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Bio-Trac 40 (Protein Bioinformatics)Bio-Trac 40 (Protein Bioinformatics)

October 9, 2008October 9, 2008

Zhang-Zhi Hu, M.D. Zhang-Zhi Hu, M.D. Research Associate ProfessorResearch Associate ProfessorProtein Information Resource, Department of Protein Information Resource, Department of Biochemistry and Molecular & Cellular BiologyBiochemistry 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

~46Human, mouse, plant, worm, yeast …

http://www.geneontology.org/GO.current.annotations.shtml

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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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http://pir.georgetown.edu/cgi-bin/batch_iprox.pl?search=1&data=gu1

57174917850711715797235198411477462622744401032898754976182615009683854123464924723020

Entrez Gene list

http://pir.georgetown.edu/pirwww/search/idmapping.shtml

UniProt Accession/ID

Batch retrieval

http://pir.georgetown.edu/pirwww/search/batch.shtml

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GO Slim

http://www.geneontology.org/GO.slims.shtml

(http://www.geneontology.org/)

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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