Array studyArray studydiscovery-drivendiscovery-driven

Where is the hypothesis ?Where is the hypothesis ?

Cell, Vol. 104, 333–339, 2001

Generation of Biological Theme by Gene Generation of Biological Theme by Gene OntologyOntology

Pathway - a direct guessPathway - a direct guess

Correlation to other gene listCorrelation to other gene list

Co-transcription control hypothesis - a wild Co-transcription control hypothesis - a wild guessguess

Gene List (expression)

Protein-protein Interaction

Function Association

GO

Pathway

MAPPFinder/GoMinerGSCope/DAVID

GenMAPP

Osprey

GSCopeDAVID

GSCopePathBlazer

Generation of Biological Theme Generation of Biological Theme by Gene Ontologyby Gene Ontology

Gene OntologyGene Ontology

Biological ProcessBiological Process

Molecular FunctionMolecular Function

Cellular LocalizationCellular Localization

Nature Genetics Vol 25, p25Nature Genetics Vol 25, p25

http://www.geneontology.org/http://www.geneontology.org/

http://cgap.nci.nih.gov/Genes/GOBrowserhttp://cgap.nci.nih.gov/Genes/GOBrowser

http://etbsun2.nlm.nih.gov:8000/perl/gennav.plhttp://etbsun2.nlm.nih.gov:8000/perl/gennav.pl

DataData

‧ ‧ 經經 Drug A Drug A 刺激後的刺激後的 BB 細胞於細胞於 44 、、 88 、、 110 0

小時後分別進行生物晶片分析小時後分別進行生物晶片分析 (4/0(4/0 、、 8/08/0 、、 10/0)10/0)

‧ ‧RNARNA DyeDye Drug Cy3(635nm)Drug Cy3(635nm) Control Cy5(532nm)Control Cy5(532nm)

Gene listGene list

Drug A Drug A 4 hr /0 hr4 hr /0 hr

Drug ADrug A 8 hr/0 hr8 hr/0 hr

Drug A 10 hr /0 hrDrug A 10 hr /0 hr

Data AnalysisData Analysis

> 2 & < 0.5

DAVID─GODAVID─GO 、 、 KEGG PathwayKEGG Pathwayhttp://apps1.niaid.nih.gov/david/http://apps1.niaid.nih.gov/david/

MappFinderMappFinderhttp://www.genmapp.org/http://www.genmapp.org/

http://discover.nci.nih.gov/gominer/http://discover.nci.nih.gov/gominer/

GoMinerGoMiner

GoMinerGoMiner

Pathway - a direct guessPathway - a direct guess

Ex. Drug A 4/0

‧‧DAVID ─ Pathway (Total Gene)DAVID ─ Pathway (Total Gene)

‧‧GenMapp ─ GenMapp ─

ResultsResults

1 Cell cycle  3.1% (33)

2 Apoptosis  2.7% (29)

3 Integrin-mediated cell adhesion  2.7% (29)

Total Gene

Total input Gene： 1071

Total input Gene： 1000

1 TGF Beta Signaling Pathway 25 2.3（ ％）2 G Protein Signaling Pathways 22 2.0（ ％）3 Apoptosis 20 1.8（ ％）4 Wnt Signaling Pathway 17 1.6（ ％）

Inflammatory Response Pathway 16 1.5（ ％）Cell Cycle 16 1.6（ ％）

Total Gene

5

Correlation to other gene listCorrelation to other gene list

Lamb et al., Cell, Vol. 114, 323–334 (2003)Lamb et al., Cell, Vol. 114, 323–334 (2003)

http://www-genome.wi.mit.edu/cgi-bin/cancer/datasets.cgi

21 genes induced by cyclin D1 & its mutant21 genes induced by cyclin D1 & its mutantin MCF-7 human mammary epithelial cellsin MCF-7 human mammary epithelial cells

Expression profiles from 190 primary human tumExpression profiles from 190 primary human tumors-search for genes significantly correlated with tors-search for genes significantly correlated with t

he level of cyclin D1he level of cyclin D1

C/EBP

Promoter AnalysisPromoter Analysis

Co-transcription control Co-transcription control hypothesis - a wild guesshypothesis - a wild guess

Strategy for expression array-based Strategy for expression array-based comparative promoter analysiscomparative promoter analysis

Werner T. Mamm Genome10(2):168-75 (1999)

human RANTES/CCL5 promoterhuman RANTES/CCL5 promoter

共同調控序列

共同調控基因

A

B

C

老鼠基因體搜尋過濾

胃癌淋巴轉移晶片研究結果 -9 genes

RT-PCRRT-PCR 可能共同調控基因

D

E

F

基因晶片結果 -36 genes 人類基因體搜尋

基因晶片結果 -30,000 genes

New HypothesisNew Hypothesis

Gene List (expression)

Protein-protein Interaction

Function Association

GO

Pathway

MAPPFinder/GoMinerGSCope/DAVID

GenMAPP

Osprey

GSCopeDAVID

GSCopePathBlazer