Molecular mechanisms of lipid metabolism abnormalities driving sepsis and atrial fibrillation: A Systematic study based on bioinformatics and machine learning

by Changze Ou, Haidong Yu, Binbin Chen, Huajun Long

Background

Sepsis and atrial fibrillation are complex, life-threatening medical conditions affecting approximately 49 million individuals globally, characterized by exceptionally high mortality rates. Lipid metabolism abnormalities play a critical role in the pathogenesis of these diseases, yet their underlying molecular mechanisms remain incompletely understood.

Objective

This innovative study systematically investigates the shared molecular mechanisms of lipid metabolism abnormalities in sepsis and atrial fibrillation using advanced bioinformatics and machine learning methodologies. Methods: We retrieved two independent research cohorts from the Gene Expression Omnibus database: sepsis-related datasets and atrial fibrillation-related datasets. A multi-dimensional analytical approach was employed, including differential expression analysis, Weighted Gene Co-expression Network Analysis, machine learning models, immune cell infiltration analysis, and gene set enrichment analysis to comprehensively elucidate the molecular mechanisms of lipid metabolism abnormalities in these diseases.

Results

Comprehensive analysis identified 13 key candidate genes, with CD81, CKAP4, and DPEP2 emerging as core characteristic genes. Functional enrichment analysis revealed these genes primarily participate in mitochondrial function regulation, complement-coagulation cascade, and cell adhesion molecular pathways. Machine learning models demonstrated exceptional diagnostic performance, with area under the curve values of 0.957 for sepsis and 1.000 for atrial fibrillation datasets. Immune cell infiltration analysis unveiled the critical roles of neutrophils and monocytes in disease progression, and revealed the profound impact of lipid metabolism abnormalities on immune regulation.

Conclusion

We discovered that lipid metabolism abnormalities significantly modulate disease progression by influencing mitochondrial function, inflammatory responses, and cell adhesion pathways. Future research necessitates further clinical validation and functional experiments to explore personalized therapeutic strategies based on lipid reprogramming.