A framework for identification of on- and off-target transcriptional responses to drug treatment.

ABSTRACT: Owing to safety concerns or insufficient efficacy, few drug candidates are approved for marketing. Drugs already on the market may be withdrawn due to adverse effects (AEs) discovered after market introduction. Comprehensively investigating the on-/off-target effects of drugs can help expose AEs during the drug development process. We have developed an integrative framework for systematic identification of on-/off-target pathways and elucidation of the underlying regulatory mechanisms, by combining promoter expression profiling after drug treatment with gene perturbation of the primary drug target. Expression profiles from statin-treated cells and HMG-CoA reductase knockdowns were analyzed using the framework, allowing for identification of not only reported adverse effects but also novel

SUBMITTER: Huang Y 

PROVIDER: S-EPMC6879629 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature