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
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Interdepartmental Program of Molecular Toxicology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
iScience. 2022 Mar 10;25(4):104052. doi: 10.1016/j.isci.2022.104052. eCollection 2022 Apr 15.
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 performance assessment. We further validated predicted drugs for nonalcoholic fatty liver disease in mice. By combining tissue- and species-specific drug signatures with gene networks, PharmOmics serves as a complementary tool to support drug characterization and network-based medicine.
由于我们对药物在不同器官和物种中的功能了解不全面,药物研发一直受到临床试验高失败率的阻碍。因此,阐明物种和组织特异性的药物功能可以为治疗效果、潜在不良反应以及有效转化医学所需的种间差异提供见解。在此,我们展示了PharmOmics,这是一个托管在交互式网络服务器上的药物知识库和分析工具。利用从不同数据库整理的人类、小鼠和大鼠的组织和物种特异性转录组数据,我们实施了一种基于基因网络的药物重新定位方法。我们通过性能评估证明了PharmOmics在检索已知治疗药物和识别具有组织毒性的药物方面的潜力。我们进一步验证了针对小鼠非酒精性脂肪性肝病的预测药物。通过将组织和物种特异性药物特征与基因网络相结合,PharmOmics作为一种补充工具,以支持药物表征和基于网络的医学。