PIR Bio-defense Related Pathogen Data Mining

NIAID

Literature Mining of Pathogenesis-Related Proteins

Biodefense Proteomics Resource Center at PIR

Dengue Virus E Proteins Bioinformatics AnalysisUS ArmyUS Army

November 19, 2007

2

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

3

Functional pathway analysis Data

integration

iProClass

Literature Mining of Pathogenesis-Related Proteins

4

Literature Mining of Pathogenesis-Related Proteins

11

22

33

nn-1-1

nn

Document retrieval(Prioritizing)

Name recognition

Passage highlighting

System adjustment

Pathogenesisrelated papers

Pathogenesisrelated papers

Priority list of pathogens…

Priority list of pathogens…

5

http://pir.georgetown.edu/iprolink/rlimsp/

RLIMS-P: Rule-based Literature Mining System for Protein Phosphorylation

6

BioThesaurus: Gene/protein name searches - synonyms, ambiguous names…

http://pir.georgetown.edu/iprolink/biothesaurus/

7

Exp. DataExp. Data

InformationInformation

KnowledgeKnowledge

Gene ID Protein ID Peptide seq.

FunctionPathwayFamily ……

Categorize,Statistics, Cross-dataset,Association

UniProtKB AC/ID1

3

2

8

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

9

Gene Ontology: Molecular Process

IP-MS Data from E2-treated breast cancer cells

Transcriptional regulation chromatin interaction

histone regulation

10

1.1. Albert Einstein College of MedicineAlbert Einstein College of MedicineT. gondii, C. parvumT. gondii, C. parvum

2.2. Caprion Pharmaceuticals Caprion Pharmaceuticals B. abortusB. abortus

3.3. Harvard Institute of Proteomics Harvard Institute of Proteomics V. choleraeV. cholerae, , B. anthracisB. anthracis

4.4. Myriad Genetics Myriad Genetics B. anthracis, Y. pestis, F. tularensis, Vaccinia, B. anthracis, Y. pestis, F. tularensis, Vaccinia, VariolaVariola

5.5. Pacific Northwest National Laboratory Pacific Northwest National Laboratory S. typhimurium, S. typhi, Vaccinia, MonkeypoxS. typhimurium, S. typhi, Vaccinia, Monkeypox

6.6. ScrippsScrippsSARS CoV, SARS CoV, InfluenzaInfluenza

7.7. University of Michigan University of Michigan B. anthracisB. anthracis

Scripps Caprion

MyriadHarvard

U of Michigan

Albert Einstein

PNNL

Resource Center

SSS

PIR VBI

DATA

NIAID

11www.proteomicsresource.org

Mouse proteins detected in B. anthracis and S. typhimurium infected macrophages

13

Integrated Analysis:Selection Pressure, Entropy; Epitope DengueDengue

DENV1DENV3DENV2DENV4

14

Additional Structure Analysis

Exposed

Result: identification of diagnostic and vaccine targets

DengueDengue

aa site Interacting residuesInteracting residuesvariant exposed