biostudies-literatureUnknown16Zhang H<h4>Background</h4>Lumbar disc degeneration, a primary cause of chronic low back pain, is closely linked to inflammatory responses and the immune microenvironment; however, its underlying mechanisms remain poorly understood.<h4>Methods</h4>This study integrated scRNA-seq and bulk RNA-seq data to identify macrophage subpopulations in degenerative tissues and constructed co-expression modules using hdWGCNA. Functional enrichment was explored through GO, KEGG, and GSEA analyses. A panel of 101 machine learning algorithms was employed to screen diagnostic genes, with ROC curves used for validation. A combined diagnostic model for LDD risk was developed based on the expression profiles of the diagnostic genes. Additionally, immune infiltration was assessed via CIBERSORT, potential therapeutic cFrontiers in immunology1671961https://www.ebi.ac.uk/biostudies/studies/S-EPMC12705385biostudies-literatureIntegration of single-cell sequencing and machine learning identifies key macrophage-associated genetic signatures in lumbar disc degeneration.PMC12705385Gao MZhu JDai BLi DZhang HXiang XPeng JfalseIntegration of single-cell sequencing and machine learning identifies key macrophage-associated genetic signatures in lumbar disc degeneration.<h4>Background</h4>Lumbar disc degeneration, a primary cause of chronic low back pain, is closely linked to inflammatory responses and the immune microenvironment; however, its underlying mechanisms remain poorly understood.<h4>Methods</h4>This study integrated scRNA-seq and bulk RNA-seq data to identify macrophage subpopulations in degenerative tissues and constructed co-expression modules using hdWGCNA. Functional enrichment was explored through GO, KEGG, and GSEA analyses. A panel of 101 machine learning algorithms was employed to screen diagnostic genes, with ROC curves used for validation. A combined diagnostic model for LDD risk was developed based on the expression profiles of the diagnostic genes. Additionally, immune infiltration was assessed via CIBERSORT, potential therapeutic c2025-01-01T00:00:00Z20252026-06-06T04:02:53.666Z2026-05-25T03:12:11.81ZS-EPMC127053854140927810.3389/fimmu.2025.1671961