基于生物信息学方法分析银屑病病理机制中的调节网络

Analysis of regulatory network in the pathogenesis of psoriasis based on bioinformatics

目的 通过生物信息学方法寻找可能调节银屑病病理过程的TF-miRNA-mRNA网络。方法 从Gene Expression Omnibus(GEO)中下载人的银屑病表达谱数据GSE166388与GSE41662。通过GEO2R和R语言对2个数据集进行各自差异表达基因及共同差异表达基因的筛选,通过R(3.6.3版本)中的clusterProfiler包对差异基因进行功能与通路的富集分析,通过STRING数据库、cytoscape软件中的MCODE和Cytohubba模块来构建PPI网络并进行关键基因筛选,通过Targetscan及miRwalk预测调节差异表达基因的潜在miRNA群。利用TRRUST预测差异表达基因相关的转录因子(TF),通过cytoscape构建miRNA-mRNA、TF-mRNA及TF-mRNA-miRNA互作网络。结果 筛选到GSE41662与GSE16638的共同差异表达基因共计57个,包括:EPSTI1、OAS1、KYNU、STAT1、IL36G等;通过GO和KEGG富集分析,57个差异表达基因被富集到IL-17信号通路、细胞因子结合受体及I型干扰素信号等通路;构建了由54个节点,86条边组成的共同差异基因的PPI网络图,同时筛选出包括STAT1、RSAD2、OAS1、EPSTI1及OASL在内的20个关键基因。最后,利用cytoscape软件构建TF-miRNA-mRNA网络RELA-STAT1-miRNA-3064-5p。结论 RELA-STAT1-miRNA-3064-5p可能是银屑病发生发展过程中的重要调节网络。

Objective To screen the potential TF-miRNA-mRNA regulatory network in the pathogenesis of psoriasis based on bioinformatics.Methods We obtained two gene series GSE166388 and GSE41662 from Gene Expression Omnibus(GEO).Differentially expressed genes(DEGs) in each GSE and the common DEGs were described by using GEO2R and R language. In addition, a series of bioinformatics analysis tools were employed including clusterProfiler(Functional enrichment analysis),the STRING database and Cytoscape software(protein-protein interaction analysis, hub gene screening and TF-mRNA-miRNA network building). Targetscan and miRwalk database were used to predict the mircoRNAs which target the common DEGs. TRRUST database was used to analyze the transcriptional factors which interact with the common DEGs. Results We found 57 common DEGs between GSE166388 and GSE41662 including EPSTI1, OAS1,KYNU,STAT1,IL36G, which enriched in IL-17R signaling, cytokine-binding receptor, type-1 interferons signaling and so forth. 20 hub genes were screened including STAT1,RSAD2,OAS1,EPSTI1 and OASL. More importantly, we built a PPI network consisting of 54 nodes and 86 edges and a TF-miRNA-mRNA network RELA-STAT1-miRNA-3064-5p. Conclusion RELA-STAT1-miRNA-3064-5p might be a relevant regulatory network in the pathogenesis of psoriasis.