Figure 2. Theoretical model of interval dN-dS fitted to simulated data and data from deep sequencing of the oesophagus.

(a) Interval dN/dS as a function of clone area for 2 simulated cohorts where driver mutations induce different biases, theoretical model captures the dynamics well and enables us to recover the bias ∆, accurately. As the number of mutations increases ability to recover the correct ∆ and the model fit (measured using R²) improves (b) and (c). (d) Data and model fit for all neutral genes, shows i-dN/dS = 1 across the frequency range and inferred bias of 0. Data and model fit for (e) NOTCH1 missense mutations in patient PD31182, (f) missense TP53 mutations in PD30273 and NOTCH1 nonsense mutations in PD31182 (g). Data are black points and model fits are solid lines with shaded areas denoting 95% CI.

Figure 2—figure supplement 1. Histogram of inferred Δ values from simulations using an exponentially distributed fitness effect.

For each panel the mean of the exponential distribution used for Δ is stated above and illustrated by the red dashed lines.

Figure 2—figure supplement 2. Model fits for all patients in the oesophagus data set.

Purple points are data and red lines model fits, shaded areas denote 95% confidence intervals. Fits were performed separately for missense, (a) and nonsense mutations, (b). Each plot is annotated with the inferred bias ∆ and the R² value.

Figure 2—figure supplement 3. Inferred biases for for each patient in the oesophagus dataset based on missense, (a) and nonsense mutations, (b).

Inferred loss replacement rates, rλ for each patient based on missense, (c) and nonsense mutations, (d).

Figure 2—figure supplement 4. Individual fits for each gene in each patient in the oesophagus dataset.

Points are data and lines are model fits. Analysis performed separately for nonsense, a and missense, b.