Fig 2. Simulations.

A. Conceptual diagram for simulations. Descriptive representation of the strain prevalence at different stages relative to vaccine introduction: pre-vaccine equilibrium, vaccine introduction, and post-vaccine equilibrium. We modeled a population of VT and NVT strains (represented as unique genotypes with alleles 1 or 0 at a locus, denoting the presence or absence of a single accessory locus) and simulated the removal of VT genotypes, following the post-vaccine population to equilibrium (details in methods). In this illustrative figure, 8 strains are shown, with their prevalence in the population evolving over time. The system is allowed to evolve until it reaches a steady state (“pre-vaccine equilibrium”). Three strains were then targeted to mimic a vaccine introduction, which removes them from the system. The predicted fitness was then estimated from the period just after the vaccine introduction, when the population has been depleted of VT but relative prevalence of NVT has not changed—a quantity that can be calculated from pre-vaccine data alone. Finally, the system reaches a second steady state (“post-vaccine equilibrium”). Different shades of blue represent the rank of the strain frequencies in the post-vaccine equilibrium. B. Predicted fitness. Comparison of the direction of prevalence change of strains from pre- to post-vaccine using simulated data and predicted fitness from these simulated data. For these 10 replicate simulations, 2,371 accessory loci and 35 randomly chosen strains were simulated, including 3 VT genotypes. For each replicate, the pre-vaccine equilibrium frequencies of the 2,371 accessory loci were varied. Final prevalence of strains was obtained by quadratic programing, and prevalence change for each NVT strain was calculated as post-vaccine prevalence minus pre-vaccine prevalence, in both cases with all NVT strains summing to 100%. Each column in the decreased and increased category represents the results from 1 simulation (i.e., the first column in the decreased category corresponds to the first column in the increased category, and the dots sum to 32). The predicted fitness of the strain accurately predicts the direction of the prevalence change in 92.8% of cases (teal dots). Gray dots represent instances in which the direction of the prevalence change was not predicted correctly in the simulation. See S1 Data and S1 Code for details. NVT, nonvaccine serotype; VT, vaccine serotype.