Coordinated DNA Methylation and Gene Expression Data for Identification of the Critical Genes Associated with Childhood Atopic Asthma

Abstract

Asthma is a chronic inflammatory disorder of airways that involves in many cells and factors. This study aimed to screen critical genes and miRNAs involved in childhood atopic asthma. DNA methylation and gene expression data (access numbers GSE65163 and GSE65204) were downloaded from Gene Expression Omnibus (GEO) database, which included 72 atopic asthmatic subject samples and 69 healthy samples. The differentially expressed genes (DEGs) with DNA methylation changes were identified, followed by Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Gene coexpression network and miRNA-target gene regulatory networks were then constructed. Besides, we screened critical drug molecules that have high correlation with atopic asthma in children. A total of 146 critical DEGs with DNA methylation changes were screened from atopic asthmatic samples compared with healthy control samples. GO and KEGG pathway enrichment analysis showed that the critical genes were mainly related to 20 GO terms and 13 KEGG pathways. In the coexpression network, tumor necrosis factor (TNF) and major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1) were identified that were significantly related to immune response process. Analysis of miRNA-target gene network showed that hsa-miR-148b had the highest number of target genes(degree = 21). Besides, we found that Alsterpaullone had a correlation value closest to -1 (correlation = -0.884, p = 0.0031), which indicated that the agent might be considered as a potential agent that antagonized to asthma. The dysregulation of TNF, HLA-DPA1, and miR-148b might be related to the immune response of childhood atopic asthma.

Keywords: atopic asthma; differentially expressed genes; regulatory network.