Fig. 4: Molecular programs driving intratumoural heterogeneity in Vκ*MYC mice with active-MM.

a Heatmap of Jaccard Index between significantly enriched Reactome terms across 41 intra-tumour malignant cell clusters. Groupings of clusters with increased similarity (Similarity Programs) were determined according to the complete linkage method for hierarchical clustering and are labelled below the heatmap. Columns are annotated with information related to sample identity, cell cycle phase, and Mki67/Top2a expression. b Map of Reactome terms with significant enrichment in malignant cell clusters from Similarity Program A (ISR-GCN2). The full hierarchy of each Reactome pathway is shown for context but only significantly enriched shared pathways are highlighted in orange. c Gene set scoring for indicated Reactome signatures calculated using Seurat’s AddModuleScore across disease groups in Vκ*MYC data (Control = 264 cells, early-MM = 168 cells, int-MM = 443 cells, active-MM = 5,969 cells). Boxplots within violin plots represent the distribution of each measurement within defined groups, where the central rectangle spans the interquartile range, the central line represents the median, and “whiskers” above and below the box show the value 1.5× the interquartile range. Statistical comparison of multiple groups (normal PCs vs. each Vκ*MYC disease group) was performed using the Wilcoxon rank-sum test (two-sided) corrected for multiple testing (Benjamini−Hochberg). Source data are provided in SourceData_Fig. 4.xlsx.