eventTiming: Estimate the time of events in tumor data

Description

Estimate the proportion of time spent between different chromosomal abnormalities based on the allele frequencies of mutated locations.

Usage

eventTiming(x, m, history, totalCopy, method=c("fullMLE","partialMLE","Bayes"),type=c("gain","CNLOH"),seqError=0, bootstrapCI=NULL, B=if(method=="Bayes") 10000 else 500, CILevel=0.95, alpha=1,tdf=4,normCont=0,verbose=TRUE,returnAssignments=FALSE,coverageCutoff=1,minMutations=10,returnData=FALSE,init=NULL,maxiter=100, tol=0.0001)

Arguments

vector. the number of reads/fragments containing the variant

vector. the number of reads/fragments covering the location with the variant (the coverage)

history

a matrix, based on the history of the region (see Details)

totalCopy

integer. the total number of copies of the tumor DNA for this region

method

what estimation method to use, one of ``fullMLE",``partialMLE",``Bayes"

type

type of region, either a gain or a CNLOH region

seqError

Probability of sequencing error

bootstrapCI

type of bootstrap confidence interval to calculate, one of ``parametric", ``nonparametric". If NULL, then the confidence interval is not calculated

number of bootstrap samples to take

CILevel

At what level the confidence intervals should be calculated.

alpha

parameter the Dirichlet prior of the bayesian estimate

tdf

parameter for the number of degrees of freedom for the t proposal density used in the bayesian estimate

normCont

the proportion of normal contamination, between 0 and 1.

verbose

logical. Whether to give additional warnings as the program is running.

returnAssignments

logical. Whether to re

coverageCutoff

minimum value for m[i]; any entries with m[i]

minMutations

minimum number of mutations required.

returnData

logical. Whether to return the input data, x and m, as a data.frame

init

initial value of multinomial parameter q passed to estimateQ.

maxiter

maximum number of iterations in calculation q.

tol

tolerance in the convergence of q

Value

A list with values
piestimate of pi vector
piCIbootstrap confidence interval, if requested
qestimate of the multinomial parameter q
perLocationProboutput from estimateQ giving per location P(P[i]|X[i],q), if requested. Only locations used in the estimation are included.
optimDetailsoptimization details from estimateQ
calllist of the parameters of the call to the function: history,totalCopy,type,exactAllele,normCont,coverageCutoff,minMutations. In addition, `alleleSet' is included in this list, which is the set of possible alleles for this history, after adjusting for normal contamination.

References

Durinck, S, et al. (2011). ``Temporal Dissection of Tumorigenesis in Primary Cancers." Cancer Discovery, 1(2): 137-143. Greenman, C D et al. (2012). ``Estimation of rearrangement phylogeny for cancer genomes." Genome Research, 22(2): 346-361. Purdom, E, et al. (submitted). ``Timing Chromosomal Abnormalities within Cancer Samples.''

Examples

Run this code

data(mutData)
ACNLOH<-matrix(c(1,3,1,0),ncol=2,nrow=2,byrow=TRUE)
onlyMuts<-subset(mutData,is.na(rsID) & position <= 1.8E7)
onlyMuts$t_depth<-onlyMuts$t_ref_count+onlyMuts$t_alt_count
x<-eventTiming(x=onlyMuts$t_alt_count,m=onlyMuts$t_depth,history=ACNLOH,totalCopy=2,type="CNLOH",normCont=0.22)
x$pi #estimate of time of stages
x$q #estimate of the multinomial (likelihood of each of the alleles)
x$call$alleleSet #possible set of alleles after adjusting for normal contamination

Run the code above in your browser using DataLab