Extended Data Fig. 3: Clonal dominance, initiating mutation, and co-mutation patterns in patients with myeloid malignancies.

a, Upset plot of co-occurring DTAI mutations in CH samples with more than one DTAI variant. Bar graph (top panel) depicts the number of samples with each mutant gene(s) and colour of bar annotating whether mutation(s) occur in the dominant clone (red) or subclones (grey). Black circles and connecting line in bottom panel demark the combination of mutations in each corresponding bar plot. b, Divergent frequency of co-mutated cells for epigenetic modifier genes (red) and signalling genes (blue). Individual samples (n = 6 samples) shown with black square. Centre line: median; box: IQR; whiskers 1.5 × IQR. A two-sided Student’s t-test was used to determine statistical significance *P < 0.1; **P < 0.01; ***P < 0.001. c, Fraction of mutant samples harbouring a homozygous mutation for the indicated given gene (at least >10% of cells). Homozygous sample denoted in blue. d, Correlation of VAF computed by scDNA sequencing to fraction of a mutant sample explained by the genetic trajectory starting with an initiating mutation in a given gene. Genes used as the initiating mutation for a given sample are denoted by colored squares (colours described in figure). Statistical significance calculated by Spearman’s rank correlation coefficient test (ρ = 0.93; P ≤ 2.2 × 10⁻¹⁶). e, Number of samples where a monoallelic clone for a given gene is observed. Dark blue denotes total number of mutant samples where single-mutant clone is present for a given gene and grey represents mutant samples where single-mutant clone is unobserved. f, Number of DNMT3A mutant samples where single-mutant clones are observed (red) or unobserved (grey) with samples categorized by DNMT3A R882 hotspot mutations, nonsense mutations, or missense mutations. A two-sided Fisher’s exact test was used to determine statistical significance (P ≤ 0.04) between DNMT3A^R882 and other missense mutations. g, Differences in dominant and subclone size in DNMT3A mutant samples (n = 61 biologically independent clones). Fraction of sample in the dominant clone or subclone(s) for DNMT3A nonsense (red), R882-missense (green), and non-R882 missense (blue) mutations shown. Centre line: median; box: IQR; whiskers 1.5 × IQR. Each mutant clone denoted by black square. A two-sided t-test correction was used to determine statistical significance pairwise between all groups. For clarity, only significant P values referenced in the text are shown. *P < 0.1. h, As in Fig. 3e, fraction of sample in single- and double-mutant clones in DNMT3A/IDH2 mutant samples. Each sample is indicated by a connecting line, absence of a line for single mutants indicates absence of clone.