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基于网络的胶质母细胞瘤中失调通路检测方法

Network-based method for detecting dysregulated pathways in glioblastoma cancer.

作者信息

Wu Hao, Dong Jihua, Wei Jicheng

机构信息

College of Information Engineering, Northwest A&F University, Yangling 712100, Shaanxi, People's Republic of China.

Department of Foreign Languages, Northwest A&F University, Yangling 712100, Shaanxi, People's Republic of China.

出版信息

IET Syst Biol. 2018 Feb;12(1):39-44. doi: 10.1049/iet-syb.2017.0033.

Abstract

The knowledge on the biological molecular mechanisms underlying cancer is important for the precise diagnosis and treatment of cancer patients. Detecting dysregulated pathways in cancer can provide insights into the mechanism of cancer and help to detect novel drug targets. Based on the wide existing mutual exclusivity among mutated genes and the interrelationship between gene mutations and expression changes, this study presents a network-based method to detect the dysregulated pathways from gene mutations and expression data of the glioblastoma cancer. First, the authors construct a gene network based on mutual exclusivity between each pair of genes and the interaction between gene mutations and expression changes. Then they detect all complete subgraphs using CFinder clustering algorithm in the constructed gene network. Next, the two gene sets whose overlapping scores are above a specific threshold are merged. Finally, they obtain two dysregulated pathways in which there are glioblastoma-related multiple genes which are closely related to the two subtypes of glioblastoma. The results show that one dysregulated pathway revolving around epidermal growth factor receptor is likely to be associated with the primary subtype of glioblastoma, and the other dysregulated pathway revolving around TP53 is likely to be associated with the secondary subtype of glioblastoma.

摘要

了解癌症背后的生物分子机制对于癌症患者的精确诊断和治疗至关重要。检测癌症中失调的信号通路可以深入了解癌症机制,并有助于发现新的药物靶点。基于突变基因之间广泛存在的相互排斥性以及基因突变与表达变化之间的相互关系,本研究提出了一种基于网络的方法,用于从胶质母细胞瘤的基因突变和表达数据中检测失调的信号通路。首先,作者基于每对基因之间的相互排斥性以及基因突变与表达变化之间的相互作用构建了一个基因网络。然后,他们使用CFinder聚类算法在构建的基因网络中检测所有完全子图。接下来,将重叠分数高于特定阈值的两个基因集合并。最后,他们获得了两个失调的信号通路,其中存在与胶质母细胞瘤相关的多个基因,这些基因与胶质母细胞瘤的两个亚型密切相关。结果表明,一个围绕表皮生长因子受体的失调信号通路可能与胶质母细胞瘤的原发性亚型相关,另一个围绕TP53的失调信号通路可能与胶质母细胞瘤的继发性亚型相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8591/8687240/1cc09aa63524/SYB2-12-39-g001.jpg

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