haplotype: Function to load tumour allele counts from a text file or...

In TitanCNA: Subclonal copy number and LOH prediction from whole genome sequencing of tumours

Description

Function to load in the allele counts from tumour sequencing data from a delimited text file or data.frame object.

Usage

    loadHaplotypeAlleleCounts(inCounts, cnfile, fun = "sum", haplotypeBinSize = 1e5, 
      minSNPsInBin = 3, chrs = c(1:22, "X"), minNormQual = 200, 
      genomeStyle = "NCBI", sep = "\t", header = TRUE, seqinfo = NULL,
      mapWig = NULL, mapThres = 0.9, centromere = NULL, minDepth = 10, maxDepth = 1000)
    
    getHaplotypesFromVCF(vcfFile, chrs = c(1:22, "X"), build = "hg19", genomeStyle = "NCBI",
      filterFlags = c("PASS", "10X_RESCUED_MOLECULE_HIGH_DIVERSITY"), 
      minQUAL = 100, minDepth = 10, minVAF = 0.25, altCountField = "AD", 
      keepGenotypes = c("1|0", "0|1", "0/1"), snpDB = NULL)
      
    loadBXcountsFromBEDDir(bxDir, chrs = c(1:22, "X", "Y"), minReads = 2)

Arguments

inCounts	Path to text file or data.frame containing tumour allele count data. inCounts must be 6 columns: chromosome, position, reference base, reference read counts, non-reference base, non-reference read counts. ‘chromosome’ column can be in ‘NCBI’ or ‘UCSC’ genome style; only autosomes, sex chromosomes, and mitochondrial chromosome are included (e.g. 1-22,X,Y,MT). The reference and non-reference base columns can be any arbitrary character; it is not used by TitanCNA.
cnfile	Path to file containing GC-bias and maappability corrected molecule coverage for given bin size.
vcfFile	Path to phased variant VCF file from LongRanger 2.1. The file name must have the suffix *phase_variants.vcf.gz.
bxDir	Path to directory containing tumor bed files for each chromosome containing BX tags.
fun	The function (‘SNP’, ‘sum’, ‘mean’) to use to summarize within each user defined bin using haplotypeBinSize and haplotype block defined by the phaseSet ID from thte 9th column of inCounts. ‘SNP’ - uses the phased allele counts each individual SNP; phased allele for the higher coverage (determined within each bin) haplotype is chosen. ‘sum’ - uses the read count sum across all phased SNPs for the higher coverage haplotype within a bin normalized by the total depth across all SNPs in a bin; each SNP in the bin is assigned this fraction. ‘mean’ - uses the mean (rounded) read count across all phased SNPs for the higher coverage haplotype within a bin normalized by the mean (rounded) depth across all SNPs in a bin; each SNP in the bin is assigned this rounded count and depth.
haplotypeBinSize	Bin size used to summarize SNPs based on phased haplotypes. See fun for the summarization approaches within a bin.
minSNPsInBin	The minimum number of SNPs required in each haplotypeBinSize for analysis. See fun for the summarization approaches within a bin.
chrs	Vector containing list of chromosomes to include in output.
minNormQual	Quality threshold to use for filtering; SNPs with lower than this value are excluded. This quality is any metric that provides the confidence of the locus being a true germline heterozygous SNP.
minReads	Minimum number of reads per barcode.
genomeStyle	The genome style to use for chromosomes. Use one of ‘NCBI’ or ‘UCSC’. It does not matter what style is found in inCounts, genomeStyle will be the style returned. Invokes setGenomeStyle.
build	Human genome reference build. Default: hg19.
snpDB	Path to SNP VCF file to use for specifying sites to retain.
minQUAL	Variants with quality (QUAL field) greater or equal to this value will be retained.
minDepth	Variants with read depth greater than or equal to this value will be retained.
maxDepth	Variants with read depth lower than or equal to this value will be retained.
minVAF	Variants with a variant/reference allele fraction of greater than or equal to this value will be retained.
altCountField	Specify the alternate count field name. Defaulat is "AD".
keepGenotypes	Genotypes to retain. Default is to keep these genotypes strings: 1|0, 0|1, 0/1
filterFlags	Specify the FILTER flags to retain.
sep	Character indicating the delimiter used for the columns for infile. Default is tab-delimited, "\t".
header	logical to indicate if the input tumour counts file contains a header line.
seqinfo	Seqinfo-class object describing chromosome information. If NULL, then will load seqinfo for hg19 system.files('extdata', 'Seqinfo_hg19.rda', package='TitanCNA'.
mapWig	Mappability score WIG file for binned data.
mapThres	Minimum mappability score of region/sequence overlapping variants to retain.
centromere	File containing reference genome gap file representing centromere locations. Usually obtained from UCSC.

Value

loadHaplotypeAlleleCounts returns a data.table containing components for

chr	Chromosome; character, genomeStyle naming convention
posn	Position; integer
phaseSet	Phase block identifier, numeric or character
refOriginal	Reference allele read count at SNP; numeric
tumDepthOriginal	Coverage at SNP; numeric
ref	Phased allele count values of higher coverage haplotype based on approach used (SNP, sum, mean); numeric
nonRef	Phased allele count values of lower coverage haplotype; tumDepth minus ref; numeric
tumDepth	Mean or sum of SNP read coverage; numeric
HapltypeRatio	Sum of read coverage of phased alleles of higher coverage haplotype normalized by tumDepth; numeric
haplotypeCount	Phased allele read count; numeric

getHaplotypesFromVCF returns a list containing 2 components

vcf.filtered	VCF object containing the list of heterozygous variants after filtering.
geno.gr	GRanges object containing the genotype information of the VCF

Author(s)

Gavin Ha <[e-mail]>

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

loadDefaultParameters, plotHaplotypeFraction

Examples

  ## Not run: 
  infile <- "test_alleleCounts_chr2_with_phaseInfo.txt"
  haplotypeBinSize <- 1e5
  phaseSummarizeFun <- "sum"
  ## will load seqinfo_hg19 provided by TitanCNA package
  data <- loadHaplotypeAlleleCounts(infile, fun = phaseSummarizeFun,
      haplotypeBinSize = haplotypeBinSize, minSNPsInBin = 3, 
      chrs = c(1:22, "X"), minNormQual = 200, 
      genomeStyle = "NCBI", seqinfo = NULL)
  
## End(Not run)
  
  ## Not run: 
  vcfFile <- "test.vcf"
  hap <- getHaplotypesFromVCF(vcfFile, chrs = c(1:22,"X"), build = "hg19",
    filterFlags = c("PASS", "10X_RESCUED_MOLECULE_HIGH_DIVERSITY"), 
    minQUAL = 100, minDepth = 10, minVAF = 0.25, 
    keepGenotypes = ("1|0", "0|1", "0/1"))
  
  
## End(Not run)

TitanCNA documentation built on Nov. 8, 2020, 8:14 p.m.