1 Bio-Trac 40 (Protein Bioinformatics) October 8, 2009 Zhang-Zhi Hu, M.D. Associate Professor Department of Oncology Department of Biochemistry and Molecular.

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Presentation transcript:

1 Bio-Trac 40 (Protein Bioinformatics) October 8, 2009 Zhang-Zhi Hu, M.D. Associate Professor Department of Oncology Department of Biochemistry and Molecular & Cellular Biology Georgetown University Medical Center Lab

2

3 GO term (GO: ) : mRNA transcription from RNA polymerase II promoter Leaf node GO search and display tool

4 Human p53 – GO annotation (UniProtKB:P04637) GO: :nucleotide-excision repair [PMID: ; evidence:IMP]

5 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 …

6 GO Slim (

7 search/idmapping.shtml ID Mapping Information matrix Functional profiling Batch gene/protein retrieval and profiling Enter ID, gi #

8 Entrez Gene list UniProt Accession/ID Batch retrieval ID mapping

9 ER positive correlation (NCI60): >0.53 ER negative correlation : (-0.38 to -0.72) ER positive correlation (NCI60): > Negative correlation (-0.38 to -0.72): Example on ERa correlated genes profiles in NCI60 cancer cell lines GO Profiling Entrez Gene ID ID Mapping

10 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. ( Transforming Growth Factor (TGF) beta signaling

11 BioCarta Cellular Pathways ( Transforming Growth Factor (TGF) beta signaling [Homo sapiens]

12 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 nucleus Object -> REACT_7382.2: Phospho-R-SMAD:CO-SMAD complex [nucleoplasm] …… ( bin/eventbrowser?DB=gk_curre nt&FOCUS_SPECIES=Homo% 20sapiens&ID=170834&) bin/eventbrowser?DB=gk_curre nt&FOCUS_SPECIES=Homo% 20sapiens&ID=170834& Reactome: events and objects (including modified forms and complex)

13 PID Transforming Growth Factor beta signaling

14 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

15 iProXpress: Integrative analysis of proteomic and gene expression data Data Information Knowledge MS spectrum Peptide ident. Protein ident. Function Pathway Family Categorize Statistics Association

16 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 ER KEGG pathway Organelle proteome data sets

17 Purine metabolic pathway Ribonucleoside diphosphate reductase subunit M2 (RRM2) DNA synthesis DNA repair ATP X dATP  ADP  dADP  dGTP X GTP dGDP  GDP