Deciphering cuproptosis-related signatures in pediatric allergic asthma using integrated scRNA-seq and bulk RNA-seq analysis.

ABSTRACT

OBJECTIVE: Allergic asthma (AA) is common in children. Excess copper is observed in AA patients. It is currently unclear whether copper imbalance can cause cuproptosis in pediatric AA. METHODS: The datasets about pediatric AA (GSE40732 and GSE40888) were obtained from Gene Expression Omnibus (GEO) database. The expression of cuproptosis-related genes (CRGs) and immune cell infiltration in pediatric AA samples were analyzed. Single-cell RNA sequencing (scRNA-seq) data (GSE193816) were used to evaluate the expression patterns of CRGs in AA. The identification of differentially expressed genes within clusters was conducted using weighted gene co-expression network analysis. Subsequently, disease progression and cuproptosis-related models were screened using random forest (RF), support vector machine (SVM), extreme gradient boosting (XGBoost), and general linear model (GLM) algorithms. RESULTS: Four CRGs were notably increased in pediatric AA samples. CD4+ T cells, macrophages and mast cells exhibited a lower cuproptosis score in AA samples, indicating that these immune cells may be closely associated with cuproptosis in AA development. Co-expression network of CRGs in AA was constructed. AA samples were divided into two cuprotosis clusters. Following construction of four machine-learning models, SVM model exhibited the highest efficacy of prediction in the testing set (AUC = 0.952). SVM model containing five important variables can be used for prediction of AA. CONCLUSION: This work provided a machine learning model containing five important variables, which may have good diagnostic efficiency for pediatric AA.