基于生物信息学筛选区分人类免疫缺陷病毒感染和人类免疫缺陷病毒/结核分枝杆菌共感染的基因表达特征

Screening gene expression signatures of infection of human immunodeficiency virus and co-infection of human immunodeficiency virus/Mycobacterium tuberculosis based on bioinformatics

  • 摘要:
    目的 筛选用于区分人类免疫缺陷病毒(HIV)感染和HIV/结核分枝杆菌(MTB)共感染的外周血潜在的基因表达特征。
    方法 首先从基因表达总览(GEO)数据库下载数据集GSE50834,分为HIV感染患者和HIV/MTB共感染患者两组进行差异分析,将差异表达基因(DEGs)进行基因本体(GO)功能注释和京都基因与基因组百科全书(KEGG)通路富集分析,然后构建蛋白质相互作用网络(PPI)并筛选关键基因,通过受试者工作特征(ROC)曲线分析关键基因的诊断价值,以及通过加权基因共表达网络(WGCNA)分析进行验证,从而得到有价值的基因表达特征。
    结果 共筛选得到100个DEGs,其中上调基因58个,下调基因42个。 GO功能注释显示,DEGs主要集中在炎症反应、细胞质膜和与碳水化合物结合等功能;KEGG通路富集分析显示,DEGs主要集中在补体凝血级联和趋化因子信号通路。 从PPI网络获得4个关键基因,ROC分析显示均有较高的诊断价值,在WGCNA连接度较高的基因集中找到了CXC基序趋化因子配体2(CXCL2)、前血小板碱性蛋白(PPBP)和CXC基序趋化因子配体10(CXCL10)基因。
    结论 CXCL2、PPBP和CXCL10基因可以作为区分HIV感染和HIV/MTB共感染重要的基因表达特征,为相关生物标志物的探索提供一定的思路。

     

    Abstract:
    Objective To screening potential gene expression signatures in peripheral blood that can be used to in the differential diagnosis of infection of human immunodeficiency virus (HIV) and the co-infection of HIV/Mycobacterium tuberculosis (MTB).
    Methods Dataset GSE50834 was downloaded from the Gene Expression Omnibus (GEO) database and divided into two groups: infection of HIV and co-infection of HIV/MTB. Differential analysis was performed to identify genes that were differentially expressed in the two groups. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted to understand the functions and pathways associated with the differentially expressed genes. A protein-protein interaction (PPI) network was constructed, and key genes were identified. The diagnostic value of these key genes was assessed using receiver operating characteristic (ROC) analysis. Additionally, weighted gene co-expression network analysis (WGCNA) was performed to further validate the potential gene expression signature.
    Results A total of 100 differentially expressed genes (DEGs) were identified, including 58 up-regulated genes and 42 down-regulated genes. GO functional annotation revealed that the DEGs were mainly associated with inflammation, plasma membrane, and carbohydrate binding. KEGG pathway enrichment analysis indicated that the DEGs were mainly involved in the complement coagulation cascade and chemokine signaling pathways. From the PPI network, 4 key genes were identified, all of which showed diagnostic value according to ROC analysis. Furthermore, WGCNA analysis identified CXC motif chemokine ligand 2 (CXCL2), pro-platelet basic protein (PPBP), and CXC motif chemokine ligand 10 (CXCL10) as genes with high connectivity.
    Conclusion Our findings suggest that CXCL2, PPBP, and CXCL10 genes coan be used as gene expression signatures for the differential diagnosis of infection of HIV and co-infection ofHIV/MTB, which can provides ideas for the exploration of related biomarkers.

     

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