The Transcriptome Characteristics of Severe Asthma From the Prospect of Co-Expressed Gene Modules
Rationale: 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 un...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.765400/full |
| _version_ | 1818919119489073152 |
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| author | Bin Li Bin Li Bin Li Wen-Xuan Sun Wan-Ying Zhang Wan-Ying Zhang Ye Zheng Lu Qiao Yue-Ming Hu Wei-Qiang Li Di Liu Bing Leng Jia-Ren Liu Jia-Ren Liu Xiao-Feng Jiang Yan Zhang |
| author_facet | Bin Li Bin Li Bin Li Wen-Xuan Sun Wan-Ying Zhang Wan-Ying Zhang Ye Zheng Lu Qiao Yue-Ming Hu Wei-Qiang Li Di Liu Bing Leng Jia-Ren Liu Jia-Ren Liu Xiao-Feng Jiang Yan Zhang |
| author_sort | Bin Li |
| collection | DOAJ |
| description | Rationale: 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.Objective: The objective of this study was to identify the features of asthma and uncover the molecular basis of severe asthma in distinct molecular phenotype.Methods: 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).Results: 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.Conclusions: Asthma is a heterogeneous disease. The co-expression analysis provides new insights into the biological mechanisms related to its phenotypes and the severity. |
| first_indexed | 2024-12-20T01:00:47Z |
| format | Article |
| id | doaj.art-a019f008fed341519ba3e07f65c7767f |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-20T01:00:47Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-a019f008fed341519ba3e07f65c7767f2022-12-21T19:58:59ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-10-011210.3389/fgene.2021.765400765400The Transcriptome Characteristics of Severe Asthma From the Prospect of Co-Expressed Gene ModulesBin Li0Bin Li1Bin Li2Wen-Xuan Sun3Wan-Ying Zhang4Wan-Ying Zhang5Ye Zheng6Lu Qiao7Yue-Ming Hu8Wei-Qiang Li9Di Liu10Bing Leng11Jia-Ren Liu12Jia-Ren Liu13Xiao-Feng Jiang14Yan Zhang15Department of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaSchool of Life Science and Technology, Computational Biology Research Center, Harbin Institute of Technology, Harbin, ChinaHeilongjiang Longwei Precision Medical Laboratory Center, Harbin, ChinaDepartment of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaHeilongjiang Longwei Precision Medical Laboratory Center, Harbin, ChinaDepartment of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaHeilongjiang Longwei Precision Medical Laboratory Center, Harbin, ChinaDepartment of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaSchool of Life Science and Technology, Computational Biology Research Center, Harbin Institute of Technology, Harbin, ChinaRationale: 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.Objective: The objective of this study was to identify the features of asthma and uncover the molecular basis of severe asthma in distinct molecular phenotype.Methods: 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).Results: 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.Conclusions: Asthma is a heterogeneous disease. The co-expression analysis provides new insights into the biological mechanisms related to its phenotypes and the severity.https://www.frontiersin.org/articles/10.3389/fgene.2021.765400/fullPhagocytosis-Th2normal-likeneutrophilsmucin-Th2Interferon-Th1 |
| spellingShingle | Bin Li Bin Li Bin Li Wen-Xuan Sun Wan-Ying Zhang Wan-Ying Zhang Ye Zheng Lu Qiao Yue-Ming Hu Wei-Qiang Li Di Liu Bing Leng Jia-Ren Liu Jia-Ren Liu Xiao-Feng Jiang Yan Zhang The Transcriptome Characteristics of Severe Asthma From the Prospect of Co-Expressed Gene Modules Frontiers in Genetics Phagocytosis-Th2 normal-like neutrophils mucin-Th2 Interferon-Th1 |
| title | The Transcriptome Characteristics of Severe Asthma From the Prospect of Co-Expressed Gene Modules |
| title_full | The Transcriptome Characteristics of Severe Asthma From the Prospect of Co-Expressed Gene Modules |
| title_fullStr | The Transcriptome Characteristics of Severe Asthma From the Prospect of Co-Expressed Gene Modules |
| title_full_unstemmed | The Transcriptome Characteristics of Severe Asthma From the Prospect of Co-Expressed Gene Modules |
| title_short | The Transcriptome Characteristics of Severe Asthma From the Prospect of Co-Expressed Gene Modules |
| title_sort | transcriptome characteristics of severe asthma from the prospect of co expressed gene modules |
| topic | Phagocytosis-Th2 normal-like neutrophils mucin-Th2 Interferon-Th1 |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.765400/full |
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