基于生物信息学分析铁死亡调控基因与脓毒症诱导肺损伤的关系
The Relationship Between Ferroptosis Regulatory Genes and Lung Injury Induced by Sepsis Based on Bioinformatics
曾琴 1谢榕城 2马杰飞 2陈斌1
作者信息
- 1. 复旦大学附属中山医院厦门医院急诊科(福建厦门 361000)
- 2. 复旦大学附属中山医院厦门医院危急重症科(福建厦门 361000)
- 折叠
摘要
目的 通过生物信息学方法探究铁死亡相关基因在脓毒症导致的肺损伤中发生发展中的作用,并预测与之密切相关的基因.方法 从基因表达数据库(gene expression database,GEO)中下载数据集GSE154653,包含正常组和脂多糖(lipopolysaccharide,LPS)诱导的脓毒症大鼠肺组织的芯片基因集共8例,并根据|log2 FC|＞1且P.adj＜0.05条件,筛选出表达差异基因(differential expression genes,DEGs).同时,将筛选出来的DEGs与从铁死亡数据库(FerrDb)中下载铁死亡的驱动和抑制基因取交集得出脓毒症铁死亡相关的差异基因(Fe-DEGs),并利用R语言、DAVID和STRING等线上工具分析Fe-DEGs的基因本体和京都基因和基因组百科全书(Gene Ontology and Kyoto encyclopedia of genes and genomes,GO-KEGG)功能及通路富集分析、PPI 网络构建.结果 生物信息学筛选出3533个表达差异基因,并取交集得到53个铁死亡相关的关键基因.进一步的GO富集分析生物学过程中主要涉及转录的正向调节、RNA聚合酶Ⅱ启动子转录的正向调节、细胞因子介导的信号通路以及血管生成的正向调节等.分子功能主要涉及相同的蛋白质结合、转录激活活性以及氧化还原酶活性等.通路富集在铁死亡、HIF-1信号通路和AGE-RAGE信号通路等.通过构建PPI网络筛选出5个Fe-DEGs关键基因,包括 CYBB、LCN2、HMOX1、TIMP1 和 CDKN1A.结论 CYBB、LCN2、HMOX1、TIMP1 和 CDKN1A 基因可能是脓毒症导致肺组织发生铁死亡的关键基因.
Abstract
Objective The role of ferroptosis-related genes in the occurrence and development of lung injury caused by sepsis was investigated by bioinformatics methods,and the closely related genes were predicted.Methods The Dataset GSE154653 was downloaded from the gene expression database(GEO),and a total of 8 cases of microarray gene set were included in normal group and lipopolysaccharide(LPS)-induced sepsis lung tissue.The differential expression genes(DEGs)were screened out under conditions of|log2 FC|＞1 and P.adj＜0.05.Meanwhile,the selected DEGs were combined with the driver and suppressor genes of ferroptosis downloaded from the ferroptosis database(FerrDb)to obtain the differential genes associated with ferroptosis in sepsis(Fe-DEGs).These Fe-DEGs were further analyzed using R language,DAVID,and STRING online tools to identify GO-KEGG functions and pathways,and the construction of PPI network.Results The Bioinformatics approach screened out 3 533 DEGs and intersected 53 key genes related to ferroptosis.The further biological process(BP)of GO enrichment analysis mainly involves the positive regulation of transcription,the positive regulation of RNA polymerase Ⅱ promoter transcription,the cytokine mediated signaling pathway,and the positive regulation of angiogenesis.The molecular function(MF)mainly involves the same protein binding,transcriptional activation activity and REDOX enzyme activity.The pathways are enriched in iron death,HIF-1 signaling pathway and AGE-RAGE signaling pathway.Five key Fe-DEGs genes were screened by constructing PPI network,including CYBB,LCN2,HMOX1,TIMP1 and CDKN1A.Conclusion CYBB、LCN2、HMOX1、TIMP1 and CDKNIA genes may be key genes involved in ferroptosis of lung tissue caused by sepsis.
关键词
脓毒症/肺损伤/铁死亡/生物信息学Key words
Sepsis/Lung injury/Ferroptosis/Bioinformatics引用本文复制引用
出版年
2024
NETL
NSTL
万方数据