Integrating gene expression and clinical data to identify drug repurposing candidates for hyperlipidemia and hypertension
Year: 2022
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $5,890
Funders: U.S. Department of Health and Human Services, Vanderbilt University, Vanderbilt University Medical Center, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of General Medical Sciences, U.S. National Library of Medicine, National Center for Advancing Translational Sciences
Awards: Illinois Precision Medicine Consortium , Healthy Americas: All of Us Research Program, G1969433312, G2187930703, Empowerment-focused Outreach, Education and Enrollment of Tennessee Older Adults in the All of Us Research Program through Community Efforts by FiftyForward, Improving precision health approaches through large-scale EHRs and biobanks, G2491195741, Research Matters: Creating Possibilities to Achieve Health and Wellness for All of Us Research Program, G323389304, G3254713460, Vanderbilt Genome-Electronic Records (VGER) Project, G3328344938, Improving Prediction of Drug Action, Medical Scientist Training Program, Pleiotropy of PCSK9 Inhibition, Precision Medicine Initiative Cohort Program Biobank, Communications Design and Development for NIH Precision Medicine Initiative Research Projects, G4198746417, G4425699080, New York City Consortium for Precision Medicine, G4591583506, G4852260362, Initiative for Maximizing Student Development, Technology to Empower Changes in Health (TECH) Network Participant Technologies Center, University of Arizona-Banner Health All of Us Research Program , G5531450241, The New England Precision Medicine Consortium of the All of Us Research Program, G5724809085, All of Us Wisconsin , Data and Research Support Center , G6230900904, G6246474086, All of Us Pennsylvania, Trans-America Consortium of the Health Care Systems Research Network for the All of Us Research Program, G6421126927, Beyond PheWAS: Recognition of Phenotype Patterns for Discovery and Translation, G6653917946, Southern All of Us Network, PheMAP: Measured, Automated Profile to Facilitate High Throughput Phenotyping, SouthEast Enrollment Center (SEEC) , The Vanderbilt Institute for Clinical and Translational Research (VICTR), Adaptive Platform for Personalized Engagement, Pharmacogenetics to improve drug therapy, G8149519509, G8355735039, G8718738308, California Precision Medicine Research Program Consortium, Communication Implementation and Coordination for NIH Precision Medicine Initiative Research Projects, Exploring Statin Pleiotropic Effects within a Very Large EHR Cohort, G892083856, G9000033427, Genetics and Triglycerides: opportunities for new approaches to identify therapies, Tissue-specific functional genomics in the acute respiratory distress syndrome, Drug repositioning for Alzheimer's disease via genetics, electronic health records, and human iPSC models, Vanderbilt Biomedical Informatics Training Program, Medical Scientist Training Program, G90053628, PRIDEnet for the All of Us Research Program
OpenAlex ID: W4206039282