Fig. 5: HSPC phylogenies for two normal unexposed and two chemotherapy-exposed adult individuals.

a,b, Phylogenies for two normal unexposed donors: one young adult (a) and one older adult (b). c,d, Phylogenies for two young adult chemotherapy-treated individuals, both with more than one chemotherapy exposure. Phylogenies were constructed using shared mutation data and the algorithm MPBoot (Methods). Branch lengths reflect the number of mutations assigned to the branch, with the terminal branches adjusted for sequence coverage; the overall root-to-tip branch lengths have been normalized to the same total length (because all colonies were collected from a single time point). The y axis represents the number of SBSs accumulating over time. Each tip on a phylogeny represents a single colony, with the respective numbers of colonies of each cell and tissue type recorded at the top. Onto these trees, we have layered clone- and colony-specific phenotypic information. We have highlighted branches on which we have identified known oncogenic drivers in 1 of 18 clonal hematopoiesis genes (Supplementary Table 2) color-coded by gene. A heat map at the bottom of each phylogeny highlights colonies from known driver clades colored by gene and the expanded clades (defined as those with a clonal fraction of >1%) in blue. In the individual in d, the AML was derived from the biallelic TP53-mutated clade carrying TP53 p.I195F and TP53 p.C176Y. Drugs not highlighted in bold text are those received by the individual at the same time but not believed to be the mutagenic agents.