Abstract：
Mutually exclusive loss-of-function alterations in gene pairs are those that occur together less frequently than may be expected and may denote a synthetically lethal relationship (SSL) between the genes. SSLs can be exploited therapeutically to selectively kill cancer cells. Here, we analysed mutation, copy number variation, and methylation levels in samples from The Cancer Genome Atlas, using the hypergeometric and the Poisson binomial tests to identify mutually exclusive inactivated genes. We focused on gene pairs where one is an inactivated tumour suppressor and the other a gene whose protein product can be inhibited by known drugs. This provided an abundance of potential targeted therapeutics and repositioning opportunities for several cancers. These data are available on the MexDrugs website, https://bioinformaticslab.sussex.ac.uk/mexdrugs.
摘要：
基因对中的互斥功能丧失改变是那些一起发生的频率低于预期的频率，并且可能表示基因之间的合成致死关系（SSL）。可以在治疗上利用SSL选择性地杀死癌细胞。这里,我们分析了突变,拷贝数变化，和来自癌症基因组图谱的样本中的甲基化水平，使用超几何和泊松二项测试来鉴定互斥的灭活基因。我们专注于基因对，其中一个是灭活的肿瘤抑制因子，另一个是其蛋白质产物可以被已知药物抑制的基因。这为几种癌症提供了丰富的潜在靶向治疗和重新定位机会。这些数据可在MexDrugs网站上获得，https://生物信息板.Sussex.AC.英国/麦克斯药。
