Extended Data Fig. 8: Methylation analysis.

a, Clustering of methylation data by PCA showing normal-derived organoids from three individuals (n = 12 biologically independent samples). b, Global methylation change in each tumour clone, expressed as the ratio of hypermethylated probes to hypomethylated probes. Hyper- and hypomethylation are assessed by comparing to the baseline methylation levels in the normal-derived clones (indicated with line at y = 1). c–e, Left, clustering of methylation data by PCA of tumour organoids from each individual, displaying the first two principal components. Clones from different segments are shown in different colours as in Extended Data Fig. 2. Right, phylogenetic trees based on expression data (as in Fig. 3b) with the main branches used for our methylation analysis indicated. c, P1, n = 20 biologically independent samples. d, P2, n = 21 biologically independent samples. e, P3, n = 17 biologically independent samples. f–h, Direction of methylation changes during tumour development. Methylation changes were assigned to either the branch of the tumour or the main subclonal branches (indicated in the phylogenetic trees in e). i–k, Relative proportion of probes in CpG islands, shores, shelves and seas that were differentially methylated in different branches (Supplementary Notes section 6).