基于GEO数据库的酒精依赖患者差异表达基因生物信息学分析

Bioinformatics analysis of differentially expressed genes in alcohol-dependent patients based on GEO database

目的通过对酒精依赖患者基因数据集进行生物信息学分析,探索酒精依赖发生发展的分子标志物。方法从基因表达数据库(GEO)下载GSE62699表达数据集,包括18例酒精依赖患者及18例健康人群的伏隔核组织样本。使用R软件筛选出差异表达基因,之后对差异表达基因进行功能注释,包括基因本体论(GO)和京都基因和基因组百科全书(KEGG)通路富集分析。利用STRING数据库构建蛋白互作(PPI)网络并进行分析,使用CytoHubba插件筛选核心基因。最后对所得到的核心基因进行验证。结果在酒精依赖患者和健康人群之间,共分析得到236个差异表达基因,包括131个上调基因105个下调基因。应用CytoHubba插件共得到11个核心基因。通过验证获得4个分子标志物。结论谷氨酸脱羧酶2(GAD2)、基质金属蛋白酶抑制剂1(TIMP1)、胆囊收缩素(CCK)、突触体相关蛋白(SNAP25)、内皮素1(EDN1)可能在酒精依赖的发生发展中发挥作用。

Objective To explore the molecular markers for the development of alcohol dependence by bioinformatics analysis of gene data set of patients with alcohol dependence.Methods The GSE62699 expression dataset was downloaded from the Gene Expression Database(GEO),including nucleus accumbens tissue samples from 18 alcoholdependent patients and 18 healthy subjects.R software was used to screen out differentially expressed genes,and then the differentially expressed genes were functionally annotated,including Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.The STRING database was used to construct and analyze the protein interaction(PPI)network,and CytoHubba was used to screen the core genes.Finally,the core genes obtained were verified.Results A total of 236 differentially expressed genes,including 131 up-regulated genes and 105 down-regulated genes,were analyzed between patients with alcohol dependence and healthy subjects.A total of 11 core genes were obtained by CytoHubba.Four molecular markers were obtained by validation.Conclusion Glutamic acid decarboxylase 2(GAD2),matrix metalloproteinase inhibitor 1(TIMP1),cholecystokinin(CCK),synaptosome associated protein(SNAP25)and endothelin1(EDN1)may play a role in the development of alcohol dependence.