Intrapatient heterogeneity in tumor organoid growth.
A: Distribution of log10(a) within the UK/UP/US datasets, where log10(a) denotes the logarithm of a with base 10. For each organoid in each dataset, the initial exponential growth rate a of the organoid was estimated using the Gompertz model (Sections “Gompertz model” and “Model fitting”). Each panel shows how the estimated values of a are distributed across individual organoids within the indicated dataset, under a logarithmic transformation of a. The logarithmic transformation is applied since the estimated values of a vary across an order of magnitude within each dataset. For each dataset, the distribution of log10(a) is consistent with a normal distribution, meaning that we fail to reject the null hypothesis of normality under a Kolmogorov-Smirnov statistical test at the 5% significance level. B: Distribution of the Gompertz parameters (a, b) within the UK/UP/US datasets, shown on a logarithmic scale. The different datasets for each patient have been combined. For each organoid in each dataset, the initial exponential growth rate a and the rate of growth decay b were estimated using the Gompertz model (Sections “Gompertz model” and “Model fitting”). Each dot in each panel represents a single organoid, where the horizontal position of the dot indicates the value of a for that organoid and the vertical position indicates the value of b. When fitting the Gompertz model to individual organoids, we set b = 10−4 as the smallest possible value for b and treat it as effectively zero. Organoids with b = 10−4 are referred to as “exponential organoids”, while the remaining organoids are referred to as “nonexponential”. The exponential organoids are all situated on the horizontal axis and their position on the axis represents their rate of exponential growth. The slanted lines indicate carrying capacities of K = 10, 102, 103, 104, where the carrying capacity is the predicted final size of the organoid under the Gompertz model (Fig 1). All organoids falling on the same line share the indicated carrying capacity. Organoids falling below the lowest line are predicted to have a final size above 104 cells.