Elements and evolutionary determinants of genomic divergence between paired primary and metastatic tumors
Fig 6
Summary of the virtual tumor dynamics and the mapping between seeding time and M-P divergence.
(A) For each simulation (a circle), we calculated the average pair-wise Fst (Fixation index) of ten randomly sampled regions of the virtual primary tumor, to reflect the between-region genetic divergence. We plotted the Fst against the average fraction of variants of the seeding cell that fell above the detection limit in the primary tumor. The size of the circle increases with the selection coefficient. For each selection level, the crossbars show the standard deviation along the two axes. Color scale indicates the proportion of variance of Bm explained by the seeding time (based on 10-quantile of all the values). (B) We group the various simulations into three representative clonal dynamics: progressive diversification (s ≤ 0.05), branched evolution (s = {0.1, 0.2}) and linear evolution (s ≥ 0.5). For each group, we plot the actual seeding time (color hues, using the fraction of the final primary tumor size at metastatic dissemination as a surrogate) on top of the corresponding Bm and Bp values. A smoothed layer shows the general distribution of the seeding time.