Systematic drug repositioning based on clinical side-effects

Drug repositioning helps fully explore indications for marketed drugs and clinical candidates. Here we show that the clinical side-effects (SEs) provide a human phenotypic profile for the drug, and this profile can suggest additional disease indications. We extracted 3,175 SE-disease relationships b...

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Bibliographic Details
Published in:PloS one 2011-12, Vol.6 (12), p.e28025
Main Authors: Yang, Lun, Agarwal, Pankaj
Format: Article
Language:English
Subjects:
Area Under Curve
Bayesian analysis
Biology
Chemistry
Clinical trials
Clinical Trials as Topic
Complications and side effects
Computer Graphics
Diabetes
Diabetes mellitus
Drug development
Drug Repositioning - statistics & numerical data
Drug-Related Side Effects and Adverse Reactions
Drugs
Edema
Enzymes
Gene expression
Humans
Hypertension
Hypoglycemia
Mathematical models
Medical Informatics - methods
Medical research
Medicine
Obsessive compulsive disorder
Parkinson's disease
Precision medicine
Primary care
Quantitative Structure-Activity Relationship
ROC Curve
Side effects
Stroke
Studies
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Summary:Drug repositioning helps fully explore indications for marketed drugs and clinical candidates. Here we show that the clinical side-effects (SEs) provide a human phenotypic profile for the drug, and this profile can suggest additional disease indications. We extracted 3,175 SE-disease relationships by combining the SE-drug relationships from drug labels and the drug-disease relationships from PharmGKB. Many relationships provide explicit repositioning hypotheses, such as drugs causing hypoglycemia are potential candidates for diabetes. We built Naïve Bayes models to predict indications for 145 diseases using the SEs as features. The AUC was above 0.8 in 92% of these models. The method was extended to predict indications for clinical compounds, 36% of the models achieved AUC above 0.7. This suggests that closer attention should be paid to the SEs observed in trials not just to evaluate the harmful effects, but also to rationally explore the repositioning potential based on this "clinical phenotypic assay".
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0028025