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NIAID. PIR Bio-defense Related Pathogen Data Mining. November 19, 2007. Literature Mining of Pathogenesis-Related Proteins. Biodefense Proteomics Resource Center at PIR. Dengue Virus E Proteins Bioinformatics Analysis. US Army. Literature Mining of Pathogenesis-Related Proteins.
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NIAID PIR Bio-defense Related Pathogen Data Mining November 19, 2007 Literature Mining of Pathogenesis-Related Proteins Biodefense Proteomics Resource Center at PIR Dengue Virus E Proteins Bioinformatics Analysis US Army
Literature Mining of Pathogenesis-Related Proteins • Objective: • To develop a text mining system for pathogenesis-related proteins in pathogens of military and biodefense relevance • To integrate the pathogenesis-related proteins into integrated protein databases for functional analysis • Priority pathogenic organisms: • Francisella tularensis – Gammaproteobacteria • Dengue virus – (+)ssRNA virus • Brucella – Alphaproteobacteria • Trypanosoma cruzi – Kinetoplastida • Integrated information for pathogenic proteins • UniProtKB • iProClass • Other pathway databases
Functional pathway analysis iProClass Data integration Literature Mining of Pathogenesis-Related Proteins
Literature Mining of Pathogenesis-Related Proteins Priority list of pathogens… 1 Document retrieval(Prioritizing) Name recognition Pathogenesis related papers 2 3 Passage highlighting n-1 System adjustment n
BioThesaurus: Gene/protein name searches - synonyms, ambiguous names… http://pir.georgetown.edu/iprolink/biothesaurus/
Exp. Data Gene ID Protein ID Peptide seq. UniProtKB AC/ID 1 Information 2 Function Pathway Family …… 3 Categorize, Statistics, Cross-dataset, Association Knowledge
Organelle proteome data sets iProXpress– Pathway Profiling ER Mit • 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. Mit ER KEGG pathway
IP-MS Data from E2-treated breast cancer cells Gene Ontology: Molecular Process Transcriptional regulation chromatin interaction histone regulation
NIAID • Albert Einstein College of MedicineT. gondii, C. parvum • Caprion Pharmaceuticals B. abortus • Harvard Institute of Proteomics V. cholerae, B. anthracis • Myriad Genetics B. anthracis, Y. pestis, F. tularensis, Vaccinia, Variola • Pacific Northwest National Laboratory S. typhimurium, S. typhi, Vaccinia, Monkeypox • ScrippsSARS CoV, Influenza • University of Michigan B. anthracis Albert Einstein PNNL U of Michigan Harvard Myriad DATA Scripps Caprion Resource Center PIR VBI SSS
Mouse proteins detected in B. anthracis and S. typhimurium infected macrophages
Integrated Analysis:Selection Pressure, Entropy; Epitope Dengue DENV1 DENV3 DENV2 DENV4
Dengue Interacting residues aa site variant exposed Interacting residues Additional Structure Analysis Exposed Result: identification of diagnostic and vaccine targets