Drug perturbation gene set enrichment analysis (dpGSEA): a new transcriptomic drug screening approach

Bibliographic Details
Title: Drug perturbation gene set enrichment analysis (dpGSEA): a new transcriptomic drug screening approach
Authors: Mike Fang, Brian Richardson, Cheryl M. Cameron, Jean-Eudes Dazard, Mark J. Cameron
Source: BMC Bioinformatics, Vol 22, Iss 1, Pp 1-14 (2021)
Publisher Information: BMC, 2021.
Publication Year: 2021
Collection: LCC:Computer applications to medicine. Medical informatics
LCC:Biology (General)
Subject Terms: Transcriptomics, Gene set enrichment analysis, Drug discovery, Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
More Details: Abstract Background In this study, we demonstrate that our modified Gene Set Enrichment Analysis (GSEA) method, drug perturbation GSEA (dpGSEA), can detect phenotypically relevant drug targets through a unique transcriptomic enrichment that emphasizes biological directionality of drug-derived gene sets. Results We detail our dpGSEA method and show its effectiveness in detecting specific perturbation of drugs in independent public datasets by confirming fluvastatin, paclitaxel, and rosiglitazone perturbation in gastroenteropancreatic neuroendocrine tumor cells. In drug discovery experiments, we found that dpGSEA was able to detect phenotypically relevant drug targets in previously published differentially expressed genes of CD4+T regulatory cells from immune responders and non-responders to antiviral therapy in HIV-infected individuals, such as those involved with virion replication, cell cycle dysfunction, and mitochondrial dysfunction. dpGSEA is publicly available at https://github.com/sxf296/drug_targeting . Conclusions dpGSEA is an approach that uniquely enriches on drug-defined gene sets while considering directionality of gene modulation. We recommend dpGSEA as an exploratory tool to screen for possible drug targeting molecules.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1471-2105
Relation: https://doaj.org/toc/1471-2105
DOI: 10.1186/s12859-020-03929-0
Access URL: https://doaj.org/article/42800fa051264c41a3470bdcf2477a85
Accession Number: edsdoj.42800fa051264c41a3470bdcf2477a85
Database: Directory of Open Access Journals
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More Details
ISSN:14712105
DOI:10.1186/s12859-020-03929-0
Published in:BMC Bioinformatics
Language:English