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Bio-Trac 40 (Protein Bioinformatics)Bio-Trac 40 (Protein Bioinformatics)
October 8, 2009October 8, 2009
Zhang-Zhi Hu, M.D. Zhang-Zhi Hu, M.D. Associate ProfessorAssociate ProfessorDepartment of OncologyDepartment of OncologyDepartment of Biochemistry and Molecular & Cellular BiologyDepartment of Biochemistry and Molecular & Cellular BiologyGeorgetown University Medical CenterGeorgetown University Medical Center
Lab
2http://www.geneontology.org/
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GO term (GO:0006366): mRNA transcription from RNA polymerase II
promoter
Leaf node
GO search and display tool
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Human p53 – GO annotation (UniProtKB:P04637)
GO:0006289:nucleotide-excision repair [PMID:7663514; evidence:IMP]
http://pir.georgetown.edu/cgi-bin/ipcEntry?id=P04637
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• Science basis of the GO: trained experts use the experimental observations from literature to associate GO terms with gene products (to annotate the entities represented in the gene/protein databases)
• Enabling data integration across databases and making them available to semantic search
GO annotation of gene products
Human, mouse, plant, worm, yeast …
http://www.geneontology.org/GO.current.annotations.shtml
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GO Slim
http://www.geneontology.org/GO.slims.shtml
(http://www.geneontology.org/)
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http://pir.georgetown.edu/pirwww/search/idmapping.shtml
ID Mapping
Information matrix
Functional profiling
Batch gene/protein retrieval and
profilingEnter ID, gi #
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Entrez Gene list
http://pir.georgetown.edu/pirwww/search/idmapping.shtml
UniProt Accession/ID
Batch retrievalhttp://pir.georgetown.edu/pirwww/search/batch.shtml
http://pir.georgetown.edu/pirwww/workshop/entrez_gene_list
http://www.uniprot.org/
ID mapping
http://www.uniprot.org/
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ER positive correlation (NCI60): >0.53
ER negative correlation : (-0.38 to -0.72)
ER positive correlation (NCI60): >0.53
209919992018261635892583332498012911477022252415618246272022001202333149428326396875170516567925803112542723254714563029760123872860828457029993108771500001543139323395431249755401413387457535163720261547499220047911812839871467798365757419650615806719725756155400500506045304642181669796549375775257177573385320941606430378365929256013850047962427151157739552595176490506252884284485513806478140628569141483275712711248907355503866174720332814656212815383715558921113262510023111899869863112814477
Negative correlation (-0.38 to -0.72):
8540558626197
57001797802119
10643301
1075100202950
109501617425691325972182
84002555292876
3001140823628
1104739451121136
273506566
641141025357102660052370810280513755714056214212274
233185166570484691
1368957076
512025718179650799719334
260315543251279
135112111322993428699859
104941048711252780471675216817
15032135
5081338015915
236452118671118414735
12392083879
112970126282
638611097556245876
558697171
64175805
490424137
2318634
1090810096
200316807827872534
25798104771716
Example on ERa correlated genes profiles in NCI60 cancer cell lines
GO Profiling
Entrez Gene ID
Entrez Gene ID
ID Mapping
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KEGG Metabolic & Regulatory Pathways KEGG is a suite of databases and associated software, integrating our current knowledge on molecular
interaction networks, the information of genes and proteins, and of chemical compounds and reactions.
(http://www.genome.ad.jp/kegg/pathway.html)
Transforming Growth Factor (TGF) beta signaling
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BioCarta Cellular Pathways
(http://www.biocarta.com/index.asp)
Transforming Growth Factor (TGF) beta signaling [Homo sapiens]
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Transforming Growth Factor (TGF) beta signaling [Homo sapiens]
Event ->REACT_6879.1: Activated type I receptor phosphorylates R-SMAD directly [Homo sapiens] Object -> REACT_7364.1: Phospho-R-SMAD [cytosol]Event -> REACT_6760.1: Phospho-R-SMAD forms a complex with CO-SMAD [Homo sapiens]Object -> REACT_7344.1: Phospho-R-SMAD:CO-SMAD complex [cytosol]Event -> REACT_6726.1: The phospho-R-SMAD:CO-SMAD transfers to the nucleusObject -> REACT_7382.2: Phospho-R-SMAD:CO-SMAD complex [nucleoplasm] ……
(http://reactome.org/cgi-bin/eventbrowser?DB=gk_current&FOCUS_SPECIES=Homo%20sapiens&ID=170834&)
Reactome: events and objects (including modified forms and complex)
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PIDTransforming Growth Factor beta signaling
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Reactome PID
~26 proteins in PID are not defined in Reactome, while only 2 in Reactome not defined in PID
Transforming Growth Factor (TGF) beta signaling
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iProXpressiProXpress: Integrative analysis of : Integrative analysis of proteomic and gene expression dataproteomic and gene expression data
DataData
InformationInformation
KnowledgeKnowledge
MS spectrum
Peptide ident.
Protein ident.
FunctionPathwayFamily
CategorizeStatisticsAssociation
http://pir.georgetown.edu/iproxpress/
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iProXpress – Pathway Profiling
• Protein information matrix: extensive annotations including protein name, family classification, function, protein-protein interaction, pathway…
• Functional profiling: iterative categorization, sorting, cross-dataset comparison, coupled with manual examination.
ER Mit
Mit
ER
KEGG pathway
• Organelle proteome data sets
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Purine metabolic pathway
Ribonucleoside diphosphate reductase subunit M2 (RRM2)
DNA synthesis DNA repair
1.17.4.1
ATP X dATP
ADP dADP
dGTP X GTP
dGDPGDP
1.17.4.1
http://www.genome.jp/kegg-bin/show_pathway?hsa00230+6241
