大气交通污染物对儿童外周血基因表达谱的影响分析

Effect of atmospheric traffic pollutants on gene expression profile in peripheral blood of children

目的采用生物信息学研究方法分析大气污染对儿童外周血基因表达谱的影响,为后期预防、诊断及治疗提供一定的理论参考依据。方法从基因芯片公共数据库(Gene Expression Omnibus, GEO)中下载一组来自不同大气污染暴露下外周血基因芯片数据,并将数据导入分析软件QOE3.1、GenClip2.0、GATHER等,分析基因表达谱、蛋白-蛋白相互作用网络、分子生物学过程及基因功能,寻找大气污染对儿童影响的关键节点基因。结果共发现差异表达基因2 172个。根据研究目的,对Fold Change≥3的223个儿童差异表达基因进行分析,结果表明这些靶基因主要参与细胞对外部刺激物的反应、细胞信号传导、核苷磷酸结合等生物学功能。进一步分析发现,NR4A1、SGK1、TUBB1、PINK1和THOC3基因为蛋白-蛋白相互作用网络中心节点,删除这些节点蛋白后,网络结构涣散,同时研究发现基因PINK1灵敏度和特异度最高,诊断价值最大。结论不同污染状态下儿童基因表达不同,差异基因主要参与细胞对外部刺激物的反应、细胞信号传导、核苷磷酸结合等生物学功能,基因PINK1的诊断能力最强。

Objective To analyze the impact of air pollution on the gene expression profile in peripheral blood of children by using bioinformatics research method, and to provide a theoretical basis for the prevention, diagnosis and treatment in the later stage.Methods A set of peripheral blood gene chip data fromchildren exposed todifferent air pollution was downloaded from the Gene Expression Omnibus, and the data were imported into the analysis software QOE3.1, GenClip2.0 and GATHER, etc. We analyzed gene expression profiles, protein-protein interaction networks, molecular biological processes and gene functions, and found key genes for the effects of air pollution on children.Results A total of 2,172 differentially expressed genes were found. According to the purpose of the study, 223 children differentially expressed genes with Fold Change ≥ 3 were analyzed. The results showed that these target genes were mainly involved in the biological functions of cells, such as cell response to external stimuli, cell signaling transduction, and nucleoside phosphate binding. Further analysis revealed that the NR4A1, SGK1, TUBB1, PINK1 and THOC3 genes were central nodes of the protein-protein interaction network. After deleting these nodule proteins, the network structure was scattered. At the same time, the gene PINK1 was found to have the highest sensitivity, specificity and diagnostic value.Conclusions The gene expression of children in different pollution states is different. The differential genes are mainly involved in the biological functions of cells, such as response to external stimuli, cell signaling transduction, and nucleoside phosphate binding. The diagnostic ability of the PINK1 gene is the strongest.