Research on identification of key genes and immune-metabolic mechanisms in atrial fibrillation through integrated...

This study aimed to integrate multiple datasets for the identification of atrial fibrillation (AF)-related differentially expressed genes (DEGs), analyze their underlying mechanisms through functional enrichment and machine learning, construct diagnostic models, and explore immune-metabolic interactions to provide novel biomarkers and theoretical foundations. Gene expression datasets were integrated and normalized, with batch effects removed using principal component analysis. Differential expression analysis, functional enrichment analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways), and machine learning-based feature gene selection and model construction were performed. Shapley additive explanations analysis was utilized to interpret the constructed models, while gene set enrichment analysis, gene set variation analysis, and immune cell infiltration analysis were conducted to investigate the associations between feature genes and immune infiltration. After integrating and normalizing gene expression data and eliminating batch effects via principal component analysis, 6 DEGs were identified, including 4 upregulated and 2 down-regulated ones. Functional enrichment analysis showed these DEGs were significantly enriched in neuro-related biological processes and pathways, indicating their key roles in AF pathogenesis. Five key feature genes were selected using LASSO, random forest, and support vector machine-recursive feature elimination algorithms. They had significant expression differences between the AF and control groups (P < .001) and were located on distinct chromosomes. The constructed random forest and support vector machine models performed excellently (area under the curve ≥ 0.85). Shapley additive explanations analysis revealed TNNI1 contributed most to model prediction, with its expression significantly positively correlated with immune cell infiltration. Gene set enrichment analysis and gene set variation analysis analyses further showed feature genes participated in AF pathogenesis by regulating immune modulation, metabolic pathways, and autophagy. Immune cell infiltration analysis found altered proportions of T-cell subsets and M0 macrophages in the AF group, along with complex links between feature gene expression and immune cell function. This study systematically elucidated the unique gene expression patterns and key regulatory pathways associated with AF, clarifying the crucial roles of feature genes in immune regulation, metabolic imbalance, and cellular dysfunction. These findings provide a theoretical basis and potential therapeutic targets for understanding AF pathogenesis and developing targeted treatment strategies.