作者：刘玲玲，王国佐，李子滢，李晟，陈彦霖，林霞，黄娟，秦莉花

单位：

1.410208湖南省长沙市，湖南中医药大学护理学院 2.410208湖南省长沙市，湖南中医药大学中西结合学院 3.410208湖南省长沙市，湖南中医药大学信息与管理学院 通信作者：秦莉花，E-mail：479157643@qq.com

Units：

1.School of Nursing, Hunan University of Chinese Medicine, Changsha 410208, China 2.School of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China 3.School of Information and Management, Hunan University of Chinese Medicine, Changsha 410208, China Corresponding author: QIN Lihua, E-mail: 479157643@qq.com

关键词：

脑出血; 计算生物学; 生物信息学; 通路; 关键基因;

Keywords：

Cerebral hemorrhage; Computational biology; Bioinformatics; Pathway; Key genes

CLC：

DOI：

10.12114/j.issn.1008-5971.2022.00.096

Funds：

国家自然科学基金青年基金项目（81904180）；湖南省社会科学成果评审委员会课题（XSP19YBZ152）；湖南省自然科学基金资助项目（2018JJ3390，2020JJ4467）；湖南省教育厅科学研究项目（20B429，18C0375）；长沙市科技计划项目（kq1801045）

摘要：

目的 基于生物信息学技术分析老年自发性脑出血的相关通路及关键基因。方法 2021年9—10月,从基因表达数据库(GEO)下载GSE24265数据集,从其中选取4个血肿周围区域样本作为实验组,相应的4个对侧灰质样本作为对照组。采用R软件及相关安装包进行数据预处理、差异基因的筛选和GO功能、KEGG通路富集分析及基因集富集分析(GSEA),采用STRING数据库对差异基因制作蛋白质互作网络(PPI),采用MCOD、cytoHubba插件进行关键基因的筛选,利用韦恩图在线工具确定老年自发性脑出血的关键基因。结果 箱式图分析结果显示,各个样本中位数基本在一个水平线上,提示样本间归一化程度好;主成分分析(PCA)散点图和统一流形逼近与投影(UMAP)图分析结果显示,各组的样本基本分开,提示后续差异分析有意义的结果可能会较多。两组样本数据比较共有415个差异基因,其中高表达53个、低表达362个。GO功能富集分析共得到226条有明显差异的GO条目,包括145条生物过程(BP)条目、44条细胞组成(CC)条目、37条分子功能(MF)条目,差异基因介导的BP主要富集于化学突触传递的调节、突触信号转导的调控、神经元投射发育的调节等,CC主要富集于突触膜、突触后密度蛋白、谷氨酸能突触等,MF主要富集于阳离子通道活性调控、门控通道活性调控、钙离子跨膜转运蛋白活性调控等。KEGG通路富集分析结果显示,差异基因主要富集于轴突导向信号通路、催产素信号通路、肥厚型心肌病等17条通路。GSEA结果显示,共有734个基因集,其中显著富集的基因集共有364个,包括人体补体系统、无意义介导的衰变、流感病毒感染等。最终筛选出老年自发性脑出血的关键基因为RPS6、RPL8、FAU、RPL35、RPS5、RPS19、RPLP1。结论 与老年自发性脑出血发病机制有关的信号通路包括轴突导向信号通路、催产素信号通路、肥厚型心肌病等;其关键基因为RPS6、RPL8、FAU、RPL35、RPS5、RPS19、RPLP1。

Abstract：

【Abstract】 Objective To analyze the related pathways and key genes in elderly spontaneous intracerebral hemorrhagebased on bioinformatics technology. Methods From September to October 2021, the GSE24265 dataset was downloaded fromgene expression omnibus (GEO) , and 4 samples from the surrounding area of the hematoma were selected as the experimentalgroup, and the corresponding 4 contralateral gray matter samples were used as the control group. R software and relatedinstallation packages were used for data preprocessing, differential gene screening and GO function, KEGG pathway enrichmentanalysis and gene set enrichment analysis (GSEA) . The STRING database was used to construct a protein-protein interactionnetworks (PPI) for differential genes, MCOD and cytoHubba plug-ins were used to screen key genes, and the Venn diagram onlinetool was used to determine the key genes of senile spontaneous intracerebral hemorrhage. Results The box plot analysis resultsshow that the median of each sample was basically on the same horizontal line, indicating that the degree of normalization betweensamples was good; the principal components analysis (PCA) scatter plot and uniform manifold approximation and projection (UMAP)plot analysis results show that, the samples of each group were basically separated, suggesting that there may be more meaningfulresults in subsequent differential analysis. There were a total of 415 differential genes in the comparison of the two groups ofsample data, of which 53 were highly expressed and 362 were low expressed. A total of 226 GO items with significant differenceswere obtained by GO functional enrichment analysis, including 145 biological process (BP) items, 44 cell composition (CC) items,37 molecular function (MF) items. BP mediated by differential genes was mainly enriched in the regulation of chemical synaptictransmission, the regulation of synaptic signal transduction, the regulation of neuronal projection development, etc. CC was mainlyenriched in synaptic membrane, postsynaptic density protein, glutamatergic synapse, etc. MF was mainly enriched in cationchannel activity regulation, gated channel activity regulation, calcium ion transmembrane transporter activity regulation, etc. Theresults of KEGG pathway enrichment analysis showed that the differential genes were mainly enriched in 17 pathways includingaxon guidance signaling pathway, oxytocin signaling pathway and hypertrophic cardiomyopathy. The GSEA results showed thatthere were a total of 734 gene sets, of which 364 were significantly enriched, including the human complement system, nonsensemediated decay, and influenza infection. Finally, the key genes of elderly spontaneous intracerebral hemorrhage were screened outas RPS6, RPL8, FAU, RPL35, RPS5, RPS19, and RPLP1. Conclusion The signaling pathways related to the pathogenesis ofelderly spontaneous intracerebral hemorrhage include axon guidance signaling pathway, oxytocin signaling pathway, hypertrophiccardiomyopathy, etc. And its key genes are RPS6, RPL8, FAU, RPL35, RPS5, RPS19, and RPLP1.

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