Synergistic epistasis among cancer drivers can rescue early tumors from the accumulation of deleterious passengers
Fig 5
Timing of tumor rescue is critically affected by the structure of the epistasis network.
(A) Distribution of tumor rescue times (understood as the time of appearance of a trigger driver in the most connected gene) in star- (brown) and clique-like (green) networks, and their variation with the mutation rate (μ), driver fitness effect (sd), fraction of genes subject to epistasis (fe), and strength of epistasis (ϵ). Histograms were obtained from 1000 independent trajectories; solid lines correspond to analytical expressions. To facilitate comparisons, all the distributions are normalized to the same total area. (B) Dependence of the median rescue times (solid lines) and their 25–75 percentiles (shaded areas) on the parameters of the model, based on analytical expressions. Parameter values: μ = 5×10−9, sd = 0.05, fe = 0.5, ϵ = 2, G = 70, rest of parameters as in Fig 2B.