Integrating gene expression and clinical data to identify drug repurposing candidates for hyperlipidemia and hypertension

Patrick Wu, QiPing Feng, Vern Eric Kerchberger, Scott D. Nelson, Qingxia Chen, Bingshan Li, Todd L. Edwards, Nancy J. Cox, Elizabeth J. Phillips, C. Michael Stein, Dan M. Roden, Joshua C. Denny and Wei-Qi Wei ()
Additional contact information
Patrick Wu: Vanderbilt University Medical Center
QiPing Feng: Vanderbilt University Medical Center
Vern Eric Kerchberger: Vanderbilt University Medical Center
Scott D. Nelson: Vanderbilt University Medical Center
Qingxia Chen: Vanderbilt University Medical Center
Bingshan Li: Vanderbilt University School of Medicine
Todd L. Edwards: Vanderbilt University Medical Center
Nancy J. Cox: Vanderbilt University Medical Center
Elizabeth J. Phillips: Vanderbilt University Medical Center
C. Michael Stein: Vanderbilt University Medical Center
Dan M. Roden: Vanderbilt University Medical Center
Joshua C. Denny: National Institutes of Health
Wei-Qi Wei: Vanderbilt University Medical Center

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Discovering novel uses for existing drugs, through drug repurposing, can reduce the time, costs, and risk of failure associated with new drug development. However, prioritizing drug repurposing candidates for downstream studies remains challenging. Here, we present a high-throughput approach to identify and validate drug repurposing candidates. This approach integrates human gene expression, drug perturbation, and clinical data from publicly available resources. We apply this approach to find drug repurposing candidates for two diseases, hyperlipidemia and hypertension. We screen >21,000 compounds and replicate ten approved drugs. We also identify 25 (seven for hyperlipidemia, eighteen for hypertension) drugs approved for other indications with therapeutic effects on clinically relevant biomarkers. For five of these drugs, the therapeutic effects are replicated in the All of Us Research Program database. We anticipate our approach will enable researchers to integrate multiple publicly available datasets to identify high priority drug repurposing opportunities for human diseases.

Date: 2022
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DOI: 10.1038/s41467-021-27751-1

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