Integrative bioinformatics and machine learning identify shared molecular mechanisms and diagnostic biomarkers...

Helicobacter pylori (H. pylori) infection and atrial fibrillation(AF) are major global health concerns. Emerging evidence has suggested a potentially chronic inflammation-mediated link between them, but the shared genetic mechanisms remain unclear.

We analyzed multidataset gene expression profiles from the Gene Expression Omnibus (GEO) database. Differential expression analysis, weighted gene co-expression network analysis (WGCNA), functional enrichment, and machine learning were employed to identify common genes, pathways, and diagnostic biomarkers. Protein-protein interaction (PPI) networks, drug-gene analysis, and molecular docking were used to identify hub genes and potential therapeutics.

We identified 73 common differentially expressed genes (DEGs) between H. pylori infection and AF, which were predominantly enriched in immune-related processes including leukocyte activation, neutrophil migration, and myeloid cell-mediated immunity. Machine learning identified 15 and 23 key feature genes for H. pylori and AF, respectively, with S100A8 emerging as a shared diagnostic biomarker. Ten hub genes including TYROBP, ITGB2, and SPI1, were identified from the PPI network. Drug repositioning analysis suggested retinoic acid, indirubin, and ropivacaine as candidate therapeutics targeting these key hub genes.

Our integrative analysis highlights the central role of immune-inflammatory pathways in linking H. pylori infection to AF. We propose S100A8 and other identified hub genes as potential biomarkers and therapeutic targets. The predicted candidate therapeutics, particularly retinoic acid, may offer novel avenues for intervention, warranting further experimental validation.