Fig. 4: Quantification of the evolutionary dynamics during treatment in a barcoded colorectal cancer cell line (SW6bc).

A A simplified schematic of the experimental design used in a long-term evolutionary resistance assay. Barcoded SW620 cells (SW6bc) were barcoded and expanded (POT) before being sampled into four replicate drug-treatment sub-populations (DT1-4) that were exposed to periodic chemotherapy treatment (5-fluoruracil: 5-Fu) and passaged at two timepoints (P1 & P2). B Population size counts at four timepoints per-replicate (DT1-4), including two intermediate population size estimates (O1 & O2) and two Passage timepoints (P1 & P2) (left panel); top 20 sequenced barcode lineage relative frequencies at the two passage timepoints, where area colour denotes lineage identity (middle panel); lineage diversity statistics of the sequenced barcode distributions at the two passage timepoints (P1 and P2) for each replicate composed of within replicate lineage diversity and between-replicate diversity dissimilarity. C Posterior predictive simulations for Model A (unidirectional transitions–top) and Model C (escape transitions – bottom) of the within and between-replicate diversity statistics (LHS) and the normalised diversity distance from the observed statistics (red points) to the simulated values (highlighted by the transition parameter μ). D The Deviance Information Criterion (DIC), a measure of model fit, for Model A & Model C (lower values indicate higher model support) calculated using the posterior predictive distributions. E The posterior distributions (n = 50, 4 experimental replicates) for parameters in Model A (the model with the highest support). Boxplots show the median, the first and third quartiles, and whiskers 1.5x the interquartile range. Parameters: ρ—pre-existing fraction of resistance, μ—sensitive to resistant transition probability per cell division, ψ— strength of the resistant phenotype, Dc—maximum strength of the drug, κ—accumulation/decay rate of the drug. F A posterior predictive simulation using Model A. Source data are provided as a Source Data file.