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基于转录组-互作组多层框架鉴定结肠腺癌的关键成分。

Identification of Key Components in Colon Adenocarcinoma Using Transcriptome to Interactome Multilayer Framework.

机构信息

Laboratory of Systems Biology and Bioinformatics (LBB), Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.

School of Mathematics, Statistics, and Computer Science, College of Science, University of Tehran, Tehran, Iran.

出版信息

Sci Rep. 2020 Mar 19;10(1):4991. doi: 10.1038/s41598-020-59605-z.

Abstract

Complexity of cascading interrelations between molecular cell components at different levels from genome to metabolome ordains a massive difficulty in comprehending biological happenings. However, considering these complications in the systematic modelings will result in realistic and reliable outputs. The multilayer networks approach is a relatively innovative concept that could be applied for multiple omics datasets as an integrative methodology to overcome heterogeneity difficulties. Herein, we employed the multilayer framework to rehabilitate colon adenocarcinoma network by observing co-expression correlations, regulatory relations, and physical binding interactions. Hub nodes in this three-layer network were selected using a heterogeneous random walk with random jump procedure. We exploited local composite modules around the hub nodes having high overlay with cancer-specific pathways, and investigated their genes showing a different expressional pattern in the tumor progression. These genes were examined for survival effects on the patient's lifespan, and those with significant impacts were selected as potential candidate biomarkers. Results suggest that identified genes indicate noteworthy importance in the carcinogenesis of the colon.

摘要

分子细胞成分在基因组到代谢组不同层次上的级联相互关系的复杂性使得理解生物事件变得极其困难。然而,在系统建模中考虑这些复杂性将产生现实可靠的输出。多层网络方法是一个相对较新的概念,可作为一种综合方法应用于多个组学数据集,以克服异质性困难。在这里,我们通过观察共表达相关性、调控关系和物理结合相互作用,采用多层框架来重建结肠腺癌网络。使用具有随机跳跃的异质随机游走程序选择这个三层网络中的枢纽节点。我们利用与癌症特异性途径具有高重叠的枢纽节点周围的局部复合模块,并研究它们在肿瘤进展中表现出不同表达模式的基因。对这些基因在患者寿命上的生存效应进行了检验,选择具有显著影响的基因作为潜在的候选生物标志物。结果表明,鉴定出的基因在结肠癌的发生中具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bd4/7081269/63d690269e4b/41598_2020_59605_Fig1_HTML.jpg

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