Extended Data Fig. 2: Assessment of clonality in CTC clusters.

a, Schematic representation of the strategy used to estimate the clonality of patient-derived and xenograft-derived CTC clusters. For each patient and xenograft, genealogical tree topologies are sampled from the posterior distribution using CTC-SCITE. For each CTC cluster, we determine the distribution of splitting scores (S), reflecting the probability of branching (versus linear) evolution between pairs of cells (orange histogram). In parallel, monoclonal CTC clusters matching the genotypes of single CTCs are simulated to provide an estimate of the distribution of splitting scores in monoclonal CTC clusters (null distribution; blue histogram). A CTC cluster is assigned oligoclonal if the mean splitting score (dashed orange vertical line) exceeds the 95-percentile of the null distribution (dotted blue vertical line). Panel a is created with BioRender.com. b, Schematic representation of the inference of splitting scores (S) for pairs of individual CTC cluster-derived cells. For a selected pair of cells within a given phylogeny sampled from the posterior distribution of tree topologies, we inspect the paths to their most recent common ancestor. A CTC cluster splits with high confidence if at least one mutation is mapped with high probability to each of the two branches, and it splits with low confidence if all mutations are mapped with low probability to one or both branches. We account for this by computing each mutation’s probability (P) of mapping to either of the two branches A (P = δ) and B (P = ε) and consider the maximum probability of any mutation mapping to it. The splitting score S reflects the lower of those two maximal probabilities.