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WeCoMXP:一种用于基因模块检测的整合共甲基化、共表达和蛋白质-蛋白质相互作用的加权连通度度量方法。

WeCoMXP: Weighted Connectivity Measure Integrating Co-Methylation, Co-Expression and Protein-Protein Interactions for Gene-Module Detection.

出版信息

IEEE/ACM Trans Comput Biol Bioinform. 2020 Mar-Apr;17(2):690-703. doi: 10.1109/TCBB.2018.2868348. Epub 2018 Sep 3.

Abstract

The identification of modules (groups of several tightly interconnected genes) in gene interaction network is an essential task for better understanding of the architecture of the whole network. In this article, we develop a novel weighted connectivity measure integrating co-methylation, co-expression, and protein-protein interactions (called WeCoMXP) to detect gene-modules for multi-omics dataset. The proposed measure goes beyond the fundamental degree centrality measure through considering some formulation of higher-order connections. Thereafter, we apply the average linkage clustering method using the corresponding dissimilarity (distance) values of WeCoMXP scores, and utilize a dynamic tree cut method for identifying some gene-modules. We validate the modules through literature search, KEGG pathway, and gene-ontology analyses on the genes representing the modules. Furthermore, the top 10 TFs/miRNAs that are connected with the maximum number of gene-modules and that regulate/target the maximum number of genes from these connected gene-modules, are identified. Moreover, our proposed method provides a better performance than the existing methods in terms of several cluster-validity indices in maximum times.

摘要

在基因交互网络中识别模块(几个紧密相互关联的基因的集合)是更好地理解整个网络结构的基本任务。在本文中,我们开发了一种新的加权连通性度量方法,该方法集成了共甲基化、共表达和蛋白质-蛋白质相互作用(称为 WeCoMXP),用于检测多组学数据集的基因模块。与基本的度中心性度量相比,所提出的度量方法通过考虑一些高阶连接的形式来进行超越。此后,我们使用相应的 WeCoMXP 分数的不相似性(距离)值应用平均链接聚类方法,并利用动态树切割方法来识别一些基因模块。我们通过对代表模块的基因进行文献搜索、KEGG 通路和基因本体分析来验证这些模块。此外,还确定了与最大数量的基因模块连接并调节/靶向来自这些连接的基因模块的最大数量的基因的前 10 个 TF/miRNA。此外,与现有的方法相比,我们的方法在最大次数的多个聚类有效性指标方面提供了更好的性能。

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