Fig. 5: Circulating mutational burden in ctDNA reflects early detection of transformed histology.

a Plasma detection rate of selected clones over time, juxtaposed with PSA levels and treatment regimen. The left y-axis corresponds to the plasma detection rate shown by each of the lines, and the right y-axis corresponds to the blue area plot of PSA levels as measured in ng/ml. The bottom track shows the timing, duration, and type of therapies. b Schematic of the phylogenetic tree, restricted to clones shared across more than one sample. Each panel represents a subset of the tree as it relates to specific sample lineages, labeled to the right of each tree. The size of each node indicates how many samples a clone is detected in. c Plasma detection rate of all non-private clones over time, corresponding to the clones in the top-most tree in the preceding (b). The shaded polygon and colored dashed lines represent the 95% bootstrap confidence intervals of the detection rate, and the black dashed line represents the clone-specific lower limit of detection. d Heatmap showing the similarity of plasma and tumor copy number profiles as measured by the cosine similarity of normalized read depth. Tumor samples are represented by each row, and cfDNA samples are measured on each column. Samples are grouped by histology. The color of each cell, and the annotated value indicate cosine similarity, The top track indicates which histology was more similar to the cfDNA at a given time point, as measured by a greater cosine similarity (P < 0.05, Welch Two Sample t-test).