Extended Data Fig. 1: Model performance in recovering driver mutation rates in simulations.
From: Synonymous mutations reveal genome-wide levels of positive selection in healthy tissues
(a) Our method is able to recover driver mutation rates accurately across a range of mutation rates (5 × 105 simulation runs were performed). At higher driver mutation rate, it is mainly limited by clonal interference which causes clones to reach sizes lower than that predicted by our theory. Best-fit values are presented with their 95% confidence intervals. (b) This shows the simulation (run no. = 15000) corresponding to driver mutation rate μb = 3 × 10-6 (τ = 1 year). The neutral mutation frequency spectrum above Ψ = 3 × 10-3 was fitted with our passenger prediction to infer the underlying driver mutation rates driving the expansions. Simulated data are presented as mean values ± sampling error. (c) The likelihood plot shows the fit for the driver mutation rate and fitness by examining the ‘nonsynonymous’ variant allele (that is driver mutation) frequency spectrum only. It is overlaid with the maximum likelihood value (white cross) and best-fit value found by the Nelder-Mead optimization algorithm (green cross). (d) The likelihood plot shows the best-fit value as well as 95% confidence intervals for the inferred total driver mutation rate from the ‘synonymous’ variant (neutral mutation) allele frequency spectrum based on the inferred fitness from the ‘nonsynonymous’ variant allele frequency spectrum.
