J Korean Med Sci.  2023 Jul;38(29):e220. 10.3346/jkms.2023.38.e220.

Machine Learning-Based Proteomics Reveals Ferroptosis in COPD PatientDerived Airway Epithelial Cells Upon Smoking Exposure

• Yoon JK
• Park S
• Lee KH
• Jeong D
• Woo J
• Park J
• Yi SM
• Han D
• Yoo CG
• Kim S
• Lee CH

• KMID: 2544943
• DOI: http://doi.org/10.3346/jkms.2023.38.e220

Abstract

Background
Proteomics and genomics studies have contributed to understanding the pathogenesis of chronic obstructive pulmonary disease (COPD), but previous studies have limitations. Here, using a machine learning (ML) algorithm, we attempted to identify pathways in cultured bronchial epithelial cells of COPD patients that were significantly affected when the cells were exposed to a cigarette smoke extract (CSE).
Methods
Small airway epithelial cells were collected from patients with COPD and those without COPD who underwent bronchoscopy. After expansion through primary cell culture, the cells were treated with or without CSEs, and the proteomics of the cells were analyzed by mass spectrometry. ML-based feature selection was used to determine the most distinctive patterns in the proteomes of COPD and non-COPD cells after exposure to smoke extract. Publicly available single-cell RNA sequencing data from patients with COPD (GSE136831) were used to analyze and validate our findings.
Results
Five patients with COPD and five without COPD were enrolled, and 7,953 proteins were detected. Ferroptosis was enriched in both COPD and non-COPD epithelial cells after their exposure to smoke extract. However, the ML-based analysis identified ferroptosis as the most dramatically different response between COPD and non-COPD epithelial cells, adjusted P value = 4.172 × 10⁻⁶ , showing that epithelial cells from COPD patients are particularly vulnerable to the effects of smoke. Single-cell RNA sequencing data showed that in cells from COPD patients, ferroptosis is enriched in basal, goblet, and club cells in COPD but not in other cell types.
Conclusion
Our ML-based feature selection from proteomic data reveals ferroptosis to be the most distinctive feature of cultured COPD epithelial cells compared to non-COPD epithelial cells upon exposure to smoke extract.

Keyword

Ferroptosis; Pulmonary Disease, Chronic Obstructive; Proteomics; Machine Learning; Epithelial Cells

Figure

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  Fig. 1 Schematic of the study protocol with detailed ML-based feature selection.CSE = cigarette smoking extract, ML = machine learning, COPD = chronic obstructive pulmonary disease.

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  Fig. 2 Venn diagram and numbers of DEPs.DEP = differentially expressed protein, CSE = cigarette smoking extract, COPD = chronic obstructive pulmonary disease.

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