脓毒症潜在相关基因的生物信息学分析及功能预测

Bioinformatics analysis and functional prediction of potential genes related to sepsis

目的 通过生物信息学方法筛选并分析与脓毒症相关的差异表达基因及关键(Hub)基因,以期为临床诊疗提供潜在靶点和生物标志物。方法 使用基因表达综合数据库(GEO)筛选脓毒症基因表达数据集,运用GEO自带在线分析工具(GEO2R)分析差异表达基因(DEGs);并结合STRING 12.0和DAVID数据库对DEGs进行富集分析;再通过Cytoscape 3.9.1软件筛选出Hub基因,并对其进行功能分析。结果 筛选出328个DEGs,其中上调基因2个,下调基因326个。富集结果显示,DEGs的功能主要与蛋白质修饰、分解代谢、蛋白酶复合物、线粒体及酶活性等有关。通过CytoHubba插件筛选出了核因子κB亚基1(NFKB1)、NEDD8、人NADH-泛醌氧化还原酶A8(NDUFA8)、POLR2F、延伸蛋白B(ELOB)、PSMB6、SEC61A1、COX4I1、人NADH-泛醌氧化还原酶B8(NDUFB8)及ATP5PD 10个Hub基因,经生物过程(BP)可视化发现这些Hub基因在生物过程中相互作用。结论 NFKB1、NEDD8、NDUFA8、POLR2F、ELOB、PSMB6、SEC61A1、COX4I1、NDUFB8及ATP5PD等10个Hub基因可能是脓毒症诊疗的潜在靶点和新型生物标志物,但部分基因对脓毒症发生发展的作用机制研究相对不足,仍需后续进一步验证。

Objective In order to provide potential targets and biomarkers for clinical diagnosis and treatment of sepsis,bioinformatics method was used to screen and analyze the differentially expressed genes and Hub genes related to sepsis.Methods The sepsis gene expression dataset was screened by using Gene Expression Omnibus(GEO) database,and the differentially expressed genes(DEGs) were analyzed by using online GEO database gene expression analysis tool(GEO2R),and DEGs were enriched by using STRING 12.0 and DAVID database.The Hub genes were screened by using Cytoscape 3.9.1 software,and their function was analyzed.Results We have screened 328 DEGs,including 2 upregulated genes and 326 downregulated genes.The enrichment results showed that the function of DEGs was mainly related to protein modification,catabolism,protease complex,mitochondria and enzyme activity,etc.Ten Hub genes,including NFKB1,NEDD8,NDUFA8,POLR2F,ELOB,PSMB6,SEC61A1,COX4I1,NDUFB8,ATP5PD,were screened out by using CytoHubba plug-in.Biological process(BP) visualization revealed that these Hub genes interacted in biological processes.Conclusions The ten Hub genes,including NFKB1,NEDD8,NDUFA8,POLR2F,ELOB,PSMB6,SEC61A1,COX4I1,NDUFB8,ATP5PD,may be potential targets and novel biomarkers for the diagnosis and treatment of sepsis.