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烧伤瘢痕组织中甲基化基因的加权基因共表达网络分析

[Weighted gene co-expression network analysis of methylated genes in burn scar tissue].

作者信息

Guo P

机构信息

Department of Plastic Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.

出版信息

Zhonghua Shao Shang Za Zhi. 2021 Dec 20;37(12):1185-1190. doi: 10.3760/cma.j.cn501120-20200311-00150.

Abstract

To investigate the methylated genes in burn scar tissue by weighted gene co-expression network analysis (WGCNA), and to discover molecular markers and therapeutic targets of scar formation. An observational research method was used. Datasets were downloaded from the National Center for Biotechnology Information Gene Expression Omnibus Database of America. The GSE136906 (=6) and GSE137134 (=6) datasets in the same batch were screened out for mRNA sequencing and methylation sequencing respectively, and the dataset GSE108110 (=9) was incorporated into support vector machine and modeling analysis. The Limma software package was used to identify the differentially expressed genes and differentially methylated genes between scar tissue after burn and normal tissue. WGCNA was used to select the module with strong correlation with clinical features of scar tissue and large number of genes. Functional enrichment analysis of the genes in the module was performed to find genes with abnormal methylation. The receiver operating characteristic (ROC) curve was used to judge diagnostic efficacy of genes with abnormal methylation for scar, and support vector machine (SVM) was used to verify. A total of 10 modules were identified, and the brown module with large number of genes was highly correlated to burn scar tissue formation. The genes in the brown module were mainly concentrated in "regulation of androgen receptor signaling pathway", "cytokine-cytokine receptor interaction", "positive regulation of insulin secretion", and so on. The model showed 35 genes with abnormal methylation status. The ROC curve (area under the curve>0.9) and SVM modeling (accuracy=93.3%) indicated that , , NNAT, and TCF7L2 genes had good diagnostic performance for scar. and can be used as potential targets for burn scar treatment.

摘要

通过加权基因共表达网络分析(WGCNA)研究烧伤瘢痕组织中的甲基化基因,以发现瘢痕形成的分子标志物和治疗靶点。采用观察性研究方法。数据集从美国国家生物技术信息中心基因表达综合数据库下载。分别筛选出同一批次的GSE136906(=6)和GSE137134(=6)数据集进行mRNA测序和甲基化测序,并将数据集GSE108110(=9)纳入支持向量机和建模分析。使用Limma软件包识别烧伤后瘢痕组织与正常组织之间的差异表达基因和差异甲基化基因。利用WGCNA选择与瘢痕组织临床特征相关性强且基因数量多的模块。对该模块中的基因进行功能富集分析以发现甲基化异常的基因。采用受试者工作特征(ROC)曲线判断甲基化异常基因对瘢痕的诊断效能,并使用支持向量机(SVM)进行验证。共识别出10个模块,基因数量多的棕色模块与烧伤瘢痕组织形成高度相关。棕色模块中的基因主要集中在“雄激素受体信号通路的调控”“细胞因子-细胞因子受体相互作用”“胰岛素分泌的正调控”等方面。该模型显示有35个基因甲基化状态异常。ROC曲线(曲线下面积>0.9)和SVM建模(准确率=93.3%)表明,NNAT和TCF7L2基因对瘢痕具有良好的诊断性能。 和 可作为烧伤瘢痕治疗的潜在靶点。

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