MutationTimeR: Timing of point mutations and copy number gains from deep...

In gerstung-lab/MutationTimeR: Timing somatic point mutations and copy number gains

Description

Timing of point mutations and copy number gains from deep sequencing

Details

This package provies functions to time copy number gains using point mutations.

Author(s)

Moritz Gerstung, EMBL-EBI, [e-mail]

References

Gerstung M, et al. The evolutionary history of 2578 cancers. DOI:10.1038/ncomms1814.

See Also

mutationTime

Examples

set.seed(42)
cn <- MutationTimeR:::refLengths[1:23]
t1 <- 0.7
purity <- 0.6
clusters <- data.frame(cluster=1:3, proportion=c(purity,purity * 0.8, purity * 0.4), n_ssms=c(100,20, 50))
time2pi <- function(N,n,t1,t2){
	if(N==2 & n ==1)
		pi <-  c(3-2*t1, t1)
	else if(N==2 & n %in% c(0,2))
		pi <- c(2 -2*t1, t1)
	else pi <- 1
	pi <- pi/sum(pi)
}
cn$major_cn <- 2 #sample(1:2, 23, replace=TRUE)
cn$minor_cn <- sample(0:2, 23, replace=TRUE)
cn$clonal_frequency <- purity
cn$timing_param <- MutationTimeR:::defineMcnStates(cn, purity=purity, clusters=clusters, deltaFreq = 0)
for(i in seq_along(cn)){
	pi <- time2pi(cn$major_cn[i], cn$minor_cn[i], t1, t2)
	pi_sub <- clusters$n_ssms
	pi_sub[1] <- pi_sub[1] * (t1*2 + (1-t1)*(cn$major_cn[i]+ cn$minor_cn[i])) / 2
	pi_sub[-1] <- pi_sub[-1] * (cn$major_cn[i]+ cn$minor_cn[i]) / 2
	pi_sub <- pi_sub/sum(pi_sub)
	pi <- c(pi * pi_sub[1], pi_sub[-1])
	cn$timing_param[[i]][,"P.m.sX"] <- pi
	cn$timing_param[[i]][,"power.m.s"] <- rep(1, length(pi))
}
cn$n.snv_mnv <- width(MutationTimeR:::refLengths[1:23])/1e6 * 10

vcf <- MutationTimeR:::simulateMutations(cn, rho=0.01, n=40)
cn_timed <- cn[,c("major_cn","minor_cn","clonal_frequency")]

mt <- mutationTime(vcf, cn_timed, clusters=clusters, n.boot=10)
mcols(cn_timed) <- cbind(mcols(cn_timed),mt$T)

info(header(vcf)) <- rbind(info(header(vcf)),MutationTimeR:::mtHeader())
info(vcf) <- cbind(info(vcf), mt$V)

plotSample(vcf,cn_timed)

gerstung-lab/MutationTimeR documentation built on Dec. 12, 2020, 9:29 p.m.