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
_version_ 1784676684281151488
author 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
author_facet 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
author_sort Chen, Yen-Wei
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8957031
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-89570312022-03-27 PharmOmics: A species- and tissue-specific drug signature database and gene-network-based drug repositioning tool 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 iScience Article 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. Elsevier 2022-03-10 /pmc/articles/PMC8957031/ /pubmed/35345455 http://dx.doi.org/10.1016/j.isci.2022.104052 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
PharmOmics: A species- and tissue-specific drug signature database and gene-network-based drug repositioning tool
title PharmOmics: A species- and tissue-specific drug signature database and gene-network-based drug repositioning tool
title_full PharmOmics: A species- and tissue-specific drug signature database and gene-network-based drug repositioning tool
title_fullStr PharmOmics: A species- and tissue-specific drug signature database and gene-network-based drug repositioning tool
title_full_unstemmed PharmOmics: A species- and tissue-specific drug signature database and gene-network-based drug repositioning tool
title_short PharmOmics: A species- and tissue-specific drug signature database and gene-network-based drug repositioning tool
title_sort pharmomics: a species- and tissue-specific drug signature database and gene-network-based drug repositioning tool
topic Article
url 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
work_keys_str_mv AT chenyenwei pharmomicsaspeciesandtissuespecificdrugsignaturedatabaseandgenenetworkbaseddrugrepositioningtool
AT diamantegraciel pharmomicsaspeciesandtissuespecificdrugsignaturedatabaseandgenenetworkbaseddrugrepositioningtool
AT dingjessica pharmomicsaspeciesandtissuespecificdrugsignaturedatabaseandgenenetworkbaseddrugrepositioningtool
AT nghiemthienxuan pharmomicsaspeciesandtissuespecificdrugsignaturedatabaseandgenenetworkbaseddrugrepositioningtool
AT yangjessica pharmomicsaspeciesandtissuespecificdrugsignaturedatabaseandgenenetworkbaseddrugrepositioningtool
AT hasungmin pharmomicsaspeciesandtissuespecificdrugsignaturedatabaseandgenenetworkbaseddrugrepositioningtool
AT cohnpeter pharmomicsaspeciesandtissuespecificdrugsignaturedatabaseandgenenetworkbaseddrugrepositioningtool
AT arnesondouglas pharmomicsaspeciesandtissuespecificdrugsignaturedatabaseandgenenetworkbaseddrugrepositioningtool
AT blencowemontgomery pharmomicsaspeciesandtissuespecificdrugsignaturedatabaseandgenenetworkbaseddrugrepositioningtool
AT garciajennifer pharmomicsaspeciesandtissuespecificdrugsignaturedatabaseandgenenetworkbaseddrugrepositioningtool
AT zagharinima pharmomicsaspeciesandtissuespecificdrugsignaturedatabaseandgenenetworkbaseddrugrepositioningtool
AT patelpaul pharmomicsaspeciesandtissuespecificdrugsignaturedatabaseandgenenetworkbaseddrugrepositioningtool
AT yangxia pharmomicsaspeciesandtissuespecificdrugsignaturedatabaseandgenenetworkbaseddrugrepositioningtool