Array study discovery-driven Where is the hypothesis ?
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Array studyArray studydiscovery-drivendiscovery-driven
Where is the hypothesis ?Where is the hypothesis ?
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Cell, Vol. 104, 333–339, 2001
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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
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Gene List (expression)
Protein-protein Interaction
Function Association
GO
Pathway
MAPPFinder/GoMinerGSCope/DAVID
GenMAPP
Osprey
GSCopeDAVID
GSCopePathBlazer
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Generation of Biological Theme Generation of Biological Theme by Gene Ontologyby Gene Ontology
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Gene OntologyGene Ontology
Biological ProcessBiological Process
Molecular FunctionMolecular Function
Cellular LocalizationCellular Localization
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Nature Genetics Vol 25, p25Nature Genetics Vol 25, p25
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http://www.geneontology.org/http://www.geneontology.org/
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http://cgap.nci.nih.gov/Genes/GOBrowserhttp://cgap.nci.nih.gov/Genes/GOBrowser
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http://etbsun2.nlm.nih.gov:8000/perl/gennav.plhttp://etbsun2.nlm.nih.gov:8000/perl/gennav.pl
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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)
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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
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DAVID─GODAVID─GO 、 、 KEGG PathwayKEGG Pathwayhttp://apps1.niaid.nih.gov/david/http://apps1.niaid.nih.gov/david/
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MappFinderMappFinderhttp://www.genmapp.org/http://www.genmapp.org/
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http://discover.nci.nih.gov/gominer/http://discover.nci.nih.gov/gominer/
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GoMinerGoMiner
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GoMinerGoMiner
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Pathway - a direct guessPathway - a direct guess
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Ex. Drug A 4/0
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‧‧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
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Correlation to other gene listCorrelation to other gene list
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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
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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
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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
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C/EBP
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Promoter AnalysisPromoter Analysis
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Co-transcription control Co-transcription control hypothesis - a wild guesshypothesis - a wild guess
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Strategy for expression array-based Strategy for expression array-based comparative promoter analysiscomparative promoter analysis
Werner T. Mamm Genome10(2):168-75 (1999)
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human RANTES/CCL5 promoterhuman RANTES/CCL5 promoter
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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
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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
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Gene List (expression)
Protein-protein Interaction
Function Association
GO
Pathway
MAPPFinder/GoMinerGSCope/DAVID
GenMAPP
Osprey
GSCopeDAVID
GSCopePathBlazer