Wang Ting, He Changhui, Hu Ming, Wu Honghua, Ou Shuteng, Li Yuke, Fan Chuping
The Affiliated Chenzhou Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Department of Pediatrics, Shenzhen Children's Hospital, Shenzhen, Guangdong, China.
Front Genet. 2022 Sep 9;13:974936. doi: 10.3389/fgene.2022.974936. eCollection 2022.
Asthma is a heterogeneous disease. There are several phenotypic classifications for childhood asthma. 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. 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. 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.
哮喘是一种异质性疾病。儿童哮喘有多种表型分类。使用无监督一致性聚类分析对来自GSE65204数据集的36名持续性哮喘儿童进行分类。鉴定了不同哮喘亚型之间的差异表达基因（DEG），并进行了加权基因共表达网络分析（WGCNA）。对DEG和关键基因模块进行了基因本体论和京都基因与基因组百科全书富集分析。构建蛋白质-蛋白质相互作用（PPI）以获得枢纽基因。最后，分析了不同亚型之间免疫微环境的差异。使用无监督一致性聚类鉴定出两个亚型（C1、C2）。不同哮喘亚型之间的DEG主要富集于免疫调节和炎症介质释放。通过WGCNA筛选出的重要模块基因主要富集于炎症介质调节方面。PPI分析发现10个枢纽基因（DRC1、TTC25、DNALI1、DNAI1、DNAI2、PIH1D3、ARMC4、RSPH1、DNAAF3和DNAH5），ROC分析表明10个枢纽基因具有可靠区分C1和C2的能力。并且我们观察到C1和C2在免疫微环境方面存在差异。利用儿童鼻上皮的基因表达谱，我们鉴定出两种具有不同基因表达模式、生物学特征和免疫微环境的哮喘亚型。这将为未来儿童哮喘分型和个性化治疗提供参考依据。
