Simulation of DTA experiments upon perturbation

Description

DTA.dynamic.generate produces the phenotype matrix and the matrix containing the simulated data according to the given parameters.

Usage

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DTA.dynamic.generate(duration = 60,lab.duration = 6,tnumber = NULL,plabel = NULL,nrgenes = 5000,mediantime.halflives = 12,mediantime.synthesisrates = 18,n = 1,ccl = NULL,check = TRUE,plots = FALSE,save.plots = FALSE,folder = NULL,condition = "",addformat = NULL,sdnoise = 0.075,nobias = FALSE,unspecific.LtoU = 0,unspec.LtoU.weighted = FALSE,unspecific.UtoL = 0,unspec.UtoL.weighted = FALSE,mu.values.mat = NULL,mu.breaks.mat = NULL,lambda.values.mat = NULL,lambda.breaks.mat = NULL,truehalflives = NULL,truesynthesisrates = NULL,genenames = NULL)

Arguments

duration

duration of the whole time course (min)

lab.duration

labeling duration for single experiments (min)

tnumber

Integer vector containing the number of uridine residues for each gene. If NULL, tnumber is sampled from an F-distribution within the function.

plabel

The labeling efficiency. If NULL, plabel is set to 0.005 within the function. For details, see supplemental material of Sun et al. (see references).

nrgenes

The number of genes the simulated experiment will have (will be cropped if it exceeds the length of tnumber).

mediantime.halflives

the median of the half life distribution

mediantime.synthesisrates

the median of the synthesis rates distribution (counts/cell/cellcycle)

n

the number of cells N(0)

ccl

The cell cycle length (in minutes).

check

if check=TRUE, control messages will be generated

plots

if plots = TRUE, control plots will be plotted

save.plots

if save.plots = TRUE, control plots will be saved

folder

folder, where to save the plots

condition

to be added to the plotnames

addformat

additional fileformat for plots to be saved

sdnoise

The amount of measurement noise (proportional to expression strength).

nobias

Should a labeling bias be added?

unspecific.LtoU

Proportion of labeled RNAs that unspecifically end up in the unlabeled fraction.

unspec.LtoU.weighted

Should unspecific proportion of labeled to unlabeled depend linearly on the length of the RNA?

unspecific.UtoL

Proportion of unlabeled RNAs that unspecifically end up in the labeled fraction.

unspec.UtoL.weighted

Should unspecific proportion of unlabeled to labeled depend linearly on the length of the RNA?

mu.values.mat

if the data should be generated using given synthesis rates, this matrix must contain the respective values for each gene

mu.breaks.mat

timepoints of synthesis rate changes, this matrix must contain the respective values for each gene, only needed when mu.values.mat is given (one column less than mu.values.mat)

lambda.values.mat

if the data should be generated using given decay rates, this matrix must contain the respective values for each gene

lambda.breaks.mat

timepoints of decay rate changes, this matrix must contain the respective values for each gene, only needed when lambda.values.mat is given (one column less than lambda.values.mat)

truehalflives

If the data should be generated using a given half-life distribution, this vector must contain the respective values for each gene.

truesynthesisrates

If the data should be generated using a given synthesis rates distribution, this vector must contain the respective values for each gene

genenames

An optional list of gene names.

Value

DTA.dynamic.generate returns a list, containing the following entries

phenomat

A matrix, containing the design of the experiment as produced by DTA.phenomat.

datamat

A matrix, containing the simulated measurements from U, L and T, according to the design given in phenomat.

tnumber

Integer vector containing the number of uridine residues for each gene.

ccl

The cell cycle length (in minutes).

truemus

A vector, containing the true synthesis rates.

truemusaveraged

A vector, containing the true synthesis rates, averaged over the labeling period.

truelambdas

A vector, containing the true decay rates.

truelambdasaveraged

A vector, containing the true decay rates, averaged over the labeling period.

truehalflives

A vector, containing the true half-lives.

truehalflivesaveraged

A vector, containing the true half-lives, averaged over the labeling period.

trueplabel

The true labeling efficiency. For details, see supplemental material of Sun et al. (see references).

truecomplete

A vector, containing the true amount of total RNA.

truelambdas

A vector, containing the true decay rates.

truemus

A vector, containing the true synthesis rates.

truehalflives

A vector, containing the true half-lives.

trueplabel

The true labeling efficiency. For details, see supplemental material of Miller et al. (see references).

truear

The true parameter ar. For details, see supplemental material of Miller et al. (see references).

truebr

The true parameter br. For details, see supplemental material of Miller et al. (see references).

truecr

The true parameter cr. For details, see supplemental material of Miller et al. (see references).

truecrbyar

The true parameter cr/ar. For details, see supplemental material of Miller et al. (see references).

truecrbybr

The true parameter cr/br. For details, see supplemental material of Miller et al. (see references).

truebrbyar

The true parameter br/ar. For details, see supplemental material of Miller et al. (see references).

trueLasymptote

The true parameter asymptote (labeled bias). For details, see supplemental material of Miller et al. (see references).

trueUasymptote

The true parameter asymptote (unlabeled bias). For details, see supplemental material of Miller et al. (see references).

Author(s)

Bjoern Schwalb schwalb@lmb.uni-muenchen.de

References

C. Miller, B. Schwalb, K. Maier, D. Schulz, S. Duemcke, B. Zacher, A. Mayer, J. Sydow, L. Marcinowski, L. Dolken, D. E. Martin, A. Tresch, and P. Cramer. Dynamic transcriptome analysis measures rates of mRNA synthesis and decay in yeast. Mol Syst Biol, 7:458, 2011. M. Sun, B. Schwalb, D. Schulz, N. Pirkl, L. Lariviere, K. Maier, A. Tresch, P. Cramer. Mutual feedback between mRNA synthesis and degradation buffers transcript levels in a eukaryote. Under review. B. Schwalb, B. Zacher, S. Duemcke, D. Martin, P. Cramer, A. Tresch. Measurement of genome-wide RNA synthesis and decay rates with Dynamic Transcriptome Analysis (DTA/cDTA). Bioinformatics.

Examples

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nrgenes = 5000
truesynthesisrates = rf(nrgenes,5,5)*18
steady = rep(1,nrgenes)
shock = 1/pmax(rnorm(nrgenes,mean = 8,sd = 4),1)
induction = pmax(rnorm(nrgenes,mean = 8,sd = 4),1)
changes.mat = cbind(steady,shock,shock*induction)
mu.values.mat = changes.mat*truesynthesisrates
mu.breaks.mat = cbind(rep(12,nrgenes),rep(18,nrgenes))
truehalflives = rf(nrgenes,15,15)*12
truelambdas = log(2)/truehalflives
changes.mat = cbind(steady,shock,shock*induction,steady)
lambda.values.mat = changes.mat*truelambdas
lambda.breaks.mat = cbind(rep(12,nrgenes),rep(18,nrgenes),rep(27,nrgenes))

### it takes several min to build sim.object (depends on the number of genes 'nrgenes') ###

sim.object = DTA.dynamic.generate(duration = 36,lab.duration = 6,nrgenes = nrgenes,mu.values.mat = mu.values.mat,mu.breaks.mat = mu.breaks.mat,lambda.values.mat = lambda.values.mat,lambda.breaks.mat = lambda.breaks.mat)

### for control plots set 'check = TRUE' ###

res = DTA.dynamic.estimate(simulation = TRUE,sim.object = sim.object,check = FALSE)

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