基于生物信息学方法筛选高砷暴露人群的关键基因

Screening of key genes in high arsenic exposure population based on bioinformatics methods

目的 利用生物信息学方法筛选高砷暴露人群关键基因及相关信号通路。方法 从高通量基因表达(gene expression omnibus, GEO)数据库下载GSE110852数据集,通过GEO2R在线工具筛选差异表达基因(differentially expressed genes, DEGs),应用R语言绘制火山图和热图。应用注释、可视化和综合发现数据库(the database for annotation, visualization and integrated discovery, DAVID)对DEGs进行基因本体(gene ontology, GO)和京都基因和基因组数据库(kyoto encyclopedia of genes and genomes, KEGG)通路富集分析,使用R语言绘制结果气泡图。通过基因/蛋白相互作用检索搜查工具(search tool for the retrieval of interacting genes/proteins, STRING)数据库构建差异表达基因的蛋白质-蛋白质相互作用(protein-protein interaction, PPI)网络,用Cytoscape软件的分子复合物检测(molecular complex detection, MCODE)插件进行子网络模块分析,筛选出可能与高砷暴露相关的关键基因,通过GSE122514数据集验证关键基因。结果 本研究应用STRING和Cytoscape构建差异表达基因的蛋白互作网络,筛选出6个与高砷暴露相关的关键基因,EGR1、EGR2、CXCL8(IL8)、PTGS2、FOS和FOSB。上述基因在GSE122514数据集得到了一致性验证,证明了筛选结果的可靠性。结论 EGR1、EGR2、CXCL8(IL8)、PTGS2、FOS和FOSB作为高砷暴露人群的关键基因,对地方性砷中毒的早期诊断和预警有重要意义。

Objective To use bioinformatics methods to screen key genes and related signaling pathways in high arsenic exposure population.Methodss GSE110852 dataset was downloaded from GEO public database.Differentially expressed genes(DEGs)were screened by GEO2R online tool,and R language was used to draw volcanic maps and heat maps.The GO(gene ontology)enrichment analysis and KEGG(kyoto encyclopedia of genes and genomes)pathway enrichment analysis were performed on DEGs using the DAVID online database,and the bubble plot was drawn using the R language GGPLOT package.The proteinprotein interaction(PPI)network of DEGs was constructed through STRING online database,and the key genes that may be associated with high arsenic exposure were screened out by the plug-in MCODE in Cytoscape software for subnetwork module analysis.Finally,the GSE122514 dataset was used to verify the key genes.Results In this study,STRING and Cytoscape were used to construct the protein interaction network of differentially expressed genes,and six key genes related to high arsenic exposure were screened out,including ECR1,EGR2,CXCL8(IL8),PTGS2,FOS and FOSB.The consistency of the above genes was verified in GSE122514 dataset,which proved the reliability of the screening results.ConclusionE GR1,EGR2,CXCL8(IL8),PTGS2,FOS and FOSB are the key genes in high arsenic exposure population,which are of great importance for the early diagnosis and early warning of endemic arsenic poisoning.