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

被引：18

作者：

Chen, Yen-Wei ^{[1
,2
]}

Diamante, Graciel ^{[1
,2
]}

Ding, Jessica ^{[1
,3
]}

Thien Xuan Nghiem ^{[1
]}

Yang, Jessica ^{[1
]}

Ha, Sung-Min ^{[1
]}

Cohn, Peter ^{[1
]}

Arneson, Douglas ^{[1
,4
]}

Blencowe, Montgomery ^{[1
,3
]}

Garcia, Jennifer ^{[1
]}

Zaghari, Nima ^{[1
]}

Patel, Paul ^{[1
]}

Yang, Xia ^{[1
,2
,3
,4
,5
]}

机构：

[1] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Interdept Program Mol Toxicol, Los Angeles, CA 90095 USA

[3] Interdept Program Mol Cellular & Integrat Physiol, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Interdept Program Bioinformat, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, Inst Quantitat & Computat Biosci, Los Angeles, CA 90095 USA

来源：

ISCIENCE | 2022年 / 25卷 / 04期

关键词：

FATTY LIVER IMPROVEMENT; NONALCOHOLIC STEATOHEPATITIS; PPAR-ALPHA; EXPRESSION; ROSIGLITAZONE; FENOFIBRATE; INTEGRATION; ACID; IDENTIFICATION; MITOCHONDRIAL;

D O I：

10.1016/j.isci.2022.104052

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：27

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