Figure 5 from Epigenetic Heritability of Cell Plasticity Drives Cancer Drug Resistance through a One-to-Many Genotype-to-Phenotype Paradigm

Epigenetic rewiring in resistant populations. A, UMAP plots for multiome samples. In the first row, different dimensionality reductions are shown: UMAP done with latent semantic index (LSI) exploiting just RNA information, LSI with just ATAC, and a combined LSI. In the second row, the combined UMAP is colored by archetypal weight. B, Clonal tree constructed using CNAs inferred from ATAC data. C, Average archetype weights. The blue barcode displays a clear difference in the ATAC profile compared with the others (gray). D and E, Average ATAC archetype weight for copy-number clones, for RNA archetypes (D) and ATAC archetypes (E). We split the tree into two major clades: The top one is more abundant in the trametinib samples, and the bottom one is more represented in the parental- and capivasertib-treated samples. The change in archetypal composition is consistent with previous observations from lentiviral lineage tracing. F and G, Average ATAC archetype weights for the violet and blue barcode in the MSI sample. H, Average ATAC archetype weights for the violet barcode in the AKT organoid under oxaliplatin treatment.