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基于多层网络控制的个体化癌症驱动基因识别方法

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目的 识别癌症驱动基因,特别是罕见或个体特异性癌症驱动基因,对精准肿瘤学至关重要。考虑到肿瘤间的高度异质性,最近有一些方法尝试在个体水平上识别癌症驱动基因。然而,这些方法大多是将多组学数据整合到单一生物分子网络(如基因调控网络或蛋白质相互作用网络)中来识别癌症驱动基因,容易忽略不同网络所特有的重要相互作用信息。为了整合不同生物分子网络的相互作用数据,促进癌症驱动基因识别,迫切需要发展一种多层网络方法。方法 本文提出了一种多层网络控制方法(PDGMN),利用多层网络识别个体化癌症驱动基因。首先,利用基因表达数据构建针对个体病人的个体化多层网络,其中包括蛋白质相互作用层和基因相互关联层。然后,整合突变数据,对个体化多层网络中的节点进行加权。最后,设计了一种加权最小顶点覆盖集识别算法,找到个体化多层网络中的最优驱动节点集,以提高个体化癌症驱动基因的识别效果。结果 在三个TCGA癌症数据集上的实验结果表明,PDGMN在个体化驱动基因识别方面优于其他现有方法,并能有效识别个体病人的罕见癌症驱动基因。特别是,在不同生物分子网络上的实验结果表明,PDGMN能够捕获不同生物分子网络的独有特征,从而改进癌症驱动基因的识别结果。结论PDGMN能有效识别个体化癌症驱动基因,并从多层网络的视角,加深我们对癌症驱动基因识别的理解。本文所用的源代码和数据集可以从https://github。com/NWPU-903PR/PDGMN 获取。
A Multiplex Network Control Method for Identifying Personalized Cancer Driver Genes
Objective Inferring cancer driver genes,especially rare or sample-specific cancer driver genes,is crucial for precision oncology.Considering the high inter-tumor heterogeneity,a few recent methods attempt to reveal cancer driver genes at the individual level.However,most of these methods generally integrate multi-omics data into a single biomolecular network(e.g.,gene regulatory network or protein-protein interaction network)to identify cancer driver genes,which results in missing important interactions highlighted in different networks.Thus,the development of a multiplex network method is imperative in order to integrate the interactions of different biomolecular networks and facilitate the identification of cancer driver genes.Methods A multiplex network control method called Personalized cancer Driver Genes with Multiplex biomolecular Networks(PDGMN)was proposed.Firstly,the sample-specific multiplex network,which contains protein-protein interaction layer and gene-gene association layer,was constructed based on gene expression data.Subsequently,somatic mutation data was integrated to weight the nodes in the sample-specific multiplex network.Finally,a weighted minimum vertex cover set identification algorithm was designed to find the optimal set of driver nodes,facilitating the identification of personalized cancer driver genes.Results The results derived from three TCGA cancer datasets indicate that PDGMN outperforms other existing methods in identifying personalized cancer driver genes,and it can effectively identify the rare driver genes in individual patients.Particularly,the experimental results indicate that PDGMN can capture the unique characteristics of different biomolecular networks to improve cancer driver gene identification.Conclusion PDGMN can effectively identify personalized cancer driver genes and broaden our understanding of cancer driver gene identification from a multiplex network perspective.The source code and datasets used in this work are available at https://github.com/NWPU-903PR/PDGMN.

multiplex biomolecular networksmultiplex network controlpersonalized cancer driver genessample-specific multiplex networkminimum vertex cover set

张桐、张绍武、李岩、谢明宇

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西北工业大学自动化学院,信息融合技术教育部重点实验室,西安 710072

平顶山学院电气与机械工程学院,平顶山 467000

多层生物分子网络 多层网络控制 个体化癌症驱动基因 个体化多层网络 最小节点覆盖集

国家自然科学基金

62173271

2024

生物化学与生物物理进展
中国科学院生物物理研究所,中国生物物理学会

生物化学与生物物理进展

CSTPCD北大核心
影响因子:0.476
ISSN:1000-3282
年,卷(期):2024.51(7)
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