Fig. 1: Endotype discovery by cluster analysis in Discovery, Replication and Combined datasets.

A f(K) metric for non-IPS and IPS regressed analyses. Significant clustering was observed (f(K) < 0.85) across all three datasets (green = Discovery, pink = Replication, blue = Combined dataset) for non-IPS-regressed analyses only (left panel). B Visualisation of data structure and IPS on UMAP by dataset, stratified by non-IPS (top panel) and IPS regressed (bottom panel) analyses. f(K) metric plots for Combined dataset stratified by C biological sex (green = female, pink = male), D advanced radiographic status (KL grades: 0-2 as ‘Non-advanced OA’ (green) and ≥3 as ‘Advanced OA’ (pink)) or E blood staining (visual blood staining: 1 as ‘No blood staining’ (green) and ≥ 2 as ‘With blood staining’ (pink)) for non-IPS and IPS regressed analyses. OA osteoarthritis, IPS intracellular protein score, UMAP Uniform Manifold Approximation and Projection, KL Kellgren Lawrence.