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Predicting synthetic lethal interactions using conserved patterns in protein interaction networks

机译:使用蛋白质相互作用网络中的保守模式预测合成致死相互作用

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摘要

In response to a need for improved treatments, a number of promising novel targeted cancer therapies are being developed that exploit human synthetic lethal interactions. This is facilitating personalised medicine strategies in cancers where specific tumour suppressors have become inactivated. Mainly due to the constraints of the experimental procedures, relatively few human synthetic lethal interactions have been identified. Here we describe SLant (Synthetic Lethal analysis via Network topology), a computational systems approach to predicting human synthetic lethal interactions that works by identifying and exploiting conserved patterns in protein interaction network topology both within and across species. SLant out-performs previous attempts to classify human SSL interactions and experimental validation of the models predictions suggests it may provide useful guidance for future SSL screenings and ultimately aid targeted cancer therapy development.
机译:为了响应对改进治疗的需求,正在开发利用人类合成致死相互作用的许多有前途的新型靶向癌症疗法。这在特定的肿瘤抑制剂已被灭活的癌症中促进了个性化的药物治疗策略。主要由于实验程序的限制,已经鉴定出相对较少的人类合成致死相互作用。在这里,我们描述SLant(通过网络拓扑进行的致命合成分析),一种预测人类合成致命相互作用的计算系统方法,该方法通过识别和利用物种内和跨物种的蛋白质相互作用网络拓扑中的保守模式来起作用。 SLant胜过先前对人类SSL相互作用进行分类的尝试,并且对模型预测的实验验证表明,它可以为将来的SSL筛选提供有用的指导,并最终帮助靶向癌症治疗的发展。

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