DGMP: Identifying Cancer Driver Genes by Jointing DGCN and MLP from Multi-omics Genomic Data

IF 11.5 2区 生物学 Q1 GENETICS & HEREDITY Genomics, Proteomics & Bioinformatics Pub Date : 2022-10-01 DOI:10.1016/j.gpb.2022.11.004
Shao-Wu Zhang, Jing-Yu Xu, Tong Zhang
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引用次数: 4

Abstract

Identification of cancer driver genes plays an important role in precision oncology research, which is helpful to understand cancer initiation and progression. However, most existing computational methods mainly used the protein–protein interaction (PPI) networks, or treated the directed gene regulatory networks (GRNs) as the undirected gene–gene association networks to identify the cancer driver genes, which will lose the unique structure regulatory information in the directed GRNs, and then affect the outcome of the cancer driver gene identification. Here, based on the multi-omics pan-cancer data (i.e., gene expression, mutation, copy number variation, and DNA methylation), we propose a novel method (called DGMP) to identify cancer driver genes by jointing directed graph convolutional network (DGCN) and multilayer perceptron (MLP). DGMP learns the multi-omics features of genes as well as the topological structure features in GRN with the DGCN model and uses MLP to weigh more on gene features for mitigating the bias toward the graph topological features in the DGCN learning process. The results on three GRNs show that DGMP outperforms other existing state-of-the-art methods. The ablation experimental results on the DawnNet network indicate that introducing MLP into DGCN can offset the performance degradation of DGCN, and jointing MLP and DGCN can effectively improve the performance of identifying cancer driver genes. DGMP can identify not only the highly mutated cancer driver genes but also the driver genes harboring other kinds of alterations (e.g., differential expression and aberrant DNA methylation) or genes involved in GRNs with other cancer genes. The source code of DGMP can be freely downloaded from https://github.com/NWPU-903PR/DGMP.

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DGMP:从多组学基因组数据中通过连接DGCN和MLP来鉴定癌症驱动基因
肿瘤驱动基因的鉴定在精确肿瘤学研究中起着重要的作用,有助于了解肿瘤的发生和发展。然而,现有的大多数计算方法主要采用蛋白-蛋白相互作用(PPI)网络,或将定向基因调控网络(grn)视为无定向基因-基因关联网络来识别癌症驱动基因,这将失去定向grn中独特的结构调控信息,从而影响癌症驱动基因的鉴定结果。在此,基于多组学泛癌症数据(即基因表达、突变、拷贝数变异和DNA甲基化),我们提出了一种将有向图卷积网络(DGCN)和多层感知器(MLP)结合起来识别癌症驱动基因的新方法(称为DGMP)。DGMP利用DGCN模型学习基因的多组学特征和GRN中的拓扑结构特征,并利用MLP对基因特征的权重增加,以减轻DGCN学习过程中对图拓扑特征的偏向。在三个grn上的结果表明,DGMP优于其他现有的最先进的方法。在DawnNet网络上的消融实验结果表明,将MLP引入DGCN可以抵消DGCN的性能下降,并且MLP与DGCN的连接可以有效提高识别癌症驱动基因的性能。DGMP不仅可以识别高度突变的癌症驱动基因,还可以识别包含其他类型改变的驱动基因(如差异表达和异常DNA甲基化)或与其他癌症基因相关的grn基因。DGMP的源代码可以从https://github.com/NWPU-903PR/DGMP免费下载。
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来源期刊
Genomics, Proteomics & Bioinformatics
Genomics, Proteomics & Bioinformatics Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
14.30
自引率
4.20%
发文量
844
审稿时长
61 days
期刊介绍: Genomics, Proteomics and Bioinformatics (GPB) is the official journal of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China. It aims to disseminate new developments in the field of omics and bioinformatics, publish high-quality discoveries quickly, and promote open access and online publication. GPB welcomes submissions in all areas of life science, biology, and biomedicine, with a focus on large data acquisition, analysis, and curation. Manuscripts covering omics and related bioinformatics topics are particularly encouraged. GPB is indexed/abstracted by PubMed/MEDLINE, PubMed Central, Scopus, BIOSIS Previews, Chemical Abstracts, CSCD, among others.
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