EMBL - European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK.
Drug Discov Today. 2013 Apr;18(7-8):350-7. doi: 10.1016/j.drudis.2012.07.014. Epub 2012 Aug 7.
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.
计算生物学的最新进展表明,细胞转录程序的任何扰动都可以用适当的“特征”来概括:一组基因和一种表达模式。因此,通过 DNA 微阵列技术获得的特征,应该有可能生成临床病理表型和药物作用的代理。最近,通过全基因组指标,对基因表达特征进行了组装和比较,通过匹配相应的特征,揭示了意想不到的药物-疾病和药物-药物“联系”。因此,预测并实验验证了现有药物的新应用。在这里,我们描述了相关的方法、案例研究和资源,同时讨论了利用现有的微阵列数据存储库作为系统药物再定位搜索空间的挑战和益处。