文章基本信息

标题：PharmOmics: A species- and tissue-specific drug signature database and gene-network-based drug repositioning tool
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作者：Yen-Wei Chen ; Graciel Diamante ; Jessica Ding 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：4
页码：1-27
DOI：10.1016/j.isci.2022.104052
语种：English
出版社：Elsevier
摘要：SummaryDrug 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 usingin silicoperformance assessment. We further validated predicted drugs for nonalcoholic fatty liver disease in mice. By combining tissue- and species-specificin vivodrug signatures with gene networks, PharmOmics serves as a complementary tool to support drug characterization and network-based medicine.Graphical abstractDisplay OmittedHighlights•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 accessBioinformatics; Biocomputational method; Systems biology; In silico biology