系统性红斑狼疮受DNA甲基化影响的关键基因分析

Analysis for Key Genes Affected by DNA Methylation in Systemic Lupus Erythematosus

摘要: 系统性红斑狼疮(SLE)是一种自身免疫性疾病，表观遗传变异在SLE的发病机制中起重要作用。已有研究证明，异常DNA甲基化发生在SLE发展的各个过程中，调控相关基因表达水平。因此，寻找受影响的关键基因有助于SLE的诊断和治疗。首先，本文从Gene Expression Omnibus (GEO)数据库中下载了基因表达数据和DNA甲基化数据，利用生物信息学的方法，对在外周血单核细胞(PBMC)的基因表达和DNA甲基化数据进行差异分析，甲基化差异表达的基因被记录为差异甲基化基因(DMG)与差异表达基因(DEG)之间的重叠基因。使用DAVID数据库对受甲基化影响基因(mDEG)的功能富集分析。然后使用STRING数据库构建蛋白质–蛋白质相互作用(PPI)网络以获得参与SLE的关键基因。之后，本研究利用受试者工作特征(ROC)曲线评估hub基因，以验证其区分SLE与健康对照组的能力。最后，我们构建了一个hub基因-miRNA网络，并对共享基因进行了功能富集。

Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease. Epigenetic variation plays an im-portant role in the pathogenesis of SLE. Studies have shown that abnormal DNA methylation occurs in various processes of SLE development, regulating the expression level of related genes. Therefore, the search for the key genes affected can help in the diagnosis and treatment of SLE. Firstly, this paper downloaded Gene Expression data and DNA methylation data from Gene Expression Omnibus (GEO) database, and used bioinformatics methods to conduct differential analysis of gene expres-sion and DNA methylation data in peripheral blood mononuclear cells (PBMC). The differentially expressed methylated genes were recorded as overlapping genes between differentially methylat-ed genes (DMG) and differentially expressed genes (DEG). Functional enrichment analysis of meth-ylation-affected genes (mDEG) using DAVID database. The STRING database was then used to con-struct a protein-protein interaction (PPI) network to obtain key genes involved in SLE. The hub gene was then evaluated using receiver operating characteristics (ROC) curves to verify its ability to distinguish SLE from healthy controls. Finally, we constructed a hub gene-mirNA network and func-tionally enriched the shared genes.