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shallowHRD_hg19_ichorCNA.R
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shallowHRD_hg19_ichorCNA.R
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##### SCRIPT : shallowHRD_hg19 #####
args = commandArgs(trailingOnly=TRUE)
path_to_ratio_file = args[1]
inputPath = normalizePath(dirname(path_to_ratio_file))
NAMEEE_intermediary1 = gsub("\\", "/", normalizePath(path_to_ratio_file), fixed = TRUE) # for window path
NAMEEE_intermediary2 = sub("*/*.bam_ratio.txt", "", NAMEEE_intermediary1)
NAMEEE = sub(".*/", "", NAMEEE_intermediary2)
output_relative_Path = args[2]
outputPath = normalizePath(output_relative_Path)
path_to_cyto = args[3]
cytoFile = normalizePath(path_to_cyto)
continue_on_error <- function() {
paste()
}
options(error=continue_on_error)
cat("======================================================== \n")
cat("Sample : ", NAMEEE, "\n")
cat("======================================================== \n")
##### Cytoband_hg19 #####
cyt_Annot<-read.csv(cytoFile,header=T,fill=T)
cyt_Annot<-cyt_Annot[,1:6]
for(k in 2:dim(cyt_Annot)[[1]]){
str1<-as.numeric(cyt_Annot[k-1,2:3])
str2<-as.numeric(cyt_Annot[k,2:3])
if(sum(abs(str1-str2))==0){cyt_Annot[k,1]<-0}
}
cyt_Annot[1:(dim(cyt_Annot)[[1]]-1),1]<-cyt_Annot[1:(dim(cyt_Annot)[[1]]-1),1]+cyt_Annot[2:dim(cyt_Annot)[[1]],1]
cyt_Annot[dim(cyt_Annot)[[1]],1]<-1
cyt_Annot<-cyt_Annot[-which(cyt_Annot[,1]==0),]
cyt_Annot[,1]<-cyt_Annot[,6]-cyt_Annot[,5]
cyt_Annot[,2]<-cyt_Annot[,2]+(cyt_Annot[,3]-1)/2
for(k in 2:dim(cyt_Annot)[[1]]){
if(cyt_Annot[k,2]==cyt_Annot[k-1,2]){cyt_Annot[k,1]<-cyt_Annot[k,6]-cyt_Annot[k-1,5];cyt_Annot[k-1,1]<-0}
}
cyt_Annot<-cyt_Annot[-which(cyt_Annot[,1]==0),]
arm_len<-cyt_Annot[,1:2]
chr_len<-arm_len
chr_len[,2]<-trunc(chr_len[,2])
for(k in 2:dim(chr_len)[[1]]){
if(chr_len[k,2]==chr_len[k-1,2]){chr_len[k,1]==chr_len[k-1,1]+chr_len[k,1]
chr_len[k-1,1]<-0
}
}
chr_len<-chr_len[-which(chr_len[,1]==0),]
chr_len<-chr_len[-dim(chr_len)[[1]],]
GG<-sum(chr_len[,1])
chr_p<-round(chr_len[,1]/GG,3)
##### LIBRARIES #####
# install.packages("ggpubr")
library("ggpubr")
library("gridExtra")
library("DescTools")
##### FUNCTIONS #####
## Function Local minima ##
localMinima <- function(x) {
y <- diff(c(.Machine$integer.max, x)) < 0L
rle(y)$lengths
y <- cumsum(rle(y)$lengths)
y <- y[seq.int(1L, length(y), 2L)]
if (x[[1]] == x[[2]]) {
y <- y[-1]
}
y
}
## Function readSegmFile ##
readSegmFile<-function(segFileName){
aa<-scan(segFileName,nlines=1,what="character",quiet = T)
k<-1
while((length(grep("#",aa))!=0)&&(grep("#",aa)==1)){
aa<-scan(segFileName,skip=k,nlines=1,what="character",quiet = T)
k<-k+1
}
tmp<-read.delim(segFileName,skip=k-1, header=T,sep="\t")
tmp<-data.matrix(tmp)
if(k==2){
results<-getInfoSegm(scan(segFileName,nlines=1,what="character",quiet = T))
homoConst<-results$homoConst
sdH<-results$sdH
p_BAF<-results$p_BAF
q_LRR<-results$q_LRR
Delta<-results$Delta
}else{homoConst<-1;sdH<-NA;p_BAF<-NA;q_LRR<-NA;Delta<-c(2,NA)}
out<-list(tmp=tmp,homoConst=homoConst,sdH=sdH,p_BAF=p_BAF,q_LRR=q_LRR,Delta=Delta)
}
## getSegmentID : gather in the same name segment of the length ##
getSegmentID<-function(THR,tmp,c_chr,c_cn,c_conf){
tmp[,c_conf]<-0;tmp[1,c_conf]<-1
for(k in 2:dim(tmp)[[1]]){
if(tmp[k,c_chr]==tmp[k-1,c_chr] & abs(tmp[k,c_cn]-tmp[k-1,c_cn])<THR){
tmp[k,c_conf]<-tmp[k-1,c_conf]
}else{tmp[k,c_conf]<-tmp[k-1,c_conf]+1}
}
out<-tmp
}
## shrinkReprTMP
shrinkReprTMP<-function(tmp,c_posS,c_posE,c_cn,c_conf){
for(k in 1:(dim(tmp)[[1]]-1)){
if(tmp[k,c_conf]==tmp[k+1,c_conf]){
tmp[k+1,c_posS]<-tmp[k,c_posS]
w<-c(tmp[k+1,c_posE]-tmp[k+1,c_posS],tmp[k,c_posE]-tmp[k,c_posS])
tmp[k+1,c_cn]<-weighted.mean(c(tmp[k+1,c_cn],tmp[k,c_cn]),w)
tmp[k,1]<-0
}
}
tt<-which(tmp[,1]==0);if(length(tt)!=0){tmp<-tmp[-tt,]}
out<-tmp
}
## Function getInfoSegm
getInfoSegm<-function(infoString){
tt<-unlist(strsplit(infoString,";"))
hh<-grep("homoConst=",tt)
if(length(hh)==1){homoConst<-as.numeric(sub("homoConst=","",tt[hh]))}else{homoConst<-1}
hh<-grep("sdH=",tt)
if(length(hh)==1){sdH<-as.numeric(sub("sdH=","",tt[hh]))}else{sdH<-NA}
hh<-grep("p=",tt)
if(length(hh)==1){p_BAF<-as.numeric(sub("p=","",tt[hh]))}else{p_BAF<-NA}
hh<-grep("q=",tt)
if(length(hh)==1){q_LRR<-as.numeric(sub("q=","",tt[hh]))}else{q_LRR<-NA}
hh<-grep("2LR=",tt)
if(length(hh)==1){Delta<-as.numeric(sub("2LR=","",tt[hh]))}else{Delta<-NA}
Delta<-c(2,Delta)
if((is.na(homoConst))||(!is.numeric(homoConst))){homoConst<-1
}else{if((homoConst<0.8)||(homoConst>1)){homoConst<-1}
}
if((is.na(sdH))||(!is.numeric(sdH))){sdH<-NA
}else{if((sdH<0.05)||(sdH>1)){sdH<-NA}
}
out<-list(homoConst=homoConst,sdH=sdH,p_BAF=p_BAF,q_LRR=q_LRR,Delta=Delta)
}
## breakSmoothToLGA
breakSmoothToLGA<-function(THR,tmp,c_ind,c_chr,c_posS,c_posE,c_cn,c_CN,c_conf){
tmp<-getSegmentID(THR=THR,tmp=tmp,c_chr=c_chr+1,c_cn=c_cn,c_conf=c_conf)
tmp<-shrinkReprTMP(tmp=tmp,c_posS=c_posS,c_posE=c_posE,c_cn=c_cn,c_conf=c_conf)
tmp[,c_ind]<-seq(1,dim(tmp)[[1]])
BreaksSmall<-0
FL<-T
while(FL){
tmp[,c_ind]<-seq(1,dim(tmp)[[1]])
kk<-which(round((tmp[,c_posE]-tmp[,c_posS])/10^6,1)<3) # segments smaller than 3Mb
if(length(kk)>0){
kk<-kk[order((tmp[kk,c_posE]-tmp[kk,c_posS])/10^6)]
for(k in 1:length(kk)){
if(kk[k]==1){
if(tmp[kk[k]+1,c_chr+1]==tmp[kk[k],c_chr+1]){
if(tmp[kk[k]+1,c_ind]!=0){
tmp[kk[k],c_ind]<-0
}
}
}
else{
if(kk[k]==dim(tmp)[[1]]){
if(tmp[kk[k]-1,c_chr+1]==tmp[kk[k],c_chr+1] & tmp[kk[k]-1,c_ind]!=0){
tmp[kk[k],c_ind]<-0}
}
else{
if(tmp[kk[k]-1,c_chr+1]==tmp[kk[k]+1,c_chr+1] & tmp[kk[k]-1,c_ind]!=0 & tmp[kk[k]+1,c_ind]!=0){tmp[kk[k],1]<-0}
if(tmp[kk[k]-1,c_chr+1]==tmp[kk[k],c_chr+1] & tmp[kk[k]+1,c_chr+1]!=tmp[kk[k],c_chr+1] & tmp[kk[k]-1,c_ind]!=0){tmp[kk[k],c_ind]<-0}
if(tmp[kk[k]+1,c_chr+1]==tmp[kk[k],c_chr+1] & tmp[kk[k]-1,c_chr+1]!=tmp[kk[k],c_chr+1] & tmp[kk[k]+1,c_ind]!=0){tmp[kk[k],c_ind]<-0}
if(tmp[kk[k]+1,c_chr+1]!=tmp[kk[k],c_chr+1] & tmp[kk[k]-1,c_chr+1]!=tmp[kk[k],c_chr+1]){tmp[kk[k],c_ind]<-0}
}
}
}
tt<-which(tmp[,c_ind]==0)
if(length(tt)>0){tmp <- tmp[-tt,];BreaksSmall<-BreaksSmall+length(tt)}
for(k in 1:(dim(tmp)[[1]]-1)){
if(round((tmp[k+1,c_posS]-tmp[k,c_posE])/10^6,1)<3){
if(tmp[k,c_chr+1]==tmp[k+1,c_chr+1] & abs(tmp[k,c_cn]-tmp[k+1,c_cn])<THR){
tmp[k+1,c_posS]<-tmp[k,c_posS]
w<-c(tmp[k+1,c_posE]-tmp[k+1,c_posS],tmp[k,c_posE]-tmp[k,c_posS])
tmp[k+1,c_cn]<-weighted.mean(c(tmp[k+1,c_cn],tmp[k,c_cn]),w)
tmp[k,c_ind]<-0
}
}
}
tt<-which(tmp[,c_ind]==0);if(length(tt)>0){tmp<-tmp[-tt,]}
}else{FL<-F}
}
tmp<-getSegmentID(THR=THR,tmp=tmp,c_chr=c_chr+1,c_cn=c_cn,c_conf=c_conf)
tmp<-shrinkReprTMP(tmp=tmp,c_posS=c_posS,c_posE=c_posE,c_cn=c_cn,c_conf=c_conf)
tmp[1,c_ind]<-BreaksSmall
out<-tmp
}
## LGA_control
LGA_control<-function(THR,lenBIN,lenMB,tmp,c_ind,c_chr,c_posS,c_posE,c_cn,c_CN,c_conf){
tmp[,c_ind]<-seq(1,dim(tmp)[[1]])
WC<-tmp[,c_CN]*0
j<-5
for(k in 2:dim(tmp)[[1]]){
if(tmp[k,c_chr+1]==tmp[k-1,c_chr+1] & round((tmp[k,c_posS]-tmp[k-1,c_posE])/10^6,1)<3){
if(round((tmp[k,c_posE]-tmp[k,c_posS])/10^6,0)>=lenMB & round((tmp[k-1,c_posE]-tmp[k-1,c_posS])/10^6,0)>=lenMB){
if(abs(tmp[k,c_cn]-tmp[k-1,c_cn])>THR*coefficient){WC[k]<-1}
}
}
}
out<-WC
}
##### Fast gathering #####
dataTable <- read.table(paste0(inputPath,"/",NAMEEE,".bam_ratio.txt"), header = TRUE)
dataTable = dataTable[,1:4]
dataTable = dataTable[which(!dataTable[,1] == "X"),]
dataTable = dataTable[which(!dataTable[,1] == "Y"),]
dataTable[,1] = as.numeric(as.character(dataTable[,1]))
dataTable = dataTable[order(dataTable[,1]),]
size_window = dataTable[2,2] - dataTable[1,2] ##### NA ou non !!!!! mean 2 by by
window_size_bench = dataTable[which(dataTable$chromosome == 1),2][1:500]
l = 500
c=1
listo=c()
for (i in (1:(l-1))){
listo = c(listo, window_size_bench[i+1] - window_size_bench[i])
}
size_window = median(listo)
L = dim(dataTable)[1]
dataTable = cbind(1:L, dataTable[,1], dataTable[,2], dataTable[,2]+size_window-1,
dataTable[,3], dataTable[,4])
dataTable = as.data.frame(dataTable)
colnames(dataTable) = c("feature", "chromosome", "start", "end", "ratio", "ratio_median")
dataTable = dataTable[which(is.na(dataTable$ratio) != TRUE),]
# dataTable = dataTable[which(!dataTable$ratio == -1),]
# dataTable = dataTable[which(!dataTable$ratio_median == -1),] ??
# No log2 transformation
# dataTable[,5] = log2(dataTable[,5])
# dataTable[,6] = log2(dataTable[,6])
ratio <- data.frame(dataTable)
short_size_window = size_window/1000
X=ratio
ratio_file_tsv = ratio # save in the moment
X=X[,-1] # feature
X=X[,-4]
## Remove spurious regions based on telomere and centromere from UCSC
X <- X[which(!(X[,1]==1 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==1 & X[,2]>=121535434 & X[,3]<=124535434)),]
X <- X[which(!(X[,1]==1 & X[,2]>=249240621 & X[,3]<=249250621)),]
X <- X[which(!(X[,1]==2 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==2 & X[,2]>=92326171 & X[,3]<=95326171)),]
X <- X[which(!(X[,1]==2 & X[,2]>=243189373 & X[,3]<=243199373)),]
X <- X[which(!(X[,1]==3 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==3 & X[,2]>=90504854 & X[,3]<=93504854)),]
X <- X[which(!(X[,1]==3 & X[,2]>=198012430 & X[,3]<=198022430)),]
X <- X[which(!(X[,1]==4 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==4 & X[,2]>=49660117 & X[,3]<=52660117)),]
X <- X[which(!(X[,1]==4 & X[,2]>=191144276 & X[,3]<=191154276)),]
X <- X[which(!(X[,1]==5 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==5 & X[,2]>=46405641 & X[,3]<=9405641)),]
X <- X[which(!(X[,1]==5 & X[,2]>=180905260 & X[,3]<=180915260)),]
X <- X[which(!(X[,1]==6 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==6 & X[,2]>=58830166 & X[,3]<=61830166)),]
X <- X[which(!(X[,1]==6 & X[,2]>=171105067 & X[,3]<=171115067)),]
X <- X[which(!(X[,1]==7 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==7 & X[,2]>=58054331 & X[,3]<=61054331)),]
X <- X[which(!(X[,1]==7 & X[,2]>=159128663 & X[,3]<=159138663)),]
X <- X[which(!(X[,1]==8 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==8 & X[,2]>=43838887 & X[,3]<=46838887)),]
X <- X[which(!(X[,1]==8 & X[,2]>=146354022 & X[,3]<=146364022)),]
X <- X[which(!(X[,1]==9 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==9 & X[,2]>=47367679 & X[,3]<=50367679)),]
X <- X[which(!(X[,1]==9 & X[,2]>=141203431 & X[,3]<=141213431)),]
X <- X[which(!(X[,1]==10 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==10 & X[,2]>=39254935 & X[,3]<=42254935)),]
X <- X[which(!(X[,1]==10 & X[,2]>=135524747 & X[,3]<=135534747)),]
X <- X[which(!(X[,1]==11 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==11 & X[,2]>=51644205 & X[,3]<=54644205)),]
X <- X[which(!(X[,1]==11 & X[,2]>=134996516 & X[,3]<=135006516)),]
X <- X[which(!(X[,1]==12 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==12 & X[,2]>=34856694 & X[,3]<=37856694)),]
X <- X[which(!(X[,1]==12 & X[,2]>=133841895 & X[,3]<=133851895)),]
X <- X[which(!(X[,1]==13 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==13 & X[,2]>=16000000 & X[,3]<=19000000)),]
X <- X[which(!(X[,1]==13 & X[,2]>=115159878 & X[,3]<=115169878)),]
X <- X[which(!(X[,1]==14 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==14 & X[,2]>=16000000 & X[,3]<=19000000)),]
X <- X[which(!(X[,1]==14 & X[,2]>=107339540 & X[,3]<=107349540)),]
X <- X[which(!(X[,1]==15 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==15 & X[,2]>=17000000 & X[,3]<=20000000)),]
X <- X[which(!(X[,1]==15 & X[,2]>=102521392 & X[,3]<=102531392)),]
X <- X[which(!(X[,1]==16 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==16 & X[,2]>=35335801 & X[,3]<=38335801)),]
X <- X[which(!(X[,1]==16 & X[,2]>=90344753 & X[,3]<=90354753)),]
X <- X[which(!(X[,1]==17 & X[,2]>=22263006 & X[,3]<=25263006)),]
X <- X[which(!(X[,1]==18 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==18 & X[,2]>=15460898 & X[,3]<=18460898)),]
X <- X[which(!(X[,1]==18 & X[,2]>=78067248 & X[,3]<=78077248)),]
X <- X[which(!(X[,1]==19 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==19 & X[,2]>=24681782 & X[,3]<=27681782)),]
X <- X[which(!(X[,1]==19 & X[,2]>=59118983 & X[,3]<=59128983)),]
X <- X[which(!(X[,1]==20 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==20 & X[,2]>=26369569 & X[,3]<=29369569)),]
X <- X[which(!(X[,1]==20 & X[,2]>=63015520 & X[,3]<=63025520)),]
X <- X[which(!(X[,1]==21 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==21 & X[,2]>=11288129 & X[,3]<=14288129)),]
X <- X[which(!(X[,1]==21 & X[,2]>=48119895 & X[,3]<=48129895)),]
X <- X[which(!(X[,1]==22 & X[,2]>=0 & X[,3]<=10000)),]
X <- X[which(!(X[,1]==22 & X[,2]>=13000000 & X[,3]<=16000000)),]
X <- X[which(!(X[,1]==22 & X[,2]>=51294566 & X[,3]<=51304566)),]
## Add chromosome arm
options(show.error.messages = FALSE)
X$chr_arm <- rep(0,nrow(X))
colnames(X) <- c("chr", "start", "end", "ratio_median", "chr_arm")
X=X[c("chr", "chr_arm", "start", "end", "ratio_median")]
X[,3]=as.numeric(as.character(X[,3]))
X[,4]=as.numeric(as.character(X[,4]))
tt <- X[,1] == 1 & X[,3] < 125000000 & X[,4] < 125000000
X[tt,2] = 1
tt <- X[,1] == 1 & X[,3] > 125000000 & X[,4] > 125000000
X[tt,2] = 2
tt <- X[,1] == 1 & X[,3] < 125000000 & X[,4] > 125000000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 125000000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 125000001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 2 & X[,3] < 93300000 & X[,4] < 93300000
X[tt,2] = 1
tt <- X[,1] == 2 & X[,3] > 93300000 & X[,4] > 93300000
X[tt,2] = 2
tt <- X[,1] == 2 & X[,3] < 93300000 & X[,4] > 93300000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 93300000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 93300001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 3 & X[,3] < 91000000 & X[,4] < 91000000
X[tt,2] = 1
tt <- X[,1] == 3 & X[,3] > 91000000 & X[,4] > 91000000
X[tt,2] = 2
tt <- X[,1] == 3 & X[,3] < 91000000 & X[,4] > 91000000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 91000000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 91000001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 4 & X[,3] < 50400000 & X[,4] < 50400000
X[tt,2] = 1
tt <- X[,1] == 4 & X[,3] > 50400000 & X[,4] > 50400000
X[tt,2] = 2
tt <- X[,1] == 4 & X[,3] < 50400000 & X[,4] > 50400000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 50400000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 50400001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 5 & X[,3] < 48400000 & X[,4] < 48400000
X[tt,2] = 1
tt <- X[,1] == 5 & X[,3] > 48400000 & X[,4] > 48400000
X[tt,2] = 2
tt <- X[,1] == 5 & X[,3] < 48400000 & X[,4] > 48400000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 48400000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 48400001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 6 & X[,3] < 61000000 & X[,4] < 61000000
X[tt,2] = 1
tt <- X[,1] == 6 & X[,3] > 61000000 & X[,4] > 61000000
X[tt,2] = 2
tt <- X[,1] == 6 & X[,3] < 61000000 & X[,4] > 61000000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 61000000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 61000001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 7 & X[,3] < 59900000 & X[,4] < 59900000
X[tt,2] = 1
tt <- X[,1] == 7 & X[,3] > 59900000 & X[,4] > 59900000
X[tt,2] = 2
tt <- X[,1] == 7 & X[,3] < 59900000 & X[,4] > 59900000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 59900000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 59900001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 8 & X[,3] < 45600000 & X[,4] < 45600000
X[tt,2] = 1
tt <- X[,1] == 8 & X[,3] > 45600000 & X[,4] > 45600000
X[tt,2] = 2
tt <- X[,1] == 8 & X[,3] < 45600000 & X[,4] > 45600000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 45600000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 45600001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 9 & X[,3] < 49000000 & X[,4] < 49000000
X[tt,2] = 1
tt <- X[,1] == 9 & X[,4] > 49000000 & X[,4] > 49000000
X[tt,2] = 2
tt <- X[,1] == 9 & X[,3] < 49000000 & X[,4] > 49000000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 49000000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 49000001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 10 & X[,3] < 40200000 & X[,4] < 40200000
X[tt,2] = 1
tt <- X[,1] == 10 & X[,3] > 40200000 & X[,4] > 40200000
X[tt,2] = 2
tt <- X[,1] == 10 & X[,3] < 40200000 & X[,4] > 40200000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 40200000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 40200001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 11 & X[,3] < 53700000 & X[,4] < 53700000
X[tt,2] = 1
tt <- X[,1] == 11 & X[,3] > 53700000 & X[,4] > 53700000
X[tt,2] = 2
tt <- X[,1] == 11 & X[,3] < 53700000 & X[,4] > 53700000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 53700000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 53700001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 12 & X[,3] < 35800000 & X[,4] < 35800000
X[tt,2] = 1
tt <- X[,1] == 12 & X[,3] > 35800000 & X[,4] > 35800000
X[tt,2] = 2
tt <- X[,1] == 12 & X[,3] < 35800000 & X[,4] > 35800000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 35800000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 35800001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 13 & X[,3] < 17900000 & X[,4] < 17900000
X[tt,2] = 1
tt <- X[,1] == 13 & X[,3] > 17900000 & X[,4] > 17900000
X[tt,2] = 2
tt <- X[,1] == 13 & X[,3] < 17900000 & X[,4] > 17900000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 17900000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 17900001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 14 & X[,3] < 17600000 & X[,4] < 17600000
X[tt,2] = 1
tt <- X[,1] == 14 & X[,3] > 17600000 & X[,4] > 17600000
X[tt,2] = 2
tt <- X[,1] == 14 & X[,3] < 17600000 & X[,4] > 17600000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 17600000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 17600001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 15 & X[,3] < 19000000 & X[,4] < 19000000
X[tt,2] = 1
tt <- X[,1] == 15 & X[,3] > 19000000 & X[,4] > 19000000
X[tt,2] = 2
tt <- X[,1] == 15 & X[,3] < 19000000 & X[,4] > 19000000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 19000000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 19000001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 16 & X[,3] < 36600000 & X[,4] < 36600000
X[tt,2] = 1
tt <- X[,1] == 16 & X[,3] > 36600000 & X[,4] > 36600000
X[tt,2] = 2
tt <- X[,1] == 16 & X[,3] < 36600000 & X[,4] > 36600000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 36600000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 36600001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 17 & X[,3] < 24000000 & X[,4] < 24000000
X[tt,2] = 1
tt <- X[,1] == 17 & X[,3] > 24000000 & X[,4] > 24000000
X[tt,2] = 2
tt <- X[,1] == 17 & X[,3] < 24000000 & X[,4] > 24000000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 24000000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 24000001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 18 & X[,3] < 17200000 & X[,4] < 17200000
X[tt,2] = 1
tt <- X[,1] == 18 & X[,3] > 17200000 & X[,4] > 17200000
X[tt,2] = 2
tt <- X[,1] == 18 & X[,3] < 17200000 & X[,4] > 17200000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 17200000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 17200001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 19 & X[,3] < 26500000 & X[,4] < 26500000
X[tt,2] = 1
tt <- X[,1] == 19 & X[,3] > 26500000 & X[,4] > 26500000
X[tt,2] = 2
tt <- X[,1] == 19 & X[,3] < 26500000 & X[,4] > 26500000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 26500000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 26500001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 20 & X[,3] < 27500000 & X[,4] < 27500000
X[tt,2] = 1
tt <- X[,1] == 20 & X[,3] > 27500000 & X[,4] > 27500000
X[tt,2] = 2
tt <- X[,1] == 20 & X[,3] < 27500000 & X[,4] > 27500000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 27500000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 27500001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 21 & X[,3] < 13200000 & X[,4] < 13200000
X[tt,2] = 1
tt <- X[,1] == 21 & X[,3] > 13200000 & X[,4] > 13200000
X[tt,2] = 2
tt <- X[,1] == 21 & X[,3] < 13200000 & X[,4] > 13200000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 13200000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 13200001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
tt <- X[,1] == 22 & X[,3] < 14700000 & X[,4] < 14700000
X[tt,2] = 1
tt <- X[,1] == 22 & X[,3] > 14700000 & X[,4] > 14700000
X[tt,2] = 2
tt <- X[,1] == 22 & X[,3] < 14700000 & X[,4] > 14700000
X[tt,2] = 1
B = X[tt,4]
X[tt,4] = 14700000
X=rbind(X[(1:which(tt==TRUE)),], c(X[tt,1], 2, 14700001, B, X[tt,5]) , X[-(1:which(tt==TRUE)),])
rownames(X) <- NULL
X[,2]<-X[,1]+(X[,2]-1)/2
tt=which(X$ratio_median==-Inf)
if (length(tt) >= 1){
X=X[-tt,]
}
X=as.matrix(X)
L = dim(X)[1]
A = matrix(0, ncol=6, nrow=L)
i=1
c=1
while (i < L){
if(X[i,2]==X[i+1,2]){
if (X[i,5]==X[i+1,5]){
n=1
while (X[i,2]==X[i+n,2] & X[i,5]==X[i+n,5] & i+n < L){
n=n+1
}
if(i+n == L){
A[c,]=c(X[i,1], X[i,2], X[i,3], X[i+n,4], X[i,5], X[i+n,4]-X[i,3]+1)
i=i+n
c=c+1
}
else{
A[c,]=c(X[i,1], X[i,2], X[i,3], X[i+n-1,4], X[i,5], X[i+n-1,4]-X[i,3]+1)
i=i+n
c=c+1
}
}
else{
A[c,]=c(X[i,1], X[i,2], X[i,3], X[i,4], X[i,5], X[i,4]-X[i,3]+1)
i=i+1
c=c+1
}
}
else{
A[c,]=c(X[i,1], X[i,2], X[i,3], X[i,4], X[i,5], X[i,4]-X[i,3]+1)
i=i+1
c=c+1
}
}
A=subset(A, A[,1] != 0)
rownames(A) <- NULL
colnames(A) <- c("chr", "chr_arm", "start", "end", "ratio_median", "size")
write.table(A, file = paste0(outputPath,"/",NAMEEE,"_ratio_median_gathered.txt"), sep = "\t", row.names = FALSE)
options(show.error.messages = TRUE)
cat("on going... \n")
##### Find Threshold #####
X = read.table(paste0(outputPath,"/",NAMEEE,"_ratio_median_gathered.txt"), sep = "\t", header = TRUE)
X = X[which(X[,6] > 2999999),]
X = X[which(X[,6] > ((quantile(X[,6])[[4]] - quantile(X[,6])[[2]])/2)),]
L=dim(X)[1]
X=data.matrix(X)
test=c()
i=1
for (i in 1:L){
v=i+1
for (y in v:L-1){
test = c(test, abs(X[i,5] - X[y,5]))}
}
minx = localMinima(density(test)$y)[2]
Threshold = density(test)$x[minx]
test = as.data.frame(test)
ploty <- ggplot(test, aes(x = test)) + geom_density() +
geom_vline(aes(xintercept = Threshold), color = "blue") +
ggtitle(paste("Density pairwise difference large segment")) + xlab("difference") +
theme(plot.title = element_text(hjust = 0.5, size = 13),
axis.text.x = element_text(size=15),
axis.title.x = element_text(size=13),
axis.text.y = element_text(size=15),
axis.title.y = element_blank(),
panel.background = element_blank())
ggsave(paste0(outputPath,"/",NAMEEE,"_THR",".jpeg"), plot = ploty, device = "jpeg", width = 20, height = 10)
##### Reading and initialisation #####
segFiles <- list.files(outputPath, pattern = paste0(NAMEEE, "_ratio_median_gathered.txt"),full.names=T)
nSample<-1
coefficient = 1.0
ColNamesTMP<-c("index", "chr","chr_arm","posStart", "posEnd", "ratio")
c_ind<-1; c_chr<-2;c_posS<-4; c_posE<-5; c_cn<-6; c_conf<-8
LLBB<-c(3,4,5,6,7,8,9,10,11) # size LGA tested
TAB<-matrix(0,nSample,20) # matrix to stock results
rownames(TAB)<-seq(1:nSample)
colnames(TAB)<-seq(1,20)
colnames(TAB)[1:6]<-c("p_BAF","q_LRR","2copyLRR","DNA_ind","All_breaks","less3Mb_breaks")
ii<-1
rownames(TAB)[ii]<-"result"
results<-readSegmFile(segFileName=segFiles[ii])
tmp<-results$tmp
tmp <- cbind(seq(1,dim(tmp)[[1]]),tmp)
colnames(tmp)[1]<-c("index")
tmp <- cbind(tmp,rep(0,nrow(tmp)))
colnames(tmp)[8]<-c("level")
graphe_I_tab = tmp
tt<-which(tmp[,c_chr+1]>23.6) # exclusion chr24 and more
if(length(tt)>0){tmp<-tmp[-tt,]}
tt<-which(tmp[,c_chr+1]==21) # exclusion short arm chr21
if(length(tt)>0){tmp<-tmp[-tt,]}
tt<-which(tmp[,c_chr+1]==22) # exclusion short arm chr22
if(length(tt)>0){tmp<-tmp[-tt,]}
graphe_II_tab = tmp
tmp[,7] = tmp[,5] - tmp[,4] + 1
tmp_3mb = tmp[which(tmp[,7] > 2999999),]
cop_tmp = tmp_3mb
THR=Threshold
if (THR > 0.45){
THR = 0.45}
if (THR < 0.025){
THR = 0.025
}
level=1
##### Gather big segment (> 3Mb) #####
options(show.error.messages = FALSE)
while (dim(cop_tmp)[1] > 1){
line_largest_index = which.max(cop_tmp[,7]) # biggest segment
largest_index = cop_tmp[line_largest_index,1] # associated index
ratio_largest = cop_tmp[line_largest_index,6] # median_ratio segment
ratio_largest = ratio_largest + 0.00001 # avoid picking same value
close_index = cop_tmp[which.min(abs(cop_tmp[,6] - ratio_largest)),1]
closest_index = c(largest_index, close_index)
## Find all value that matches the two closest index fit with THR
L=dim(cop_tmp)[1]
for (i in 1:L){
validation = 0
n = length(closest_index)
for (g in 1:n){
if (abs(cop_tmp[i,6] - cop_tmp[which((cop_tmp[,1]==closest_index[g])),6]) < THR){
validation = validation + 1}
}
if (validation == n){
closest_index = c(closest_index, cop_tmp[i,1])}}
closest_index = unique(closest_index)
## Assign level based on the index of close segment in genome
n = length(closest_index)
for (i in 1:n){
tmp_3mb[which((tmp_3mb[,1] == closest_index[i])),8] = level
cop_tmp <- cop_tmp[which(!(cop_tmp[,1]==closest_index[i])),]
}
dim(tmp_3mb)
dim(cop_tmp)
level = level + 1
}
## Gather with level
options(show.error.messages = TRUE)
L1 = dim(tmp_3mb)[1]
A = matrix(0, ncol=8, nrow=L1)
i=1
c=1
while (i<L1+1){
if (i==L1){
A[c,]=c(tmp_3mb[i,1], tmp_3mb[i,2], tmp_3mb[i,3], tmp_3mb[i,4], tmp_3mb[i,5], tmp_3mb[i,6], tmp_3mb[i,5]-tmp_3mb[i,4]+1, tmp_3mb[i,8]) # segment pas sur deux lignes, a stocker seul
i=i+1
c=c+1}
else{
if(tmp_3mb[i,3] == tmp_3mb[i+1,3]){
if (tmp_3mb[i,8] == tmp_3mb[i+1,8]){
n=1
somme=tmp_3mb[i,6]
while (tmp_3mb[i,8] == tmp_3mb[i+n,8] && tmp_3mb[i,3] == tmp_3mb[i+n,3]){
somme = somme + tmp_3mb[i+n,6]
n = n + 1
if(i+n == L1+1){
break}}
A[c,]=c(tmp_3mb[i,1], tmp_3mb[i,2], tmp_3mb[i,3], tmp_3mb[i,4], tmp_3mb[i+n-1,5], (somme)/n, tmp_3mb[i+n-1,5]- tmp_3mb[i,4]+1, tmp_3mb[i,8])
i=i+n
c=c+1}
else{
A[c,]=c(tmp_3mb[i,1], tmp_3mb[i,2], tmp_3mb[i,3], tmp_3mb[i,4], tmp_3mb[i,5], tmp_3mb[i,6], tmp_3mb[i,5]-tmp_3mb[i,4]+1, tmp_3mb[i,8]) # segment pas sur deux lignes, a stocker seul
i=i+1
c=c+1}}
else{
A[c,]=c(tmp_3mb[i,1], tmp_3mb[i,2], tmp_3mb[i,3], tmp_3mb[i,4], tmp_3mb[i,5], tmp_3mb[i,6], tmp_3mb[i,5]-tmp_3mb[i,4]+1, tmp_3mb[i,8])
i=i+1
c=c+1}
}
}
A=subset(A, A[,1] != 0)
rownames(A) <- NULL
colnames(A) <- c("index", "chr", "chr_arm", "start", "end", "ratio_median", "size", "level")
tmp_3mb=A
graphe_III_tab = tmp_3mb
##### Reput small segment & Smoothing to final segmentation #####
options(show.error.messages = FALSE)
tmp_0.1_3mb=tmp[which(tmp[,7] > 99999),]
tmp_0.1_3mb=tmp_0.1_3mb[which(tmp_0.1_3mb[,7] < 2999999),]
L_3mb=dim(tmp_3mb)[1]
l_0.1_3mb=dim(tmp_0.1_3mb)[1]
values = unique(tmp_0.1_3mb[,3][!tmp_0.1_3mb[,3] %in% tmp_3mb[,3]])
length=length(values)
for (missing_chr_arm in values){
c=1
L_3mb=dim(tmp_3mb)[1]
while(c < L_3mb+1){
if (missing_chr_arm > max(tmp_3mb[,3])){
tmp_3mb=rbind(tmp_3mb, tmp_0.1_3mb[which(tmp_0.1_3mb[,3] == missing_chr_arm),])}
else if (missing_chr_arm < tmp_3mb[c,3]){
if (c==1){
tmp_3mb=rbind(tmp_0.1_3mb[which(tmp_0.1_3mb[,3] == missing_chr_arm),] , tmp_3mb[1:L_3mb,])
c=L_3mb+1}
else{
tmp_3mb=rbind(tmp_3mb[1:(c-1),], tmp_0.1_3mb[which(tmp_0.1_3mb[,3] == missing_chr_arm),] , tmp_3mb[c:L_3mb,])}
c=L_3mb+1}
else{
c=c+1
}
}
}
for (missing_chr_arm in values){
tmp_0.1_3mb <- tmp_0.1_3mb[which(!(tmp_0.1_3mb[,3]==missing_chr_arm)),]}
L_3mb=dim(tmp_3mb)[1]
l_0.1_3mb=dim(tmp_0.1_3mb)[1]
i=1
c=1
while (i < l_0.1_3mb + 1){
c=1 # reset
L_3mb=dim(tmp_3mb)[1]
while (c < L_3mb+1){
if (tmp_0.1_3mb[i,3] == tmp_3mb[c,3]){
if (tmp_0.1_3mb[i,5] < tmp_3mb[c,4]){ ############### 1 - Before all segments chr_arm
if (c==1){
if (abs(tmp_0.1_3mb[i,6] - tmp_3mb[c,6]) > THR){ # No gathering
tmp_3mb=rbind(c(tmp_0.1_3mb[i,1],tmp_0.1_3mb[i,2],tmp_0.1_3mb[i,3],tmp_0.1_3mb[i,4],tmp_0.1_3mb[i,5],
tmp_0.1_3mb[i,6],tmp_0.1_3mb[i,5]-tmp_0.1_3mb[i,4]+1, tmp_0.1_3mb[i,8]) , tmp_3mb[c:L_3mb,])
i=i+1
c=L_3mb+1}
else{ # gathering