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Predicting adverse drug reactions using publicly available PubChem BioAssay data
Y Pouliot1, A P Chiang, A J Butte
1Division of Systems Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.
Clinical Pharmacology and Therapeutics
|May 27, 2011
Summary
Predicting adverse drug reactions (ADRs) using preclinical screening data is possible. Computational models correlated organ system-specific ADRs with PubChem BioAssay data, aiding drug safety assessments.
Area of Science:
- Pharmacovigilance and Computational Toxicology
- Drug Discovery and Development
- Bioinformatics and Cheminformatics
Background:
- Adverse drug reactions (ADRs) pose significant risks, necessitating early prediction before market release.
- Preclinical data, particularly from compound screening, offers potential for identifying ADRs.
- Publicly available databases like PubChem BioAssay contain valuable screening data for analysis.
Purpose of the Study:
- To develop computational models correlating postmarketing ADRs with preclinical compound screening data.
- To investigate the association between ADRs at the organ system level (System Organ Classes - SOCs) and screening data.
- To assess the predictive capability of these models for identifying potential ADRs of new drugs.
Main Methods:
- Generated logistic regression models to correlate postmarketing ADRs with PubChem BioAssay screening data.
- Analyzed ADRs based on System Organ Classes (SOCs).
- Validated model predictions against established drugs with known ADRs.
Main Results:
- Nine out of 19 considered SOCs showed significant correlation with preclinical screening data.
- Retropredictions for six of eight established drugs were supported by existing knowledge.
- Identified significant correlations between specific screening assays and organ system-specific ADRs.
Conclusions:
- Computational models can effectively predict organ system-specific ADRs using preclinical screening data.
- This approach can inform drug labeling and marketing regarding potential ADRs.
- Predictions were made for SOC-specific ADRs associated with three unapproved or recently introduced drugs.
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