Identification of candidate aberrant differentially methylated/expressed genes in asthma

Allergy Asthma Clin Immunol. 2022 Dec 22;18(1):108. doi: 10.1186/s13223-022-00744-5.

Abstract

Background: Asthma is an important non-communicable disease worldwide. DNA methylation is associated with the occurrence and development of asthma. We are aimed at assuring differential expressed genes (DEGs) modified by aberrantly methylated genes (DMGs) and pathways related to asthma by integrating bioinformatics analysis.

Methods: One mRNA dataset (GSE64913) and one gene methylation dataset (GSE137716) were selected from the Gene Expression Omnibus (GEO) database. Functional enrichment analysis was performed using GeneCodies 4.0 database. All gene expression matrices were analyzed by Gene set enrichment analysis (GSEA) software. STRING was applied to construct a protein-protein interaction (PPI) network to find the hub genes. Then, electronic validation was performed to verify the hub genes, followed by the evaluation of diagnostic value. Eventually, quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of hub genes.

Results: In total, 14 hypomethylated/high-expression genes and 10 hypermethylated/low-expression genes were obtained in asthma. Among them, 10 hub genes were identified in the PPI network. Functional analysis demonstrated that the differentially methylated/expressed genes were primarily associated with the lung development, cytosol and protein binding. Notably, HLA-DOA was enriched in asthma. FKBP5, WNT5A, TM4SF1, PDK4, EPAS1 and GMPR had potential diagnostic value for asthma.

Conclusion: The project explored the pathogenesis of asthma, which may provide a research basis for the prediction and the drug development of asthma.

Keywords: Asthma; Bioinformatics analysis; DNA methylation; Diagnosis; Differentially expressed genes.