Extended Data Fig. 6: Relationship between drug sensitivity and CIMP.

a, Hierarchical clustering of CRC organoids based using variably methylated probes (probes in CpG island and with an SD of M-value > 3). The CRC organoids were assigned to either CIMP⁺ or CIMP^– based on the cluster membership. b, Association between methylation clusters and consensus molecular subtypes (CMS). The integers indicate the number of samples assigned to each subtype. c, Principal component analysis of the organoid transcriptomes. Each dot represents one organoid line. d, The relationship between the expression levels of the 50 CIMP genes and the responses to the 56 drugs. The expression of the CIMP genes were ranked based on the Spearman’s correlation between the gene expression value and the IC₅₀ value of the drugs, and were summarized as the normalized enrichment score by gene set enrichment analysis. The drugs of which the resistance or sensitivity was significantly associated with the expression of the CIMP genes are highlighted in red (positive NES, FDR < 0.01) or blue (negative NES, FDR < 0.01), respectively. NES, normalized enrichment score. e, Response of normal, CIMP^– CRC and CIMP⁺ CRC organoids treated to paclitaxel. Representative images from three technical replicates with similar results. Scale bar, 500 μm. f, Response of tubular adenoma (Ad3) and serrated lesion (SL3) organoids treated to paclitaxel. Representative images from three technical replicates with similar results. Scale bar, 500 μm.