Extended Data Fig. 3: Phylogenetic trees with branch-specific mutational signature profiles.
From: Timing and trajectory of BCR::ABL1-driven chronic myeloid leukaemia
a. The graph shows the cosine similarity for single nucleotide variant (SNV) attribution to a combination of mutational signatures “SBS1”, “SBSblood” and “SBS18”, compared to attribution to SBS1 and SBSblood only. The change in the cosine similarity between the sigfit based posterior mean reconstructed signature and the observed signature is indicated by the directionality of the arrows, showing that for branches within the CML clade, particularly, early branches of the clonal expansion, as well as for early-in-life mutations, the cosine similarity improves with the inclusion of attribution to “SBS18”. Of note, there is little improvement in cosine similarity with the addition of SBS18 attribution for wildtype colonies or the trunk of the CML clade, ie., the pre-CML lineage, suggesting that SBS18 is not active outside of rapid expansion. Branches are categorised into five groups (i) branches of the BCR::ABL1-positive clonal expansion (“CML (mutant)”), (ii) ancestral branch of BCR::ABL1-colonies representing the lineage of origin of the CML (“Pre-CML (trunk)”), (iii) earliest mutations within the CML clade (ie., the shared branches within the clonal expansion, “Early CML (internal)”), (iv) branches of BCR::ABL1-negative colonies (“WildType, WT”), and (v) early-in-life branches (“Early life”). b. Phylogenetic trees of 9 patients with proportions of mutational signatures annotated to their branches. Bar plots show the proportion of SBS1, SBSblood and SBS18 contributing to SNVs spectra of different branch types. Bars represent posterior means with 95% credible intervals as error bars. The Y-axis shows the time in years since conception. The branches are categorised into four groups (i) branches of the BCR::ABL1-positive clonal expansion (“CML”), (ii) ancestral branch of BCR::ABL1-colonies representing the lineage of origin of the CML (“Pre CML”), (iii) the earliest mutations within the CML (ie., the shared branches within the clonal expansion, “Early CML”), and (iv) the branches of BCR::ABL1-negative colonies (wild-type, WT).
