Allele-specific mutational cooccurrences in RNA splicing factor mutations. (A) Oncoprint indicating cellular-level cooccurrence of mutations in select cases of double splicing factor mutations (the clinical diagnosis and sample ID is listed above each Oncoprint). Each column in the heat map (left) depicts an individual cell, with the genotype of each sequenced cell for each variant. Clustering is based on the genotypes of driver mutations, and the horizontal bar depicts the detected clones in each case. Mutant and wild-type cells are indicated in blue and white, respectively. The subclones located to the right of the red line comprised <1% of the total sequence cells, because 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 vertical bar indicates the association of the colors with the log OR. Cooccurrence 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. (B) Fish plots showing the inferred clonal hierarchy based on the single-cell genotype data for the 3 patients in panel A. (C) Oncoprint, as in panel A, but evaluating cellular cooccurrence or mutual exclusivity of deleterious ZRSR2 mutations with mutations in other splicing factors (left) or with one another (right). CMML, chronic myelomonocytic leukemia; MDS-MLD, myelodysplastic syndrome with multilineage dysplasia; MDS/MPN-U with >15% RS, MDS/myeloproliferative neoplasm unclassified with >15% ring sideroblasts.