基于蛋白互作网络的白内障致病基因挖掘

Exploration of pathogenic genes of cataracts based on protein-protein interaction networks

目的筛选自测的白内障差异表达基因与IMPC、MGI和Cat-Map、GWAS Catalog数据库中白内障相关基因,并进行生物信息学分析,从而探究白内障发病过程的潜在致病基因及信号通路。方法收集白内障患者及对照透明晶状体前囊膜,提取总RNA,建库测序,分析差异表达基因。分别下载IMPC、MGI和GWAS Catalog数据库中白内障表型相关基因数据,下载最新的Cat-Map数据,进行白内障易感基因注释,分析各数据库数据的特征,分析差异基因,GO富集分析、KEGG富集分析、蛋白质相互作用(PPI)网络分析。结果白内障易感SNP注释分析共找到21个潜在靶基因。IMPC、MGI、Cat-Map数据库和SNP靶基因富集于RNA聚合酶启动子的调控、蛋白质结合、细胞分裂、过氧化物酶体、细胞代谢方面。核心蛋白的PPI网络集中于过氧化物酶体家族及功能相关基因。白内障患者及对照透明晶状体前囊膜测序数据差异表达基因富集于MAPK信号通路、信号转导、离子转运、代谢、过氧化物酶体、细胞黏附等通路。IMPC、MGI、Cat-Map数据库和SNP靶基因基因集与白内障患者测序差异表达数据相比,差异基因富集于细胞内信号转导、MAPK信号通路、昼夜节律、c-AMP、钙离子通路等。基于PPI网络分析鉴定出白内障新的TRIM22、OAS3、EPSTI1、ZC3HAV1、SP110、PARP12蛋白网络。结论TRIM22、OAS3、EPSTI1、ZC3HAV1、SP110、PARP12的PPI网络所涉及的通路及生物学功能可能是白内障新的致病机制。

Objective To screen self-assessed differentially expressed genes of cataracts and cataract-related genes from the International Mouse Phenotyping Consortium(IMPC),Mouse Genome Informatics(MGI),Cat-Map and GWAS Catalog and perform bioinformatics analysis,exploring potential pathogenic genes and signaling pathways in cataract pathogenesis.Methods The transparent anterior lens capsules of cataract patients and personnel in the control group were collected,total ribonucleic acid(RNA)was extracted,the library was constructed for sequencing,and differentially expressed genes were analyzed.Data about the cataract phenotype-related genes was downloaded from IMPC,MGI and GWAS Catalog,the latest data from Cat-Map was downloaded,cataract susceptible gene annotation was performed,the characteristics of data from each database and the differentially expressed genes were analyzed,and Gene Ontology enrichment analysis,Kyoto Encyclopedia of Genes and Genomes enrichment analysis and protein-protein interaction(PPI)network analysis were carried out.Results Cataract susceptible single nucleotide polymorphism(SNP)annotation found a total of 21 potential target genes.IMPC,MGI,Cat-Map,and SNP target genes were enriched in the regulation of RNA polymerase promoters,protein binding,cell division,peroxisome,and cell metabolism.The PPI network of core proteins focused on the peroxisome family and function-related genes.The differentially expressed genes obtained from sequencing data of transparent anterior lens capsules of cataract patients and personnel in the control group were enriched in mitogen-activated protein kinase(MAPK)signaling pathway,signal transduction,ion transport,metabolism,peroxisome,and cell adhesion pathways.Compared with the sequencing differentially expressed data of cataract patients,the differentially expressed genes obtained from IMPC,MGI,Cat-Map,and SNP target gene sets were enriched in intracellular signal transduction,MAPK signaling pathway,circadian rhythm,cyclic adenosine monophosphate,and calcium pathway.TRIM22,OAS3,EPSTI1,ZC3HAV1,SP110 and PARP12 protein networks of cataracts were identified based on the PPI networks.Conclusion The pathways and biological functions involved in the PPI networks of TRIM22,OAS3,EPSTI1,ZC3HAV1,SP110 and PARP12 may be a new pathogenic mechanism for cataracts.