Fig. 2. Distinct patterns of mutation co-occurrence associate with overall survival.

a Co-occurrence and mutual exclusivity of the most frequent mutations present in de novo AML was performed using a two-sided Fisher’s Exact test. Significant associations (FDR < 0.05) are colored according to the odds ratio of co-occurrence (red) or mutual exclusivity (blue). Points are sized based on the number of patients with co-occurring mutations for each genotype. b Summary of pairwise mutations and their association with prognosis based on Cox proportional-hazards regression modeling. Significant genotypes (FDR < 0.05) are colored according to the log-transformed hazard ratio compared to wild-type patients, with green depicting better prognosis (HR ≤ 1) and purple representing worse prognosis (HR ≥ 1). Points are sized based on the number of patients with co-occurring mutations for each genotype. c Scatterplot of the correlation between the odds ratio and hazard ratio of co-occurring mutations from a, b. Percentages indicate the fraction of genotypes per quadrant which associate with significant (Bonferroni FDR < 0.05) survival associations. For each error band, the measure of center is the line of best fit as derived from linear regression between the odds ratio and hazard ratio for each group. Shaded bands represent 95% confidence intervals for each linear regression. Points are sized based on the number of patients with co-occurring mutations for each genotype and colored according to the log-transformed hazard ratio compared to wild-type patients, with green depicting better prognosis (HR ≤ 1) and purple representing worse prognosis (HR ≥ 1). d Frequency distribution of the number of de novo patients with the most frequent 3-way mutation combinations. Bars are colored based on the association with a significant survival correlation (p ≤ 0.05) compared to patients with only two genes mutated: red = a significant survival association, gray = no significant association. e Forrest plot (left) and Kaplan–Meier plots (right; Bonferroni FDR ≤ 0.15) depicting survival analysis between triple-mutated and double-mutated genotypes. For the forest plot (left), points represent the hazard ratios calculated between triple vs. double-mutated patients using a Cox proportional-hazards model. Significant genotypes (two-sided log-rank p ≤ 0.05) are colored: green represents cases where the presence of all three mutations correlated with improved survival, while purple hits represent genotypes where all three mutations correlated with worse survival. q-values were calculated in terms of the false discovery rate using Bonferroni correction. Points are sized relative to the number of patients with all three mutations and bars represent the 95% confidence intervals of the hazard ratios. Source data are provided as a Source Data file.