Fig. 3: Transcriptional profiling identifies clonal cooperation by reciprocity in RAS and MYC pathways.

a, PCA of comparison between major and minor clones, showing the first two principal components (PC1 and PC2). Major clones connect to corresponding minor clones. Colour represents location in the small intestine. b, Box plot of difference in principal component within major–minor pairs for each of PC1–PC3. Two-tailed one-sample Wilcoxon signed-rank test. c, Heat map with hierarchical clustering shows top 50 differentially expressed genes between the major and minor clones. d, Volcano plot showing normalized gene set enrichment scores for Hallmark Pathways in the comparison between major and minor clones. Dotted line denotes a false discovery rate (FDR) of 0.05. EMT, epithelial–mesenchymal transition. e,f, NES of Kras_Signaling_Up (e) and Myc_Targets_v1 (f) for Hallmark Pathways in monoclonal tumours relative to major clones and minor clones. n = 20 biological replicates (20 monoclonal tumours from 2 mice). Values represent FDR from gene set enrichment analysis. g, Volcano plot of differentially expressed genes between major and minor clones. Secretory genes are labelled in red and stem cell genes are labelled in blue. FC, fold change. h–k, Transcript counts for Atoh1 (h), Chga (i), Hdac2 (j) and Cdk4 (k) in individual major and minor pairs. Paired two-tailed Wilcoxon tests. l, Kaplan–Meier survival curves for wild type + ENU, Trp53^null (P) + ENU, Kras^G12D/+ (K) + ENU, Kras^G12D/+;Trp53^null (KP) + ENU and Apc^het + ENU. n = 32 mice for wild type + ENU, 9 mice for P + ENU, 12 mice for K + ENU, 5 mice for KP + ENU and 49 mice for Apc^het + ENU. m, Heterotypic fraction across models described in l. Assessment based on 22 coloured tumours for wild type + ENU, 249 for Apc^het + ENU, 90 for Kras^G12D/+ + ENU, 144 for Trp53^null + ENU and 185 for Kras^G12D/+;Trp53^null + ENU. n = 20 biological replicates per group in a–k.

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