Simulate one replicate of multi-label NR-seq data

Generalizes SimulateOneRep() to simulate any combination of mutation types. Currently, no kinetic model is used to relate certain parameters to the fractions of reads belonging to each simulated mutational population. Instead these fractions are drawn from a Dirichlet distribution with gene-specific parameters.

Usage

SimulateMultiLabel(
  nfeatures,
  populations = c("TC"),
  fraction_design = create_fraction_design(populations),
  fractions_matrix = NULL,
  read_vect = NULL,
  sample_name = "sampleA",
  feature_prefix = "Gene",
  kdeg_vect = NULL,
  ksyn_vect = NULL,
  logkdeg_mean = -1.9,
  logkdeg_sd = 0.7,
  logksyn_mean = 2.3,
  logksyn_sd = 0.7,
  phighs = stats::setNames(rep(0.05, times = length(populations)), populations),
  plows = stats::setNames(rep(0.002, times = length(populations)), populations),
  seqdepth = nfeatures * 2500,
  readlength = 200,
  alpha_min = 3,
  alpha_max = 6,
  Ucont = 0.25,
  Acont = 0.25,
  Gcont = 0.25,
  Ccont = 0.25
)

Arguments

nfeatures: Number of "features" (e.g., genes) to simulate data for
populations: Vector of mutation populations you want to simulate.
fraction_design: Fraction design matrix, specifying which potential mutational populations should actually exist. See ?EstimateFractions for more details.
fractions_matrix: Matrix of fractions of each mutational population to simulate. If not provided, this will be simulated. One row for each feature, one column for each mutational population, rows should sum to 1.
read_vect: Vector of length = nfeatures; specifies the number of reads to be simulated for each feature. If this is not provided, the number of reads simulated is equal to round(seqdepth * (ksyn_i/kdeg_i)/sum(ksyn/kdeg)). In other words, the normalized steady-state abundance of a feature is multiplied by the total number of reads to be simulated and rounded to the nearest integer.
sample_name: Character vector to assign to sample column of output simulated data table (the cB table).
feature_prefix: Name given to the i-th feature is paste0(feature_prefix, i). Shows up in the feature column of the output simulated data table.
kdeg_vect: Vector of length = nfeatures; specifies the degradation rate constant to use for each feature's simulation. If this is not provided and fn_vect is, then kdeg_vect = -log(1 - fn_vect)/label_time. If both kdeg_vect and fn_vect are not provided, each feature's kdeg_vect value is drawn from a log-normal distrubition with meanlog = logkdeg_mean and sdlog = logkdeg_sd. kdeg_vect is actually only simulated in the case where read_vect is also not provided, as it will be used to simulate read counts as described above.
ksyn_vect: Vector of length = nfeatures; specifies the synthesis rate constant to use for each feature's simulation. If this is not provided, and read_vect is also not provided, then each feature's ksyn_vect value is drawn from a log-normal distribution with meanlog = logksyn_mean and sdlog = logksyn_sd. ksyn's do not need to be simulated if read_vect is provided, as they only influence read counts.
logkdeg_mean: If necessary, meanlog of a log-normal distribution from which kdegs are simulated
logkdeg_sd: If necessary, sdlog of a log-normal distribution from which kdegs are simulated
logksyn_mean: If necessary, meanlog of a log-normal distribution from which ksyns are simulated
logksyn_sd: If necessary, sdlog of a log-normal distribution from which ksyns are simulated
phighs: Vector of probabilities of mutation rates in labeled reads of each type denoted in populations. Should be a named vector, with names being the corresponding population.
plows: Vector of probabilities of mutation rates in unlabeled reads of each type denoted in populations. Should be a named vector, with names being the corresponding population.
seqdepth: Only relevant if read_vect is not provided; in that case, this is the total number of reads to simulate.
readlength: Length of simulated reads. In this simple simulation, all reads are simulated as being exactly this length.
alpha_min: Minimum possible value of alpha element of Dirichlet random variable
alpha_max: Maximum possible value of alpha element of Dirichlet random variable
Ucont: Probability that a nucleotide in a simulated read is a U.
Acont: Probability that a nucleotide in a simulated read is an A.
Gcont: Probability that a nucleotide in a simulated read is a G.
Ccont: Probability that a nucleotide in a simulated read is a C.

Examples

simdata <- SimulateMultiLabel(3)
#> Warning: The `x` argument of `as_tibble.matrix()` must have unique column names if
#> `.name_repair` is omitted as of tibble 2.0.0.
#> ℹ Using compatibility `.name_repair`.
#> ℹ The deprecated feature was likely used in the EZbakR package.
#>   Please report the issue to the authors.