Fig. 6.

Distribution of most common mutation at ${\text{WT}}_{\frac{1}{2}}$ for three protocols, simulated 50 000 times each. The protocol has a significant effect on mutant distribution (χ²-test, χ²=56929, p<10⁻¹⁶). The vertical blue line shows the expected frequency assuming all mutations were equally likely and equally fit. Unobserved mutations and double (or higher) mutants are not shown. For these simulations, doses were set such that Bosutinib caused 50% inhibition and Ponatinib caused 75% inhibition. The simulation protocol was 3:1 Bosutinib:Ponatinib, i.e., Bosutinib was used during 1800 timesteps (ca. 3 months), followed by Ponatinib during 600 timesteps (ca. 1 month) etc