Cargando…

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

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,...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957031/
https://www.ncbi.nlm.nih.gov/pubmed/35345455
http://dx.doi.org/10.1016/j.isci.2022.104052
Descripción
Sumario: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.