Fig. 2: The cellular-level mutual exclusivity of AML driver mutations.

a–d Cell-level mutual exclusivity patterns of driver mutations in individual samples for four representative cases. a KRAS, NRAS, FLT3-non-ITD, and FLT3-ITD, b IDH1 and IDH2, c IDH1 p.R132C, IDH1 p.R132H, and TET2, d TP53 and PPM1D variants did not co-occur in the same cellular populations. Mut mutated, WT wild type, Missing missing genotype. Heat maps (left) show the genotype of each sequenced cell for each variant, with clustering based on the genotypes of driver mutations. Each column represents a cell at the indicated scale. Cells with mutations and wild-type cells are indicated in blue and white, respectively. Cells with missing genotypes are indicated in gray. The subclones located to the right of the red line comprised <1% of the total sequenced cells, and such small subclones can represent false positive or negative genotypes as a result of allele dropout or multiplets. The figures on the right show the pairwise association of mutations. The color and size of each panel represent the degree of the logarithmic odds ratio (log OR). The bar on the right side is a key indicating the association of the colors with the log OR. Co-occurrence and mutual exclusivity are indicated by red and blue, respectively. The statistical significance of the associations based on the false discovery rate (FDR) is indicated by the asterisks (*FDR < 0.1, **FDR < 0.05, ***FDR < 0.001). e Pairwise association of driver mutations in AML based on single-cell DNA sequencing (left) and bulk sequencing data (right). For each pair of mutations, their dependency was summarized as log OR, with positive values (red) indicating a degree of co-occurrence and negative values (blue) indicating a degree of mutual exclusivity. The statistical significance of the associations based on the q value is indicated by the dots and asterisks (^**q < 0.1, *q < 0.01).