Nothing
R/Misc.R
In RSVSim: RSVSim: an R/Bioconductor package for the simulation of structural variations
Defines functions
.testSVSim
.subtractIntervals
.getDummyDataframe
.getHG19
.loadFromBSGenome_TandemRepeats
.loadFromUCSC_SegDups
.loadFromUCSC_RepeatMasks
.readRepeatMaskerOutput
.getOverlap
.compareSV
.getSVSizes
setMethod("estimateSVSizes",
signature(n="numeric", svSizes="missing", default="character"),
function(n, svSizes, minSize, maxSize, default, hist){
if(!(default %in% c("deletions", "insertions", "inversions", "tandemDuplications"))){
stop("Invalid argument: No default values for SV type ", default)
}
## Default shape parameters were estimated from DGV release 2012-03-29
## Only studies with "method=sequencing" and size between 500bp and 10kb were selected (for insertions the extreme peak between 6000bp and 6200bp has been removed)
## SVs left: 1129 Deletions, 490 Insertions, 202 Inversions, 145 Tandem Duplications
if(default == "deletions"){
shape1=0.3692374
shape2=2.689951
}
if(default == "insertions"){
shape1=0.7106429
shape2=2.274061
}
if(default == "inversions"){
shape1=0.5786958
shape2=1.83066
}
if(default == "tandemDuplications"){
shape1=0.4084596
shape2=1.998082
}
if(any(is.na(c(minSize, maxSize)))){
return(.getSVSizes(n=n, shape1=shape1, shape2=shape2, min=500, max=10000, hist=hist))
}else{
return(.getSVSizes(n=n, shape1=shape1, shape2=shape2, min=minSize, max=maxSize, hist=hist))
}
})
setMethod("estimateSVSizes",
signature(n="numeric", svSizes="missing", default="missing"),
function(n, svSizes, minSize, maxSize, default, hist){
stop("Missing argument(s): Please give either a set of SVs or choose a set of default values.")
})
setMethod("estimateSVSizes",
signature(n="numeric", svSizes="numeric", default="missing"),
function(n, svSizes, minSize, maxSize, default, hist){
require(MASS)
## calculate the two shape parameters from given set of SVs
min = min(svSizes)
max = max(svSizes)
svSizes = (svSizes-min)/(max-min+1)
## make sure values are >0 and <1
svSizes[svSizes == 0] = svSizes[svSizes == 0] + 1e-5
svSizes[svSizes == 1] = svSizes[svSizes == 1] - 1e-5
# m = mean(svSizes)
# m = (m-min)/(max-min)
# v = var(svSizes)
# v = v/(max-min)^2
## shape parameters for beta distribution
# shape1 = m*(((m*(1-m))/v)-1)
# shape2 = (1-m)*(((m*(1-m))/v)-1)
beta = suppressWarnings(fitdistr(svSizes, "beta", start=list(shape1=0.1, shape2=0.1)))
shape1 = beta$estimate[1]
shape2 = beta$estimate[2]
if(any(c(is.na(minSize), is.na(maxSize)))){
return(.getSVSizes(n=n, shape1=shape1, shape2=shape2, min=min, max=max, hist=hist))
}else{
return(.getSVSizes(n=n, shape1=shape1, shape2=shape2, min=minSize, max=maxSize, hist=hist))
}
})
.getSVSizes <- function(n, shape1, shape2, min, max, hist){
simSizes = rbeta(n, shape1=shape1, shape2=shape2)
simSizes = round((simSizes*(max-min+1))+min)
if(hist == TRUE){
hist(simSizes)
}
return(simSizes)
}
setMethod("compareSV",
signature("data.frame", "data.frame"),
function(querySVs, simSVs, tol){
simSVs_overlap = .compareSV(querySVs, simSVs, tol)
return(simSVs_overlap)
})
setMethod("compareSV",
signature("character", "data.frame"),
function(querySVs, simSVs, tol){
querySVs= read.table(querySVs, sep="\t", header=FALSE, stringsAsFactors=FALSE, fill=TRUE)
simSVs_overlap = .compareSV(querySVs, simSVs, tol)
return(simSVs_overlap)
})
setMethod("compareSV",
signature("character", "character"),
function(querySVs, simSVs, tol){
simSVs = read.table(simSVs, fill=TRUE, header=TRUE)
querySVs= read.table(querySVs, sep="\t", header=FALSE, stringsAsFactors=FALSE, fill=TRUE)
simSVs_overlap = .compareSV(querySVs, simSVs, tol)
return(simSVs_overlap)
})
## deletions: (1) BED with colums chr,start,end(,bpSeq) or (2) BEDPE with colums chr,start1,end1,chr,start2,end2(,bpSeq)
## insertions: BEDPE with columns chrA,startA,endA, chrB,startB,endB(, bpSeq); two rows for one SV (5' and 3' breakpoint respectively)
## inversions: (1) BED with colums chr,start,end(,bpSeq1, bpSeq2) or (2) BEDPE with colums chr,start1,end1,chr,start2,end2(,bpSeq1, bpSeq2)
## tandem duplications: (1) BED with colums chr,start,end or (2) BEDPE with colums chr,start1,end1,chr,start2,end2
## translocations: BEDPE with columns chrA,startA,endA, chrB,startB,endB, (bpSeq1, bpSeq2)
.compareSV <- function(querySVs, simSVs, tol){
## get the type of SV by checking the column names in simSVs
type = NA
if(all(c("Name", "Chr", "Start", "End", "Size", "BpSeq") %in% colnames(simSVs))){
type = "deletion"
}
if(all(c("Name", "Chr", "Start", "End", "Size", "BpSeq_5prime", "BpSeq_3prime") %in% colnames(simSVs))){
type = "inversion"
}
if(all(c("Name", "ChrA", "StartA", "EndA", "ChrB", "StartB", "EndB", "Size", "Copied", "BpSeqA", "BpSeqB_5prime", "BpSeqB_3prime") %in% colnames(simSVs))){
type = "insertion"
}
if(all(c("Name", "Chr", "Start", "End", "Size", "Duplications", "BpSeq") %in% colnames(simSVs))){
type = "tandemDuplication"
}
if(all(c("Name", "ChrA", "StartA", "EndA", "SizeA", "ChrB", "StartB", "EndB", "SizeB", "Balanced", "BpSeqA", "BpSeqB") %in% colnames(simSVs))){
type = "translocation"
}
if(is.na(type)){
stop("Invalid input: Format of the second set of SVs differs from the output format of the simulator.")
}
## load user-supplied set of svs (BED- or BEDPE-file)
querySVs_Bp1 = querySVs_Bp1 = NULL
## split BED input into appropriate GRanges objects, which depends on the number of given columns (BED or BEDPE, with or without bpSeq)
## give every SV an id to remember which breakpoints belong together after GRanges sorted the coordinates
## inversions
if(ncol(querySVs) == 8){
querySVs_Bp1 = GRanges(IRanges(querySVs[, 2], querySVs[, 3]), seqnames=querySVs[, 1], bpSeq1=querySVs[, 7], bpSeq2=querySVs[, 8], id=1:nrow(querySVs))
querySVs_Bp2 = GRanges(IRanges(querySVs[, 5], querySVs[, 6]), seqnames=querySVs[, 4], bpSeq1=querySVs[, 7], bpSeq2=querySVs[, 8], id=1:nrow(querySVs))
}
## translocations, insertions or deletions
if(ncol(querySVs) == 7){
querySVs_Bp1 = GRanges(IRanges(querySVs[, 2], querySVs[, 3]), seqnames=querySVs[, 1], bpSeq=querySVs[, 7], id=1:nrow(querySVs))
querySVs_Bp2 = GRanges(IRanges(querySVs[, 5], querySVs[, 6]), seqnames=querySVs[, 4], bpSeq=querySVs[, 7], id=1:nrow(querySVs))
}
## translocations, inversions, insertions or deletions (no bpSeq)
if(ncol(querySVs) == 6){
querySVs_Bp1 = GRanges(IRanges(querySVs[, 2], querySVs[, 3]), seqnames=querySVs[, 1], bpSeq=NA, bpSeq2=NA, id=1:nrow(querySVs))
querySVs_Bp2 = GRanges(IRanges(querySVs[, 5], querySVs[, 6]), seqnames=querySVs[, 4], bpSeq=NA, bpSeq2=NA, id=1:nrow(querySVs))
}
## inversions
if(ncol(querySVs) == 5){
querySVs_Bp1 = GRanges(IRanges(querySVs[, 2], querySVs[, 2]), seqnames=querySVs[, 1], bpSeq1=querySVs[, 4], bpSeq2=querySVs[, 5], id=1:nrow(querySVs))
querySVs_Bp2 = GRanges(IRanges(querySVs[, 3], querySVs[, 3]), seqnames=querySVs[, 1], bpSeq1=querySVs[, 4], bpSeq2=querySVs[, 5], id=1:nrow(querySVs))
}
## deletions
if(ncol(querySVs) == 4){
querySVs_Bp1 = GRanges(IRanges(querySVs[, 2], querySVs[, 2]), seqnames=querySVs[, 1], bpSeq=querySVs[, 4], id=1:nrow(querySVs))
querySVs_Bp2 = GRanges(IRanges(querySVs[, 3], querySVs[, 3]), seqnames=querySVs[, 1], bpSeq=querySVs[, 4], id=1:nrow(querySVs))
}
## deletions, inversions (no bpSeq)
if(ncol(querySVs) == 3){
querySVs_Bp1 = GRanges(IRanges(querySVs[, 2], querySVs[, 2]), seqnames = querySVs[, 1], bpSeq=NA, bpSeq1=NA, bpSeq2=NA, id=1:nrow(querySVs))
querySVs_Bp2 = GRanges(IRanges(querySVs[, 3], querySVs[, 3]), seqnames = querySVs[, 1], bpSeq=NA, bpSeq1=NA, bpSeq2=NA, id=1:nrow(querySVs))
}
if(all(is.null(querySVs_Bp1), is.null(querySVs_Bp2))){
stop("Invalid SV file: Please make sure, that the SV file is in BED (chr,start,end) or BEDPE format (chr1,start1,end1,chr2,start2,end2) and contains only the breakpoint sequence(s) as additional column")
}
numOverlaps = 0
## For deletions and tandem duplications compare the 1 breakpoint and the 1 breakpoint sequence
if(type == "deletion" | type == "tandemDuplication"){
simSVs$Overlap = ""
simSVs$OverlapBpSeq = NA
for(v in 1:nrow(simSVs)){
simSV = simSVs[v, ]
## check correct start and end coordinate
chr = as.character(simSV$Chr)
simSV_Bp1 = GRanges(IRanges(simSV$Start, simSV$Start), seqnames=chr)
simSV_Bp2 = GRanges(IRanges(simSV$End, simSV$End), seqnames=chr)
overlap = .getOverlap(list(simSV_Bp1, simSV_Bp2), list(querySVs_Bp1[seqnames(querySVs_Bp1) == chr], querySVs_Bp2[seqnames(querySVs_Bp2) == chr]), list(simSV$BpSeq, querySVs_Bp1[seqnames(querySVs_Bp1) == chr]$bpSeq), list(NA, NA), tol, type)
if(!is.null(overlap)){
simSVs$Overlap[v] = overlap[[1]]
simSVs$OverlapBpSeq[v] = overlap[[2]]
numOverlaps = numOverlaps + overlap[[4]]
}
}
}
## For inversions compare the 1 breakpoint and the 2 breakpoint sequences
## seq|invseq|seq
if(type == "inversion"){
simSVs$Overlap = ""
simSVs$OverlapBpSeq_5prime = NA
simSVs$OverlapBpSeq_3prime = NA
for(v in 1:nrow(simSVs)){
simSV = simSVs[v, ]
## check correct start and end coordinate
chr = as.character(simSV$Chr)
simSV_Bp1 = GRanges(IRanges(simSV$Start, simSV$Start), seqnames=chr)
simSV_Bp2 = GRanges(IRanges(simSV$End, simSV$End), seqnames=chr)
overlap = .getOverlap(list(simSV_Bp1, simSV_Bp2), list(querySVs_Bp1[seqnames(querySVs_Bp1) == chr], querySVs_Bp2[seqnames(querySVs_Bp2) == chr]), list(simSV$BpSeq_5prime, querySVs_Bp1[seqnames(querySVs_Bp1) == chr]$bpSeq1), list(simSV$BpSeq_3prime, querySVs_Bp1[seqnames(querySVs_Bp1) == chr]$bpSeq2), tol, type)
if(!is.null(overlap)){
simSVs$Overlap[v] = overlap[[1]]
simSVs$OverlapBpSeq_5prime[v] = overlap[[2]]
simSVs$OverlapBpSeq_3prime[v] = overlap[[3]]
numOverlaps = numOverlaps + overlap[[4]]
}
}
}
## For insertions compare the 2 breakpoints and 2 breakpoint sequences
## chrB|chrA|chrB
if(type == "insertion"){
simSVs$Overlap_5prime = ""
simSVs$Overlap_3prime = ""
simSVs$OverlapBpSeq_5prime = NA
simSVs$OverlapBpSeq_3prime = NA
for(v in 1:nrow(simSVs)){
simSV = simSVs[v, ]
## Compare breakpoint at chrB|chrA (5', i.e. start)
simSV_Bp1 = GRanges(IRanges(simSV$StartB, simSV$StartB), seqnames=simSV$ChrB)
simSV_Bp2 = GRanges(IRanges(simSV$StartA, simSV$StartA), seqnames=simSV$ChrA)
chr1 = as.character(seqnames(simSV_Bp1))
chr2 = as.character(seqnames(simSV_Bp2))
querySVs_Bp12 = c(querySVs_Bp1, querySVs_Bp2)
overlap = .getOverlap(list(simSV_Bp1, simSV_Bp2), list(querySVs_Bp12[seqnames(querySVs_Bp12) == chr1], querySVs_Bp12[seqnames(querySVs_Bp12) == chr2]), list(simSV$BpSeqB_5prime, querySVs_Bp12[seqnames(querySVs_Bp12) == chr1]$bpSeq), list(NA, NA), tol, type)
if(!is.null(overlap)){
simSVs$Overlap_5prime[v] = overlap[[1]]
simSVs$OverlapBpSeq_5prime[v] = overlap[[2]]
numOverlaps = numOverlaps + overlap[[4]]
}
## Compare second breakpoint at chrA|chrB (3', i.e. end)
simSV_Bp1 = GRanges(IRanges(simSV$EndA, simSV$EndA), seqnames=simSV$ChrA)
simSV_Bp2 = GRanges(IRanges(simSV$StartB, simSV$StartB), seqnames=simSV$ChrB)
chr1 = as.character(seqnames(simSV_Bp1))
chr2 = as.character(seqnames(simSV_Bp2))
overlap = .getOverlap(list(simSV_Bp1, simSV_Bp2), list(querySVs_Bp12[seqnames(querySVs_Bp12) == chr1], querySVs_Bp12[seqnames(querySVs_Bp12) == chr2]), list(simSV$BpSeqB_3prime, querySVs_Bp12[seqnames(querySVs_Bp12) == chr1]$bpSeq), list(NA, NA), tol, type)
if(!is.null(overlap)){
simSVs$Overlap_3prime[v] = overlap[[1]]
simSVs$OverlapBpSeq_3prime[v] = overlap[[2]]
numOverlaps = numOverlaps + overlap[[4]]
}
}
}
## For translocations compare the 2 breakpoints and 1 breakpoint sequence
if(type == "translocation"){
simSVs$Overlap = ""
simSVs$OverlapBpSeq_A = NA
simSVs$OverlapBpSeq_B = NA
for(v in 1:nrow(simSVs)){
simSV = simSVs[v, ]
## Breakpoints can be either on 5' terminal or on 3' terminal
## Only check one breakpoint since the coordinates are only switched between chrB|chrA and chrA|chrB, but practically the same
if(simSV$StartB == 1){
simSV_Bp1 = GRanges(IRanges(simSV$EndB, simSV$EndB), seqnames=simSV$ChrB) ## 5', i.e. check the ends
}else{
simSV_Bp1 = GRanges(IRanges(simSV$StartB, simSV$StartB), seqnames=simSV$ChrB) ## 3', i.e. check the starts
}
if(simSV$StartA == 1){
simSV_Bp2 = GRanges(IRanges(simSV$EndA, simSV$EndA), seqnames=simSV$ChrA) ## 5', i.e. check the ends
}else{
simSV_Bp2 = GRanges(IRanges(simSV$StartA, simSV$StartA), seqnames=simSV$ChrA) ## 3', i.e. check the starts
}
chr1 = as.character(seqnames(simSV_Bp1))
chr2 = as.character(seqnames(simSV_Bp2))
querySVs_Bp12 = c(querySVs_Bp1, querySVs_Bp2)
## If translocation is not balanced, the breakpoint sequence on chrA does not need to be checked
if(simSV$Balanced == FALSE){
overlap = .getOverlap(list(simSV_Bp1, simSV_Bp2), list(querySVs_Bp12[seqnames(querySVs_Bp12) == chr1], querySVs_Bp12[seqnames(querySVs_Bp12) == chr2]), list(simSV$BpSeqB, querySVs_Bp12[seqnames(querySVs_Bp12) == chr1]$bpSeq), list(NA, NA), tol, type)
if(!is.null(overlap)){
simSVs$Overlap[v] = overlap[[1]]
simSVs$OverlapBpSeq_B[v] = overlap[[2]]
numOverlaps = numOverlaps + overlap[[4]]
}
}else{
overlap = .getOverlap(list(simSV_Bp1, simSV_Bp2), list(querySVs_Bp12[seqnames(querySVs_Bp12) == chr1], querySVs_Bp12[seqnames(querySVs_Bp12) == chr2]), list(simSV$BpSeqB, querySVs_Bp12[seqnames(querySVs_Bp12) == chr1]$bpSeq), list(simSV$BpSeqA, querySVs_Bp12[seqnames(querySVs_Bp12) == chr2]$bpSeq), tol, type)
if(!is.null(overlap)){
simSVs$Overlap[v] = overlap[[1]]
simSVs$OverlapBpSeq_B[v] = overlap[[2]]
simSVs$OverlapBpSeq_A[v] = overlap[[3]]
numOverlaps = numOverlaps + overlap[[4]]
}
}
}
}
## report sensitivity and precision
if(type == "insertion"){
tp = numOverlaps
fp = nrow(querySVs) - tp
fn = sum(simSVs$Overlap_5prime == "") + sum(simSVs$Overlap_3prime == "")
}
else{
tp = numOverlaps
fp = nrow(querySVs) - tp
fn = sum(simSVs$Overlap == "")
}
sensitivity = round((tp / (tp + fn)) * 100)
precision = round((tp / (tp + fp)) * 100)
message("Sensitivity: ", sensitivity, "%")
message("Precision: ", precision, "%")
return(simSVs)
}
.getOverlap <- function(sim, query, bpSeqA, bpSeqB, tol, type){
## simple substitution matrix, which only counts matches
substitutionMatrix = nucleotideSubstitutionMatrix(match = 1, mismatch = 0, baseOnly = FALSE, type = "DNA")
start(query[[1]]) = start(query[[1]]) - tol
end(query[[1]]) = end(query[[1]]) + tol
start(query[[2]]) = start(query[[2]]) - tol
end(query[[2]]) = end(query[[2]]) + tol
overlap1 = as.matrix(findOverlaps(sim[[1]], query[[1]]))
overlap2 = as.matrix(findOverlaps(sim[[2]], query[[2]]))
if(nrow(overlap1) > 0 & nrow(overlap2) > 0){
hit1 = overlap1[, "subjectHits"]
hit2 = overlap2[, "subjectHits"]
# if(query[[1]]$id[hit1] == query[[2]]$id[hit2]){
## for insertions and translocations, which have two breakpoints on two chromosomes, return two overlapping regions (separated by "; ")
## deletions, inversions and tandem duplications have only start and end, so return just one overlapping region
## returned regions include the given tolerance
if(type == "insertion" | type == "translocation"){
overlap = paste(paste(seqnames(query[[1]])[hit1], ":", start(query[[1]])[hit1]+tol, "-", end(query[[1]])[hit1]-tol, ", ", seqnames(query[[2]])[hit2], ":", start(query[[2]])[hit2]+tol, "-", end(query[[2]])[hit2]-tol, sep=""), collapse=", ")
}else{
overlap = paste(paste(seqnames(query[[1]])[hit1], ":", start(query[[1]])[hit1]+tol, "-", end(query[[2]])[hit2]-tol, sep=""), collapse=", ")
}
numOverlaps = length(hit1)
bpSeqAlnScoreA = bpSeqAlnScoreB = NA
if(!any(is.na(bpSeqA[[2]]))){
## align all overlaps and report the one with the maximum overlap
bpSeqAlnScoreA = vector()
for(h in hit1){
bpSeqAlnScoreA = c(bpSeqAlnScoreA, pairwiseAlignment(bpSeqA[[1]], bpSeqA[[2]][h], type="local", substitutionMatrix=substitutionMatrix, gapOpening=0, gapExtension=0, scoreOnly=TRUE))
}
bpSeqAlnScoreA = max(bpSeqAlnScoreA)
bpSeqAlnScoreA = round((bpSeqAlnScoreA / nchar(bpSeqA[[1]])) * 100)
}
if(!any(is.na(bpSeqB[[2]]))){
bpSeqAlnScoreB = vector()
for(h in hit2){
bpSeqAlnScoreB = c(bpSeqAlnScoreB, pairwiseAlignment(bpSeqB[[1]], bpSeqB[[2]][h], type="local", substitutionMatrix=substitutionMatrix, gapOpening=0, gapExtension=0, scoreOnly=TRUE))
}
bpSeqAlnScoreB = max(bpSeqAlnScoreB)
bpSeqAlnScoreB = round((bpSeqAlnScoreB / nchar(bpSeqB[[1]])) * 100)
}
return (list(overlap, bpSeqAlnScoreA, bpSeqAlnScoreB, numOverlaps))
}
return (NULL)
}
.readRepeatMaskerOutput <- function(file, save=TRUE){
t = read.table(file, skip=2, fill=TRUE, stringsAsFactors=FALSE, colClasses=c("numeric","numeric","numeric","numeric","character","numeric","numeric","character","character","character","character","character","character","character","numeric"))
t = t[t[, 5] %in% paste("chr", c(1:22,"X","Y"), sep=""), ]
t = t[t[, 11] %in% c("LINE/L1","LINE/L2","SINE/Alu","SINE/MIR"), ]
t[, 11] = gsub("LINE/","", t[, 11])
t[, 11] = gsub("SINE/","", t[, 11])
repeats = GRanges(IRanges(t[, 6], t[, 7]), seqnames=t[, 5], type=t[, 11])
linesL1 = repeats[repeats$type == "L1"]
linesL2 = repeats[repeats$type == "L2"]
sinesAlu = repeats[repeats$type == "Alu"]
sinesMIR = repeats[repeats$type == "MIR"]
## load previously saved segmental duplications to avoid import from UCSC browser
if(file.exists(file.path(path.package("RSVSim"), "data", "segmentalDuplications.RData"))){
data("segmentalDuplications", package="RSVSim", envir=environment())
}else{
require(rtracklayer)
segDups = .loadFromUCSC_SegDups()
}
trs = .loadFromBSGenome_TandemRepeats()
repeats = list(linesL1, linesL2, sinesAlu, sinesMIR, segDups, trs)
if(save == TRUE){
save(repeats, file=file.path(path.package("RSVSim"), "data", "repeats_hg19.RData"), compress="xz")
}
return(repeats)
}
## Loading the rmsk-track from UCSC may take up to 40 Minutes
.loadFromUCSC_RepeatMasks <- function(save=TRUE, verbose){
## from UCSV
require(rtracklayer)
chrs = paste("chr", c(1), sep="")
mySession = browserSession("UCSC")
genome(mySession) = "hg19"
rmskTrack = ucscTableQuery(mySession, track="rmsk")
chrs = paste("chr", c(1:22,"X","Y"), sep="")
repeats = GRanges()
if(verbose==TRUE) pb = txtProgressBar(min = 0, max = length(chrs), style = 3)
for(i in 1:length(chrs)){
c = chrs[i]
rmskTrackChr = rmskTrack
range(rmskTrackChr) = range(rmskTrackChr)[seqnames(range(rmskTrackChr)) == c]
repeats_df = getTable(rmskTrackChr)
repeats = c(repeats, GRanges(IRanges(repeats_df$genoStart, repeats_df$genoEnd), seqnames=factor(repeats_df$genoName, levels=chrs), type=as.character(repeats_df$repFamily)))
if(verbose==TRUE) setTxtProgressBar(pb, i)
}
if(verbose==TRUE) close(pb)
linesL1 = repeats[repeats$type == "L1"]
linesL2 = repeats[repeats$type == "L2"]
sinesAlu = repeats[repeats$type == "Alu"]
sinesMIR = repeats[repeats$type == "MIR"]
## load previously saved segmental duplications to avoid import from UCSC browser
if(file.exists(file.path(path.package("RSVSim"), "data", "segmentalDuplications.RData"))){
data("segmentalDuplications", package="RSVSim", envir=environment())
}else{
segDups = .loadFromUCSC_SegDups()
}
trs = .loadFromBSGenome_TandemRepeats()
repeats = list(linesL1, linesL2, sinesAlu, sinesMIR, segDups, trs)
if(save == TRUE){
save(repeats, file=file.path(path.package("RSVSim"), "data", "repeats_hg19.RData"), compress="xz")
}
return(repeats)
}
.loadFromUCSC_SegDups <- function(){
chrs = paste("chr", c(1:22,"X","Y"), sep="")
mySession = browserSession("UCSC")
genome(mySession) = "hg19"
segDups = getTable(ucscTableQuery(mySession, track="genomicSuperDups"))
segDups = segDups[segDups$chrom %in% chrs & segDups$otherChrom %in% chrs, ]
segDups = c(
GRanges(IRanges(segDups$chromStart, segDups$chromEnd), seqnames=as.character(segDups$chrom)),
GRanges(IRanges(segDups$otherStart, segDups$otherEnd), seqnames=as.character(segDups$otherChrom))
)
segDups$type = "SD"
return(segDups)
}
.loadFromBSGenome_TandemRepeats <- function(){
## this function requires BSgenome.Hsapiens.UCSC.hg19.masked to be loaded
require(BSgenome.Hsapiens.UCSC.hg19.masked)
Hsapiens_masked = BSgenome.Hsapiens.UCSC.hg19.masked
chrs = paste("chr", c(1:22,"X","Y"), sep="")
tr = GRanges()
seqlevels(tr) = chrs
for(c in chrs){
t = as(masks(Hsapiens_masked[[c]])["TRF"], "data.frame")
t = GRanges(IRanges(t$start, t$end), seqnames=c)
seqlevels(t) = chrs
tr = c(tr, t)
}
tr$type = "TR"
return(tr)
}
##########################################################################################################
## Methods for internal use only
##########################################################################################################
.getHG19 <- function(chrs){
## use library BSgenome.Hsapiens.UCSC.hg19 as default genome
require(BSgenome.Hsapiens.UCSC.hg19)
require(BSgenome.Hsapiens.UCSC.hg19.masked)
Hsapiens_masked = BSgenome.Hsapiens.UCSC.hg19.masked
if(any(is.na(chrs))){
chrs = names(Hsapiens)[1:24]
}
genome = DNAStringSet()
gaps = data.frame()
for(c in chrs){
genome = append(genome, DNAStringSet(DNAString(Hsapiens[[c]])))
g = as(masks(Hsapiens_masked[[c]])["AGAPS"], "data.frame")
g$seqnames = c
gaps = rbind(gaps, g)
}
names(genome) = chrs
gaps = GRanges(IRanges(gaps$start, gaps$end), seqnames=gaps$seqnames)
return(list(genome, gaps))
}
.getDummyDataframe <- function(){
return(data.frame(seqnames=0,start=0,end=0,mechanism="", bpRegion="", stringsAsFactors=FALSE)[-1, ])
}
## subtract interval list from other interval list (both GRanges objects)
## e.g. subtract gaps from genome ranges
.subtractIntervals <- function(subject, subtrahend){
# diff = setdiff(disjoin(c(subject,subtrahend)), subtrahend)
diff = setdiff(subject, subtrahend)
seqlevels(diff) = unique(as.character(seqnames(diff)))
return(diff)
}
subject = GRanges(IRanges(c(1,11,21),c(10,20,30)), seqnames=c("A","B","C"), type=c("t1","t2","t3"))
names(subject) = c("t1","t2")
subtrahend = GRanges(IRanges(c(4,6),c(14,16)), seqnames=c("A","B"), type=c("t4","t5"))
names(subtrahend) = c("t3","t4")
## These functions are only for internal purposes
.testSVSim <- function(){
runs = 10
for(i in 1:runs){
message("+++++++++++++++ Test run ", i, " ++++++++++++++++++++++++++++++")
size1 = 20000000
size2 = 15000000
size3 = 10000000
size4 = 5000000
size5 = 1000000
size6 = 500000
genome = DNAStringSet(c(
paste(sample(c("A","G","T","C"), size1, replace=TRUE), collapse=""),
paste(sample(c("A","G","T","C"), size2, replace=TRUE), collapse=""),
paste(sample(c("A","G","T","C"), size3, replace=TRUE), collapse=""),
paste(sample(c("A","G","T","C"), size4, replace=TRUE), collapse=""),
paste(sample(c("A","G","T","C"), size5, replace=TRUE), collapse=""),
paste(sample(c("A","G","T","C"), size6, replace=TRUE), collapse="")
))
names(genome) = c("chr1","chr2","chr3","chr4","chr5","chr6")
dels = 100
ins = 100
invs = 100
dups = 100
trans = 5
sizeDels = sample(1000:5000, dels, replace=TRUE)
sizeIns = sample(1000:5000, ins, replace=TRUE)
sizeInvs = sample(1000:5000, invs, replace=TRUE)
sizeDups = sample(1000:5000, dups, replace=TRUE)
bpSeqSize = 300
sim = simulateSV(output=NA, genome=genome, dels=dels, ins=ins, invs=invs, dups=dups, trans=trans, sizeDels=sizeDels, sizeIns=sizeIns, sizeInvs=sizeInvs, sizeDups=sizeDups, maxDups=10, bpSeqSize=bpSeqSize, random=TRUE, repeatBias=FALSE, percSNPs=0, indelProb=0)
## sim2 is for testing the non-random implementation of predefined sv regions
regionsDels = GRanges(IRanges(metadata(sim)$deletions$Start, metadata(sim)$deletions$End), seqnames=metadata(sim)$deletions$Chr)
regionsIns = GRanges(IRanges(metadata(sim)$insertions$StartA, metadata(sim)$insertions$EndA), seqnames=metadata(sim)$insertions$ChrA, chrB=metadata(sim)$insertions$ChrB, startB=metadata(sim)$insertions$StartB, endB=metadata(sim)$insertions$EndB)
regionsInvs = GRanges(IRanges(metadata(sim)$inversions$Start, metadata(sim)$inversions$End), seqnames=metadata(sim)$inversions$Chr)
regionsDups = GRanges(IRanges(metadata(sim)$tandemDuplications$Start, metadata(sim)$tandemDuplications$End), seqnames=metadata(sim)$tandemDuplications$Chr)
regionsTrans = GRanges(IRanges(metadata(sim)$translocations$StartA, metadata(sim)$translocations$EndA), seqnames=metadata(sim)$translocations$ChrA, chrB=metadata(sim)$translocations$ChrB, startB=metadata(sim)$translocations$StartB, endB=metadata(sim)$translocations$EndB)
sim2 = simulateSV(output=NA, genome=genome, dels=dels, ins=ins, invs=invs, dups=dups, trans=trans, sizeDels=sizeDels, sizeIns=sizeIns, sizeInvs=sizeInvs, sizeDups=sizeDups, regionsDels=regionsDels, regionsIns=regionsIns, regionsInvs=regionsInvs, regionsDups=regionsDups, regionsTrans=regionsTrans, maxDups=10, bpSeqSize=bpSeqSize, random=FALSE, repeatBias=FALSE, percSNPs=0, indelProb=0)
sim = sim2
bpSeqSize = bpSeqSize / 2
maxMismatch = 0
for(type in c("deletions","insertions","inversions","tandemDuplications","translocations")){
sv = metadata(sim)[[type]]
## Deletions ################################
if(type == "deletions"){
iscorrect = c()
for(i in 1:nrow(sv)){
seq = DNAString(sv$BpSeq[i])
aln = matchPattern(subseq(seq, 1, bpSeqSize), genome[[as.character(sv$Chr[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == (sv$Start[i] - bpSeqSize))
aln = matchPattern(subseq(seq, bpSeqSize+1, bpSeqSize*2), genome[[as.character(sv$Chr[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == (sv$End[i] + bpSeqSize))
iscorrect = c(iscorrect, s & e)
}
message(type, ": ", round(sum(iscorrect)/nrow(sv), digits=2)*100, " % correct ")
if(any(!iscorrect)){
message(type, paste(sv$Type[!iscorrect], collapse=","), " are not correct")
}
}
## Inversions ################################
if(type == "inversions"){
iscorrect = c()
for(i in 1:nrow(sv)){
## 5' breakpoint sequence
seq = DNAString(sv$BpSeq_5prime[i])
aln = matchPattern(subseq(seq, 1, bpSeqSize), genome[[as.character(sv$Chr[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == (sv$Start[i] - bpSeqSize))
aln = matchPattern(reverseComplement(subseq(seq, bpSeqSize+1, bpSeqSize*2)), genome[[as.character(sv$Chr[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == sv$End[i])
iscorrect = c(iscorrect, s & e)
## 3' breakpoint sequence
seq = DNAString(sv$BpSeq_3prime[i])
aln = matchPattern(reverseComplement(subseq(seq, 1, bpSeqSize)), genome[[as.character(sv$Chr[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == sv$Start[i])
aln = matchPattern(subseq(seq, bpSeqSize+1, bpSeqSize*2), genome[[as.character(sv$Chr[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == (sv$End[i]+ bpSeqSize))
iscorrect = c(iscorrect, s & e)
}
message(type, ": ", round(sum(iscorrect)/(nrow(sv)*2), digits=2)*100, " % correct ")
if(any(!iscorrect)){
message(type, paste(sv$Type[!iscorrect], collapse=","), " are not correct")
}
}
## Insertions ################################
if(type == "insertions"){
iscorrect = c()
for(i in 1:nrow(sv)){
## breakpoint sequence A (deleted segment)
seq = DNAString(sv$BpSeqA[i])
aln = matchPattern(subseq(seq, 1, bpSeqSize), genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == (sv$StartA[i] - bpSeqSize))
aln = matchPattern(subseq(seq, bpSeqSize+1, bpSeqSize*2), genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == (sv$EndA[i] + bpSeqSize))
iscorrect = c(iscorrect, s & e)
## breakpoint sequence B 5'
seq = DNAString(sv$BpSeqB_5prime[i])
aln = matchPattern(subseq(seq, 1, bpSeqSize), genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == (sv$StartB[i] - bpSeqSize))
aln = matchPattern(subseq(seq, bpSeqSize+1, bpSeqSize*2), genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (start(aln) == sv$StartA[i])
iscorrect = c(iscorrect, s & e)
## breakpoint sequence B 3'
seq = DNAString(sv$BpSeqB_3prime[i])
aln = matchPattern(subseq(seq, 1, bpSeqSize), genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (end(aln) == sv$EndA[i])
aln = matchPattern(subseq(seq, bpSeqSize+1, bpSeqSize*2), genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (start(aln) == sv$StartB[i])
iscorrect = c(iscorrect, s & e)
}
message(type, ": ", round(sum(iscorrect)/(nrow(sv)*3), digits=2)*100, " % correct ")
if(any(!iscorrect)){
message(type, paste(sv$Type[!iscorrect], collapse=","), " are not correct")
}
}
## Tandem duplications ################################
if(type == "tandemDuplications"){
iscorrect = c()
for(i in 1:nrow(sv)){
seq = DNAString(sv$BpSeq[i])
aln = matchPattern(subseq(seq, 1, bpSeqSize), genome[[as.character(sv$Chr[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (end(aln) == sv$End[i])
aln = matchPattern(subseq(seq, bpSeqSize+1, bpSeqSize*2), genome[[as.character(sv$Chr[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (start(aln) == sv$Start[i])
## also test the number of duplication
aln = matchPattern(seq, sim[[as.character(sv$Chr[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
d = ((length(aln)+1) == sv$Duplications[i])
iscorrect = c(iscorrect, s & e & d)
}
message(type, ": ", round(sum(iscorrect)/nrow(sv), digits=2)*100, " % correct ")
if(any(!iscorrect)){
message(type, paste(sv$Type[!iscorrect], collapse=","), " are not correct")
}
}
## Translocations ################################
if(type == "translocations"){
iscorrect = c()
for(i in 1:nrow(sv)){
## breakpoint sequence A
seq = DNAString(sv$BpSeqA[i])
## case xxx... <-> ...xxx
if(sv$StartA[i] == 1 & sv$StartB[i] != 1){
seq1 = reverseComplement(subseq(seq, 1, bpSeqSize))
aln = matchPattern(seq1, genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == sv$StartB[i])
seq2 = subseq(seq, bpSeqSize+1, bpSeqSize*2)
aln = matchPattern(seq2, genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == sv$EndA[i] + bpSeqSize)
}
## case ...xxx <-> xxx...
if(sv$StartA[i] != 1 & sv$StartB[i] == 1){
seq1 = subseq(seq, 1, bpSeqSize)
aln = matchPattern(seq1, genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == sv$StartA[i] - bpSeqSize)
seq2 = reverseComplement(subseq(seq, bpSeqSize+1, bpSeqSize*2))
aln = matchPattern(seq2, genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == sv$EndB[i])
}
## case xxx... <-> xxx...
if(sv$StartA[i] == 1 & sv$StartB[i] == 1){
seq1 = subseq(seq, 1, bpSeqSize)
aln = matchPattern(seq1, genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (end(aln) == sv$EndB[i])
seq2 = subseq(seq, bpSeqSize+1, bpSeqSize*2)
aln = matchPattern(seq2, genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == (sv$EndA[i] + bpSeqSize))
}
## case ...xxx <-> ...xxx
if(sv$StartA[i] != 1 & sv$StartB[i] != 1){
seq1 = subseq(seq, 1, bpSeqSize)
aln = matchPattern(seq1, genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == sv$StartA[i] - bpSeqSize)
seq2 = subseq(seq, bpSeqSize+1, bpSeqSize*2)
aln = matchPattern(seq2, genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (start(aln) == sv$StartB[i])
}
iscorrect = c(iscorrect, s & e)
## breakpoint sequence B
seq = DNAString(sv$BpSeqB[i])
if(sv$Balanced[i] == TRUE){
## case xxx... <-> ...xxx
if(sv$StartA[i] == 1 & sv$StartB[i] != 1){
seq1 = subseq(seq, 1, bpSeqSize)
aln = matchPattern(seq1, genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == sv$StartB[i] - bpSeqSize)
seq2 = reverseComplement(subseq(seq, bpSeqSize+1, bpSeqSize*2))
aln = matchPattern(seq2, genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == sv$EndA[i])
}
## case ...xxx <-> xxx...
if(sv$StartA[i] != 1 & sv$StartB[i] == 1){
seq1 = reverseComplement(subseq(seq, 1, bpSeqSize))
aln = matchPattern(seq1, genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == sv$StartA[i])
seq2 = subseq(seq, bpSeqSize+1, bpSeqSize*2)
aln = matchPattern(seq2, genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == sv$EndB[i] + bpSeqSize)
}
## case xxx... <-> xxx...
if(sv$StartA[i] == 1 & sv$StartB[i] == 1){
seq1 = subseq(seq, 1, bpSeqSize)
aln = matchPattern(seq1, genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (end(aln) == sv$EndA[i])
seq2 = subseq(seq, bpSeqSize+1, bpSeqSize*2)
aln = matchPattern(seq2, genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == (sv$EndB[i] + bpSeqSize))
}
## case ...xxx <-> ...xxx
if(sv$StartA[i] != 1 & sv$StartB[i] != 1){
seq1 = subseq(seq, 1, bpSeqSize)
aln = matchPattern(seq1, genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == sv$StartB[i] - bpSeqSize)
seq2 = subseq(seq, bpSeqSize+1, bpSeqSize*2)
aln = matchPattern(seq2, genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (start(aln) == sv$StartA[i])
}
iscorrect = c(iscorrect, s & e)
}else{
seq = DNAString(sv$BpSeqB[i])
aln = matchPattern(seq, genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == (sv$StartB[i] - bpSeqSize)) | (end(aln) == (sv$EndB[i] + bpSeqSize))
iscorrect = c(iscorrect, s)
}
}
message(type, ": ", round(sum(iscorrect)/(nrow(sv)*2), digits=2)*100, " % correct ")
if(any(!iscorrect)){
message(type, paste(sv$Type[!iscorrect], collapse=","), " are not correct")
}
}
}
}
}
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Defines functions .testSVSim .subtractIntervals .getDummyDataframe .getHG19 .loadFromBSGenome_TandemRepeats .loadFromUCSC_SegDups .loadFromUCSC_RepeatMasks .readRepeatMaskerOutput .getOverlap .compareSV .getSVSizes
setMethod("estimateSVSizes",
signature(n="numeric", svSizes="missing", default="character"),
function(n, svSizes, minSize, maxSize, default, hist){
if(!(default %in% c("deletions", "insertions", "inversions", "tandemDuplications"))){
stop("Invalid argument: No default values for SV type ", default)
}
## Default shape parameters were estimated from DGV release 2012-03-29
## Only studies with "method=sequencing" and size between 500bp and 10kb were selected (for insertions the extreme peak between 6000bp and 6200bp has been removed)
## SVs left: 1129 Deletions, 490 Insertions, 202 Inversions, 145 Tandem Duplications
if(default == "deletions"){
shape1=0.3692374
shape2=2.689951
}
if(default == "insertions"){
shape1=0.7106429
shape2=2.274061
}
if(default == "inversions"){
shape1=0.5786958
shape2=1.83066
}
if(default == "tandemDuplications"){
shape1=0.4084596
shape2=1.998082
}
if(any(is.na(c(minSize, maxSize)))){
return(.getSVSizes(n=n, shape1=shape1, shape2=shape2, min=500, max=10000, hist=hist))
}else{
return(.getSVSizes(n=n, shape1=shape1, shape2=shape2, min=minSize, max=maxSize, hist=hist))
}
})
setMethod("estimateSVSizes",
signature(n="numeric", svSizes="missing", default="missing"),
function(n, svSizes, minSize, maxSize, default, hist){
stop("Missing argument(s): Please give either a set of SVs or choose a set of default values.")
})
setMethod("estimateSVSizes",
signature(n="numeric", svSizes="numeric", default="missing"),
function(n, svSizes, minSize, maxSize, default, hist){
require(MASS)
## calculate the two shape parameters from given set of SVs
min = min(svSizes)
max = max(svSizes)
svSizes = (svSizes-min)/(max-min+1)
## make sure values are >0 and <1
svSizes[svSizes == 0] = svSizes[svSizes == 0] + 1e-5
svSizes[svSizes == 1] = svSizes[svSizes == 1] - 1e-5
# m = mean(svSizes)
# m = (m-min)/(max-min)
# v = var(svSizes)
# v = v/(max-min)^2
## shape parameters for beta distribution
# shape1 = m*(((m*(1-m))/v)-1)
# shape2 = (1-m)*(((m*(1-m))/v)-1)
beta = suppressWarnings(fitdistr(svSizes, "beta", start=list(shape1=0.1, shape2=0.1)))
shape1 = beta$estimate[1]
shape2 = beta$estimate[2]
if(any(c(is.na(minSize), is.na(maxSize)))){
return(.getSVSizes(n=n, shape1=shape1, shape2=shape2, min=min, max=max, hist=hist))
}else{
return(.getSVSizes(n=n, shape1=shape1, shape2=shape2, min=minSize, max=maxSize, hist=hist))
}
})
.getSVSizes <- function(n, shape1, shape2, min, max, hist){
simSizes = rbeta(n, shape1=shape1, shape2=shape2)
simSizes = round((simSizes*(max-min+1))+min)
if(hist == TRUE){
hist(simSizes)
}
return(simSizes)
}
setMethod("compareSV",
signature("data.frame", "data.frame"),
function(querySVs, simSVs, tol){
simSVs_overlap = .compareSV(querySVs, simSVs, tol)
return(simSVs_overlap)
})
setMethod("compareSV",
signature("character", "data.frame"),
function(querySVs, simSVs, tol){
querySVs= read.table(querySVs, sep="\t", header=FALSE, stringsAsFactors=FALSE, fill=TRUE)
simSVs_overlap = .compareSV(querySVs, simSVs, tol)
return(simSVs_overlap)
})
setMethod("compareSV",
signature("character", "character"),
function(querySVs, simSVs, tol){
simSVs = read.table(simSVs, fill=TRUE, header=TRUE)
querySVs= read.table(querySVs, sep="\t", header=FALSE, stringsAsFactors=FALSE, fill=TRUE)
simSVs_overlap = .compareSV(querySVs, simSVs, tol)
return(simSVs_overlap)
})
## deletions: (1) BED with colums chr,start,end(,bpSeq) or (2) BEDPE with colums chr,start1,end1,chr,start2,end2(,bpSeq)
## insertions: BEDPE with columns chrA,startA,endA, chrB,startB,endB(, bpSeq); two rows for one SV (5' and 3' breakpoint respectively)
## inversions: (1) BED with colums chr,start,end(,bpSeq1, bpSeq2) or (2) BEDPE with colums chr,start1,end1,chr,start2,end2(,bpSeq1, bpSeq2)
## tandem duplications: (1) BED with colums chr,start,end or (2) BEDPE with colums chr,start1,end1,chr,start2,end2
## translocations: BEDPE with columns chrA,startA,endA, chrB,startB,endB, (bpSeq1, bpSeq2)
.compareSV <- function(querySVs, simSVs, tol){
## get the type of SV by checking the column names in simSVs
type = NA
if(all(c("Name", "Chr", "Start", "End", "Size", "BpSeq") %in% colnames(simSVs))){
type = "deletion"
}
if(all(c("Name", "Chr", "Start", "End", "Size", "BpSeq_5prime", "BpSeq_3prime") %in% colnames(simSVs))){
type = "inversion"
}
if(all(c("Name", "ChrA", "StartA", "EndA", "ChrB", "StartB", "EndB", "Size", "Copied", "BpSeqA", "BpSeqB_5prime", "BpSeqB_3prime") %in% colnames(simSVs))){
type = "insertion"
}
if(all(c("Name", "Chr", "Start", "End", "Size", "Duplications", "BpSeq") %in% colnames(simSVs))){
type = "tandemDuplication"
}
if(all(c("Name", "ChrA", "StartA", "EndA", "SizeA", "ChrB", "StartB", "EndB", "SizeB", "Balanced", "BpSeqA", "BpSeqB") %in% colnames(simSVs))){
type = "translocation"
}
if(is.na(type)){
stop("Invalid input: Format of the second set of SVs differs from the output format of the simulator.")
}
## load user-supplied set of svs (BED- or BEDPE-file)
querySVs_Bp1 = querySVs_Bp1 = NULL
## split BED input into appropriate GRanges objects, which depends on the number of given columns (BED or BEDPE, with or without bpSeq)
## give every SV an id to remember which breakpoints belong together after GRanges sorted the coordinates
## inversions
if(ncol(querySVs) == 8){
querySVs_Bp1 = GRanges(IRanges(querySVs[, 2], querySVs[, 3]), seqnames=querySVs[, 1], bpSeq1=querySVs[, 7], bpSeq2=querySVs[, 8], id=1:nrow(querySVs))
querySVs_Bp2 = GRanges(IRanges(querySVs[, 5], querySVs[, 6]), seqnames=querySVs[, 4], bpSeq1=querySVs[, 7], bpSeq2=querySVs[, 8], id=1:nrow(querySVs))
}
## translocations, insertions or deletions
if(ncol(querySVs) == 7){
querySVs_Bp1 = GRanges(IRanges(querySVs[, 2], querySVs[, 3]), seqnames=querySVs[, 1], bpSeq=querySVs[, 7], id=1:nrow(querySVs))
querySVs_Bp2 = GRanges(IRanges(querySVs[, 5], querySVs[, 6]), seqnames=querySVs[, 4], bpSeq=querySVs[, 7], id=1:nrow(querySVs))
}
## translocations, inversions, insertions or deletions (no bpSeq)
if(ncol(querySVs) == 6){
querySVs_Bp1 = GRanges(IRanges(querySVs[, 2], querySVs[, 3]), seqnames=querySVs[, 1], bpSeq=NA, bpSeq2=NA, id=1:nrow(querySVs))
querySVs_Bp2 = GRanges(IRanges(querySVs[, 5], querySVs[, 6]), seqnames=querySVs[, 4], bpSeq=NA, bpSeq2=NA, id=1:nrow(querySVs))
}
## inversions
if(ncol(querySVs) == 5){
querySVs_Bp1 = GRanges(IRanges(querySVs[, 2], querySVs[, 2]), seqnames=querySVs[, 1], bpSeq1=querySVs[, 4], bpSeq2=querySVs[, 5], id=1:nrow(querySVs))
querySVs_Bp2 = GRanges(IRanges(querySVs[, 3], querySVs[, 3]), seqnames=querySVs[, 1], bpSeq1=querySVs[, 4], bpSeq2=querySVs[, 5], id=1:nrow(querySVs))
}
## deletions
if(ncol(querySVs) == 4){
querySVs_Bp1 = GRanges(IRanges(querySVs[, 2], querySVs[, 2]), seqnames=querySVs[, 1], bpSeq=querySVs[, 4], id=1:nrow(querySVs))
querySVs_Bp2 = GRanges(IRanges(querySVs[, 3], querySVs[, 3]), seqnames=querySVs[, 1], bpSeq=querySVs[, 4], id=1:nrow(querySVs))
}
## deletions, inversions (no bpSeq)
if(ncol(querySVs) == 3){
querySVs_Bp1 = GRanges(IRanges(querySVs[, 2], querySVs[, 2]), seqnames = querySVs[, 1], bpSeq=NA, bpSeq1=NA, bpSeq2=NA, id=1:nrow(querySVs))
querySVs_Bp2 = GRanges(IRanges(querySVs[, 3], querySVs[, 3]), seqnames = querySVs[, 1], bpSeq=NA, bpSeq1=NA, bpSeq2=NA, id=1:nrow(querySVs))
}
if(all(is.null(querySVs_Bp1), is.null(querySVs_Bp2))){
stop("Invalid SV file: Please make sure, that the SV file is in BED (chr,start,end) or BEDPE format (chr1,start1,end1,chr2,start2,end2) and contains only the breakpoint sequence(s) as additional column")
}
numOverlaps = 0
## For deletions and tandem duplications compare the 1 breakpoint and the 1 breakpoint sequence
if(type == "deletion" | type == "tandemDuplication"){
simSVs$Overlap = ""
simSVs$OverlapBpSeq = NA
for(v in 1:nrow(simSVs)){
simSV = simSVs[v, ]
## check correct start and end coordinate
chr = as.character(simSV$Chr)
simSV_Bp1 = GRanges(IRanges(simSV$Start, simSV$Start), seqnames=chr)
simSV_Bp2 = GRanges(IRanges(simSV$End, simSV$End), seqnames=chr)
overlap = .getOverlap(list(simSV_Bp1, simSV_Bp2), list(querySVs_Bp1[seqnames(querySVs_Bp1) == chr], querySVs_Bp2[seqnames(querySVs_Bp2) == chr]), list(simSV$BpSeq, querySVs_Bp1[seqnames(querySVs_Bp1) == chr]$bpSeq), list(NA, NA), tol, type)
if(!is.null(overlap)){
simSVs$Overlap[v] = overlap[[1]]
simSVs$OverlapBpSeq[v] = overlap[[2]]
numOverlaps = numOverlaps + overlap[[4]]
}
}
}
## For inversions compare the 1 breakpoint and the 2 breakpoint sequences
## seq|invseq|seq
if(type == "inversion"){
simSVs$Overlap = ""
simSVs$OverlapBpSeq_5prime = NA
simSVs$OverlapBpSeq_3prime = NA
for(v in 1:nrow(simSVs)){
simSV = simSVs[v, ]
## check correct start and end coordinate
chr = as.character(simSV$Chr)
simSV_Bp1 = GRanges(IRanges(simSV$Start, simSV$Start), seqnames=chr)
simSV_Bp2 = GRanges(IRanges(simSV$End, simSV$End), seqnames=chr)
overlap = .getOverlap(list(simSV_Bp1, simSV_Bp2), list(querySVs_Bp1[seqnames(querySVs_Bp1) == chr], querySVs_Bp2[seqnames(querySVs_Bp2) == chr]), list(simSV$BpSeq_5prime, querySVs_Bp1[seqnames(querySVs_Bp1) == chr]$bpSeq1), list(simSV$BpSeq_3prime, querySVs_Bp1[seqnames(querySVs_Bp1) == chr]$bpSeq2), tol, type)
if(!is.null(overlap)){
simSVs$Overlap[v] = overlap[[1]]
simSVs$OverlapBpSeq_5prime[v] = overlap[[2]]
simSVs$OverlapBpSeq_3prime[v] = overlap[[3]]
numOverlaps = numOverlaps + overlap[[4]]
}
}
}
## For insertions compare the 2 breakpoints and 2 breakpoint sequences
## chrB|chrA|chrB
if(type == "insertion"){
simSVs$Overlap_5prime = ""
simSVs$Overlap_3prime = ""
simSVs$OverlapBpSeq_5prime = NA
simSVs$OverlapBpSeq_3prime = NA
for(v in 1:nrow(simSVs)){
simSV = simSVs[v, ]
## Compare breakpoint at chrB|chrA (5', i.e. start)
simSV_Bp1 = GRanges(IRanges(simSV$StartB, simSV$StartB), seqnames=simSV$ChrB)
simSV_Bp2 = GRanges(IRanges(simSV$StartA, simSV$StartA), seqnames=simSV$ChrA)
chr1 = as.character(seqnames(simSV_Bp1))
chr2 = as.character(seqnames(simSV_Bp2))
querySVs_Bp12 = c(querySVs_Bp1, querySVs_Bp2)
overlap = .getOverlap(list(simSV_Bp1, simSV_Bp2), list(querySVs_Bp12[seqnames(querySVs_Bp12) == chr1], querySVs_Bp12[seqnames(querySVs_Bp12) == chr2]), list(simSV$BpSeqB_5prime, querySVs_Bp12[seqnames(querySVs_Bp12) == chr1]$bpSeq), list(NA, NA), tol, type)
if(!is.null(overlap)){
simSVs$Overlap_5prime[v] = overlap[[1]]
simSVs$OverlapBpSeq_5prime[v] = overlap[[2]]
numOverlaps = numOverlaps + overlap[[4]]
}
## Compare second breakpoint at chrA|chrB (3', i.e. end)
simSV_Bp1 = GRanges(IRanges(simSV$EndA, simSV$EndA), seqnames=simSV$ChrA)
simSV_Bp2 = GRanges(IRanges(simSV$StartB, simSV$StartB), seqnames=simSV$ChrB)
chr1 = as.character(seqnames(simSV_Bp1))
chr2 = as.character(seqnames(simSV_Bp2))
overlap = .getOverlap(list(simSV_Bp1, simSV_Bp2), list(querySVs_Bp12[seqnames(querySVs_Bp12) == chr1], querySVs_Bp12[seqnames(querySVs_Bp12) == chr2]), list(simSV$BpSeqB_3prime, querySVs_Bp12[seqnames(querySVs_Bp12) == chr1]$bpSeq), list(NA, NA), tol, type)
if(!is.null(overlap)){
simSVs$Overlap_3prime[v] = overlap[[1]]
simSVs$OverlapBpSeq_3prime[v] = overlap[[2]]
numOverlaps = numOverlaps + overlap[[4]]
}
}
}
## For translocations compare the 2 breakpoints and 1 breakpoint sequence
if(type == "translocation"){
simSVs$Overlap = ""
simSVs$OverlapBpSeq_A = NA
simSVs$OverlapBpSeq_B = NA
for(v in 1:nrow(simSVs)){
simSV = simSVs[v, ]
## Breakpoints can be either on 5' terminal or on 3' terminal
## Only check one breakpoint since the coordinates are only switched between chrB|chrA and chrA|chrB, but practically the same
if(simSV$StartB == 1){
simSV_Bp1 = GRanges(IRanges(simSV$EndB, simSV$EndB), seqnames=simSV$ChrB) ## 5', i.e. check the ends
}else{
simSV_Bp1 = GRanges(IRanges(simSV$StartB, simSV$StartB), seqnames=simSV$ChrB) ## 3', i.e. check the starts
}
if(simSV$StartA == 1){
simSV_Bp2 = GRanges(IRanges(simSV$EndA, simSV$EndA), seqnames=simSV$ChrA) ## 5', i.e. check the ends
}else{
simSV_Bp2 = GRanges(IRanges(simSV$StartA, simSV$StartA), seqnames=simSV$ChrA) ## 3', i.e. check the starts
}
chr1 = as.character(seqnames(simSV_Bp1))
chr2 = as.character(seqnames(simSV_Bp2))
querySVs_Bp12 = c(querySVs_Bp1, querySVs_Bp2)
## If translocation is not balanced, the breakpoint sequence on chrA does not need to be checked
if(simSV$Balanced == FALSE){
overlap = .getOverlap(list(simSV_Bp1, simSV_Bp2), list(querySVs_Bp12[seqnames(querySVs_Bp12) == chr1], querySVs_Bp12[seqnames(querySVs_Bp12) == chr2]), list(simSV$BpSeqB, querySVs_Bp12[seqnames(querySVs_Bp12) == chr1]$bpSeq), list(NA, NA), tol, type)
if(!is.null(overlap)){
simSVs$Overlap[v] = overlap[[1]]
simSVs$OverlapBpSeq_B[v] = overlap[[2]]
numOverlaps = numOverlaps + overlap[[4]]
}
}else{
overlap = .getOverlap(list(simSV_Bp1, simSV_Bp2), list(querySVs_Bp12[seqnames(querySVs_Bp12) == chr1], querySVs_Bp12[seqnames(querySVs_Bp12) == chr2]), list(simSV$BpSeqB, querySVs_Bp12[seqnames(querySVs_Bp12) == chr1]$bpSeq), list(simSV$BpSeqA, querySVs_Bp12[seqnames(querySVs_Bp12) == chr2]$bpSeq), tol, type)
if(!is.null(overlap)){
simSVs$Overlap[v] = overlap[[1]]
simSVs$OverlapBpSeq_B[v] = overlap[[2]]
simSVs$OverlapBpSeq_A[v] = overlap[[3]]
numOverlaps = numOverlaps + overlap[[4]]
}
}
}
}
## report sensitivity and precision
if(type == "insertion"){
tp = numOverlaps
fp = nrow(querySVs) - tp
fn = sum(simSVs$Overlap_5prime == "") + sum(simSVs$Overlap_3prime == "")
}
else{
tp = numOverlaps
fp = nrow(querySVs) - tp
fn = sum(simSVs$Overlap == "")
}
sensitivity = round((tp / (tp + fn)) * 100)
precision = round((tp / (tp + fp)) * 100)
message("Sensitivity: ", sensitivity, "%")
message("Precision: ", precision, "%")
return(simSVs)
}
.getOverlap <- function(sim, query, bpSeqA, bpSeqB, tol, type){
## simple substitution matrix, which only counts matches
substitutionMatrix = nucleotideSubstitutionMatrix(match = 1, mismatch = 0, baseOnly = FALSE, type = "DNA")
start(query[[1]]) = start(query[[1]]) - tol
end(query[[1]]) = end(query[[1]]) + tol
start(query[[2]]) = start(query[[2]]) - tol
end(query[[2]]) = end(query[[2]]) + tol
overlap1 = as.matrix(findOverlaps(sim[[1]], query[[1]]))
overlap2 = as.matrix(findOverlaps(sim[[2]], query[[2]]))
if(nrow(overlap1) > 0 & nrow(overlap2) > 0){
hit1 = overlap1[, "subjectHits"]
hit2 = overlap2[, "subjectHits"]
# if(query[[1]]$id[hit1] == query[[2]]$id[hit2]){
## for insertions and translocations, which have two breakpoints on two chromosomes, return two overlapping regions (separated by "; ")
## deletions, inversions and tandem duplications have only start and end, so return just one overlapping region
## returned regions include the given tolerance
if(type == "insertion" | type == "translocation"){
overlap = paste(paste(seqnames(query[[1]])[hit1], ":", start(query[[1]])[hit1]+tol, "-", end(query[[1]])[hit1]-tol, ", ", seqnames(query[[2]])[hit2], ":", start(query[[2]])[hit2]+tol, "-", end(query[[2]])[hit2]-tol, sep=""), collapse=", ")
}else{
overlap = paste(paste(seqnames(query[[1]])[hit1], ":", start(query[[1]])[hit1]+tol, "-", end(query[[2]])[hit2]-tol, sep=""), collapse=", ")
}
numOverlaps = length(hit1)
bpSeqAlnScoreA = bpSeqAlnScoreB = NA
if(!any(is.na(bpSeqA[[2]]))){
## align all overlaps and report the one with the maximum overlap
bpSeqAlnScoreA = vector()
for(h in hit1){
bpSeqAlnScoreA = c(bpSeqAlnScoreA, pairwiseAlignment(bpSeqA[[1]], bpSeqA[[2]][h], type="local", substitutionMatrix=substitutionMatrix, gapOpening=0, gapExtension=0, scoreOnly=TRUE))
}
bpSeqAlnScoreA = max(bpSeqAlnScoreA)
bpSeqAlnScoreA = round((bpSeqAlnScoreA / nchar(bpSeqA[[1]])) * 100)
}
if(!any(is.na(bpSeqB[[2]]))){
bpSeqAlnScoreB = vector()
for(h in hit2){
bpSeqAlnScoreB = c(bpSeqAlnScoreB, pairwiseAlignment(bpSeqB[[1]], bpSeqB[[2]][h], type="local", substitutionMatrix=substitutionMatrix, gapOpening=0, gapExtension=0, scoreOnly=TRUE))
}
bpSeqAlnScoreB = max(bpSeqAlnScoreB)
bpSeqAlnScoreB = round((bpSeqAlnScoreB / nchar(bpSeqB[[1]])) * 100)
}
return (list(overlap, bpSeqAlnScoreA, bpSeqAlnScoreB, numOverlaps))
}
return (NULL)
}
.readRepeatMaskerOutput <- function(file, save=TRUE){
t = read.table(file, skip=2, fill=TRUE, stringsAsFactors=FALSE, colClasses=c("numeric","numeric","numeric","numeric","character","numeric","numeric","character","character","character","character","character","character","character","numeric"))
t = t[t[, 5] %in% paste("chr", c(1:22,"X","Y"), sep=""), ]
t = t[t[, 11] %in% c("LINE/L1","LINE/L2","SINE/Alu","SINE/MIR"), ]
t[, 11] = gsub("LINE/","", t[, 11])
t[, 11] = gsub("SINE/","", t[, 11])
repeats = GRanges(IRanges(t[, 6], t[, 7]), seqnames=t[, 5], type=t[, 11])
linesL1 = repeats[repeats$type == "L1"]
linesL2 = repeats[repeats$type == "L2"]
sinesAlu = repeats[repeats$type == "Alu"]
sinesMIR = repeats[repeats$type == "MIR"]
## load previously saved segmental duplications to avoid import from UCSC browser
if(file.exists(file.path(path.package("RSVSim"), "data", "segmentalDuplications.RData"))){
data("segmentalDuplications", package="RSVSim", envir=environment())
}else{
require(rtracklayer)
segDups = .loadFromUCSC_SegDups()
}
trs = .loadFromBSGenome_TandemRepeats()
repeats = list(linesL1, linesL2, sinesAlu, sinesMIR, segDups, trs)
if(save == TRUE){
save(repeats, file=file.path(path.package("RSVSim"), "data", "repeats_hg19.RData"), compress="xz")
}
return(repeats)
}
## Loading the rmsk-track from UCSC may take up to 40 Minutes
.loadFromUCSC_RepeatMasks <- function(save=TRUE, verbose){
## from UCSV
require(rtracklayer)
chrs = paste("chr", c(1), sep="")
mySession = browserSession("UCSC")
genome(mySession) = "hg19"
rmskTrack = ucscTableQuery(mySession, track="rmsk")
chrs = paste("chr", c(1:22,"X","Y"), sep="")
repeats = GRanges()
if(verbose==TRUE) pb = txtProgressBar(min = 0, max = length(chrs), style = 3)
for(i in 1:length(chrs)){
c = chrs[i]
rmskTrackChr = rmskTrack
range(rmskTrackChr) = range(rmskTrackChr)[seqnames(range(rmskTrackChr)) == c]
repeats_df = getTable(rmskTrackChr)
repeats = c(repeats, GRanges(IRanges(repeats_df$genoStart, repeats_df$genoEnd), seqnames=factor(repeats_df$genoName, levels=chrs), type=as.character(repeats_df$repFamily)))
if(verbose==TRUE) setTxtProgressBar(pb, i)
}
if(verbose==TRUE) close(pb)
linesL1 = repeats[repeats$type == "L1"]
linesL2 = repeats[repeats$type == "L2"]
sinesAlu = repeats[repeats$type == "Alu"]
sinesMIR = repeats[repeats$type == "MIR"]
## load previously saved segmental duplications to avoid import from UCSC browser
if(file.exists(file.path(path.package("RSVSim"), "data", "segmentalDuplications.RData"))){
data("segmentalDuplications", package="RSVSim", envir=environment())
}else{
segDups = .loadFromUCSC_SegDups()
}
trs = .loadFromBSGenome_TandemRepeats()
repeats = list(linesL1, linesL2, sinesAlu, sinesMIR, segDups, trs)
if(save == TRUE){
save(repeats, file=file.path(path.package("RSVSim"), "data", "repeats_hg19.RData"), compress="xz")
}
return(repeats)
}
.loadFromUCSC_SegDups <- function(){
chrs = paste("chr", c(1:22,"X","Y"), sep="")
mySession = browserSession("UCSC")
genome(mySession) = "hg19"
segDups = getTable(ucscTableQuery(mySession, track="genomicSuperDups"))
segDups = segDups[segDups$chrom %in% chrs & segDups$otherChrom %in% chrs, ]
segDups = c(
GRanges(IRanges(segDups$chromStart, segDups$chromEnd), seqnames=as.character(segDups$chrom)),
GRanges(IRanges(segDups$otherStart, segDups$otherEnd), seqnames=as.character(segDups$otherChrom))
)
segDups$type = "SD"
return(segDups)
}
.loadFromBSGenome_TandemRepeats <- function(){
## this function requires BSgenome.Hsapiens.UCSC.hg19.masked to be loaded
require(BSgenome.Hsapiens.UCSC.hg19.masked)
Hsapiens_masked = BSgenome.Hsapiens.UCSC.hg19.masked
chrs = paste("chr", c(1:22,"X","Y"), sep="")
tr = GRanges()
seqlevels(tr) = chrs
for(c in chrs){
t = as(masks(Hsapiens_masked[[c]])["TRF"], "data.frame")
t = GRanges(IRanges(t$start, t$end), seqnames=c)
seqlevels(t) = chrs
tr = c(tr, t)
}
tr$type = "TR"
return(tr)
}
##########################################################################################################
## Methods for internal use only
##########################################################################################################
.getHG19 <- function(chrs){
## use library BSgenome.Hsapiens.UCSC.hg19 as default genome
require(BSgenome.Hsapiens.UCSC.hg19)
require(BSgenome.Hsapiens.UCSC.hg19.masked)
Hsapiens_masked = BSgenome.Hsapiens.UCSC.hg19.masked
if(any(is.na(chrs))){
chrs = names(Hsapiens)[1:24]
}
genome = DNAStringSet()
gaps = data.frame()
for(c in chrs){
genome = append(genome, DNAStringSet(DNAString(Hsapiens[[c]])))
g = as(masks(Hsapiens_masked[[c]])["AGAPS"], "data.frame")
g$seqnames = c
gaps = rbind(gaps, g)
}
names(genome) = chrs
gaps = GRanges(IRanges(gaps$start, gaps$end), seqnames=gaps$seqnames)
return(list(genome, gaps))
}
.getDummyDataframe <- function(){
return(data.frame(seqnames=0,start=0,end=0,mechanism="", bpRegion="", stringsAsFactors=FALSE)[-1, ])
}
## subtract interval list from other interval list (both GRanges objects)
## e.g. subtract gaps from genome ranges
.subtractIntervals <- function(subject, subtrahend){
# diff = setdiff(disjoin(c(subject,subtrahend)), subtrahend)
diff = setdiff(subject, subtrahend)
seqlevels(diff) = unique(as.character(seqnames(diff)))
return(diff)
}
subject = GRanges(IRanges(c(1,11,21),c(10,20,30)), seqnames=c("A","B","C"), type=c("t1","t2","t3"))
names(subject) = c("t1","t2")
subtrahend = GRanges(IRanges(c(4,6),c(14,16)), seqnames=c("A","B"), type=c("t4","t5"))
names(subtrahend) = c("t3","t4")
## These functions are only for internal purposes
.testSVSim <- function(){
runs = 10
for(i in 1:runs){
message("+++++++++++++++ Test run ", i, " ++++++++++++++++++++++++++++++")
size1 = 20000000
size2 = 15000000
size3 = 10000000
size4 = 5000000
size5 = 1000000
size6 = 500000
genome = DNAStringSet(c(
paste(sample(c("A","G","T","C"), size1, replace=TRUE), collapse=""),
paste(sample(c("A","G","T","C"), size2, replace=TRUE), collapse=""),
paste(sample(c("A","G","T","C"), size3, replace=TRUE), collapse=""),
paste(sample(c("A","G","T","C"), size4, replace=TRUE), collapse=""),
paste(sample(c("A","G","T","C"), size5, replace=TRUE), collapse=""),
paste(sample(c("A","G","T","C"), size6, replace=TRUE), collapse="")
))
names(genome) = c("chr1","chr2","chr3","chr4","chr5","chr6")
dels = 100
ins = 100
invs = 100
dups = 100
trans = 5
sizeDels = sample(1000:5000, dels, replace=TRUE)
sizeIns = sample(1000:5000, ins, replace=TRUE)
sizeInvs = sample(1000:5000, invs, replace=TRUE)
sizeDups = sample(1000:5000, dups, replace=TRUE)
bpSeqSize = 300
sim = simulateSV(output=NA, genome=genome, dels=dels, ins=ins, invs=invs, dups=dups, trans=trans, sizeDels=sizeDels, sizeIns=sizeIns, sizeInvs=sizeInvs, sizeDups=sizeDups, maxDups=10, bpSeqSize=bpSeqSize, random=TRUE, repeatBias=FALSE, percSNPs=0, indelProb=0)
## sim2 is for testing the non-random implementation of predefined sv regions
regionsDels = GRanges(IRanges(metadata(sim)$deletions$Start, metadata(sim)$deletions$End), seqnames=metadata(sim)$deletions$Chr)
regionsIns = GRanges(IRanges(metadata(sim)$insertions$StartA, metadata(sim)$insertions$EndA), seqnames=metadata(sim)$insertions$ChrA, chrB=metadata(sim)$insertions$ChrB, startB=metadata(sim)$insertions$StartB, endB=metadata(sim)$insertions$EndB)
regionsInvs = GRanges(IRanges(metadata(sim)$inversions$Start, metadata(sim)$inversions$End), seqnames=metadata(sim)$inversions$Chr)
regionsDups = GRanges(IRanges(metadata(sim)$tandemDuplications$Start, metadata(sim)$tandemDuplications$End), seqnames=metadata(sim)$tandemDuplications$Chr)
regionsTrans = GRanges(IRanges(metadata(sim)$translocations$StartA, metadata(sim)$translocations$EndA), seqnames=metadata(sim)$translocations$ChrA, chrB=metadata(sim)$translocations$ChrB, startB=metadata(sim)$translocations$StartB, endB=metadata(sim)$translocations$EndB)
sim2 = simulateSV(output=NA, genome=genome, dels=dels, ins=ins, invs=invs, dups=dups, trans=trans, sizeDels=sizeDels, sizeIns=sizeIns, sizeInvs=sizeInvs, sizeDups=sizeDups, regionsDels=regionsDels, regionsIns=regionsIns, regionsInvs=regionsInvs, regionsDups=regionsDups, regionsTrans=regionsTrans, maxDups=10, bpSeqSize=bpSeqSize, random=FALSE, repeatBias=FALSE, percSNPs=0, indelProb=0)
sim = sim2
bpSeqSize = bpSeqSize / 2
maxMismatch = 0
for(type in c("deletions","insertions","inversions","tandemDuplications","translocations")){
sv = metadata(sim)[[type]]
## Deletions ################################
if(type == "deletions"){
iscorrect = c()
for(i in 1:nrow(sv)){
seq = DNAString(sv$BpSeq[i])
aln = matchPattern(subseq(seq, 1, bpSeqSize), genome[[as.character(sv$Chr[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == (sv$Start[i] - bpSeqSize))
aln = matchPattern(subseq(seq, bpSeqSize+1, bpSeqSize*2), genome[[as.character(sv$Chr[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == (sv$End[i] + bpSeqSize))
iscorrect = c(iscorrect, s & e)
}
message(type, ": ", round(sum(iscorrect)/nrow(sv), digits=2)*100, " % correct ")
if(any(!iscorrect)){
message(type, paste(sv$Type[!iscorrect], collapse=","), " are not correct")
}
}
## Inversions ################################
if(type == "inversions"){
iscorrect = c()
for(i in 1:nrow(sv)){
## 5' breakpoint sequence
seq = DNAString(sv$BpSeq_5prime[i])
aln = matchPattern(subseq(seq, 1, bpSeqSize), genome[[as.character(sv$Chr[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == (sv$Start[i] - bpSeqSize))
aln = matchPattern(reverseComplement(subseq(seq, bpSeqSize+1, bpSeqSize*2)), genome[[as.character(sv$Chr[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == sv$End[i])
iscorrect = c(iscorrect, s & e)
## 3' breakpoint sequence
seq = DNAString(sv$BpSeq_3prime[i])
aln = matchPattern(reverseComplement(subseq(seq, 1, bpSeqSize)), genome[[as.character(sv$Chr[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == sv$Start[i])
aln = matchPattern(subseq(seq, bpSeqSize+1, bpSeqSize*2), genome[[as.character(sv$Chr[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == (sv$End[i]+ bpSeqSize))
iscorrect = c(iscorrect, s & e)
}
message(type, ": ", round(sum(iscorrect)/(nrow(sv)*2), digits=2)*100, " % correct ")
if(any(!iscorrect)){
message(type, paste(sv$Type[!iscorrect], collapse=","), " are not correct")
}
}
## Insertions ################################
if(type == "insertions"){
iscorrect = c()
for(i in 1:nrow(sv)){
## breakpoint sequence A (deleted segment)
seq = DNAString(sv$BpSeqA[i])
aln = matchPattern(subseq(seq, 1, bpSeqSize), genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == (sv$StartA[i] - bpSeqSize))
aln = matchPattern(subseq(seq, bpSeqSize+1, bpSeqSize*2), genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == (sv$EndA[i] + bpSeqSize))
iscorrect = c(iscorrect, s & e)
## breakpoint sequence B 5'
seq = DNAString(sv$BpSeqB_5prime[i])
aln = matchPattern(subseq(seq, 1, bpSeqSize), genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == (sv$StartB[i] - bpSeqSize))
aln = matchPattern(subseq(seq, bpSeqSize+1, bpSeqSize*2), genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (start(aln) == sv$StartA[i])
iscorrect = c(iscorrect, s & e)
## breakpoint sequence B 3'
seq = DNAString(sv$BpSeqB_3prime[i])
aln = matchPattern(subseq(seq, 1, bpSeqSize), genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (end(aln) == sv$EndA[i])
aln = matchPattern(subseq(seq, bpSeqSize+1, bpSeqSize*2), genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (start(aln) == sv$StartB[i])
iscorrect = c(iscorrect, s & e)
}
message(type, ": ", round(sum(iscorrect)/(nrow(sv)*3), digits=2)*100, " % correct ")
if(any(!iscorrect)){
message(type, paste(sv$Type[!iscorrect], collapse=","), " are not correct")
}
}
## Tandem duplications ################################
if(type == "tandemDuplications"){
iscorrect = c()
for(i in 1:nrow(sv)){
seq = DNAString(sv$BpSeq[i])
aln = matchPattern(subseq(seq, 1, bpSeqSize), genome[[as.character(sv$Chr[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (end(aln) == sv$End[i])
aln = matchPattern(subseq(seq, bpSeqSize+1, bpSeqSize*2), genome[[as.character(sv$Chr[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (start(aln) == sv$Start[i])
## also test the number of duplication
aln = matchPattern(seq, sim[[as.character(sv$Chr[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
d = ((length(aln)+1) == sv$Duplications[i])
iscorrect = c(iscorrect, s & e & d)
}
message(type, ": ", round(sum(iscorrect)/nrow(sv), digits=2)*100, " % correct ")
if(any(!iscorrect)){
message(type, paste(sv$Type[!iscorrect], collapse=","), " are not correct")
}
}
## Translocations ################################
if(type == "translocations"){
iscorrect = c()
for(i in 1:nrow(sv)){
## breakpoint sequence A
seq = DNAString(sv$BpSeqA[i])
## case xxx... <-> ...xxx
if(sv$StartA[i] == 1 & sv$StartB[i] != 1){
seq1 = reverseComplement(subseq(seq, 1, bpSeqSize))
aln = matchPattern(seq1, genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == sv$StartB[i])
seq2 = subseq(seq, bpSeqSize+1, bpSeqSize*2)
aln = matchPattern(seq2, genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == sv$EndA[i] + bpSeqSize)
}
## case ...xxx <-> xxx...
if(sv$StartA[i] != 1 & sv$StartB[i] == 1){
seq1 = subseq(seq, 1, bpSeqSize)
aln = matchPattern(seq1, genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == sv$StartA[i] - bpSeqSize)
seq2 = reverseComplement(subseq(seq, bpSeqSize+1, bpSeqSize*2))
aln = matchPattern(seq2, genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == sv$EndB[i])
}
## case xxx... <-> xxx...
if(sv$StartA[i] == 1 & sv$StartB[i] == 1){
seq1 = subseq(seq, 1, bpSeqSize)
aln = matchPattern(seq1, genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (end(aln) == sv$EndB[i])
seq2 = subseq(seq, bpSeqSize+1, bpSeqSize*2)
aln = matchPattern(seq2, genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == (sv$EndA[i] + bpSeqSize))
}
## case ...xxx <-> ...xxx
if(sv$StartA[i] != 1 & sv$StartB[i] != 1){
seq1 = subseq(seq, 1, bpSeqSize)
aln = matchPattern(seq1, genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == sv$StartA[i] - bpSeqSize)
seq2 = subseq(seq, bpSeqSize+1, bpSeqSize*2)
aln = matchPattern(seq2, genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (start(aln) == sv$StartB[i])
}
iscorrect = c(iscorrect, s & e)
## breakpoint sequence B
seq = DNAString(sv$BpSeqB[i])
if(sv$Balanced[i] == TRUE){
## case xxx... <-> ...xxx
if(sv$StartA[i] == 1 & sv$StartB[i] != 1){
seq1 = subseq(seq, 1, bpSeqSize)
aln = matchPattern(seq1, genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == sv$StartB[i] - bpSeqSize)
seq2 = reverseComplement(subseq(seq, bpSeqSize+1, bpSeqSize*2))
aln = matchPattern(seq2, genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == sv$EndA[i])
}
## case ...xxx <-> xxx...
if(sv$StartA[i] != 1 & sv$StartB[i] == 1){
seq1 = reverseComplement(subseq(seq, 1, bpSeqSize))
aln = matchPattern(seq1, genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == sv$StartA[i])
seq2 = subseq(seq, bpSeqSize+1, bpSeqSize*2)
aln = matchPattern(seq2, genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == sv$EndB[i] + bpSeqSize)
}
## case xxx... <-> xxx...
if(sv$StartA[i] == 1 & sv$StartB[i] == 1){
seq1 = subseq(seq, 1, bpSeqSize)
aln = matchPattern(seq1, genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (end(aln) == sv$EndA[i])
seq2 = subseq(seq, bpSeqSize+1, bpSeqSize*2)
aln = matchPattern(seq2, genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (end(aln) == (sv$EndB[i] + bpSeqSize))
}
## case ...xxx <-> ...xxx
if(sv$StartA[i] != 1 & sv$StartB[i] != 1){
seq1 = subseq(seq, 1, bpSeqSize)
aln = matchPattern(seq1, genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == sv$StartB[i] - bpSeqSize)
seq2 = subseq(seq, bpSeqSize+1, bpSeqSize*2)
aln = matchPattern(seq2, genome[[as.character(sv$ChrA[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
e = (start(aln) == sv$StartA[i])
}
iscorrect = c(iscorrect, s & e)
}else{
seq = DNAString(sv$BpSeqB[i])
aln = matchPattern(seq, genome[[as.character(sv$ChrB[i])]], with.indels=TRUE, max.mismatch=maxMismatch)
s = (start(aln) == (sv$StartB[i] - bpSeqSize)) | (end(aln) == (sv$EndB[i] + bpSeqSize))
iscorrect = c(iscorrect, s)
}
}
message(type, ": ", round(sum(iscorrect)/(nrow(sv)*2), digits=2)*100, " % correct ")
if(any(!iscorrect)){
message(type, paste(sv$Type[!iscorrect], collapse=","), " are not correct")
}
}
}
}
}
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