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首页> 外文期刊>Journal of Bioinformatics and Computational Biology >Predicting essential genes and synthetic lethality via influence propagation in signaling pathways of cancer cell fates
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Predicting essential genes and synthetic lethality via influence propagation in signaling pathways of cancer cell fates

机译：通过影响癌细胞命运的信号通路中的传播来预测必需基因和合成致死率

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摘要

A major goal of personalized anti-cancer therapy is to increase the drug effects while reducing the side effects as much as possible. A novel therapeutic strategy called synthetic lethality (SL) provides a great opportunity to achieve this goal. SL arises if mutations of both genes lead to cell death while mutation of either single gene does not. Hence, the SL partner of a gene mutated only in cancer cells could be a promising drug target, and the identification of SL pairs of genes is of great significance in pharmaceutical industry. In this paper, we propose a hybridized method to predict SL pairs of genes. We combine a data-driven model with knowledge of signalling pathways to simulate the influence of single gene knock-down and double genes knock-down to cell death. A pair of genes is considered as an SL candidate when double knock-down increases the probability of cell death significantly, but single knock-down does not. The single gene knock-down is confirmed according to the human essential genes database. Our validation against literatures shows that the predicted SL candidates agree well with wet-lab experiments. A few novel reliable SL candidates are also predicted by our model.
机译：个性化抗癌治疗的主要目标是增加药物作用，同时尽可能减少副作用。一种称为合成致死性（SL）的新型治疗策略为实现该目标提供了绝佳机会。如果两个基因的突变均导致细胞死亡而单个基因的突变均不导致细胞死亡，则出现SL。因此，仅在癌细胞中突变的基因的SL伴侣可能是有希望的药物靶标，并且SL对基因的鉴定在制药工业中具有重要意义。在本文中，我们提出了一种预测SL对基因的杂交方法。我们将数据驱动的模型与信号通路的知识相结合，以模拟单基因敲低和双基因敲低对细胞死亡的影响。当双敲除显着增加细胞死亡的可能性而单敲除则不然时，一对基因被视为SL候选。根据人类必需基因数据库确认了单个基因的敲低。我们根据文献进行的验证表明，预测的SL候选者与湿实验室实验非常吻合。我们的模型还预测了一些新颖的可靠SL候选者。

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