自发性脑出血后脑组织差异基因的生物信息学分析

Bioinformatics analysis of differential genes in brain tissue after spontaneous intracerebral hemorrhage

目的利用基因表达数据库(gene expression omnibus,GEO)探究自发性脑出血后脑组织中的差异表达基因,为探寻脑出血后脑组织继发性脑损伤的发病机制提供新思路,为脑出血的治疗提供新的治疗靶点。方法选取数据库中编号为GSE24265的芯片作为研究对象,应用R语言中的相关函数筛选出芯片中符合条件的差异基因,进一步对差异基因进行功能富集分析,并构建差异基因对应的蛋白质间相互作用网络图,根据蛋白质间相互作用的关系作用对数筛选关键差异基因。结果筛选出脑出血后脑组织中差异表达的基因70个,其中表达上调基因62个,表达下调基因8个。基因本体(gene ontology,GO)富集分析结果显示差异基因主要分布在细胞的胞质囊腔、特定分泌颗粒、分泌颗粒内腔、分泌颗粒膜、血红蛋白与珠蛋白复合体、内吞作用囊泡上,中性粒细胞激活、中性粒细胞介导的免疫反应、白细胞、粒细胞的驱化生物过程中,以及趋化因子活性、趋化因子受体结合、G蛋白耦联受体、细胞因子活性、细胞因子受体结合、氧载体活性、葡萄糖跨膜转运蛋白活性等功能活动中。京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析显示,差异基因主要介导Toll受体转导通路、肿瘤坏死因子(tumor necrosis factor,TNF)信号通路、沙门菌感染、吞噬体、疟疾、军团病、细胞因子受体相互作用、趋化因子信号通路、南美锥虫病趋化因子等信号通路。通过蛋白质相互作用网络,进一步挖掘得到可能在脑出血后参与脑组织继发性脑损伤进程的20个关键基因,包括CXCL8、IL6、TLR2、CXCL1、CCL4、SERPINE1、CCL20、PPBP、TIMP1、TREM1、CD163、HMOX1等。结论本研究从生物信息学角度分析GEO数据库的原始表达谱芯片数据,通过关键差异基因分析,发现了与自发性脑出血相关的关键差异基因和信号通路,为后续的研究提供重要的参考。

Objective To explore the differential genes in brain tissues after spontaneous intracerebral hemorrhage by using gene expression omnibus(GEO)database,to clarify new ideas for the exploration of its pathophysiological process,and to offer new therapeutic targets for the treatment of intracerebral hemorrhage.Methods GSE24265 was selected as the research object,and functions in Rstudio were used to screen out eligible differential genes in the chip,and functional enrichment analysis was conducted on differential genes so as to construct the network diagram of protein-protein interaction corresponding to differential genes and screen key differential genes according to protein-protein interaction.Results Seventy differentially expressed genes were screened out including 62 up-regulated genes and 8 down-regulated genes.Gene ontology(GO)?enrichment analysis results showed that the genetic variation was mainly distributed in the lumen of the?endoplasmic reticulum,specific secretory granules,secretory granules lumen,secretory granules film,hemoglobin and pearl protein complexes,endocytic vesicle in cellular component.In terms of biological process,it was concentrated in the process of neutrophil activation,neutrophils-mediated immune response,biological drive of leukocytes and granulocytes.In molecular function,it was enriched in chemokine activity,chemokine mediated by receptors,activities of cytokine mediated by G protein coupled receptors and cytokine receptors,as well as oxygen carrier activity and glucose transmembrane transport protein activity.Kyoko encyclopedia of genes and genonmes(KEGG)pathway enrichment analysis showed that differences mainly mediated Toll receptor gene transduction pathways,TNF signaling pathways,salmonella infection,phagosome,malaria,legionnaires’disease,cell factor receptor interaction,chemokine signaling pathways,chagas disease chemokine signaling pathways,etc.Through protein interaction network,further excavation revealed 20 key genes,which might be involved in the process of secondary brain damage in brain tissue after intracerebral hemorrhage,including CXCL8,IL6,TLR2,CXCL1,CCL4,SERPINE1,CCL20,PPBP,TIMP1,TREM1,CD163,HMOX1,etc.Conclusion This study analyzes the original expression profile chip data of GEO database from the perspective of bioinformatics,and identifies key differential genes and pathways related to spontaneous intracerebral hemorrhage,providing important references for subsequent studies.