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Assay Drug Dev Technol. 2019 Nov/Dec;17(8):352-363. doi: 10.1089/adt.2019.950. Epub 2019 Nov 26.

Systematically Prioritizing Candidates in Genome-Based Drug Repurposing.

Author information

1
Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, Tennessee.
2
Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee.
3
Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
4
Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee.

Abstract

Drug repurposing is the application of approved drugs to treat diseases separate and distinct from their original indications. Herein, we define the scope of all practical precision drug repurposing using DrugBank, a publicly available database of pharmacological agents, and BioVU, a large, de-identified DNA repository linked to longitudinal electronic health records at Vanderbilt University Medical Center. We present a method of repurposing candidate prioritization through integration of pharmacodynamic and marketing variables from DrugBank with quality control thresholds for genomic data derived from the DNA samples within BioVU. Through the synergy of delineated "target-action pairs," along with target genomics, we identify ∼230 "pairs" that represent all practical opportunities for genomic drug repurposing. From this analysis, we present a pipeline of 14 repurposing candidates across 7 disease areas that link to our repurposability platform and present high potential for randomized controlled trial startup in upcoming months.

KEYWORDS:

drug repurposing; genomics; informatics; phenome-wide association study (PheWAS); precision medicine

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