Fig. 1

Definition of co-expression modules in the human (a). Hierarchical cluster dendrogram derived from merged human gene expression data (derived from n = 129 arrays and 5982 genes) defines 12 modules. Branches of the dendrogram represent groups of genes. Dynamic tree-cutting was used to define modules; where these had significant overlap, they were assigned the same label (arbitrary module color). The co-expression distance (1-topological overlap (TO)) between the genes is defined by the y-axis; the genes are plotted along the x-axis; b top band—gene modules (clusters of highly co-expressed genes) coded by color; unassigned genes are colored “gray”. Key modules of interest (H2 and H4) are annotated; the associated consensus modules (C1 to C5), modules found in both rat and human networks, are also defined above the module bar. Alphanumeric module codes are provided in Supplementary Fig. 4a; bands 2–4—selected samples showing positive or negative correlations with genes enriched in each module (see figure key—red corresponds to positive correlation). Clinical samples represent whole-cartilage gene expression derived from human donors; gene expression profiles from samples were allocated to one of three clinical sample groups (“Clinical Groups 1–3”); a fourth (“Articular cartilage”) represents ostensibly normal cartilage. The overlap between human and consensus modules is provided in Supplementary Fig. 4b. “Clinical Group 2” shows a positive correlation with H2 and H4 modules, which overlap with the C4 and C5 consensus modules; c module eigengene expression (y-axis) is defined for two consensus modules (C4 and C5) across selected samples (x-axis) relative to all samples contributing to the human network (“Other”). For both consensus modules there is a significant difference in the expression of the corresponding module eigengenes across samples using a non-parametric Kruskal–Wallis one-way analysis of variance (C4, brown—p = 1.6e−09; C5, yellow—p = 2.7e−11) with high expression found in “Clinical Group 2” relative to normal articular cartilage. Overall, whole-cartilage samples demonstrate heterogenous gene expression and differ in their association with network modules