Transcriptional data: a new gateway to drug repositioning?

TLDR

Recent advances in computational biology show that perturbations to a cell’s transcriptional programme can be summarised by a gene‑expression signature, enabling the generation of proxies for clinicopathological phenotypes and drug effects via DNA microarray data. This study aims to describe methods, case studies, and resources for using microarray data repositories as a systematic search space for drug repositioning, while outlining associated challenges and benefits. The authors outline how existing microarray repositories can be leveraged to identify drug‑repositioning opportunities through signature comparison and resource integration. Comparative analysis of genome‑wide expression signatures has uncovered unexpected drug‑disease and drug‑drug connections, leading to predicted and experimentally validated novel applications for existing drugs.

Abstract

Recent advances in computational biology suggest that any perturbation to the transcriptional programme of the cell can be summarised by a proper 'signature': a set of genes combined with a pattern of expression. Therefore, it should be possible to generate proxies of clinicopathological phenotypes and drug effects through signatures acquired via DNA microarray technology. Gene expression signatures have recently been assembled and compared through genome-wide metrics, unveiling unexpected drug-disease and drug-drug 'connections' by matching corresponding signatures. Consequently, novel applications for existing drugs have been predicted and experimentally validated. Here, we describe related methods, case studies and resources while discussing challenges and benefits of exploiting existing repositories of microarray data that could serve as a search space for systematic drug repositioning.