Transcriptional data: a new gateway to drug repositioning?
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. âº Can every biological state be represented by a given gene expression signature? âº Recently, signatures have been used as proxies of clinicopathological phenotypes. âº Drug–drug/drug–disease ‘connections’ have been inferred by signature matching. âº This allowed the prediction of new application for already approved drugs. âº A massive amount of public transcriptional data is ready to be exploited in this way.