Extended Data Fig. 9: Multiomics intra-tumor heterogeneity (ITH) of 13 multiregion samples.

a) Intratumoral heterogeneity (ITH) score, ranging from 0% (no ITH) to 100% (ITH greater than the maximum observed intertumor heterogeneity in the cohort), for each sample (row) and each MOFA latent factor (column). The score is computed as the percentage of inter-tumor distances in a MOFA factor that are lower than the observed intratumor distance between regions. The four samples with ITH score greater than 50% are highlighted in color. b) Relationship between histopathological heterogeneity and cancer task specialization. Ternary plots depicting task specialization in three cancer tasks (see Fig. 2). For each histopathological feature, a colored arrow connects regions from tumors with differences in this feature. Numbers correspond to the percentage of this feature in the tumor as estimated by our pathologist. The right ternary plot represents all samples with no histopathological ITH. c) Epithelial to mesenchymal transition (EMT) score and innate immune composition score as a function of MOFA’s Morphology factor. Small points correspond to all samples from the MESOMICS cohort, and large points connected by segments to regions from the 3 patients with CIMP factor ITH highlighted in (a). Blue bands correspond to 95% confidence intervals, and P values to two-sided t-tests. d) Lollipop plot of the estimated proportion of immune cells in two regions of a sample with ITH in the adaptive-response factor highlighted in (a). e) CIMP index in regions of two tumors with substantial ITH in the CIMP factor highlighted in (a) (colored points connected by an arc), compared to that of the rest of the cohort (grey points).