Simulation of DTA experiments

Description

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

Usage

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DTA.generate(timepoints, tnumber = NULL, plabel = NULL, nrgenes = 5000, mediantime = 12, ccl = 150, delaytime = 0, sdnoise = 0.075, nobias = FALSE, unspecific.LtoU = 0, unspec.LtoU.weighted = FALSE, unspecific.UtoL = 0, unspec.UtoL.weighted = FALSE, truehalflives = NULL, truecomplete = NULL, genenames = NULL, cDTA = FALSE)

Arguments

timepoints

Integer vector containing the labeling times for which the samples should be generated.

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

The median of the randomly drawn half-life distribution.

ccl

The cell cycle length (in minutes).

delaytime

Estimates the delay between the moment of 4sU/4tU labeling and actual incorporation of it into mRNA.

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?

truehalflives

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

truecomplete

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

genenames

An optional list of gene names.

cDTA

cDTA = FALSE does not rescale L and U.

Value

DTA.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).

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. Doelken, 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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sim.object = DTA.generate(timepoints=rep(c(6,12),2))

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

res.sim = DTA.estimate(ratiomethod = "bias",simulation = TRUE,sim.object = sim.object,check = FALSE)

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