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###########################################################################/**
# @RdocDefault testAllelicBalanceByBAFs
#
# @title "Tests for allelic balance in a genomic region"
#
# \description{
# @get "title".
# }
#
# @synopsis
#
# \arguments{
# \item{betaT}{A @numeric @vector of J tumor allele B fractions (BAFs).}
# \item{muN}{A @numeric @vector of J normal (germline) genotypes.}
# \item{flavor}{A @character specifying the type of test to be performed.}
# \item{...}{Not used.}
# \item{verbose}{See @see "R.utils::Verbose".}
# }
#
# \value{
# A @list of class "htest".
# }
#
# @examples "../incl/callAllelicBalanceByBAFs.PairedPSCBS.Rex"
#
# @author "HB, PN"
#
# @keyword internal
#*/###########################################################################
setMethodS3("testAllelicBalanceByBAFs", "default", function(betaT, muN, flavor=c("var", "mean"), ..., verbose=FALSE) {
# - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
# Validate arguments
# - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
# Argument 'betaT':
betaT <- Arguments$getDoubles(betaT)
nbrOfLoci <- length(betaT)
length2 <- rep(nbrOfLoci, times=2)
# Argument 'muN':
muN <- Arguments$getDoubles(muN, length=length2)
# Argument 'flavor':
flavor <- match.arg(flavor)
# Argument 'verbose':
verbose <- Arguments$getVerbose(verbose)
if (verbose) {
pushState(verbose)
on.exit(popState(verbose))
}
verbose && enter(verbose, "Testing for allelic balance by allele B fractions (BAFs)")
verbose && cat(verbose, "Number of loci: ", nbrOfLoci)
verbose && cat(verbose, "Requested flavor: ", flavor)
verbose && cat(verbose, "Tumor allele B fractions:")
verbose && str(verbose, betaT)
verbose && cat(verbose, "Match-normal genotypes:")
verbose && str(verbose, muN)
# - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
# Drop loci with missing signals or missing genotypes
# - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
verbose && enter(verbose, "Dropping loci with missing signals or missing genotypes")
keep <- (is.finite(betaT) & is.finite(muN))
keep <- which(keep)
if (length(keep) < nbrOfLoci) {
betaT <- betaT[keep]
muN <- muN[keep]
nbrOfLoci <- length(betaT)
verbose && cat(verbose, "Number of SNPs with finite signals: ", nbrOfLoci)
verbose && cat(verbose, "Tumor allele B fractions:")
verbose && str(verbose, betaT)
verbose && cat(verbose, "Match-normal genotypes:")
verbose && str(verbose, muN)
}
# Not needed anymore
keep <- NULL
verbose && exit(verbose)
# - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
# Get homozygous and heterozygous centered BAF signals
# - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
verbose && enter(verbose, "Getting homozygous and heterozygous centered BAF signals")
# AA SNPs
isAA <- (muN == 0)
idxs <- which(isAA)
yAA <- betaT[idxs]
yAA <- yAA - mean(yAA)
# BB SNPs
isBB <- (muN == 1)
idxs <- which(isBB)
yBB <- betaT[idxs]
yBB <- yBB - mean(yBB)
# AB SNPs
isAB <- (muN == 1/2)
idxs <- which(isAB)
yAB <- betaT[idxs]
yAB <- yAB - mean(yAB)
# Homozygous SNPs
homs <- c(yAA, yBB)
nHoms <- length(homs)
# Heterozygous SNPs
hets <- yAB
nHets <- length(hets)
# All other SNPs (for curiousity only)
## isOther <- (!isAA & !isAB & !isBB)
## idxs <- which(isOther)
## nOthers <- length(idxs)
# Not needed anymore
isAA <- isBB <- isAB <- idxs <- yAA <- yBB <- yAB <- NULL
verbose && cat(verbose, "Number of homozygous SNPs: ", nHoms)
verbose && cat(verbose, "Number of heterozygous SNPs: ", nHets)
verbose && exit(verbose)
# Default statistics
res <- list(statistic=NA, p.value=NA)
# - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
# Sanity checks
# - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
nMin <- min(nHoms, nHets)
# Sanity check
if (nMin <= 1) {
warning(sprintf("Cannot infer allelic balance. Too few (homozygous, heterozygous) data points. Will return NA: (%d,%d)", nHoms, nHets))
return(res)
}
# Need to fall back on another test than the requested one?
if (flavor == "var") {
if (nMin <= 2) {
warning(sprintf("Cannot infer allelic balance using the heterozygous-homozygous variance test. Will use the mean test instead. Too few (homozygous, heterozygous) data points: (%d,%d)", nHoms, nHets))
flavor <- "mean"
verbose && cat(verbose, "Adjusted flavor: ", flavor)
}
} else if (flavor == "mean") {
}
# - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
# Testing for allelic balance
# - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
if (flavor == "var") {
res <- var.test(hets, homs, alternative="greater")
} else if (flavor == "mean") {
sigmaHat <- sd(homs, na.rm=TRUE)
stat <- mean(abs(hets), na.rm=TRUE) / sigmaHat
p <- 1 - pnorm(stat)
res <- list(statistic=stat, p.value=p)
class(res) <- c("htest", class(res))
}
verbose && str(verbose, res)
# Sanity check
verbose && exit(verbose)
res
}, protected=TRUE) # testAllelicBalanceByBAFs()
#############################################################################
# HISTORY
# 2010-09-08 [PN,HB]
# o Harmonized code. Added more verbose output. Added more code comments.
# o Renamed to testAllelicBalanceByBAFs() from AI.test().
# o Added an Rdoc skeleton.
# o Renamed arguments.
# 2010-08-25 [PN]
# o Created.
#############################################################################
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