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哮喘中 DNA 甲基化的全景:数据挖掘与验证。

The landscape of DNA methylation in asthma: a data mining and validation.

机构信息

The Area B of International Medical Department, Gansu Provincial Maternity and Child-care Hospital, Lanzhou, Gansu, People's Republic of China.

出版信息

Bioengineered. 2021 Dec;12(2):10063-10072. doi: 10.1080/21655979.2021.1997088.

Abstract

Human asthma is caused by interactions between a range of genetic and environmental factors. However, the specific pathogenesis of asthma remains controversial. This study explored the contribution of DNA methylation to asthma using computer learning methods. Relevant datasets and information related to patients with asthma were collected from the Gene Expression Omnibus (GEO) database. A multivariate linear regression model was established. Differentially expressed genes and DNA methylation sites were identified. The results showed that the expression of 169 genes was significantly different between the two groups. Through differential analysis of methylation and differential analysis of gene expression, 44 differentially expressed genes that may be affected by DNA methylation modification were identified. The results of the multiple linear regression model showed that DNA methylation could explain 9.81% of the variation in gene expression. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the differentially expressed genes, , and , were related to the occurrence of asthma, and expression was significantly reduced in allergic asthma. There was a positive correlation between cg04933135 and expression, and cg04933135 was a differential site for DNA methylation. Using blood samples from asthma patients, we confirmed that expression is down-regulated, which may be affected by abnormal DNA methylation. DNA methylation plays an important role in the development of asthma, and HLA-DMB which modified by abnormal DNA methylation can be regarded as a new biomarker of asthma.

摘要

人类哮喘是由一系列遗传和环境因素相互作用引起的。然而,哮喘的确切发病机制仍存在争议。本研究采用计算机学习方法探讨 DNA 甲基化对哮喘的贡献。从基因表达综合数据库(GEO)中收集了与哮喘患者相关的相关数据集和信息。建立了多变量线性回归模型。鉴定了差异表达基因和 DNA 甲基化位点。结果表明,两组间有 169 个基因的表达存在显著差异。通过甲基化差异分析和基因表达差异分析,鉴定出 44 个可能受 DNA 甲基化修饰影响的差异表达基因。多元线性回归模型的结果表明,DNA 甲基化可以解释 9.81%的基因表达变化。基因本体论和京都基因与基因组百科全书分析表明,差异表达基因与哮喘的发生有关,在过敏性哮喘中表达明显降低。cg04933135 与 表达呈正相关,cg04933135 是 DNA 甲基化的差异位点。使用哮喘患者的血液样本,我们证实 表达下调,这可能受到异常 DNA 甲基化的影响。DNA 甲基化在哮喘的发展中起着重要作用,异常 DNA 甲基化修饰的 HLA-DMB 可以作为哮喘的一个新的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/566e/8809922/bd63c85f490f/KBIE_A_1997088_F0001_OC.jpg

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