mleAF: Estimate the most likely allele frequency

In cancerTiming: Estimation of Temporal Ordering of Cancer Abnormalities

Description

Estimate the number of copies a mutation is found in, based on which allele value maximizes the binomial likelihood after correcting for normal contamination and seqError.

Usage

mleAF(x, m, totalCopy, maxCopy=totalCopy, seqError = 0, normCont = 0)

Arguments

x	vector. the number of reads/fragments containing the variant
m	vector. the number of reads/fragments covering the location with the variant (the coverage)
totalCopy	The total number of copies (maternal and paternal combined), can be vector with length equal to length(x)
maxCopy	The maximum number of copies of either maternal or paternal alleles, can be vector with length equal to length(x)
seqError	The probability of sequencing error per base, can be vector with length equal to length(x)
normCont	Percentage of normal contamination, can be vector with length equal to length(x)

Details

maxCopy and totalCopy are used to determine the possible allele frequencies in a pure tumor cell, given by 1:maxCopy/totalCopy. The default of maxCopy=totalCopy ensures that all theoretically possible alleles are considered given the lack of further information, but in general will not be correct. For example, if the region has allelic copy 2/3, then there are only three possible allele frequencies rather than five.

Value

List with following values:

perLocationProb	matrix of dimension (number of locations) x (number of possible allele frequencies), with each row corresponding to a given location and each column giving the probability of observing the data for that location for each of the possible allele frequencies
assignments	data.frame of dimension (number of locations) x 3, with columns ncopies=estimate of number of copies mutation is found in, based on which maximizes the likelihood, totalCopy=totalCopy given by user, AF=estimate of true allele frequency given by ncopies/totalCopy
alleleSet	Only returned if the parameters totalCopy, maxCopy, seqError, and normCont are of length=1. A data.frame with rows equal to number of possible alleles and three columns, tumorAF=the allele frequency in the pure tumor, AF= the corresponding allele frequency after adjusting for normal contamination and sequencing error, frequency = number of locations with that allele frequency.

Author(s)

Elizabeth Purdom

References

Greenman, C D et al. 2012. “Estimation of rearrangement phylogeny for cancer genomes." Genome Research 22(2):346-361.

Examples

	#example of CNLOH
	m<-c(24,41,40,15)
	x<-c(13,21,17,12)
	nc<-c(0.27,0.39,0.49,0.22)
	mleAF(x=x,m=m,totalCopy=2,maxCopy=2,normCont=nc)
	mleAF(x=x,m=m,totalCopy=c(2,3,2,3),maxCopy=2,normCont=nc)
	#note the difference in output if instead all data is from 
	#same sample (shares normal Contamination estimate)
	mleAF(x=x,m=m,totalCopy=2,maxCopy=2,normCont=nc[1])

Example output

$perLocationProb
$perLocationProb[[1]]
         1          2 
0.03448164 0.02319894 

$perLocationProb[[2]]
          1           2 
0.002753931 0.055357832 

$perLocationProb[[3]]
          1           2 
0.008295823 0.071004350 

$perLocationProb[[4]]
          1           2 
0.001278722 0.245705383 


$assignments
  nCopies totalCopy tumorAF
1       1         2     0.5
2       2         2     1.0
3       2         2     1.0
4       2         2     1.0

$perLocationProb
$perLocationProb[[1]]
         1          2 
0.03448164 0.02319894 

$perLocationProb[[2]]
           1            2 
7.248131e-05 1.050877e-01 

$perLocationProb[[3]]
          1           2 
0.008295823 0.071004350 

$perLocationProb[[4]]
           1            2 
0.0000403241 0.0374898869 


$assignments
  nCopies totalCopy   tumorAF
1       1         2 0.5000000
2       2         3 0.6666667
3       2         2 1.0000000
4       2         3 0.6666667

$perLocationProb
                1            2
[1,] 0.0344816351 2.319894e-02
[2,] 0.0196600698 1.538210e-03
[3,] 0.0935096652 3.515097e-05
[4,] 0.0006513988 2.051054e-01

$assignments
  nCopies totalCopy tumorAF
1       1         2     0.5
2       1         2     0.5
3       1         2     0.5
4       2         2     1.0

$alleleSet
  tumorAF    AF Freq
1     0.5 0.365    3
2     1.0 0.730    1

cancerTiming documentation built on May 2, 2019, 9:28 a.m.