create_synthetic_data function

Creates a synthetic limited proteolysis proteomics dataset

This function creates a synthetic limited proteolysis proteomics dataset that can be used to test functions while knowing the ground truth.

create_synthetic_data(
  n_proteins,
  frac_change,
  n_replicates,
  n_conditions,
  method = "effect_random",
  concentrations = NULL,
  median_offset_sd = 0.05,
  mean_protein_intensity = 16.88,
  sd_protein_intensity = 1.4,
  mean_n_peptides = 12.75,
  size_n_peptides = 0.9,
  mean_sd_peptides = 1.7,
  sd_sd_peptides = 0.75,
  mean_log_replicates = -2.2,
  sd_log_replicates = 1.05,
  effect_sd = 2,
  dropout_curve_inflection = 14,
  dropout_curve_sd = -1.2,
  additional_metadata = TRUE
)

Arguments

• n_proteins: a numeric value that specifies the number of proteins in the synthetic dataset.

• frac_change: a numeric value that specifies the fraction of proteins that has a peptide changing in abundance. So far only one peptide per protein is changing.

• n_replicates: a numeric value that specifies the number of replicates per condition.

• n_conditions: a numeric value that specifies the number of conditions.

• method: a character value that specifies the method type for the random sampling of significantly changing peptides. If method = "effect_random", the effect for each condition is randomly sampled and conditions do not depend on each other. If method = "dose_response", the effect is sampled based on a dose response curve and conditions are related to each other depending on the curve shape. In this case the concentrations argument needs to be specified.

• concentrations: a numeric vector of length equal to the number of conditions, only needs to be specified if method = "dose_response". This allows equal sampling of peptide intensities. It ensures that the same positions of dose response curves are sampled for each peptide based on the provided concentrations.

• median_offset_sd: a numeric value that specifies the standard deviation of normal distribution that is used for sampling of inter-sample-differences. Default is 0.05.

• mean_protein_intensity: a numeric value that specifies the mean of the protein intensity distribution. Default: 16.8.

• sd_protein_intensity: a numeric value that specifies the standard deviation of the protein intensity distribution. Default: 1.4.

• mean_n_peptides: a numeric value that specifies the mean number of peptides per protein. Default: 12.75.

• size_n_peptides: a numeric value that specifies the dispersion parameter (the shape parameter of the gamma mixing distribution). Can be theoretically calculated as mean + mean^2/variance, however, it should be rather obtained by fitting the negative binomial distribution to real data. This can be done by using the optim function (see Example section). Default: 0.9.

• mean_sd_peptides: a numeric value that specifies the mean of peptide intensity standard deviations within a protein. Default: 1.7.

• sd_sd_peptides: a numeric value that specifies the standard deviation of peptide intensity standard deviation within a protein. Default: 0.75.

• mean_log_replicates, sd_log_replicates: a numeric value that specifies the meanlog

  and sdlog of the log normal distribution of replicate standard deviations. Can be obtained by fitting a log normal distribution to the distribution of replicate standard deviations from a real dataset. This can be done using the optim function (see Example section). Default: -2.2 and 1.05.

• effect_sd: a numeric value that specifies the standard deviation of a normal distribution around mean = 0 that is used to sample the effect of significantly changeing peptides. Default: 2.

• dropout_curve_inflection: a numeric value that specifies the intensity inflection point of a probabilistic dropout curve that is used to sample intensity dependent missing values. This argument determines how many missing values there are in the dataset. Default: 14.

• dropout_curve_sd: a numeric value that specifies the standard deviation of the probabilistic dropout curve. Needs to be negative to sample a droupout towards low intensities. Default: -1.2.

• additional_metadata: a logical value that determines if metadata such as protein coverage, missed cleavages and charge state should be sampled and added to the list.

Returns

A data frame that contains complete peptide intensities and peptide intensities with values that were created based on a probabilistic dropout curve.

Examples

create_synthetic_data(
  n_proteins = 10,
  frac_change = 0.1,
  n_replicates = 3,
  n_conditions = 2
)

# determination of mean_n_peptides and size_n_peptides parameters based on real data (count)
# example peptide count per protein
count <- c(6, 3, 2, 0, 1, 0, 1, 2, 2, 0)
theta <- c(mu = 1, k = 1)
negbinom <- function(theta) {
  -sum(stats::dnbinom(count, mu = theta[1], size = theta[2], log = TRUE))
}
fit <- stats::optim(theta, negbinom)
fit

# determination of mean_log_replicates and sd_log_replicates parameters
# based on real data (standard_deviations)

# example standard deviations of replicates
standard_deviations <- c(0.61, 0.54, 0.2, 1.2, 0.8, 0.3, 0.2, 0.6)
theta2 <- c(meanlog = 1, sdlog = 1)
lognorm <- function(theta2) {
  -sum(stats::dlnorm(standard_deviations, meanlog = theta2[1], sdlog = theta2[2], log = TRUE))
}
fit2 <- stats::optim(theta2, lognorm)
fit2