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Identifying aberrant pathways through integrated analysis of knowledge in pharmacogenomics
Robert Hoehndorf1, Michel Dumontier, Georgios V Gkoutos
1Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK. rh497@cam.ac.uk
Bioinformatics (Oxford, England)
|June 20, 2012
Summary
Integrating pharmacogenomics databases using biomedical ontologies enables novel analyses. This approach identifies disease pathways and chemical associations, improving drug repurposing and understanding disease mechanisms.
Area of Science:
- Bioinformatics
- Computational Biology
- Pharmacogenomics
Background:
- Complex diseases often arise from disrupted biological pathways, not single gene defects.
- Targeting these pathways for diagnosis and treatment requires integrated data on drugs, genes, diseases, and pathways.
- Current pharmacogenomics information is fragmented across multiple databases.
Purpose of the Study:
- To demonstrate a method for integrating distributed pharmacogenomics databases.
- To leverage integrated biomedical ontologies for novel biomedical analyses.
- To identify disease pathways and chemical-pathway associations for improved drug discovery and repurposing.
Main Methods:
- Integration of pharmacogenomics databases by aligning their underlying biomedical ontologies.
- Utilizing ontology meta-data to enrich analyses with background biological knowledge.
- Performing multi-ontology enrichment analysis using the Human Disease Ontology to identify disease pathways.
- Conducting enrichment analysis over a chemical ontology to find significant chemical-pathway associations.
Main Results:
- Successful integration of pharmacogenomics databases through ontology alignment.
- Identification of disease pathways via multi-ontology enrichment analysis.
- Discovery of significant associations between chemicals and biological pathways.
- Creation of a valuable resource linking drugs, pathways, and diseases.
Conclusions:
- Integrated pharmacogenomics data, enabled by biomedical ontologies, facilitates advanced research.
- The identified drug-pathway and disease-pathway associations are crucial for understanding disease mechanisms.
- This approach enhances computational drug repurposing strategies and accelerates biomedical discovery.
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