Table2_Subtyping children with asthma by clustering analysis of mRNA expression data.xlsx

Background: Asthma is a heterogeneous disease. There are several phenotypic classifications for childhood asthma.
Methods: Unsupervised consensus cluster analysis was used to classify 36 children with persistent asthma from the GSE65204 dataset. The differentially expressed genes (DEGs) between different asthma subtypes were identified, and weighted gene co-expression network analysis (WGCNA) was carried out. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed for DEGs and critical gene modules. Protein–protein interactions (PPI) were constructed to obtain the hub genes. Finally, differences in the immune microenvironment were analyzed between different subtypes.
Results: Two subtypes (C1, C2) were identified using unsupervised consensus clustering. The DEGs between different asthma subtypes were mainly enriched in immune regulation and the release of inflammatory mediators. The important modular genes screened by WGCNA were mainly enriched in aspects of inflammatory mediator regulation. PPI analysis found 10 hub genes (DRC1, TTC25, DNALI1, DNAI1, DNAI2, PIH1D3, ARMC4, RSPH1, DNAAF3, and DNAH5), and ROC analysis demonstrated that 10 hub genes had a reliably ability to distinguish C1 from C2. And we observed differences between C1 and C2 in their immune microenvironment.
Conclusion: Using the gene expression profiles of children’s nasal epithelium, we identified two asthma subtypes that have different gene expression patterns, biological characteristics, and immune microenvironments. This will provide a reference point for future childhood asthma typing and personalized therapy.

背景：哮喘是一类异质性疾病，儿童哮喘存在多种表型分型方式。
方法：本研究采用无监督共识聚类分析，对GSE65204数据集中共36例持续性哮喘患儿进行分型。首先鉴定不同哮喘亚型间的差异表达基因（DEGs），并开展加权基因共表达网络分析（WGCNA）；随后对差异表达基因及关键基因模块进行基因本体（Gene Ontology, GO）和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析；通过构建蛋白质-蛋白质相互作用（PPI）网络筛选核心基因；最后分析不同哮喘亚型间的免疫微环境差异。
结果：通过无监督共识聚类共鉴定出两种哮喘亚型（C1、C2）。不同亚型间的差异表达基因主要富集于免疫调控及炎症介质释放相关通路；经WGCNA筛选得到的关键模块基因，主要富集于炎症介质调控相关领域。PPI分析共得到10个核心基因（DRC1、TTC25、DNALI1、DNAI1、DNAI2、PIH1D3、ARMC4、RSPH1、DNAAF3及DNAH5），ROC分析显示这10个核心基因可有效区分C1与C2亚型。此外，本研究还观察到C1与C2亚型在免疫微环境上存在显著差异。
结论：本研究基于儿童鼻上皮细胞的基因表达谱，成功鉴定出两种具有不同基因表达模式、生物学特征及免疫微环境的哮喘亚型。该研究结果可为未来儿童哮喘分型及个性化治疗提供重要参考依据。