Molecular Phenotyping Based on Blood Transcriptome-Associated Clusters in Asthma: Findings From Two Korean Asthma Cohorts.
22 affiliations
- 1Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Korea.
- 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Korea.
- 3Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
- 4Department of Internal Medicine, Korea University Medical Center Anam Hospital, Seoul, Korea.
- 5Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea.
- 6Department of Internal Medicine, Konkuk University College of Medicine, Seoul, Korea.
- 7DNA Link, Seoul, Korea.
- 8Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
- 9Department of Internal Medicine, Inje University Haeundae Paik Hospital, Busan, Korea.
- 10Department of Pulmonology and Allergy, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea.
- 11Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.
- 12Department of Internal Medicine, Nowon Eulji Hospital, Eulji University School of Medicine, Seoul, Korea.
- 13Department of Internal Medicine, Pusan National University Hospital, Pusan National University College of Medicine, Busan, Korea.
- 14Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
- 15Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
- 16Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea.
- 17Department of Allergy and Clinical Immunology, Kangwon National University School of Medicine, Chuncheon, Korea.
- 18Department of Allergy and Clinical Immunology, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Korea.
- 19Division of Allergy, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
- 20National Heart and Lung Institute, Imperial College London, and Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK.
- 21Interdisciplinary Program of Bioinformatics, College of Natural Science, Seoul National University, Seoul, Korea. [email protected].
- 22Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, Ulsan University School of Medicine, Seoul, Korea. [email protected].
Abstract
Purpose
Asthma is heterogeneous in its molecular and clinical manifestations, complicating treatment. In this study, we investigated the molecular phenotypes of asthma using RNA-sequencing (RNA-seq) of peripheral blood mononuclear cells to advance precision medicine approaches.Methods
We analyzed peripheral blood RNA-seq data from 456 participants from the Cohort for Reality and Evolution of Adult Asthma in Korea, including 23 patients with severe asthma and 433 with non-severe asthma to identify blood transcriptome-associated clusters (B-TACs) that correlate with distinct inflammatory processes. This included a meta-analysis of differentially expressed genes to refine gene selection for defining B-TACs. Gene Set Variation Analysis was used to assess the differential activation of biological pathways across B-TACs. We validated these findings in the Precision Medicine Intervention in Severe Asthma cohort of 122 patients, focusing on cluster stability, clinical correlates, and treatment responsiveness.Results
Our analysis identified 3 B-TACs (B-TAC1, B-TAC2 and B-TAC3) with B-TAC1 and B-TAC2 showing higher blood eosinophil levels than B-TAC3. B-TAC1 was characterized by a clear T2-high inflammatory profile, whereas B-TAC2 exhibited a mixed molecular phenotype with both T2-high and non-T2 features. B-TAC3 was associated with low T2 and inflammasome-related inflammation profiles. Validation using the PRISM cohort underscored the stability of B-TAC1 and B-TAC2. Notably, patients with B-TAC2 molecular phenotype had lower biologics use and tended to have less favorable treatment outcomes than those with B-TAC1.Conclusions
We discovered and validated 3 B-TACs, with B-TAC2 displaying a mixed T2-high and non-T2 phenotype, suggesting a potential reduction in responsiveness to biologic treatments. These findings provide molecular insights that may guide the development of personalized treatment strategies for asthma.
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BibTeX
@article{kim2026molecular,
title = {{Molecular Phenotyping Based on Blood Transcriptome-Associated Clusters in Asthma: Findings From Two Korean Asthma Cohorts.}},
author = {Eunse Kim and So-Young Park and Byung Keun Kim and Min-Hye Kim and Ji-Yong Moon and Jong Eun Lee and Hye Yoon Jang and Eunsoon Shin and Jae-Woo Jung and Taehoon Lee and Chan Sun Park and Jeong-Hee Choi and Sujeong Kim and Sang-Hoon Kim and Hye-Kyung Park and Sae-Hoon Kim and Sang-Ha Kim and Joo-Hee Kim and Jae-Woo Kwon and Young-Joo Cho and Byung-Jae Lee and Ian M Adcock and Kian Fan Chung and Sungho Won and Tae-Bum Kim},
journal = {Allergy, asthma \& immunology research},
year = {2026},
month = sep,
doi = {10.4168/aair.2026.18.5.652},
url = {https://europepmc.org/article/MED/42845223},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Molecular Phenotyping Based on Blood Transcriptome-Associated Clusters in Asthma: Findings From Two Korean Asthma Cohorts.
AU - Eunse Kim
AU - So-Young Park
AU - Byung Keun Kim
AU - Min-Hye Kim
AU - Ji-Yong Moon
AU - Jong Eun Lee
AU - Hye Yoon Jang
AU - Eunsoon Shin
AU - Jae-Woo Jung
AU - Taehoon Lee
AU - Chan Sun Park
AU - Jeong-Hee Choi
AU - Sujeong Kim
AU - Sang-Hoon Kim
AU - Hye-Kyung Park
AU - Sae-Hoon Kim
AU - Sang-Ha Kim
AU - Joo-Hee Kim
AU - Jae-Woo Kwon
AU - Young-Joo Cho
AU - Byung-Jae Lee
AU - Ian M Adcock
AU - Kian Fan Chung
AU - Sungho Won
AU - Tae-Bum Kim
PY - 2026
DA - 2026/09/01
JO - Allergy, asthma & immunology research
DO - 10.4168/aair.2026.18.5.652
UR - https://europepmc.org/article/MED/42845223
AB - Purpose Asthma is heterogeneous in its molecular and clinical manifestations, complicating treatment. In this study, we investigated the molecular phenotypes of asthma using RNA-sequencing (RNA-seq) of peripheral blood mononuclear cells to advance precision medicine approaches.Methods We analyzed peripheral blood RNA-seq data from 456 participants from the Cohort for Reality and Evolution of Adult Asthma in Korea, including 23 patients with severe asthma and 433 with non-severe asthma to identify blood transcriptome-associated clusters (B-TACs) that correlate with distinct inflammatory processes. This included a meta-analysis of differentially expressed genes to refine gene selection for defining B-TACs. Gene Set Variation Analysis was used to assess the differential activation of biological pathways across B-TACs. We validated these findings in the Precision Medicine Intervention in Severe Asthma cohort of 122 patients, focusing on cluster stability, clinical correlates, and treatment responsiveness.Results Our analysis identified 3 B-TACs (B-TAC1, B-TAC2 and B-TAC3) with B-TAC1 and B-TAC2 showing higher blood eosinophil levels than B-TAC3. B-TAC1 was characterized by a clear T2-high inflammatory profile, whereas B-TAC2 exhibited a mixed molecular phenotype with both T2-high and non-T2 features. B-TAC3 was associated with low T2 and inflammasome-related inflammation profiles. Validation using the PRISM cohort underscored the stability of B-TAC1 and B-TAC2. Notably, patients with B-TAC2 molecular phenotype had lower biologics use and tended to have less favorable treatment outcomes than those with B-TAC1.Conclusions We discovered and validated 3 B-TACs, with B-TAC2 displaying a mixed T2-high and non-T2 phenotype, suggesting a potential reduction in responsiveness to biologic treatments. These findings provide molecular insights that may guide the development of personalized treatment strategies for asthma.
SN - 2092-7355
SN - 2092-7363
ER -