PharmOmics: A species- and tissue-specific drug signature database and gene-network-based drug repositioning tool

• Published in: iScience 2022-04, Vol.25 (4), p.104052, Article 104052
• Main Authors: Chen, Yen-Wei, Diamante, Graciel, Ding, Jessica, Nghiem, Thien Xuan, Yang, Jessica, Ha, Sung-Min, Cohn, Peter, Arneson, Douglas, Blencowe, Montgomery, Garcia, Jennifer, Zaghari, Nima, Patel, Paul, Yang, Xia
• Format: Article
• Language: English
• Subjects: Biocomputational method; Bioinformatics; In silico biology; Systems biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.104052

Drug development has been hampered by a high failure rate in clinical trials due to our incomplete understanding of drug functions across organs and species. Therefore, elucidating species- and tissue-specific drug functions can provide insights into therapeutic efficacy, potential adverse effects, and interspecies differences necessary for effective translational medicine. Here, we present PharmOmics, a drug knowledgebase and analytical tool that is hosted on an interactive web server. Using tissue- and species-specific transcriptome data from human, mouse, and rat curated from different databases, we implemented a gene-network-based approach for drug repositioning. We demonstrate the potential of PharmOmics to retrieve known therapeutic drugs and identify drugs with tissue toxicity using in silico performance assessment. We further validated predicted drugs for nonalcoholic fatty liver disease in mice. By combining tissue- and species-specific in vivo drug signatures with gene networks, PharmOmics serves as a complementary tool to support drug characterization and network-based medicine. [Display omitted] •Development of PharmOmics, a platform for drug repositioning and toxicity prediction•Contains >18000 species/tissue-specific gene signatures for 941 drugs and chemicals•Benchmarked and validated network-based drug repositioning and toxicity prediction•PharmOmics is freely accessible via an online web server to facilitate user access Bioinformatics; Biocomputational method; Systems biology; In silico biology