Multi-omics integration at cell type resolution uncovers gene-metabolite mechanisms underlying osteoarthritis heterogeneity.

ABSTRACT: Metabolic dysregulation is an important factor for osteoarthritis pathogenesis, but comprehensive studies of underlying mechanisms and pathways are rare. We analyzed newly generated metabolomics data on bone marrow from 119 osteoarthritis patients, along with single-cell transcriptomics data to reconstruct networks of gene-metabolite associations at cell type resolution. Hubs of these networks - cell type-specific as well as pan-cell type hubs - revealed key molecular factors of osteoarthritis heterogeneity. Systems-level analysis of hubs revealed major roles for glycerophospholipid, glycerolipid and sphingolipid metabolism pathways, along with lipid signaling. We used Machine Learning models of gene-metabolite relationships to discover cell types most relevant to each metabolite. Integrat

SUBMITTER: Ojha A 

PROVIDER: S-EPMC12622010 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature