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

Yen-Wei Chen; Graciel Diamante; Jessica Ding; Thien Xuan Nghiem; Jessica Yang; Sung-Min Ha; Peter Cohn; Douglas Arneson; Montgomery Blencowe; Jennifer Garcia; Nima Zaghari; Paul Patel; Xia Yang

doi:10.1016/j.isci.2022.104052

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

iScience. 2022 Mar 10;25(4):104052. doi: 10.1016/j.isci.2022.104052. eCollection 2022 Apr 15.

Authors

Yen-Wei Chen^{1

2}, Graciel Diamante^{1

2}, Jessica Ding^{1

3}, Thien Xuan Nghiem¹, Jessica Yang¹, Sung-Min Ha¹, Peter Cohn¹, Douglas Arneson^{1

4}, Montgomery Blencowe^{1

3}, Jennifer Garcia¹, Nima Zaghari¹, Paul Patel¹, Xia Yang^{1

2

3

4

5}

Affiliations

¹ Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² Interdepartmental Program of Molecular Toxicology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Interdepartmental Program of Molecular, Cellular, & Integrative Physiology, Los Angeles, Los Angeles, CA 90095, USA.
⁴ Interdepartmental Program of Bioinformatics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁵ Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Abstract

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.

Keywords: Biocomputational method; Bioinformatics; In silico biology; Systems biology.

Abstract

Grants and funding