Lectin Microarray-based Glycomics and Machine Learning Identify Shared Osteoarthritis Biomarkers in Humans, Dogs, and Horses

Abstract

Post-traumatic osteoarthritis (PTOA) is a common sequela to joint injury in both humans and companion animal species such as horses and dogs. Despite the increasing prevalence of osteoarthritis (OA) in humans, investigation of glycosylation changes associated with OA remains in its infancy. Recent advances, such as lectin microarray analysis, now enable detailed glycan profiling in complex biofluids such as synovial fluid. Using lectin microarray technology, this study characterized glycosylation patterns in synovial fluid samples from healthy and OA-affected joints in horses, dogs, and humans. Comparative glycan-binding profiles within and between species revealed conserved and distinct glycomic signatures associated with OA. Machine learning models, including classification algorithms, effectively distinguished OA from healthy joints, identifying key lectins and glycan epitopes crucial to these predictions. The identified lectin markers reflect specific glycosylation pathways and potential inflammatory mechanisms, demonstrating their value in differentiating between healthy and OA phenotypes. Our findings underscore the promise of integrated glycomic profiling and machine learning to enhance our understanding of glycan involvement in the pathogenesis of OA and to facilitate the development of diagnostic and therapeutic strategies applicable to both veterinary and human medicine. In BriefOsteoarthritis affects humans and companion animals; however, its molecular features remain unclear. Using lectin microarrays and machine learning, we identified conserved and species-specific glycan signatures in synovial fluid that differentiate between control and osteoarthritic joints. This One Health approach highlights shared molecular mechanisms of joint degeneration and establishes data-driven glycomic profiling as a framework for understanding osteoarthritis across species. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=162 SRC="FIGDIR/small/682971v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@1644beaorg.highwire.dtl.DTLVardef@1b4133dorg.highwire.dtl.DTLVardef@15b286aorg.highwire.dtl.DTLVardef@1ba5d62_HPS_FORMAT_FIGEXP M_FIG C_FIG