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Chinese Journal of Hygiene Rescue(Electronic Edition) ›› 2025, Vol. 11 ›› Issue (02): 86-101. doi: 10.3877/cma.j.issn.2095-9133.2025.02.004

• Original Articles • Previous Articles     Next Articles

Machine learning and omics-driven dissection of mitophagy and ferroptosis in sepsis-associated ARDS: unraveling key genetic roles and immune regulatory mechanisms

Fanyan Ou1, Qian Guo2, Lixiong Zeng1, Qiuli Chen1, Houyu Gan1, Jie Yang3,()   

  1. 1. Department of Clinical Pathology, the Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, China
    2. Department of General Practice, the Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, China
    3. Clinical Medical Research Center, the Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, China
  • Received:2025-01-24 Online:2025-04-18 Published:2025-06-26
  • Contact: Jie Yang

Abstract:

Objective

To explore the roles and immune regulatory mechanisms of key genes in mitophagy and ferroptosis in sepsis-induced acute respiratory distress syndrome (ARDS) using an integrative analysis of machine learning and transcriptomics.

Methods

The DEGs from the GSE32707 dataset in the GEO database were obtained and the differential genes screened. The core genes were identified and validated by secondary screening of DEGs with LASSO regression and the SVM-RFE algorithm, and their diagnostic performance with ROC curves was evaluated. DEGs-related biological pathways and immune cell interactions were investigated via GSEA and immune infiltration analysis. The hub genes by intersecting mitophagy-related genes, ferroptosis markers, and core DEGs were determined. A multi-dimensional regulatory network was established by predicting miRNA targets (using miRWalk, etc.) and ubiquitination interactions (using UbiBrowser), and then potential regulatory mechanisms of hub genes were explored.

Results

Initially, 576 DEGs were screened. Then, 12 core genes were identified via machine learning algorithms. GSEA and immune infiltration analysis showed these core genes were significantly enriched in immune-related pathways. By integrating mitophagy and ferroptosis-related genes with core DEGs, FTH1 was identified as a hub gene, whose expression positively correlated with neutrophil levels and CCR. Mechanistic exploration suggested FTH1 expression might be regulated by miR-224-5p and interact with the E3 ubiquitin ligase SMURF1, implying its potential involvement in disease progression via ubiquitination modification.

Conclusion

This study, combining machine learning and multi-omics integration, first identifies FTH1 as a key regulator of mitophagy and ferroptosis in sepsis-related ARDS. It reveals a regulatory network where FTH1 might be targeted by miR-224-5p and interact with SMURF1, offering new directions and a theoretical basis for developing early immunointervention targets for this disease.

Key words: Sepsis, Acute respiratory distress syndrome, Mitophagy, Ferroptosis, Immunomodulation

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