In ada-w-yan/reassortment: Modelling Evolution of Strain Mixtures Including Reassortment

Introduction

This vignette contains code to reproduce the modelling analysis and figures in the manuscript "Favipiravir-resistant virus shows potential for transmission", using data and functions in the reassortment package.

Main text

knitr::opts_chunk$set(eval = FALSE)

library(reassortment)

devtools::load_all()

run_default_pars is the function used to conduct simulations.

run_default_pars(sim_name = "default")

runs model simulations for default parameter values, which are those for Fig. 3a in the manuscript, and Table 1 in the Appendix. The results are saved in results/default/results.rds (the argument sim_name specifies the output folder). The input parameter values (i.e. the default values in this case) are saved in results/default/inputs.rds.

results.rds contains a data frame:

results <- readRDS("results/default/results.rds")
head(results)
tail(results)

run is a integer from 1 to 100 (the number of stochastic simulations per scenario). There are 20 rows for each run number. Rows number 1, 2, 3... for a given run number contain the proportions of each strain for generations 1, 2, 3... MM, MW, WM and WW are the double mutant, PB1 K229R, PA P653L, and WT respectively.

plot_multirun_strains(results)

plots Fig. 3A in the manuscript.

The optional arguments to run_default_pars change the default parameter values.

• MOI: multiplicity of infection (default 1)
• iv: initial proportion of each strain, in order of MM, MW, WM, WW (default c(95,0,0,5))
• fitness_MW: fitness of PB1 K229R relative to WT (default 0.01)
• fitness_WM: fitness of PA P653L relative to WT (default 1.25)
• fitness_MM: fitness of PB1 K229R PA P653L relative to WT (default 1)
• mutation_prob: mutation probability per generation (default 2e-4)
• reassort: logical. if TRUE (default), both reassortment and mutation occur; if FALSE, only mutation occurs
• pop_size: size of virus population (default 1e6)
• burst size: burst size per cell at MOI = 1 (default 10)
• MOI_dependent_burst_size: if TRUE (default), the burst size for a given cell scales linearly with the MOI for that cell; if FALSE, the burst size is independent of the MOI
• choose_strain_by_fitness: if FALSE (default), the strain composition of a cell's progeny is independent of strain fitness; if TRUE, the probability of each progeny being of a given strain is proportinal to its fitness

For example, to simulate Figs. 3B-D:

run_default_pars(fitness_WM = 1, sim_name = "B")
run_default_pars(fitness_MW = 1, sim_name = "C")
run_default_pars(reassort = FALSE, sim_name = "D")

Sensitivity analysis

Fig. 1

# enumerate all combinations of fitness_WM and reassort
par_grid <- expand.grid(fitness_WM = c(1, 1.1, 1.5, 1.75, 2), reassort = c(FALSE, TRUE))
par_grid$sim_name <- paste0("fitness_WM_", num2str(par_grid$fitness_WM), "_", par_grid$reassort)
Map(run_default_pars, fitness_WM = par_grid$fitness_WM, 
    reassort = par_grid$reassort, sim_name = par_grid$sim_name)

Fig. 2

par_grid <- expand.grid(fitness_MM = c(0.8, 0.9, 1.1, 1.2), reassort = c(FALSE, TRUE))
par_grid$sim_name <- paste0(n"fitness_MM_", um2str(par_grid$fitness_MM), "_", par_grid$reassort)
Map(run_default_pars, fitness_MM = par_grid$fitness_MM, 
    reassort = par_grid$reassort, sim_name = par_grid$sim_name)

Fig. 3

par_grid <- expand.grid(mutation_prob = c(2e-3, 2e-5), reassort = c(FALSE, TRUE))
par_grid$sim_name <- paste0("mutation_prob_", num2str(par_grid$mutation_prob), "_", par_grid$reassort)
Map(run_default_pars, mutation_prob = par_grid$mutation_prob, 
    reassort = par_grid$reassort, sim_name = par_grid$sim_name)

Fig. 4

par_grid <- expand.grid(MOI = .1, reassort = c(FALSE, TRUE))
par_grid$sim_name <- paste0("MOI_", num2str(par_grid$MOI), "_", par_grid$reassort)
Map(run_default_pars, MOI = par_grid$MOI, 
    reassort = par_grid$reassort, sim_name = par_grid$sim_name)

par_grid <- expand.grid(MOI_dependent_burst_size = FALSE, reassort = c(FALSE, TRUE))
par_grid$sim_name <- paste0("MOI_dependent_burst_size_", par_grid$MOI_dependent_burst_size, "_", par_grid$reassort)
Map(run_default_pars, MOI_dependent_burst_size = par_grid$MOI_dependent_burst_size, 
    reassort = par_grid$reassort, par_grid$sim_name)

par_grid <- expand.grid(choose_strain_by_fitness = TRUE, reassort = c(FALSE, TRUE))
par_grid$sim_name <- paste0("choose_strain_by_fitness_", par_grid$choose_strain_by_fitness, "_", par_grid$reassort)
Map(run_default_pars, choose_strain_by_fitness = par_grid$choose_strain_by_fitness, 
    reassort = par_grid$reassort, par_grid$sim_name)

ada-w-yan/reassortment documentation built on April 10, 2021, 12:03 a.m.