目的 通过生物信息学方法分析肥胖和腰椎间盘突出症共享基因特征和生物学机制,为探索治疗肥胖和腰椎间盘突出症提供新靶点和新思路.方法 从基因表达综合数据库中下载肥胖和腰椎间盘突出症的数据集,分析得到二者的差异共表达基因.对这些基因进行基因本体论(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析.利用STRING数据库构建蛋白质-蛋白质相互作用网络(protein-protein Interaction,PPI)并检测网络中的枢纽基因,将其与铁死亡基因集取交集.使用单样本基因集富集分析(single-sample gene set enrichment analysis,ssGSEA)计算肥胖和正常对照之间,以及腰椎间盘突出症和正常对照之间免疫细胞浸润的差异.通过人类微小核糖核酸(micro ribonucleic acid,miRNA)疾病数据库和StarBase数据库获得与肥胖和腰椎间盘突出症相关miRNA及其相应的靶基因.最后利用获得的靶基因和共享基因的交集,构建与这2种疾病相关的miRNAs-mRNAs调控网络.结果 在GSE15653和GSE124272 2个数据集中共筛选得到250个差异共表达基因.功能富集分析表明,信号转导、对内质网应激的反应、细胞外外泌体、细胞质、蛋白质以及蛋白激酶结合可能与肥胖合并腰椎间盘突出症有关.KEGG富集分析表明,肿瘤坏死因子信号通路和磷脂酰肌醇3-激酶/蛋白激酶B信号通路可能参与肥胖诱导腰椎间盘突出症的机制.PPI网络构建表明,肥胖合并腰椎间盘突出症的机制可能与JUN、HIF1A、ALDH18A1、MCM6、DLGAP5、BARD1和WRN等靶基因密切相关.结论 通过生物信息学方法确定肥胖与腰椎间盘突出症之间的共享关键基因和通路,有助于进一步揭示肥胖和腰椎间盘突出症的共同发病机制以及潜在的治疗靶点.
Integrative bioinformatics analysis of shared genetic signatures and biological mechanisms of obesity and lumbar disc herniation
Objective To analyze the shared gene signatures and biological mechanisms of obesity and lumbar disc herniation using bioinformatics methods in order to provide new targets for related treatments.Methods The dataset of obesity and lumbar disc herniation was downloaded from the Gene Expression Omnibus(GEO)database while the differentially co-expressed genes of obesity and lumbar disc herniation were obtained by analysis.These genes were analyzed via gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Then,a protein-protein interaction(PPI)network was constructed using the search tool for recurring instances of neighboring genes(STRING)database and the hub genes in the network were detected and intersected with the ferroptosis gene set.Differences in immune cell infiltration between the obese and normal control and between lumbar disc herniation and normal control were identified using single-sample gene get enrichment analysis(ssGSEA).Micro ribonucleic acids(miRNAs)associated with obesity and lumbar disc herniation and their corresponding target genes were obtained via the human microRNA disease database(HMDD)and StarBase databases.Finally,the miRNAs-mRNAs regulatory network associated with these two diseases was constructed by using the intersection of previously obtained target genes and shared genes.Results A total of 250 differentially co-expressed genes were screened in GSE15653 and GSE124272.Functional enrichment analysis indicated that signal transduction,responses to endoplasmic reticulum stress,exosomes,cytoplasm,proteins,and protein kinase binding might be associated with obesity and lumbar disc herniation.KEGG enrichment analysis indicated that tumor necrosis factor(TNF)signaling pathway and phosphatidyl-inositol 3-kinase/serine-threonine kinase(PI3K-Akt)signaling pathway were possibly involved in the mechanism of obesity-induced lumbar disc herniation.The construction of the PPI network indicated that the mechanism between obesity and lumbar disc herniation might be closely related to such target genes as JUN,HIF1A,ALDH18A1,MCM6,DLGAP5,BARD1 and WRN.Conclusion The shared key genes and pathways between obesity and lumbar disc herniation are identified,which can shed light on the common pathogenesis and potential therapeutic targets of obesity and lumbar disc herniation.
NETL
NSTL
万方数据
