GSE134817
Promoter activity profiling reveals on- and off-target transcriptional responses to drug treatment
Owing to safety concerns or insufficient potential for efficacy, only 0.01% to 0.02% of new drug candidates are approved for marketing. Drugs already on the market may be withdrawn or restricted to certain uses due to adverse effects (AEs) discovered after market introduction.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. In this study, we developed an integrative framework for systematic identification of on-/off-target pathways and elucidation of the underlying mechanisms, by combining 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 candidates of off-target effects from statin treatment. Our findings may provide new insights for finding new usages or potential side effects of drug treatment. Overall design: CAGE profiling in three different cell types after treatment with four different statins and two siRNAs targeting HMG-CoA reductase (HMGCR), including replicates and control samples.