摘要
目的:采用生物信息学策略筛选肺动脉高压(PAH)的差异基因,为其治疗提供新靶点。方法:在基因表达综合数据库(GEO)中下载芯片数据集GSE113439,样本总数26例,正常组11例,PAH组15例。利用GEO2R进行数据分析,以|logFC|>1,且P<0.01为标准筛选差异基因。对差异基因进行基因本体论(GO)及基因组百科全书(KEGG)通路富集分析,构建蛋白-蛋白互作网络,筛选关键基因。结果:共筛选出差异基因603个,其中上调基因502个,下调基因101个;基因本体论分析表明,差异基因主要参与DNA修复、细胞有丝分裂、DNA复制及细胞对DNA损伤刺激的反应等生物学过程,细胞组件主要是中心体、核质、核仁、细胞膜、细胞质;分子功能主要有解旋酶活性、微管结合、Ploy(A)RNA结合、ATP结合、蛋白结合。KEGG信号通路富集在同源重组、类风湿性关节炎、核质转运、真核生物核糖体生物合成、单纯疱疹病毒1感染。应用STRING数据库构建蛋白相互作用网络,采用Cytoscape软件中的cytoHubba筛选出DDX21、CDK1、POLR2B、TOP2A、EPRS、CDC5L、HSP90AA1、PLK48个上调关键基因。结论:筛选出PAH发病机制中的关键基因,可能为PAH的进一步研究及后续药物靶向治疗提供理论依据。
Objective:To screen the differential genes of pulmonary arterial hypertension(PAH)by using bioinformatics strategy and provide new targets for the treatment.Methods:The chip dataset GSE113439 was downloaded from Gene Expression Omnibus(GEO)database.The total number of samples was 26 cases,11 cases in healthy group,and 15 cases in PAH group.The data were analyzed using GEO2R.The|logFC|>1 and P<0.01 was used as the standard to screen the differentially expressed genes.Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for differentially expressed genes.Protein-protein interaction networks were constructed to screen key genes.Results:A total of 603 differentially expressed genes were screened,including 502 up-regulated genes and 101 down-regulated genes.GO analysis showed that the differential genes were mainly involved in biological processes such as DNA repair,cell mitosis,DNA replication and cellular response to DNA damage stimuli.Cell components were mainly centrosome,nucleoplasm,nucleolus,cell membrane and cytoplasm.The molecular functions were mainly unwinding activity,microtubule binding,Ploy(A)RNA binding,ATP binding,and protein binding.KEGG signaling pathway was enriched in homologous recombination,rheumatoid arthritis,nucleoplasmic transport,eukaryotic ribosomal biosynthesis,and herpes simplex virus 1 infection.The STRING database was used to construct a protein interaction network.CytoHubba in Cytoscape software was used to screen out 8 up-regulated key genes,including DDX21,CDK1,POLR2B,TOP2A,EPRS,CDC5L,HSP90AA1,PLK4.Conclusion:Key genes in the PAH pathogenesis are screened,which may provide theoretical basis for further PAH research and subsequent drug targeted therapy.
作者
吴洁
马虹
Wu Jie;Ma Hong(Department of General Medicine,The Sixth People's Hospital of Chengdu,Chengdu 610051,Sichuan Province,China)
出处
《中国社区医师》
2023年第23期59-61,共3页
Chinese Community Doctors
关键词
肺动脉高压
生物信息学
差异基因
Pulmonary arterial hypertension
Bioinformatics
Differential genes