AUTHOR=Li Bin , Sun Wen-Xuan , Zhang Wan-Ying , Zheng Ye , Qiao Lu , Hu Yue-Ming , Li Wei-Qiang , Liu Di , Leng Bing , Liu Jia-Ren , Jiang Xiao-Feng , Zhang Yan 

TITLE=The Transcriptome Characteristics of Severe Asthma From the Prospect of Co-Expressed Gene Modules

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.765400

DOI=10.3389/fgene.2021.765400

ISSN=1664-8021

ABSTRACT=<p><bold>Rationale:</bold> Severe asthma is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of asthmatic bronchial epithelial cells have provided biological insights and underscored possible pathological mechanisms; however, the molecular basis in severe asthma is still poorly understood.</p><p><bold>Objective:</bold> The objective of this study was to identify the features of asthma and uncover the molecular basis of severe asthma in distinct molecular phenotype.</p><p><bold>Methods:</bold> The k-means clustering and differentially expressed genes (DEGs) were performed in 129 asthma individuals in the Severe Asthma Research Program. The DEG profiles were analyzed by weighted gene co-expression network analysis (WGCNA), and the expression value of each gene module in each individual was annotated by gene set variation analysis (GSVA).</p><p><bold>Results:</bold> Expression analysis defined five stable asthma subtype (AS): 1) Phagocytosis-Th2, 2) Normal-like, 3) Neutrophils, 4) Mucin-Th2, and 5) Interferon-Th1 and 15 co-expressed gene modules. “Phagocytosis-Th2” enriched for receptor-mediated endocytosis, upregulation of Toll-like receptor signal, and myeloid leukocyte activation. “Normal-like” is most similar to normal samples. “Mucin-Th2” preferentially expressed genes involved in O-glycan biosynthesis and unfolded protein response. “Interferon-Th1” displayed upregulation of genes that regulate networks involved in cell cycle, IFN gamma response, and CD8 TCR. The dysregulation of neural signal, REDOX, apoptosis, and O-glycan process were related to the severity of asthma. In non-TH2 subtype (Neutrophils and Interferon-Th1) with severe asthma individuals, the neural signals and IL26-related co-expression module were dysregulated more significantly compared to that in non-severe asthma. These data infer differences in the molecular evolution of asthma subtypes and identify opportunities for therapeutic development.</p><p><bold>Conclusions:</bold> Asthma is a heterogeneous disease. The co-expression analysis provides new insights into the biological mechanisms related to its phenotypes and the severity.</p>