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基于加权基因共表达网络分析(WGCNA)鉴定肥胖相关的枢纽基因和关键通路

WGCNA-Based Identification of Hub Genes and Key Pathways Involved in Obesity.

作者信息

Yuan Yin, Yue Shujiao, Wu Zixuan, Sun Xuan, Wang Hongwu

机构信息

College of Public Health and Health Sciences, Tianjin University of Traditional Chinese Medicine, Tianjin, 301600, China.

College of Integrated Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301600, China.

出版信息

Mol Biotechnol. 2025 Sep 16. doi: 10.1007/s12033-025-01503-8.

Abstract

The prevalence of obesity is increasing year by year, but its characteristic molecular targets are still unclear, and the available therapeutic approaches are relatively limited. Therefore, it is crucial to elucidate the molecular mechanisms underlying the pathogenesis of obesity and to explore potential molecular targets for obesity drug therapy. The expression dataset (GSE73304) was downloaded from the gene expression omnibus database for between-group differential expression gene analyses (DEGs), genome enrichment analysis (GSEA), and weighted gene co-expression network analysis (WGCNA) in healthy and obese populations. Intersecting genes obtained from DEGs and WGCNA difference modules were analyzed with three machine learning methods (LASSO, RandomForest, SVM-REF) to obtain obesity characteristic Genes. Analysis of ROC curves, intergroup differences, and intergene correlations for Genes characterizing obesity. The results of the study showed that 10 specimens and their Gene expression matrices were collected from each of the normal and obese patient groups, yielding 1937 DEGs. GSEA results showed that DEGs were enriched for 32 significant KEGG pathways. Forty gene co-expression modules of the gene expression matrix were constructed by WGCNA. Forty-five intersecting genes were obtained from DEGs and WGCNA significant difference module, which were associated with cellular differentiation, mitochondria, and a variety of endocrine factors and hormones. Eleven genes, including XLOC_004699, RIMBP2, COX6B2, OR5T1, RXFP2, XLOC_003676, XLOC_013038, VAX1, Q07610, XLOC_011515, and PTPN3, were obtained as the obesity characterization Genes through machine learning analysis of intersecting Genes. Based on WGCNA and machine learning, this study found that 11 genes, including RIMBP2, COX6B2, and OR5T1, differed significantly between healthy and obese populations and were closely associated with multiple molecular mechanisms, and these genes may be potential targets for drug therapy and diagnostic biomarkers.

摘要

肥胖症的患病率逐年上升,但其特征性分子靶点仍不明确,且现有的治疗方法相对有限。因此,阐明肥胖症发病机制的分子机制并探索肥胖症药物治疗的潜在分子靶点至关重要。从基因表达综合数据库下载表达数据集(GSE73304),用于健康人群和肥胖人群的组间差异表达基因分析(DEG)、基因组富集分析(GSEA)和加权基因共表达网络分析(WGCNA)。对从DEG和WGCNA差异模块获得的交集基因用三种机器学习方法(LASSO、随机森林、支持向量机-REF)进行分析,以获得肥胖特征基因。对表征肥胖的基因进行ROC曲线、组间差异和基因间相关性分析。研究结果显示,从正常患者组和肥胖患者组各收集了10个样本及其基因表达矩阵,共获得1937个差异表达基因。GSEA结果显示,差异表达基因在32条显著的KEGG通路中富集。通过WGCNA构建了基因表达矩阵的40个基因共表达模块。从差异表达基因和WGCNA显著差异模块中获得45个交集基因,这些基因与细胞分化、线粒体以及多种内分泌因子和激素有关。通过对交集基因的机器学习分析,获得了包括XLOC_004699、RIMBP2、COX6B2、OR5T1、RXFP2、XLOC_003676、XLOC_013038、VAX1、Q07610、XLOC_011515和PTPN3在内的11个基因作为肥胖特征基因。基于WGCNA和机器学习,本研究发现包括RIMBP2、COX6B2和OR5T1在内的11个基因在健康人群和肥胖人群之间存在显著差异,且与多种分子机制密切相关,这些基因可能是药物治疗的潜在靶点和诊断生物标志物。

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