基于GEO特发性肺动脉高压芯片数据的生物信息学分析

Bioinformatics Analysis of Idiopathic Pulmonary Arterial Hypertension Microarray Based on GEO Database

目的:运用生物信息学分析方法挖掘特发性肺动脉高压(idiopathic pulmonary arterial hypertension,IPAH)相关的关键基因并探讨其发病机制。方法:从GEO数据库中下载与IPAH相关的高通量基因表达谱芯片数据,用GEO2R在线分析平台挑选出健康人与IPAH有显著差异表达的基因;通过DAVID 6.8软件对所选择的差异表达基因进行GO功能富集分析和KEGG信号通路分析;并采用STRING、Cytoscape等工具对其进行蛋白质相互作用网的构建及可视化分析。结果:⑴通过分析得到116个差异表达基因,其中上调基因41个,下调基因75个。⑵GO功能富集分析发现这些基因主要参与氧气运输、小胶质细胞活化、血液凝固、趋化作用、神经元凋亡过程的正调控、炎性反应、cAMP反应等众多生物学过程。⑶KEGG信号通路结果主要富集在甲型流感、Toll样受体、细胞因子-细胞因子受体相互作用、趋化因子、单纯疱疹感染、EB病毒感染、破骨细胞分化、NF-kappa B等信号通路。⑷基于String数据库型筛选出9个得分较高的中心基因,包括CXCL8、JUN、CCR2、CXCR4、FPR2、HBE1、CX3CR1、PPBP和GPR183。Cytoscape软件的MCODE插件共筛选出三个显著模块,涉及基因主要参与细胞对激素刺激的反应、G蛋白耦联等生物学过程,通路主要富集在趋化因子、细胞因子-细胞因子受体相互作用、破骨细胞分化等。结论:生物信息学分析显示CXCL8、JUN、CCR2、CXCR4、FPR2、HBE1、CX3CR1、PPBP和GPR183可能是IPAH相关的重要候选基因,为该疾病进一步的功能研究提供了理论依据。

Objective Exploring the key genes related to the idiopathic pulmonary arterial hypertension(IPAH) by bioinformatics analysis and exploring its pathogenesis. Methods The high throughput gene expression profile data related to IPAH were downloaded from GEO database, and the genes with significant difference between healthy people and IPAH were selected by the online analysis platform of GEO2 R. The GO functional enrichment analysis and KEGG signal pathway analysis were carried out by DAVID 6.8 software. The protein-protein interaction(PPI) network was constructed and visualized by using String, Cytoscape and other tools. Results ⑴116 differentially expressed genes were identified, including 41 up-regulated genes and 75 down regulated genes. ⑵GO functional enrichment analysis showed that these genes were mainly involved in oxygen transport, microglia activation, blood coagulation, chemotaxis, positive regulation of neuronal apoptosis, inflammatory response, cAMP reaction, etc. ⑶KEGG signal pathway was mainly enriched in influenza A, Toll-like receptor, cytokine-cytokine receptor interaction, chemokines, herpes simplex infection, EB virus infection, osteoclast differentiation, NF-kappa B and so on. ⑷Based on the string database, nine central genes with high scores were screened, including CXCL8, JUN, CCR2, CXCR4, FPR2, HBE1, CX3 CR1, PPBP and GPR183. Three significant modules were screened out by Cytoscape software and MCODE plugin, which involved in cellular response to hormone stimulation, G-protein coupled receptor and other biological processes, and the pathway mainly enriched in chemokines, cytokine-cytokine receptor interaction, osteoclast differentiation and so on. Conclusion Bioinformatics analysis showed that CXCL8, JUN, CCR2, CXCR4, FPR2, HBE1, CX3 CR1, PPBP and GPR183 may be important candidate genes related to IPAH, which provides a theoretical basis for further functional study of the disease.