阿尔茨海默病差异表达基因的生物信息学分析

A bioinformatics analysis of differentially expressed genes in Alzheimer's disease

目的:应用生物信息学方法分析阿尔茨海默病(Alzheimer’s disease,AD)不同病情程度的差异表达基因(differentially expressed genes,DEGs),在分子水平上探讨AD的发病制,为研究AD提供新思路。方法:从基因表达综合数据库(gene expression omnibus,GEO)下载基因芯片数据集GSE28146,使用在线分析工具GEO2R分别筛选AD轻度组、中度组和重度组与正常对照组比较的DEGs。运用DAVID数据库对筛选出的DEGs进行基因本体(gene ontology,GO)富集分析和京都基因与基因百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路分析,通过STRING数据库构建蛋白相互作用网络,并采用Cytoscape软件筛选关键基因。结果:AD轻度组、中度组和重度组分别筛选出881、896和1142个DEGs。GO功能富集显示:轻度组与凋亡相关过程的激活、调节免疫反应、蛋白质磷酸化等生物过程密切相关,中度组与炎症反应、凋亡调节、钙离子的释放等生物过程密切相关,重度组与NF-κB的激活、蛋白质磷酸化和去磷酸化、细胞外基质的降解等生物过程密切相关。KEGG分析显示:轻度组主要富集到p53和TGF-β等信号通路,中度组主要富集到癌症途径、自然杀伤细胞介导的细胞毒性、细胞黏附分子等信号通路,重度组主要富集到细胞周期、Hippo信号通路、神经活性配体-受体相互作用等信号通路。蛋白互作网路分析各组富集程度最高的前5个关键基因:轻度组为GART、EHMT2、KRAS、ESR1、CD44;中度组为CBLB、HERC1、UBE2G1、UBE2M、HECW2;重度组为UBE2C、SOCS3、FBXW7、UBE3B、UBA6。结论:采用生物信息学方法分析不同病情程度的AD,所富集的信号通路和筛选出的关键基因可能在AD发生发展过程中起重要作用,为进一步深入研究AD提供了依据和思路。

Objective:To investigate the differentially expressed genes(DEGs)in different stages of Alzheimer’s disease(AD)through a bioinformatics analysis and the pathogenesis of AD at the molecular level,and to provide new ideas for the research on AD.Methods:The microarray dataset GSE28146 was downloaded from gene expression omnibus(GEO),and the GEO2 R online software was used to screen out DEGs between the control group and the mild/moderate/severe AD groups.The DAVID database was used to perform genetic ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of DEGs,the STRING database was used to establish a protein-protein interaction network,and the Cytoscape software was used to screen out the hub genes.Results:A total of 881,896,and 1142 DEGs were screened out in the mild,moderate,and severe AD groups,respectively,compared with the control group.The GO functional enrichment analysis showed that the DEGs in the mild AD group were closely associated with the activation of apoptosis-related processes,regulation of immune response,and protein phosphorylation,those in the moderate AD group were closely associated with inflammatory response,apoptosis regulation,and release of calcium ions,and those in the severe AD group were closely associated with the activation of nuclear factor-kappa B,protein phosphorylation and dephosphorylation,and degradation of extracellular matrix.The KEGG analysis showed that the DEGs in the mild AD group were mainly enriched in the p53 and TGF-h signaling pathways,those in the moderate group were mainly involved in the signaling pathways of cancer,natural killer cell-mediated cytotoxicity,and cell adhesion molecules,and those in the severe AD group were mainly enriched in the signaling pathways involving cell cycle,Hippo signaling pathway,and neuroactive ligand-receptor interaction.The protein-protein interaction network analysis showed that the top5 hub genes with the highest degree of enrichment were GART,EHMT2,KRAS,ESR1,and CD44 in the mild AD group,CBLB,HERC1,UBE2 G1,UBE2 M,and HECW2 in the moderate AD group,and UBE2 C,SOCS3,FBXW7,UBE3 B,and UBA6 in the severe AD group.Conclusion:The bioinformatics analysis of different stages of AD shows that the enriched signal pathways and the hub genes may play an important role in the development and progression of AD,which provide a basis and new ideas for further research on AD.