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共表达分析提供了人类扩张型心肌病的重要模块和途径。

Co-expression analysis provides important module and pathways of human dilated cardiomyopathy.

机构信息

Department of Cardiology, Huadu District People's Hospital, Southern Medical University, Guangzhou, China.

Xuzhou Medical University, Xuzhou, China.

出版信息

J Cell Physiol. 2020 Jan;235(1):494-503. doi: 10.1002/jcp.28989. Epub 2019 Jun 24.

Abstract

Dilated cardiomyopathy (DCM) is a heart disease that injured greatly to the people wordwide. Systemic co-expression analysis for this cancer is still limited, although massive clinic experiments and gene profiling analyses had been well performed previously. Here, using the public RNA-Seq data "GSE116250" and gene annotation of Ensembl database, we built the co-expression modules for DCM by Weighted Gene Co-Expression Network Analysis, and investigated the function enrichment and protein-protein interaction (PPI) network of co-expression genes of each module by Database for Annotation, Visualization, and Integrated Discovery and Search Tool for the Retrieval of Interacting Genes/Proteins database, respectively. First, 5,000 genes in the 37 samples were screened and 11 co-expression modules were conducted. The number of genes for each module ranged from 77 to 936, with a mean of 455. Second, interaction relationships of hub-genes between pairwise modules showed great differences, suggesting relatively high-scale independence of the modules. Third, functional enrichments of the co-expression modules exhibited great differences. We found that genes in module 3 were significantly enriched in the pathways of focal adhesion and ubiquitin-mediated proteolysis. This module was inferred as the key module involved in DCM. In addition, PPI analysis revealed that the genes HSP90AA1, CTNNB1, MAPK1, GART, and PPP2CA owned the largest number of adjacency genes, unveiling that they may function importantly during the occurrence of DCM. Focal adhesion and ubiquitin-mediated proteolysis play important roles in human DCM.

摘要

扩张型心肌病(DCM)是一种对全世界人民伤害极大的心脏病。尽管此前已经进行了大量的临床实验和基因谱分析,但针对这种癌症的系统共表达分析仍然有限。在这里,我们使用公共 RNA-Seq 数据“GSE116250”和 Ensembl 数据库的基因注释,通过加权基因共表达网络分析构建了 DCM 的共表达模块,并分别使用数据库注释、可视化和综合发现以及用于检索相互作用基因/蛋白质的数据库(Database for Annotation, Visualization, and Integrated Discovery and Search Tool for the Retrieval of Interacting Genes/Proteins database),研究了每个模块的共表达基因的功能富集和蛋白质-蛋白质相互作用(PPI)网络。首先,从 37 个样本中筛选出 5000 个基因,并进行了 11 个共表达模块。每个模块的基因数量从 77 到 936 不等,平均为 455。其次,模块之间的枢纽基因相互作用关系显示出很大的差异,表明模块具有相对较高的独立性。第三,共表达模块的功能富集差异很大。我们发现模块 3 中的基因在粘着斑和泛素介导的蛋白水解途径中显著富集。这个模块被推断为涉及 DCM 的关键模块。此外,PPI 分析表明 HSP90AA1、CTNNB1、MAPK1、GART 和 PPP2CA 等基因拥有最多的相邻基因,揭示了它们在 DCM 发生过程中可能具有重要作用。粘着斑和泛素介导的蛋白水解在人类 DCM 中起着重要作用。

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