Figure 4.
Inference of mutational history from single-cell genotype data using the infSCITE algorithm. (A) Clonal architecture analysis for X09, XB37, and XB47. Only cells with complete genotype from one diagnostic sample (X09: n = 2101 cells, XB37: n = 1905 cells, and XB47: n = 1484 cells) are included. The heatmap shows the genotype consequence of each identified somatic variant in the given clone without zygosity (wild type [WT] = gray, mutated [Mut] = dark blue). The horizontal bar at the top illustrates the clonal composition. The clone name matches the name in the circles of the corresponding phylogenetic tree in panel B. Wild-type genotypes that are likely the result of ADO (supplemental Figure 3) are not computed as a separate clone. (B) Phylogenetic trees illustrating the maximum likelihood order at which mutations were acquired during T-ALL development in the indicated patients. The mutational history was reconstructed with the genotype data from the samples at diagnosis (PB for X09, BM for XB37 and XB47; BM and PB for XF91, XF97, and XF100). Arrows are labeled with the mutations acquired and illustrate branching or linear patterns of clonal evolution, with dotted arrows indicating less probable paths. Circles represent the clones (clone names are matched with those in Figure 2B or 4A) and the size of the circle denotes the relative clone size in the samples (frequency indicated next to the circles).