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基于影响最大化方法的转录调控网络中癌症驱动基因的发现。

Cancer driver gene discovery in transcriptional regulatory networks using influence maximization approach.

机构信息

Department of Information Technology Engineering, Faculty of Industrial and Systems, Tarbiat Modares University, Tehran, Iran.

Department of Information Technology Engineering, Faculty of Industrial and Systems, Tarbiat Modares University, Tehran, Iran.

出版信息

Comput Biol Med. 2019 Nov;114:103362. doi: 10.1016/j.compbiomed.2019.103362. Epub 2019 Jul 17.

Abstract

Cancer driver genes (CDGs) are the genes whose mutations cause tumor growth. Several computational methods have been previously developed for finding CDGs. Most of these methods are sequence-based, that is, they rely on finding key mutations in genomic data to predict CDGs. In the present work, we propose iMaxDriver as a network-based tool for predicting driver genes by application of influence maximization algorithm on human transcriptional regulatory network (TRN). In the first step of this approach, the TRN is pruned and weighted by exploiting tumor-specific gene expression (GE) data. Then, influence maximization approach is used to find the influence of each gene. The top genes with the highest influence rate are selected as the potential driver genes. We compared the performance of our CDG prediction method with fifteen other computational tools, based on a benchmark of three different cancer types. Our results show that iMaxDriver outperforms most of the state-of-the-art algorithms for CDG prediction. Furthermore, iMaxDriver is able to correctly predict many CDGs that are overlooked by all previously published tools. Due to this relative orthogonality, iMaxDriver can be considered as a complementary approach to the sequence-based CDG prediction methods.

摘要

癌症驱动基因(CDGs)是指其突变导致肿瘤生长的基因。先前已经开发了几种用于寻找 CDGs 的计算方法。这些方法大多是基于序列的,也就是说,它们依赖于在基因组数据中寻找关键突变来预测 CDGs。在本工作中,我们提出了 iMaxDriver,这是一种基于网络的工具,通过在人类转录调控网络(TRN)上应用影响最大化算法来预测驱动基因。在该方法的第一步中,通过利用肿瘤特异性基因表达(GE)数据,修剪和加权 TRN。然后,使用影响最大化方法来找到每个基因的影响。选择具有最高影响率的顶级基因作为潜在的驱动基因。我们基于三种不同癌症类型的基准,将我们的 CDG 预测方法的性能与其他十五种计算工具进行了比较。我们的结果表明,iMaxDriver 在 CDG 预测方面优于大多数最先进的算法。此外,iMaxDriver 能够正确预测许多被所有先前发表的工具忽略的 CDGs。由于这种相对正交性,iMaxDriver 可以被视为序列基 CDG 预测方法的补充方法。

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