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肺栓塞患者DNA甲基化联合基因表达差异分析

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目的 通过整合生物信息学分析筛选与肺栓塞相关的遗传和表观遗传表达差异.方法 以2019年就诊与新疆医科大学第三附属医院肺栓塞患者及健康体检者4例作为研究对象,利用高通量测序技术及甲基化芯片技术检测、筛选并整合外周血差异基因组和表观基因组数据来识别致肺栓塞发病的甲基化驱动基因及差异表达基因,行GO及KEGG富集分析.结果 将肺栓塞组和健康对照组间DNA甲基化和基因表达数据进行共表达分析,基因上游区域差异甲基化与基因表达呈负相关,其中共筛选出基因上游区域显著甲基化基因有8个,采用独立样本的T检验及Pearson相关性分析,肺栓塞组中TSS1500显著甲基化基因有6个,分别为TSPO2、C1QA、AQP1、TNFSF9、MIA、STAB1,对应基因的差异表达倍数 log2FC 分别是 1.298,1.629,1.024,2.746,2.539,1.060,基因表达与基因甲基化之间的相关度分别是-0.908,-0.900,-0.824,-0.784,-0.783,-0.779,两组间甲基化差异分别是-0.049,-0.053,-0.048,-0.057,-0.050,-0.053(P<0.05).TSS200区域显著甲基化基因有3个,分别为TSPO2,SLCP9A3,SIGLEC1,基因表达差异倍数log2FC分别是1.298,-2.252,1.866,基因表达与基因甲基化之间的相关度分别是-0.860,-0.774,-0.739,两组间甲基化差异分别是-0.051,0.027,-0.048(P<0.05).肺栓塞组中在TSS区域有TSPO2、C1QA、AQP1、TNFSF9、MIA、STAB1、SIGLEC1共7个基因呈现低甲基化高表达状态.SLC9A3基因呈现高甲基化低表达.GO功能分析中,在补体活化、免疫反应、激活蛋白级联等得到显著富集.在KEGG信号通路中,免疫系统、细菌感染以及信号分子及相互作用方面得到显著富集,从而调控肺栓塞的发生.结论 基于DNA甲基化和基因表达的联合分析,发现了肺栓塞发生发展的新思路,后续可进行更加深入的研究.
Differential analysis of DNA methylation combined with gene expression in patients with pulmonary embolism
Objective To screen genetic and epigenetic expression differences associated with pulmonary embolism through integrated bioinformatics analysis.Methods Four patients with pulmonary embolism and healthy physical examination in the Third Affiliated Hospital of Xinjiang Medical University in 2019 were selected as the research objects,using high-throughput sequencing technologies and methylation chip technology to detect,screening and integrated peripheral blood difference genomes and the epigenome data to identify the pathogenesis of pulmonary embolism caused by methylation of drive and differentially expressed genes,GO and KEGG enrichment analysis were performed.Results Coexpression analysis of DNA methylation and gene expression data between the pulmonary embolism group and the healthy control group showed that differential methylation in the upstream region of genes was negatively correlated with gene expression.Among them,8 significantly methylated genes in the upstream region of genes were screened out,and independent sample t-test and Pearson correlation analysis were done.In the pulmonary embolism group,there were 6 significant methylated genes of TSS1500,namely TSPO2,C1QA,AQP1,TNFSF9,MIA and STAB1,and the differential expression multiple log2FC of corresponding genes was 1.298,1.629,1.024,2.746,2.539,1.060,respectively.The correlation between gene expression and gene methylation were-0.908,-0.900,-0.824,-0.784,-0.783,-0.779,respectively,and the methylation differences between the two groups were-0.049,-0.053,-0.048,-0.057,-0.050,respectively.-0.053(P<0.05).There were three significantly methylated genes in the TSS200 region,namely TSPO2,SLC9A,and SIGLEC1.The gene expression differential multiple log2FC was 1.298,-2.252,and 1.866,respectively.The correlation between gene expression and gene methylation was-0.860,-0.774,and-0.739,respectively.The methylation difference between the two groups was-0.051,0.027,-0.048(P<0.05).In the pulmonary embolism group,7 genes,including TSPO2,C1QA,AQP1,TNFSF9,MIA,STAB1 and SIGLEC1,showed hypomethylation and high expression in the TSS region.SLC9A3 gene showed high methylation and low expression.In the analysis of GO function,significant enrichment was obtained in complement activation,immune response and activation protein cascade.In the KEGG signaling pathway,the immune system,bacterial infection,and signaling molecules and interactions are significantly enriched,thereby regulating the occurrence of pulmonary embolism.Conclusions Based on the combined analysis of DNA methylation and gene expression,a new idea of the occurrence and development of pulmonary embolism has been found,which can be further studied in the future.

Pulmonary embolismDNA methylationGene expressionConjoint analysis

曹嘉芮、李伟、曹国磊、何丽丽、牛海文、李晓晗、罗琴

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新疆医科大学附属肿瘤医院重症医学科,乌鲁木齐 830011

新疆医科大学附属肿瘤医院日间病房二病区,乌鲁木齐 830011

新疆医科大学附属肿瘤医院呼吸神经内科,乌鲁木齐 830011

惠州市第六人民医院消化内科,惠州 516200

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肺栓塞 DNA甲基化 基因表达 联合分析

新疆维吾尔族自治区自然科学基金重点项目

2022D01D74

2024

中华急诊医学杂志
中华医学会

中华急诊医学杂志

CSTPCD北大核心
影响因子:1.556
ISSN:1671-0282
年,卷(期):2024.33(2)
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