Between-tumor and within-tumor heterogeneity in invasive potential
(A) Bootstrap replicates were used to increase robustness to limited number of tumors and organoids per tumor. Bootstraps were conducted for all 52 tumors and then, with increasing stringency, for tumors generating at least 2 through 10 organoids, with 30 tumors meeting the final requirement (solid line). The average number of organoids per tumor increased from 15.8 to 22.9 for these replicates (dashed line). (B) Three generative models were considered for between-tumor and within-tumor variation in logarithmic-scale organoid invasiveness: Model 0 assumes a single mean and variance shared by all tumors; Model 1 assumes a shared variance, but assigns each tumor its own mean; Model 2 assigns each tumor its own mean and variance. Converged estimates were obtained from 10,000 bootstrap replicates for thresholds of 1 organoid per tumor up to 10 organoids per tumor. For these thresholds, the posterior probability is 55-65% for Model 1 (green bars), with the remaining probability assigned to Model 2 (blue bars). Model 0 (red bars) had vanishing probability, not visible on this scale.