Integrative multi-omics and machine learning identify CHRNA1 putative circadian-immune hub in COPD
Lan Zhang1, Zhifei Li1, Tiansheng Xia1
1Department of Respiratory and Critical Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Plos One
|July 31, 2026
Summary
Circadian rhythm disruption is linked to chronic obstructive pulmonary disease (COPD). CHRNA1, a circadian rhythm gene, is upregulated in COPD patients and associated with inflammation, suggesting its potential as a biomarker and therapeutic target.
Area of Science:
- Pulmonary Medicine
- Chronobiology
- Immunology
Background:
- Circadian rhythm disruption is a growing concern in chronic inflammatory disorders.
- Its role and mechanisms in chronic obstructive pulmonary disease (COPD) are not well understood.
- Identifying circadian biomarkers could offer new diagnostic and therapeutic avenues for COPD.
Purpose of the Study:
- To identify circadian rhythm-associated biomarkers in COPD.
- To explore their diagnostic value and correlation with immune responses.
- To investigate potential therapeutic targets related to circadian disruption in COPD.
Main Methods:
- Integrated four lung transcriptomic datasets for DECRRGs identification.
- Applied machine learning and logistic regression for risk stratification model.
- Utilized CIBERSORT and single-cell RNA sequencing for immune infiltration and gene localization.
- Validated CHRNA1 expression in peripheral blood via qRT-PCR.
Main Results:
- Identified eight circadian rhythm-associated genes, with CHRNA1 as a consistently upregulated hub gene in COPD.
- The risk stratification model showed good discriminatory ability (AUC=0.856).
- CHRNA1 upregulation correlated with pro-inflammatory immune cells (M1 macrophages, CD8+ T cells) and was predominantly expressed in pulmonary B cells.
Conclusions:
- CHRNA1 is a potential circadian rhythm-associated immunomodulator in COPD, consistently upregulated and linked to inflammation.
- Single-cell analysis indicates predominant CHRNA1 expression in pulmonary B cells.
- The study highlights the translational potential of targeting circadian disruption in COPD, with predicted therapeutics and risk models requiring further validation.
