Package 'DEploid'

Deconvolute Mixed Genomes with Unknown Proportions

Description

Traditional phasing programs are limited to diploid organisms. Our method modifies Li and Stephens algorithm with Markov chain Monte Carlo (MCMC) approaches, and builds a generic framework that allows haplotype searches in a multiple infection setting. This package is primarily developed as part of #' the Pf3k project, which is a global collaboration using the latest sequencing technologies to provide a high-resolution view of natural variation in the malaria parasite Plasmodium falciparum. Parasite DNA are extracted from patient blood sample, which often contains more than one parasite strain, with unknown proportions. This package is used for deconvoluting mixed haplotypes, #' and reporting the mixture proportions from each sample.

Author(s)

Zhu Sha

Maintainer: Joe Zhu [email protected]

---

Compute observed WSAF

Description

Compute observed allele frequency within sample from the allele counts.

Usage

computeObsWSAF(alt, ref)

Arguments

alt	Numeric array of alternative allele count.
ref	Numeric array of reference allele count.

Value

Numeric array of observed allele frequency within sample.

See Also

histWSAF for histogram.

Examples

# Example 1
refFile = system.file("extdata", "PG0390-C.test.ref", package = "DEploid")
altFile = system.file("extdata", "PG0390-C.test.alt", package = "DEploid")
PG0390CoverageT = extractCoverageFromTxt(refFile, altFile)
obsWSAF = computeObsWSAF(PG0390CoverageT$altCount, PG0390CoverageT$refCount)

# Example 2
vcfFile = system.file("extdata", "PG0390-C.test.vcf.gz", package = "DEploid")
PG0390CoverageV = extractCoverageFromVcf(vcfFile)
obsWSAF = computeObsWSAF(PG0390CoverageV$altCount, PG0390CoverageV$refCount)

---

Deconvolute mixed haplotypes

Description

Deconvolute mixed haplotypes, and reporting the mixture proportions from each sample This function provieds an interface for calling dEploid from R. The command line options are passed via the args argument

Usage

dEploid(args)

Arguments

args	String of dEploid input.

Value

A list with members of haplotypes, proportions and log likelihood of the MCMC chain.

• Haps Haplotypes at the final iteration in plain text file.

• Proportions MCMC updates of the proportion estimates.

• llks Log likelihood of the MCMC chain.

Seeding

The R version of DEploid uses random number from R's random generator. Therefore, the '-seed' argument of the command line version will be ignored, and no seed is given in the output. Use the R function 'set.seed' prior to calling this function to ensure reproduciblity of results.

See Also

• vignette('dEploid-Arguments') for an overview of commandline arguments

Examples

## Not run: 
vcfFile = system.file("extdata", "PG0390-C.test.vcf.gz", package = "DEploid")
plafFile = system.file("extdata", "labStrains.test.PLAF.txt", package = "DEploid")
set.seed(1234)
PG0390.deconv = dEploid(paste("-vcf", vcfFile, "-plaf", plafFile, "-noPanel"))

## End(Not run)

---

Extract read counts from plain text file

Description

Extract read counts from tab-delimited text files of a single sample.

Usage

extractCoverageFromTxt(refFileName, altFileName)

Arguments

refFileName	Path of the reference allele count file.
altFileName	Path of the alternative allele count file.

Value

A data.frame contains four columns: chromosomes, positions, reference allele count, alternative allele count.

Note

The allele count files must be tab-delimited. The allele count files contain three columns: chromosomes, positions and allele count.

Examples

refFile = system.file("extdata", "PG0390-C.test.ref", package = "DEploid")
altFile = system.file("extdata", "PG0390-C.test.alt", package = "DEploid")
PG0390 = extractCoverageFromTxt(refFile, altFile)

---

Extract read counts from VCF

Description

Extract read counts from VCF file of a single sample.

Usage

extractCoverageFromVcf(vcfFileName, ADFieldIndex = 2)

Arguments

vcfFileName	Path of the VCF file.
ADFieldIndex	Index of the AD field of the sample field. For example, if the format is "GT:AD:DP:GQ:PL", the AD index is 2 (by default).

Value

A data.frame contains four columns: chromosomes, positions, reference allele count, alternative allele count.

Note

The VCF file should only contain one sample. If more samples present in the VCF, it only returns coverage for of the first sample.

Examples

vcfFile = system.file("extdata", "PG0390-C.test.vcf.gz", package = "DEploid")
PG0390 = extractCoverageFromVcf(vcfFile)

---

Extract PLAF

Description

Extract population level allele frequency (PLAF) from text file.

Usage

extractPLAF(plafFileName)

Arguments

plafFileName

Path of the PLAF text file.

Value

A numeric array of PLAF

Note

The text file must have header, and population level allele frequency recorded in the "PLAF" field.

Examples

plafFile = system.file("extdata", "labStrains.test.PLAF.txt",
  package = "DEploid")
plaf = extractPLAF(plafFile)

---

Extract VCF information

Description

Extract VCF information

Usage

extractVcf(filename)

Arguments

filename

VCF file name.

Value

A dataframe list with members of haplotypes, proportions and log likelihood of the MCMC chain.

• CHROM SNP chromosomes.

• POS SNP positions.

• refCount reference allele count.

• altCount alternative allele count.

See Also

• extractCoverageFromVcf

• extractCoverageFromTxt

Examples

vcfFile = system.file("extdata", "PG0390-C.test.vcf.gz", package = "DEploid")
vcf = extractVcf(vcfFile)

---

Painting haplotype according the reference panel

Description

Plot the posterior probabilities of a haplotype given the refernece panel.

Usage

haplotypePainter(
  posteriorProbabilities,
  title = "",
  labelScaling,
  numberOfInbreeding = 0
)

Arguments

posteriorProbabilities	Posterior probabilities matrix with the size of number of loci by the number of reference strain.
title	Figure title.
labelScaling	Scaling parameter for plotting.
numberOfInbreeding	Number of inbreeding strains copying from.

---

WSAF histogram

Description

Produce histogram of the allele frequency within sample.

Usage

histWSAF(
  obsWSAF,
  exclusive = TRUE,
  title = "Histogram 0<WSAF<1",
  cex.lab = 1,
  cex.main = 1,
  cex.axis = 1
)

Arguments

obsWSAF	Observed allele frequency within sample
exclusive	When TRUE 0 < WSAF < 1; otherwise 0 <= WSAF <= 1.
title	Histogram title
cex.lab	Label size.
cex.main	Title size.
cex.axis	Axis text size.

Value

histogram

Examples

# Example 1
refFile = system.file("extdata", "PG0390-C.test.ref", package = "DEploid")
altFile = system.file("extdata", "PG0390-C.test.alt", package = "DEploid")
PG0390Coverage = extractCoverageFromTxt(refFile, altFile)
obsWSAF = computeObsWSAF(PG0390Coverage$altCount, PG0390Coverage$refCount)
histWSAF(obsWSAF)
myhist = histWSAF(obsWSAF, FALSE)

# Example 2
vcfFile = system.file("extdata", "PG0390-C.test.vcf.gz", package = "DEploid")
PG0390CoverageV = extractCoverageFromVcf(vcfFile)
obsWSAF = computeObsWSAF(PG0390CoverageV$altCount, PG0390CoverageV$refCount)
histWSAF(obsWSAF)
myhist = histWSAF(obsWSAF, FALSE)

---

Plot coverage

Description

Plot alternative allele count vs reference allele count at each site.

Usage

plotAltVsRef(
  ref,
  alt,
  title = "Alt vs Ref",
  exclude.ref = c(),
  exclude.alt = c(),
  potentialOutliers = c(),
  cex.lab = 1,
  cex.main = 1,
  cex.axis = 1
)

Arguments

ref	Numeric array of reference allele count.
alt	Numeric array of alternative allele count.
title	Figure title, "Alt vs Ref" by default
exclude.ref	Numeric array of reference allele count at sites that are not deconvoluted.
exclude.alt	Numeric array of alternative allele count at sites that are not deconvoluted
potentialOutliers	Index of potential outliers.
cex.lab	Label size.
cex.main	Title size.
cex.axis	Axis text size.

Examples

# Example 1
refFile = system.file("extdata", "PG0390-C.test.ref", package = "DEploid")
altFile = system.file("extdata", "PG0390-C.test.alt", package = "DEploid")
PG0390CoverageT = extractCoverageFromTxt(refFile, altFile)
plotAltVsRef(PG0390CoverageT$refCount, PG0390CoverageT$altCount)

# Example 2
vcfFile = system.file("extdata", "PG0390-C.test.vcf.gz", package = "DEploid")
PG0390CoverageV = extractCoverageFromVcf(vcfFile)
plotAltVsRef(PG0390CoverageV$refCount, PG0390CoverageV$altCount)

---

Plot coverage

Description

Plot alternative allele count vs reference allele count at each site.

Usage

plotAltVsRefPlotly(ref, alt, title = "Alt vs Ref", potentialOutliers = c())

Arguments

ref	Numeric array of reference allele count.
alt	Numeric array of alternative allele count.
title	Figure title, "Alt vs Ref" by default
potentialOutliers	Index of potential outliers.

Examples

# Example 1
refFile = system.file("extdata", "PG0390-C.test.ref", package = "DEploid")
altFile = system.file("extdata", "PG0390-C.test.alt", package = "DEploid")
PG0390CoverageT = extractCoverageFromTxt(refFile, altFile)
plotAltVsRefPlotly(PG0390CoverageT$refCount, PG0390CoverageT$altCount)

# Example 2
vcfFile = system.file("extdata", "PG0390-C.test.vcf.gz", package = "DEploid")
PG0390CoverageV = extractCoverageFromVcf(vcfFile)
plotAltVsRefPlotly(PG0390CoverageV$refCount, PG0390CoverageV$altCount)

---

WSAF histogram

Description

Produce histogram of the allele frequency within sample.

Usage

plotHistWSAFPlotly(obsWSAF, exclusive = TRUE, title = "Histogram 0<WSAF<1")

Arguments

obsWSAF	Observed allele frequency within sample
exclusive	When TRUE 0 < WSAF < 1; otherwise 0 <= WSAF <= 1.
title	Figure title, "Histogram 0<WSAF<1" by default

Value

histogram

Examples

# Example 1
refFile = system.file("extdata", "PG0390-C.test.ref", package = "DEploid")
altFile = system.file("extdata", "PG0390-C.test.alt", package = "DEploid")
PG0390Coverage = extractCoverageFromTxt(refFile, altFile)
obsWSAF = computeObsWSAF(PG0390Coverage$altCount, PG0390Coverage$refCount)
plotHistWSAFPlotly(obsWSAF)
myhist = plotHistWSAFPlotly(obsWSAF)

# Example 2
vcfFile = system.file("extdata", "PG0390-C.test.vcf.gz", package = "DEploid")
PG0390CoverageV = extractCoverageFromVcf(vcfFile)
obsWSAF = computeObsWSAF(PG0390CoverageV$altCount, PG0390CoverageV$refCount)
plotHistWSAFPlotly(obsWSAF)
myhist = plotHistWSAFPlotly(obsWSAF)

---

Plot WSAF

Description

Plot observed alternative allele frequency within sample against expected WSAF.

Usage

plotObsExpWSAF(
  obsWSAF,
  expWSAF,
  title = "WSAF(observed vs expected)",
  cex.lab = 1,
  cex.main = 1,
  cex.axis = 1
)

Arguments

obsWSAF	Numeric array of observed WSAF.
expWSAF	Numeric array of expected WSAF.
title	Figure title.
cex.lab	Label size.
cex.main	Title size.
cex.axis	Axis text size.

Examples

## Not run: 
vcfFile = system.file("extdata", "PG0390-C.test.vcf.gz", package = "DEploid")
PG0390CoverageV = extractCoverageFromVcf(vcfFile)
obsWSAF = computeObsWSAF(PG0390CoverageV$altCount, PG0390CoverageV$refCount)
plafFile = system.file("extdata", "labStrains.test.PLAF.txt",
 package = "DEploid")
PG0390.deconv = dEploid(paste("-vcf", vcfFile,
                                       "-plaf", plafFile, "-noPanel"))
prop = PG0390.deconv$Proportions[dim(PG0390.deconv$Proportions)[1],]
expWSAF = t(PG0390.deconv$Haps) %*% prop
plotObsExpWSAF(obsWSAF, expWSAF)

## End(Not run)

---

Plot WSAF

Description

Plot observed alternative allele frequency within sample against expected WSAF.

Usage

plotObsExpWSAFPlotly(obsWSAF, expWSAF, title = "WSAF(observed vs expected)")

Arguments

obsWSAF	Numeric array of observed WSAF.
expWSAF	Numeric array of expected WSAF.
title	Figure title, "WSAF(observed vs expected)" by default

Examples

## Not run: 
vcfFile = system.file("extdata", "PG0390-C.test.vcf.gz", package = "DEploid")
PG0390CoverageV = extractCoverageFromVcf(vcfFile)
obsWSAF = computeObsWSAF(PG0390CoverageV$altCount, PG0390CoverageV$refCount)
plafFile = system.file("extdata", "labStrains.test.PLAF.txt",
 package = "DEploid")
PG0390CoverageV.deconv = dEploid(paste("-vcf", vcfFile,
                                       "-plaf", plafFile, "-noPanel"))

prop = PG0390CoverageV.deconv$Proportions[dim(PG0390CoverageV.deconv
                                              $Proportions)[1],]

expWSAF = t(PG0390CoverageV.deconv$Haps) %*% prop
plotObsExpWSAFPlotly(obsWSAF, expWSAF)

## End(Not run)

---

Plot proportions

Description

Plot the MCMC samples of the proportion, indexed by the MCMC chain.

Usage

plotProportions(
  proportions,
  title = "Components",
  cex.lab = 1,
  cex.main = 1,
  cex.axis = 1
)

Arguments

proportions	Matrix of the MCMC proportion samples. The matrix size is number of the MCMC samples by the number of strains.
title	Figure title.
cex.lab	Label size.
cex.main	Title size.
cex.axis	Axis text size.

Examples

## Not run: 
plafFile = system.file("extdata", "labStrains.test.PLAF.txt",
    package = "DEploid")
panelFile = system.file("extdata", "labStrains.test.panel.txt",
    package = "DEploid")
refFile = system.file("extdata", "PG0390-C.test.ref", package = "DEploid")
altFile = system.file("extdata", "PG0390-C.test.alt", package = "DEploid")
PG0390CoverageT = extractCoverageFromTxt(refFile, altFile)
PG0390Coverage.deconv = dEploid(paste("-ref", refFile, "-alt", altFile,
    "-plaf", plafFile, "-noPanel"))
plotProportions(PG0390Coverage.deconv$Proportions, "PG0390-C proportions")

## End(Not run)

---

Plot WSAF vs PLAF

Description

Plot allele frequencies within sample against population level.

Usage

plotWSAFvsPLAF(
  plaf,
  obsWSAF,
  expWSAF = c(),
  potentialOutliers = c(),
  title = "WSAF vs PLAF",
  cex.lab = 1,
  cex.main = 1,
  cex.axis = 1
)

Arguments

plaf	Numeric array of population level allele frequency.
obsWSAF	Numeric array of observed altenative allele frequencies within sample.
expWSAF	Numeric array of expected WSAF from model.
potentialOutliers	Index of potential outliers.
title	Figure title, "WSAF vs PLAF" by default
cex.lab	Label size.
cex.main	Title size.
cex.axis	Axis text size.

Examples

# Example 1
refFile = system.file("extdata", "PG0390-C.test.ref", package = "DEploid")
altFile = system.file("extdata", "PG0390-C.test.alt", package = "DEploid")
PG0390CoverageT = extractCoverageFromTxt(refFile, altFile)
obsWSAF = computeObsWSAF(PG0390CoverageT$altCount, PG0390CoverageT$refCount)
plafFile = system.file("extdata", "labStrains.test.PLAF.txt",
  package = "DEploid")
plaf = extractPLAF(plafFile)
plotWSAFvsPLAF(plaf, obsWSAF)

# Example 2
vcfFile = system.file("extdata", "PG0390-C.test.vcf.gz", package = "DEploid")
PG0390CoverageV = extractCoverageFromVcf(vcfFile)
obsWSAF = computeObsWSAF(PG0390CoverageV$altCount, PG0390CoverageV$refCount)
plafFile = system.file("extdata", "labStrains.test.PLAF.txt",
  package = "DEploid")
plaf = extractPLAF(plafFile)
plotWSAFvsPLAF(plaf, obsWSAF)

---

Plot WSAF vs PLAF

Description

Plot allele frequencies within sample against population level.

Usage

plotWSAFVsPLAFPlotly(
  plaf,
  obsWSAF,
  ref,
  alt,
  title = "WSAF vs PLAF",
  potentialOutliers = c()
)

Arguments

plaf	Numeric array of population level allele frequency.
obsWSAF	Numeric array of observed altenative allele frequencies within sample.
ref	Numeric array of reference allele count.
alt	Numeric array of alternative allele count.
title	Figure title, "WSAF vs PLAF" by default
potentialOutliers	Index of potential outliers.

Examples

# Example 1
refFile = system.file("extdata", "PG0390-C.test.ref", package = "DEploid")
altFile = system.file("extdata", "PG0390-C.test.alt", package = "DEploid")
PG0390CoverageT = extractCoverageFromTxt(refFile, altFile)
obsWSAF = computeObsWSAF(PG0390CoverageT$altCount, PG0390CoverageT$refCount)
plafFile = system.file("extdata", "labStrains.test.PLAF.txt",
  package = "DEploid")
plaf = extractPLAF(plafFile)
plotWSAFVsPLAFPlotly(plaf, obsWSAF, PG0390CoverageT$refCount,
               PG0390CoverageT$altCount)

# Example 2
vcfFile = system.file("extdata", "PG0390-C.test.vcf.gz", package = "DEploid")
PG0390CoverageV = extractCoverageFromVcf(vcfFile)
obsWSAF = computeObsWSAF(PG0390CoverageV$altCount, PG0390CoverageV$refCount)
plafFile = system.file("extdata", "labStrains.test.PLAF.txt",
  package = "DEploid")
plaf = extractPLAF(plafFile)
plotWSAFVsPLAFPlotly(plaf, obsWSAF, PG0390CoverageV$refCount,
               PG0390CoverageV$altCount)

---