPVVYAT GQTETTNYMA MELLGKSLED
101
LVSSVPRFSQ KTILMLAGQM ISCVEFVHKH NFIHRDIKPD NFAMGVSENS
151
NKIYIIDFGL SKKYIDQNNR HIRNCTGKSL TGTARYSSIN ALEGKEQSIR
201
DDMESLVYVW VYLLHGRLPW MSLPTTGRKK YEAILMKKRS TKPEELCLGL
251
NSFFVNYLIA VRSLKFEEEP NYAMYRKMIY DAMIADQIPF DYRYDWVKTR
301
IVRPQRENQS QLSERQEGKC PNSAEFDGFS SIKGYSSHRQ VQSPVSSRDV
351
IKNSSSSPSK DILQSSTLDE SSQDKKPIKA VESNQKPYTP PRTINTTETR
401
MRSKTTINTA RTTAKNSSAV KKESSATRTV KKETHPATTK TTKTVNRQLN
451
SSTTKPATTS SHKDSEPASS RRTSTLRSSR RQNDGIRPAK ERTALFTATA
501
SKPPVSYRTG MLPKWMMAPL TSRR
PfCK1
Yeast CK1
Mouse CK1
Human CK1-δ
B
I
O
I
N
F
O
R
M
A
T
I
C
S
I
C
S
疾病預測及診斷,新基因的發現
基因演化整體功能及其網路調節系統
藥物設計及生物大分子結構
GENOMICS
GENE EXPRESSION ANALYSIS
PROTEOMICS
MEDICAL INFORMATICS
B
I
O
I
N
F
O
R
M
A
T
Focuses in Bioinformatics
Perturbation
Dynamic Response
Environment
Medication
Genetic Engineering
Gene Expression
Protein Expression
Virtual Cell
Analysis
BioChip
DataBase
Genotype/Phenotype
Biology
Molecular Biology
Bio Chemistry
Genetics
Symbolic
Algorithms/
Computing
Genome Sequencing
Goals Leading Toward Predictive
Biology
Gene Sequence Data
Gene Identification
IL-3
Structure Prediction
FAS-L
IGF1
IGF1R
FAS
mitogen
IL-3R
FADD/MORT
IRS1
FLICE
P21
Cyclin D1
RAS
pRb
P16
Cdk4
ICE
PI 3-K
Protein Circuit &
Regulatory Network
Discovery
P53
P27
P107
Bin-1
E2F
CPP32
AKT/PKB
apoptosis
Bcl-XL
BAD
Mad
Max
C-Myc
C-Myc
Max
Max
Mad
Cyclin E
Cdc25A
?
cell proliferation
Cyclin E
Cdk2
p
Cdk2
P27
p
Cyclin E
Cyclin E
Cdk2
p
Cdk2
Biosimulation
Reconstructing Cellular
Functions
Reductionistic
Approach
(Genome Sequencing,
DNA arrays, proteomics)
20th Century
Biology
Integrative
Approach
(Bioinformatics,
Systems Science,
modeling &
simulation)
21th Century
Biology
Hallmarks of Cancer
D. Hanahan and R. A. Weinberg. Cell., 100(1):57–70 Review, 2000.
Platform for Systems
Biology
• Objective is to link gene response, protein activity,
metabolite dynamics to disease and interventions
Gene
Quantitative
Comparisons
protein index
metabolite index
Protein
Complex Cellular Samples
bodyfluids, tissue
BioSystematics
TM
Dynamics
i.e. environmental + time
Metabolite
Targets
Biomarkers
9
8
7
6
5
4
3
2
1
0 ppm
SYSTEMS BIOLOGY
R
HO
Genomics
Proteomics
Metabolomics
Transcriptomics
Functional Proteomics/Genomics
Systems Biology
Q. As a biologist, what skills do I need to make the transition to bioinformatics?
The fact is that many of the jobs available CURRENTLY involve the design and
implementation of programs and systems for the storage, management and
analysis of vast amounts of DNA sequence data. Such positions require in-depth
programming and relational database skills which very few biologists possess,
and so it is largely the computational specialists who are filling these roles. This
is not to say the computer-savvy biologist doesn't play an important role. As the
bioinformatics field matures there will be a huge demand for outreach to the
biological community, as well as the need for individuals with the in-depth
biological background necessary to sift through gigabases of genomic sequence
in search of novel targets. It will be in these areas that biologists with the
necessary computational skills will find their niche.
A. Molecular biology packages (GCG, BLAST etc),
Web and programming skills including HTML, Perl, JAVA and C++,
Familiar with a variety of operating systems (especially UNIX),
Relational database skills such as SQL, Sybase or Oracle,
Statistics,
Structural biology and modeling,
Mathematical optimization,
Computer graphics theory and linear algebra.
You will need to be able to readily pick up, use and understand the tools and
databases designed by computer programmers, and
To communicate biological science requirements to core computer scientists.