基于GEO数据库的溃疡性结肠炎和克罗恩病的生物信息学分析

Bioinformatics Analysis in UC and CD Based on the GEO Database

目的通过生物信息学方法寻找并分析溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD)的差异基因,从而在基因水平上为鉴别UC和CD提供新的理论基础。方法从Gene Expresion omnibus(GEO)数据库下载GSE75214基因芯片,利用GEO2R在线分析及交叉分析得到UC和CD的共有差异表达基因(differentially expressed genes,DEGs)和特有DEGs;并对这些基因进行功能富集分析、蛋白互作网络分析,并筛选关键基因。结果UC和CD中共有DEGs 37个,UC特有DEGs 61个,CD特有DEGs 16个。UC和CD共有DEGs参与的生物过程主要富集在炎症反应、对脂多糖反应、免疫反应等方面,在细胞组成方面主要富集在细胞外外泌体、细胞外空间等部位,在分子功能方面主要富集于钙离子结合、血红素结合等方面,参与通路主要富集于IL-17调控信号通路等;UC特有DEGs在生物过程方面主要富集在内肽酶活性的负调控,在细胞组成方面主要富集在质膜,在分子功能上主要富集于丝氨酸内肽酶抑制剂活性,在通路主要富集于代谢通路;而CD特有DEGs在生物过程主要富集在蛋白水解,在细胞组成上主要富集在细胞外空间及细胞外区域,在分子功能上主要富集于清道夫受体活性,在通路上主要富集于细胞因子及细胞因子受体相互作用。筛选出UC和CD共有DEGs和特有DEGs中的10个关键基因。结论本研究提示UC和CD是同一种疾病的不同表现形式,为UC和CD在基因分子水平上的异同提供了理论依据;关键基因的筛选及比较,为进一步诊断和鉴别两者在基因水平上提供了新方向,并有望成为两者的鉴别诊断标志物。

Objective Providing a new theoretical basis for the identification between ulcerative colitis(UC)and Crohn’s disease(CD)by finding and analyzing differentially expressed genes(DEGs)through bioinformatics approaches.Methods The gene chip GSE75214 was downloaded from GEO database.GEO2R online analysis and cross analysis were used to obtain the common differentially expressed genes(DEGs)and specific DEGs of UC and CD.The functional enrichment analysis,protein-protein interaction network analysis and screening of key genes were carried out for these genes.Results There were 37 common DEGs in UC and CD,61 specific DEGs in UC,and 16 specific DEGs in CD.In biological processes,the common DEGs in UC and CD were enriched in inflammatory response,lipopolysaccharide response,immune response;in cellular components,these DEGs were involved in extracellular exosome and extracellular space;in molecular functions,these DEGs were mainly concentrated on calcium binding and heme binding;these DEGs were involved in IL-17 signaling pathway.Specific DEGs of UC in biological processes were enriched in negative regulation of endopeptidase activity;in cellular components,they were concentrated on plasma membrane;these DEGs were enriched in serine-type endopeptidase inhibitor activity in molecular functions;they were involved in metabolic pathways.Specific DEGs of CD were enriched in roteolysis in biological processes,extracellular space and extracellular region in cellular components,scavenger receptor activity in molecular functions;these DEGs were involved in cytokine-cytokine receptor interaction.Ten hub genes were screened in common and specific DEGs respectively in UC and CD.Conclusion UC and CD are different manifestations of the same disease,providing a theoretical basis for the similarities and differences between UC and CD at the genetic and molecular level.Hub genes provides a new direction for further diagnosis and identification at the genetic level,and these genes are expected to be a differential diagnostic marker between UC and CD.