偏头痛皮质扩散性抑制的差异表达基因生物信息分析和治疗药物预测

Bioinformatics analysis and therapeutic drug prediction for migraine mouse models after the cortical spreading depression of migraine

目的对家族性偏瘫性偏头痛1型(FHM1)小鼠诱发CSD后皮质转录本中发现的差异表达基因(DEGs)进行生物信息学分析和治疗药物预测。方法利用R软件中的Deseq2包从基因芯片公共数据库(GEO)发表的FHM1小鼠诱发CSD后皮质转录本中筛选出DEGs和基因本体论(GO)功能富集分析,并利用clusterProfiler包进行信号通路功能富集分析(GSEA)以及STRING 11.0、CMap等分析平台构建蛋白质相互作用网络和化合物预测,同时利用Cytoscape中的cytohubba插件筛选出核心DEGs并对其进行功能注释。结果FHM1型小鼠CSD发作后共筛选出155个上调基因和35个下调基因。DEGs主要富集于细胞通讯、小分子GTP酶介导的信号转导、轴突的发育以及细胞内转运的调节等生物学过程和一些免疫炎症反应相关通路以及microRNA、细胞因子信号通路上,并筛选出芹菜素、1,4-屈烯醌、非诺特罗等可逆转DEGs的小分子化合物。结论FHM1型小鼠CSD发作后与健康对照组小鼠相比DEGs存在明显差异。多个信号通路、多个蛋白质相互作用方式为理解偏头痛CSD发作后皮质的病理过程提供了帮助。

Objective To analyze the differential expression genes(DEGs)in cortical transcripts of CSD induced by familial hemiplegic migraine type 1(FHM1)mice and to predict therapeutic agents.Methods DEGs and gene ontology(GO)funct ional enrichment analysis were screened from cortical transcripts of CSD induced by FHM1 mice published in gene chip public database(GEO)by Deseq2 package in R software.ClusterProfiler package was used for signal pathway functional enrichment analysis(GSEA),STRING 11.0,CMap and other analysis platforms to construct protein interaction networks and compound prediction.At the same time,CytoHubba plug-in in Cytoscape was used to screen out the core DEGs and annotate its functions.Results A total of 155 up-regulated genes and 35 down-regulated genes were screened after CSD onset in FHM1 mice.DEGs are mainly enriched in biological processes such as cell communication,small molecule GTP-mediated signal transduction,axon development,and intracellular transport regulation,as well as some inflammatory immune response-related pathways,microRNA,and cytokine signaling pathways.Lemepromazine,podophyllotoxin,W-13 hydrochloride,and other small molecule compounds that can reverse DEGs were screened.Conclusion After CSD onset,the DEGs of FHM1 mice are significantly different from those of healthy control mice.Multiple signaling pathways and multiple protein interaction modes help understand the pathological process of cortex after a CSD attack in migraine.