Fig. 5.
Range of applicability of various models of intratumoral diversity vs. the number of cells in the tumor N(t) when the mutation was acquired. Sequencing to a depth D queries, on average, mutational events occurring when N(t) = D. Stochastic models such as that of Bozic et al. (26, 32) are more accurate than deterministic models at early times when the tumor is small. Models without the infinite-sites assumption (this manuscript) are more accurate than those with it (22, 26, 32) for larger tumor masses in which the number of cell approaches or exceeds the reciprocal of the effective mutation rate. The white parts of the bar represent zones where a method is not the best method but is within 10% of the best method. The solid bars indicate the method is the best method or within 1% of it. In the range of N(t) ∼ D corresponding to typical current experimental depths, all 3 methods are within less than 1% of each other. Parameters are b = 0.25/d, d = 0.18/d, and kmut-eff = 6.1 × 10−7.