TitanCNA (version 1.10.0)

loadDefaultParameters: Load TITAN parameters

Description

Load TITAN model parameters based on maximum copy number and number of clonal clusters.

Usage

loadDefaultParameters(copyNumber = 5, numberClonalClusters = 1, skew = 0, symmetric = TRUE, data = NULL)

Arguments

copyNumber

Maximum number of absolute copies to account for in the model. Default (and recommended) is 5.

numberClonalClusters

Number of clonal clusters to use in the analysis. Each cluster represents a potential clone. Using ‘1’ treats the sample as being clonal (no subclonality). ‘2’ or higher treats the tumour data as being subclonal.

skew

numeric float indicating the heterozygous baseline shift for the allelic ratios towards 1. This is may be required for SOLiD data, but for most cases, this argument can be omitted.

symmetric

logical; if TRUE, then treat genotypes as symmetric. See Details.

data

data is the output of function loadAlleleCounts. If provided and symmetric=TRUE, then it will compute the median allelic ratio to use as the baseline for heterozygous genotypes; otherwise, the baseline will default to 0.55 (reference/depth) if data=NULL. If symmetric=FALSE, this argument will not be used.

Value

list containing 4 sets of parameters, each as a component:

genotypeParams

Parameters for copy number and allelic ratios geneotype states

normalParams

Parameters for normal contamination

ploidyParams

Parameters for average tumour ploidy

sParams

Parameters for modeling subclonality: clonal clusters and cellular prevalence

Details

Generally, TitanCNA should be run once for each number of clonal clusters in the range of 1 to 5. Then, use model selection to choose the run with the optimal number of clusters. If the allelic ratio data is skewed towards one allele, then use skew to help define the baseline. For example, if the data is skewed towards the reference, then use 0.1 so that the heterozygous baseline is at 0.6. The allelic ratio baseline is normally at 0.5. sParams, which represents the parameters for estimation of subclonality, always contains values for one cluster that represents the clonally dominant cluster (events present in nearly all tumour cells) with an initial value of sParams$s_0[1] = 0.001. Setting symmetric to TRUE will treat reference and non-reference alleles the same. For example, genotypes AA (homozygous for reference allele) and BB (homozygous for non-reference allele) as being equivalent. This will reduce the state space substantially.

References

Ha, G., Roth, A., Khattra, J., Ho, J., Yap, D., Prentice, L. M., Melnyk, N., McPherson, A., Bashashati, A., Laks, E., Biele, J., Ding, J., Le, A., Rosner, J., Shumansky, K., Marra, M. A., Huntsman, D. G., McAlpine, J. N., Aparicio, S. A. J. R., and Shah, S. P. (2014). TITAN: Inference of copy number architectures in clonal cell populations from tumour whole genome sequence data. Genome Research, 24: 1881-1893. (PMID: 25060187)

See Also

loadAlleleCounts

Examples

  #### LOAD PARAMETERS ####
  numClusters <- 2
  params <- loadDefaultParameters(copyNumber = 5, 
                                  numberClonalClusters = numClusters)