Fig. 1

Mutational landscapes, and dominant/secondary mutations. a Frequency of the 36 mutated genes (dark bars) and copy-number alterations (gray bars). b Clinical features associated with genetic hits. Effect of frequent genetic hits (>2%, n = 30) were assessed. Bubble sizes encode the frequency of mutations in 1809 patients; odds ratios (OR) of MDS (n = 1583) vs. MDS/MPN (n = 226) and low- (n = 1043) vs. high risk (n = 766) are plotted on the x-axes. Negative log10 false discovery rates (FDR, i.e., q-values) are shown on the y-axes; our FDR cutoff of interest, 0.1, is shown as a dashed horizontal red line. c The recent advanced algorithm called PyClone allowed the inference of clonal structure. All 3971 mutations, identified in 1809 samples, were evaluated in each sample. Multiple clones were found in 859 samples. The bar graphs and pie chart show the number and the fraction of samples with different number of clones, respectively. d Clonal evolution of MDS. Ancestral/initial hits were classified dominant, and subsequent/secondary hits were classified as secondary mutations. e Representative three samples with multiple clones. Copy-number-adjusted variant allele frequencies (aVAFs) (y-axis) and mutated genes (x-axis) in three illustrative samples are shown. Blue and red squares depict dominant and secondary mutations. Circles with different colors show the different clones estimated by PyClone²⁸. f Sequencing read counts and raw VAFs. This scatter plot depicts 3971 mutations identified in 1809 patients. Blue and red bars indicate dominant and secondary mutations, respectively. Dotted vertical and horizontal lines depict mean total read counts and VAFs, respectively. g Distribution of dominant, co-dominant, and secondary mutations in all 36 genes in our panel. Dominant (n = 2155) and secondary mutations (n = 1816) are shown. Pie charts show the fraction of dominant mutations for each gene. The top five most frequently mutated genes are indicated in the left (MDS, sAML from MDS) and right (MDS/MPN, sAML form MDS/MPN), respectively. h Distribution of aVAFs between dominant vs. secondary mutations. Dot plots depict dominant (blue) and secondary (red) mutations. Box and whiskers indicate median and minimum to maximum of aVAFs for dominant and secondary mutations. ***P < 0.0001 (Mann–Whitney’s U test).