ArticlePloS one2025
HLX and SLC25A20: Immunologic regulators bridging ankylosing spondylitis and uveitis via multi-omics integration and machine learning.
Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- The Role of MicroRNAs and Other Molecular Biomarkers in Uveitis: Protocol for a Scoping Review.JMIR research protocols · 2026Article
- Explainable machine learning-based identification of transcriptomic biomarkers in CD1c+ dendritic cells for non-infectious uveitis: an integrative analysis of bulk RNA-seq data.Frontiers in bioinformatics · 2026Article
- Research advancements in DNA methylation pertaining to ankylosing spondylitis.Frontiers in immunology · 2026Review
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6 authors.
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Abstract
backgroundAnkylosing spondylitis (AS), a chronic inflammatory disorder affecting axial joints, is frequently complicated by uveitis. However, the molecular mechanisms linking AS to secondary uveitis remain poorly understood.
methodsWe integrated transcriptomic datasets from AS (GSE73754) and uveitis (GSE194060) cohorts to identify shared molecular pathways. Differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning (LASSO, SVM-RFE, random forest) were combined to prioritize biomarkers. Molecular docking was performed to evaluate drug-target interactions using Vina scores (≤-7 kcal/mol threshold).
resultsCross-disease analysis revealed 697 overlapping dysregulated genes (481 upregulated, 216 downregulated), enriched in GTPase signaling and immune pathways. WGCNA identified disease-specific co-expression modules (AS: brown/tan modules, r = 0.39/0.35; uveitis: brown module, r = 0.49). Machine learning nominated HLX and SLC25A20 as core biomarkers, demonstrating robust diagnostic accuracy in discovery (AS AUC: 0.688/0.700; uveitis AUC: 0.867/0.838) and validation cohorts (AS AUC: 0.653/0.667; uveitis AUC: 0.662/0.736). Immune profiling linked HLX to neutrophil infiltration (r = 0.55, p < 0.01) and SLC25A20 to T helper cell regulation (r = 0.36, p < 0.01). Molecular docking identified high-affinity ligands for SLC25A20, including amiodarone (-8.0 kcal/mol) and estradiol (-7.7 kcal/mol), with folic acid showing dual binding potential (HLX: -7.5 kcal/mol; SLC25A20: -8.2 kcal/mol).
conclusionHLX and SLC25A20 emerge as immunologic regulators bridging AS and uveitis pathogenesis. These findings provide actionable targets for precision diagnostics and therapeutic development in AS-associated uveitis.
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