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转录组数据:药物重定位的新途径?

Transcriptional data: a new gateway to drug repositioning?

机构信息

EMBL - European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK.

出版信息

Drug Discov Today. 2013 Apr;18(7-8):350-7. doi: 10.1016/j.drudis.2012.07.014. Epub 2012 Aug 7.

DOI:10.1016/j.drudis.2012.07.014
PMID:22897878
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3625109/
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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0383/3625109/03c93d1ce6f5/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0383/3625109/319e8a5bc94c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0383/3625109/03c93d1ce6f5/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0383/3625109/319e8a5bc94c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0383/3625109/03c93d1ce6f5/gr2.jpg

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Bioinformatics. 2012 Apr 15;28(8):1114-21. doi: 10.1093/bioinformatics/bts090. Epub 2012 Feb 21.
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In silico transcriptome screens identify epidermal growth factor receptor inhibitors as therapeutics for noise-induced hearing loss.计算机转录组筛选鉴定表皮生长因子受体抑制剂可作为治疗噪声性听力损失的药物。
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