The distribution of fitness effects (DFE) of new beneficial mutations is a key quantity that dictates the dynamics of adaptation. The barcode lineage tracking (BLT) approach is an important advance toward measuring DFEs. BLT experiments enable researchers to track the frequencies of ~10 5 barcoded lineages in large microbial populations and detect up to thousands of nascent beneficial mutations in a single experiment. However, reliably identifying adapted lineages and estimating the fitness effects of driver mutations remains a challenge because lineage dynamics are subject to demographic and measurement noise and competition with other lineages. We show that the commonly used Levy-Blundell method for analyzing BLT data and its improved version FitMut2 can produce biased fitness estimates, particularly if selection is strong. To address this problem, we develop a new method called BASIL (BAyesian Selection Inference for Lineage tracking data), which dynamically updates the belief distribution of each lineage’s fitness and size based on the number of barcode reads. We calibrate BASIL’s model of noise with new experimental data and find that noise variance scales non-linearly with lineage abundance. We test how BASIL and FitMut2 perform on simulated data and on down-sampled data from the original BLT data by Levy et al and find that BASIL is both more robust and more accurate than FitMut2. Our work paves the way for a systematic inference of the distribution of fitness effects of new beneficial mutations from BLT experiments in a variety of scenarios.
Kuo et al. (Fri,) studied this question.