Identification of a Methylated Site Signature and Subtypes in Childhood Allergic Asthma

Abstract

Background: To construct a signature of methylated sites and subtypes of allergic asthma in children. Methods: We identified differentially expressed genes (DEGs) and methylated probes (DEMPs) in children with allergic asthma using the Gene Expression Omnibus database. Weighted gene co-expression network analysis was used to identify key DEMPs and their corresponding genes. Functional analyses were conducted to determine the functions of the DEGs and DEMPs. Subtype analysis was used to explore the clinical features of allergic asthma. Meanwhile, the DEGs were intersected with DEMP corresponding genes, and Least Absolute Shrinkage and Selection Operator (LASSO) was further used to screen the optimal methylated probes to construct a risk score signature. A receiver operating characteristic curve was used to evaluate the performance of the risk score. Results: In total, 438 DEGs and 1216 key DEMPs (corresponding to 927 genes) were identified. These DEGs and DEMP-corresponding genes were enriched in pathways and functions related to allergic asthmatic progression, such as natural killer cell-mediated cytotoxicity, defense response to virus, lymphocyte-mediated immunity, and cell adhesion-related biological processes. Subtypes classified based on methylated probes could better reflect the clinical characteristics of asthma. Cluster 1 showed mainly hypomethylation, while cluster 2 showed mainly hypermethylation. A significant correlation was found between our subtypes and previously identified subtypes: cluster 1 contained more PC20 subtypes, whereas cluster 2 contained more lung function subtypes. We identified 14 DEMPs in children with allergic asthma after LASSO regression, and the risk score showed strong efficacy (area under the receiver operating characteristic curve = 0.811) in the diagnosis of allergic asthma. Conclusions: The DEGs and DEMPs identified in this study are related to the progression of allergic asthma. In addition, our results provide a diagnostic signature for allergic asthma, which was demonstrated to be effective in the clinical diagnosis of the disease.