基于蛋白质-蛋白质相互作用网络的燃煤污染型氟暴露人群血浆微小RNA靶基因模块化分析

Modular analysis of target genes of microRNAs in plasma of coal-burning fluoride exposed population based on protein-protein interaction network

目的建立燃煤污染型氟暴露人群血浆中差异表达的5个微小RNA(microRNA,miRNA)靶基因的蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,筛选具有重要作用的基因及基因模块。方法将本课题组前期筛选的燃煤污染型氟暴露人群血浆中差异表达的5个miRNA(hsa-miRNA-3131、hsa-miRNA-4516、hsa-miRNA-6501-5p、hsa-miRNA-10b-5p、hsa-miRNA-4683)的靶基因定位到STRING在线数据库(https://string-db.org),筛选PPI网络。使用Cytoscape v3.6.0软件对PPI网络可视化,通过NetworkAnalyzer插件得到拓扑属性值度和拓扑属性值介数,筛选PPI网络的中心节点(度和介数均最高的节点)。同时,采用CytoHubba插件中的最大团中心(MCC)分析方法来确定PPI网络中的重要节点。通过MCODE插件进行聚类分析,筛选PPI网络的基因模块。将基因模块所包含的蛋白质名称在线提交KOBAS v3.0数据库(http://kobas.cbi.pku.edu.cn/),对MCODE插件筛选出的基因模块进行KEGG(Kyoto Encyclopedia of Genes and Genomes)通路富集分析。结果靶基因的PPI网络由1035个节点和4346个边组成。泛素蛋白A-52残基核糖体蛋白融合产物1(UBA52)的度(101)和介数(0.01072389)均最高,为PPI网络的中心节点。经MCC分析,UBA52为PPI网络中的重要节点。从PPI网络中选择排名前5的基因模块,5个基因模块的KEGG通路富集分析中高度富集的基因通路分别为泛素介导的蛋白水解、剪接体、内吞作用、神经活性配体-受体相互作用、囊泡转运。结论成功建立了燃煤污染型氟暴露人群血浆中差异表达的5个miRNA靶基因的PPI网络,筛选出UBA52基因和5个基因模块主要通路。

Objective To establish a protein-protein interaction(PPI)network of 5 microRNA(miRNA)target genes differentially expressed in the plasma of coal-burning fluoride exposed population,and to screen genes and gene modules with important roles.Methods Five miRNA(hsa-miRNA-3131,hsa-miRNA-4516,hsa-miRNA-6501-5p,hsa-miRNA-10b-5p,hsa-miRNA-4683)target genes differentially expressed in the plasma of coal-burning fluoride exposed population screened by our previous study were mapped to the STRING online database(https://string-db.org),and the PPI network was screened.The Cytoscape v3.6.0 software was used to visualize the PPI network,the topological attribute values degree and betweenness centrality were obtained by the NetworkAnalyzer plug-in,and the central node was filtered in the network(the node with the highest degree and the highest betweenness centrality).At the same time,the maximal clique centrality(MCC)analysis method in the CytoHubba plug-in was used to determine the important nodes in the PPI network.The cluster analysis was conducted by the MCODE plug-in,and the gene modules were screened in the PPI network.The protein names contained in the gene modules were submitted online to the KOBAS v3.0 database(http://kobas.cbi.pku.edu.cn/),and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was performed on the gene modules selected by the MCODE plug-in.Results The PPI network of target genes was consisted of 1035 nodes and 4346 edges.The degree(101)and betweenness centrality(0.01072389)of ubiquitin A-52 residue ribosomal protein fusion product 1(UBA52)were the highest,which was the central node of the PPI network.According to MCC analysis,UBA52 was an important node in the PPI network.The top 5 gene modules were selected from the PPI network,and the highly enriched gene pathways in the KEGG pathway enrichment analysis of the 5 gene modules included ubiquitin mediated proteolysis,spliceosome,endocytosis,neuroactive ligand-receptor interaction and vesicular transport.Conclusion The PPI network of 5 miRNA target genes differentially expressed in the plasma of people exposed to coal-burning pollution of fluoride is successfully established,and the UBA52 gene and the 5 main pathways of gene modules are selected.