婴儿猝死综合征与婴儿感染性猝死共同相关基因的筛选及其调控网络的生物信息学分析  

Screening of Genes Co-Associated with Sudden Infant Death Syndrome and Infectious Sudden Death in Infancy and Bioinformatics Analysis of Their Regulatory Networks

作　　者：孙语新 龚晓娟 郝秀丽 田雨馨 陈艺铭 张宝 阎春霞[1,2,3] SUN Yu-xin;GONG Xiao-juan;HAO Xiu-li;TIAN Yu-xin;CHEN Yi-ming;ZHANG Bao;YAN Chun-xia(College of Forensic Medicine,Xi’an Jiaotong University Health Science Center,Xi’an 710061,China;NHC Key Laboratory of Forensic Medicine,Xi’an Jiaotong University,Xi’an 710061,China;Bio-evidence Sciences Academy,Western China Science and Technology Innovation Harbour,Xi’an Jiaotong University,Xi’an 712000,China)

机构地区：[1]西安交通大学医学部法医学院,陕西西安710061 [2]国家卫生健康委员会法医学重点实验室西安交通大学,陕西西安710061 [3]中国西部科技创新港西安交通大学生物证据研究院,陕西西安712000

出　　处：《法医学杂志》2023年第5期433-440,共8页Journal of Forensic Medicine

摘　　要：目的应用生物信息学方法筛选出经尸体检验确诊的婴儿猝死综合征(sudden infant death syndrome,SIDS)和婴儿感染性猝死(infectious sudden death in infancy,ISDI)死者脑、心脏和肝组织中共有的差异表达mRNA,探讨SIDS与ISDI的共有分子标记和发生机制。方法下载GSE70422、GSE136992数据集,用R软件limma包筛选SIDS和ISDI死者不同组织样本中差异表达的mRNA,进行重叠分析,并用R软件clusterProfiler包进行基因本体论(gene ontology,GO)和京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析,使用STRING数据库构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,基于cytoHubba插件筛选hub基因。结果与数据集中的对照组相比,SIDS和ISDI死者组织样本中有19个显著的共同差异基因,其中心脏组织中16个、肝组织中3个,心脏组织星形肌动蛋白1(astrotactin 1,ASTN1)基因表达差异最显著。PPI网络确定了Ras同源基因家族成员A(ras homolog family member A,RHOA)、整合素亚单位α1(integrin subunit alpha 1,ITGA1)和H2B簇状组蛋白5(H2B clustered histone 5,H2BC5)是hub基因。GO和KEGG分析结果表明,共同差异基因富集在肌动蛋白细胞骨架的调节、黏着斑及对霉酚酸的反应等分子通路中。结论ASTN1、RHOA和ITGA1可能参与SIDS与ISDI的发生发展。共同差异基因富集在免疫与炎症反应相关通路中,说明SIDS与ISDI在免疫与炎症反应方面可能存在共同的分子调控机制。这些发现有望为SIDS与ISDI的分子解剖和法医学鉴定提供新的生物标记。Objective The common differentially expressed mRNAs in brain,heart and liver tissues of deceased sudden infant death syndrome(SIDS)and infectious sudden death in infancy(ISDI)confirmed by autopsy was screened by bioinformatics to explore the common molecular markers and pathogenesis of SIDS and ISDI.Methods The datasets of GSE70422 and GSE136992 were down-loaded,the limma of R software was used to screen differentially expressed mRNA in different tissue samples of SIDS and ISDI decedents for overlapping analysis.The clusterProfiler of R software was used to conduct gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrich-ment analysis.The protein-protein interaction(PPI)network was constructed by STRING database,while the hub gene was screened by cytoHubba plug-in.Results Compared with the control group,there were 19 significant differentially expressed genes in the tissue samples of SIDS and ISDI dece-dents,among which 16 in the heart tissue and 3 in the liver tissue,and the astrotactin 1(ASTN1)gene expression difference in the heart tissue was most significant.The PPI network identified Ras ho-molog family member A(RHOA),integrin subunit alpha 1(ITGA1),and H2B clustered histone 5(H2BC5)were hub genes.The analysis of GO and KEGG showed that differentially expressed genes were enriched in the molecular pathways of actin cytoskeleton regulation,focal adhesion and response to mycophenolic acid.Conclusion ASTN1,RHOA and ITGA1 may participate in the development of SIDS and ISDI.The enrichment of differentially expressed genes in immune and inflammatory pathways suggests a common molecular regulatory mechanism between SIDS and ISDI.These findings are ex-pected to provide new biomarkers for molecular anatomy and forensic identification of SIDS and ISDI.

关 键 词：法医病理学 生物信息学 婴儿猝死综合征 婴儿感染性死亡 差异基因表达 基因集合富集分析 发病机制 

分 类 号：R89[医药卫生—法医学] DF795.1[医药卫生—临床医学] D919.1[政治法律—诉讼法学]