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R/MVP.FarmCPU.r
In rMVP: Memory-Efficient, Visualize-Enhanced, Parallel-Accelerated GWAS Tool
Defines functions
FarmCPU.Prior
FarmCPU.Remove
FarmCPU.SUB
FarmCPU.Burger
FarmCPU.LM
FarmCPU.Specify
FarmCPU.BIN
`FarmCPU.FaSTLMM.LL`
`MVP.FarmCPU`
# Licensed under the Apache License, Version 2.0 (the "License");
# you may not use this file except in compliance with the License.
# You may obtain a copy of the License at
#
# http://www.apache.org/licenses/LICENSE-2.0
#
# Unless required by applicable law or agreed to in writing, software
# distributed under the License is distributed on an "AS IS" BASIS,
# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
# See the License for the specific language governing permissions and
# limitations under the License.
#' Perform GWAS using FarmCPU method
#'
#' Date build: Febuary 24, 2013
#' Last update: May 25, 2017
#' Requirement: Y, GD, and CV should have same taxa order. GD and GM should have the same order on SNPs
#'
#' @author Xiaolei Liu and Zhiwu Zhang
#'
#' @param phe phenotype, n by t matrix, n is sample size, t is number of phenotypes
#' @param geno genotype, m by n matrix, m is marker size, n is sample size. This is Pure Genotype Data Matrix(GD). THERE IS NO COLUMN FOR TAXA.
#' @param map SNP map information, m by 3 matrix, m is marker size, the three columns are SNP_ID, Chr, and Pos
#' @param CV covariates, n by c matrix, n is sample size, c is number of covariates
#' @param P start p values for all SNPs
#' @param method.sub method used in substitution process, five options: 'penalty', 'reward', 'mean', 'median', or 'onsite'
#' @param method.sub.final method used in substitution process, five options: 'penalty', 'reward', 'mean', 'median', or 'onsite'
#' @param method.bin method for selecting the most appropriate bins, three options: 'static', 'EMMA' or 'FaST-LMM'
#' @param bin.size bin sizes for all iterations, a vector, the bin size is always from large to small
#' @param bin.selection number of selected bins in each iteration, a vector
#' @param memo a marker on output file name
#' @param Prior prior information, four columns, which are SNP_ID, Chr, Pos, P-value
#' @param ncpus number of threads used for parallele computation
#' @param maxLoop maximum number of iterations
#' @param threshold.output only the GWAS results with p-values lower than threshold.output will be output
#' @param converge a number, 0 to 1, if selected pseudo QTNs in the last and the second last iterations have a certain probality (the probability is converge) of overlap, the loop will stop
#' @param iteration.output whether to output results of all iterations
#' @param p.threshold if all p values generated in the first iteration are bigger than p.threshold, FarmCPU stops
#' @param QTN.threshold in second and later iterations, only SNPs with lower p-values than QTN.threshold have chances to be selected as pseudo QTNs
#' @param bound maximum number of SNPs selected as pseudo QTNs in each iteration
#' @param verbose whether to print detail.
#'
#' @return a m by 4 results matrix, m is marker size, the four columns are SNP_ID, Chr, Pos, and p-value
#' @export
#'
#' @examples
#' \donttest{
#' phePath <- system.file("extdata", "07_other", "mvp.phe", package = "rMVP")
#' phenotype <- read.table(phePath, header=TRUE)
#' idx <- !is.na(phenotype[, 2])
#' phenotype <- phenotype[idx, ]
#' print(dim(phenotype))
#' genoPath <- system.file("extdata", "06_mvp-impute", "mvp.imp.geno.desc", package = "rMVP")
#' genotype <- attach.big.matrix(genoPath)
#' genotype <- deepcopy(genotype, cols=idx)
#' print(dim(genotype))
#' mapPath <- system.file("extdata", "06_mvp-impute", "mvp.imp.geno.map", package = "rMVP")
#' map <- read.table(mapPath , head = TRUE)
#'
#' farmcpu <- MVP.FarmCPU(phe=phenotype,geno=genotype,map=map,maxLoop=2,method.bin="static")
#' str(farmcpu)
#' }
#'
`MVP.FarmCPU` <- function(phe, geno, map, CV=NULL, P=NULL, method.sub="reward", method.sub.final="reward",
method.bin=c("EMMA", "static", "FaST-LMM"), bin.size=c(5e5,5e6,5e7), bin.selection=seq(10,100,10),
memo="MVP.FarmCPU", Prior=NULL, ncpus=2, maxLoop=10,
threshold.output=.01, converge=1, iteration.output=FALSE, p.threshold=NA,
QTN.threshold=0.01, bound=NULL, verbose=TRUE){
#print("--------------------- Welcome to FarmCPU ----------------------------")
if(!is.big.matrix(geno)) stop("genotype should be in 'big.matrix' format.")
if(sum(is.na(phe[, 2])) != 0) stop("NAs are not allowed in phenotype.")
if(nrow(phe) != ncol(geno)) stop("number of individuals not match in phenotype and genotype.")
echo=TRUE
nm=nrow(map)
if(!is.null(CV)){
CV=as.matrix(CV)
CV.index <- apply(CV, 2, function(x) length(table(x)) > 1)
CV <- CV[, CV.index, drop=FALSE]
npc=ncol(CV)
}else{
npc=0
}
method.bin=match.arg(method.bin)
map <- as.matrix(map)
suppressWarnings(max.chr <- max(as.numeric(map[, 2]), na.rm=TRUE))
if(is.infinite(max.chr)) max.chr <- 0
map.xy.index <- which(!as.numeric(map[, 2]) %in% c(0 : max.chr))
if(length(map.xy.index) != 0){
chr.xy <- unique(map[map.xy.index, 2])
for(i in 1:length(chr.xy)){
map[map[, 2] == chr.xy[i], 2] <- max.chr + i
}
}
map[, 1] = 1:nrow(map)
suppressWarnings(map <- matrix(as.numeric(map), nrow(map)))
if(sum(is.na(map[,3]) != 0)) stop("Non-digital characters or NAs are not allowed in map for FarmCPU")
if(!is.na(p.threshold)) QTN.threshold = max(p.threshold, QTN.threshold)
name.of.trait=colnames(phe)[2]
if(!is.null(memo)) name.of.trait=paste(memo,".",name.of.trait,sep="")
theLoop=0
theConverge=0
seqQTN.save=c(0)
seqQTN.pre=c(-1)
isDone=FALSE
name.of.trait2=name.of.trait
while(!isDone) {
theLoop=theLoop+1
logging.log(paste("Current loop: ",theLoop," out of maximum of ", maxLoop, sep=""), "\n", verbose = verbose)
spacer="0"
if(theLoop>9){
spacer=""
}
if(iteration.output){
name.of.trait2=paste("Iteration_",spacer,theLoop,".",name.of.trait,sep="")
}
#Step 2a: Set prior
myPrior=FarmCPU.Prior(GM=map,P=P,Prior=Prior)
#Step 2b: Set bins
if(theLoop<=2){
myBin=FarmCPU.BIN(Y=phe[,c(1,2)],GDP=geno,GM=map,CV=CV,P=myPrior,method=method.bin,b=bin.size,s=bin.selection,theLoop=theLoop,bound=bound,ncpus=ncpus, verbose = verbose)
}else{
myBin=FarmCPU.BIN(Y=phe[,c(1,2)],GDP=geno,GM=map,CV=theCV,P=myPrior,method=method.bin,b=bin.size,s=bin.selection,theLoop=theLoop,ncpus=ncpus, verbose = verbose)
}
#Step 2c: Remove bin dependency
#Remove QTNs in LD
seqQTN=myBin$seqQTN
if(theLoop==2){
if(!is.na(p.threshold)){
if(min(myPrior,na.rm=TRUE)>p.threshold){
seqQTN=NULL
logging.log("Top snps have little effect, set seqQTN to NULL!", "\n", verbose = verbose)
}
}else{
if(min(myPrior,na.rm=TRUE)>0.01/nm){
seqQTN=NULL
logging.log("Top snps have little effect, set seqQTN to NULL!", "\n", verbose = verbose)
}
}
}
#when FarmCPU can not work, make a new QQ plot and manhatthan plot
if(theLoop==2&&is.null(seqQTN)){
#Report
P=myGLM$P[,ncol(myGLM$P)]
P[P==0] <- min(P[P!=0],na.rm=TRUE)*0.01
results = cbind(myGLM$B, myGLM$S, P)
colnames(results) = c("effect", "se", "p")
break
}#force to exit for GLM model while seqQTN=NULL and h2=0
if (!any(is.null(seqQTN.save)) && theLoop > 1) {
if (!(0 %in% seqQTN.save || -1 %in% seqQTN.save) && !is.null(seqQTN)) {
#Force previous QTNs in the model
seqQTN <- union(seqQTN,seqQTN.save)
}
}
if(theLoop!=1){
seqQTN.p=myPrior[seqQTN]
if(theLoop==2){
index.p=seqQTN.p<QTN.threshold
#if(!is.na(p.threshold)){
#index.p=seqQTN.p<p.threshold
#}
seqQTN.p=seqQTN.p[index.p]
seqQTN=seqQTN[index.p]
seqQTN.p=seqQTN.p[!is.na(seqQTN)]
seqQTN=seqQTN[!is.na(seqQTN)]
}else{
index.p=seqQTN.p<QTN.threshold
#if(!is.na(p.threshold)){
#index.p=seqQTN.p<p.threshold
#}
index.p[seqQTN%in%seqQTN.save]=TRUE
seqQTN.p=seqQTN.p[index.p]
seqQTN=seqQTN[index.p]
seqQTN.p=seqQTN.p[!is.na(seqQTN)]
seqQTN=seqQTN[!is.na(seqQTN)]
}
}
myRemove=FarmCPU.Remove(GDP=geno,GM=map,seqQTN=seqQTN,seqQTN.p=seqQTN.p,threshold=.7)
#Recoding QTNs history
seqQTN=myRemove$seqQTN
theConverge=length(intersect(seqQTN,seqQTN.save))/length(union(seqQTN,seqQTN.save))
circle=(length(union(seqQTN,seqQTN.pre))==length(intersect(seqQTN,seqQTN.pre)))
#handler of initial status
if(is.null(seqQTN.pre)){circle=FALSE
}else{
if(seqQTN.pre[1]==0) circle=FALSE
if(seqQTN.pre[1]==-1) circle=FALSE
}
logging.log("seqQTN:", "\n", verbose = verbose)
if(is.null(seqQTN)){
logging.log("NULL", "\n", verbose = verbose)
}else{
logging.log(seqQTN, "\n", verbose = verbose)
}
if(theLoop==maxLoop){
logging.log(paste("Total number of possible QTNs in the model is: ", length(seqQTN),sep=""), "\n", verbose = verbose)
}
isDone=((theLoop>=maxLoop) | (theConverge>=converge) | circle )
seqQTN.pre=seqQTN.save
seqQTN.save=seqQTN
#Step 3: Screen with bins
rm(myBin)
gc()
theCV=CV
if(!is.null(myRemove$bin)){
if(length(myRemove$seqQTN) == 1){
#myRemove$bin = as.matrix(myRemove$bin)
myRemove$bin = t(myRemove$bin)
}
theCV=cbind(CV,myRemove$bin)
}
myGLM=FarmCPU.LM(y=phe[,2],GDP=geno,w=theCV,ncpus=ncpus,npc=npc, verbose=verbose)
if(!is.null(seqQTN)){
if(ncol(myGLM$P) != (npc + length(seqQTN) + 1)) stop("wrong dimensions.")
}
#Step 4: Background unit substitution
if(!isDone){
myGLM=FarmCPU.SUB(GM=map,GLM=myGLM,QTN=map[myRemove$seqQTN, , drop=FALSE],method=method.sub)
}else{
myGLM=FarmCPU.SUB(GM=map,GLM=myGLM,QTN=map[myRemove$seqQTN, , drop=FALSE],method=method.sub.final)
}
P=myGLM$P[,ncol(myGLM$P)]
P[P==0] <- min(P[P!=0], na.rm=TRUE)*0.01
results = cbind(myGLM$B, myGLM$S, P)
colnames(results) = c("effect", "se", "p")
} #end of while loop
#print("****************FarmCPU ACCOMPLISHED****************")
return(results)
}#The MVP.FarmCPU function ends here
#' FarmCPU.FaSTLMM.LL
#' Evaluation of the maximum likelihood using FaST-LMM method
#'
#' Last update: January 11, 2017
#' Requirement: pheno, snp.pool, and X0 must have same taxa order.
#' Requirement: No missing data
#'
#' @author Xiaolei Liu (modified)
#'
#' @param pheno a two-column phenotype matrix
#' @param snp.pool matrix for pseudo QTNs
#' @param X0 covariates matrix
#' @param ncpus number of threads used for parallel computation
#'
#' @return
#' Output: beta - beta effect
#' Output: delta - delta value
#' Output: LL - log-likelihood
#' Output: vg - genetic variance
#' Output: ve - residual variance
#'
`FarmCPU.FaSTLMM.LL` <- function(pheno, snp.pool, X0=NULL, ncpus=2){
y=pheno
p=0
deltaExpStart = -5
deltaExpEnd = 5
snp.pool=snp.pool[,]
if(!is.null(snp.pool)&&any(apply(snp.pool, 2, var)==0)){
deltaExpStart = 100
deltaExpEnd = deltaExpStart
}
if(is.null(X0)) {
X0 = matrix(1, nrow(snp.pool), 1)
}
X=X0
#########SVD of X
K.X.svd <- svd(snp.pool)
d=K.X.svd$d
d=d[d>1e-08]
d=d^2
U1=K.X.svd$u
U1=U1[,1:length(d)]
#handler of single snp
if(is.null(dim(U1))) U1=matrix(U1,ncol=1)
n=nrow(U1)
U1TX=crossprod(U1,X)
U1TY=crossprod(U1,y)
yU1TY <- y-U1%*%U1TY
XU1TX<- X-U1%*%U1TX
IU = -tcrossprod(U1)
diag(IU) = rep(1,n) + diag(IU)
IUX=crossprod(IU,X)
IUY=crossprod(IU,y)
#Iteration on the range of delta (-5 to 5 in glog scale)
delta.range <- seq(deltaExpStart,deltaExpEnd,by=0.1)
m <- length(delta.range)
#for (m in seq(deltaExpStart,deltaExpEnd,by=0.1)){
beta.optimize.parallel <- function(ii){
#p=p+1
delta <- exp(delta.range[ii])
#----------------------------calculate beta-------------------------------------
#######get beta1
beta1=0
for(i in 1:length(d)){
one=matrix(U1TX[i,], nrow=1)
beta=crossprod(one,(one/(d[i]+delta))) #This is not real beta, confusing
beta1= beta1+beta
}
#######get beta2
beta2=0
for(i in 1:nrow(U1)){
one=matrix(IUX[i,], nrow=1)
beta = crossprod(one)
beta2= beta2+beta
}
beta2<-beta2/delta
#######get beta3
beta3=0
for(i in 1:length(d)){
one1=matrix(U1TX[i,], nrow=1)
one2=matrix(U1TY[i,], nrow=1)
beta=crossprod(one1,(one2/(d[i]+delta)))
beta3= beta3+beta
}
###########get beta4
beta4=0
for(i in 1:nrow(U1)){
one1=matrix(IUX[i,], nrow=1)
one2=matrix(IUY[i,], nrow=1)
beta=crossprod(one1,one2)
beta4= beta4+beta
}
beta4<-beta4/delta
#######get final beta
zw1 <- ginv(beta1+beta2)
#zw1 <- try(solve(beta1+beta2))
#if(inherits(zw1, "try-error")){
#zw1 <- ginv(beta1+beta2)
#}
zw2=(beta3+beta4)
beta=crossprod(zw1,zw2)
#----------------------------calculate LL---------------------------------------
####part 1
part11<-n*log(2*3.14)
part12<-0
for(i in 1:length(d)){
part12_pre=log(d[i]+delta)
part12= part12+part12_pre
}
part13<- (nrow(U1)-length(d))*log(delta)
part1<- -1/2*(part11+part12+part13)
###### part2
part21<-nrow(U1)
######part221
part221=0
for(i in 1:length(d)){
one1=U1TX[i,]
one2=U1TY[i,]
part221_pre=(one2-one1%*%beta)^2/(d[i]+delta)
part221 = part221+part221_pre
}
part222=0
for(i in 1:n){
one1=XU1TX[i,]
one2=yU1TY[i,]
part222_pre=((one2-one1%*%beta)^2)/delta
part222= part222+part222_pre
}
part22<-n*log((1/n)*(part221+part222))
part2<- -1/2*(part21+part22)
################# likihood
LL<-part1+part2
part1<-0
part2<-0
return(list(beta=beta,delta=delta,LL=LL))
}
llresults <- lapply(1:m, beta.optimize.parallel)
for(i in 1:m){
if(i == 1){
beta.save = llresults[[i]]$beta
delta.save = llresults[[i]]$delta
LL.save = llresults[[i]]$LL
}else{
if(llresults[[i]]$LL > LL.save){
beta.save = llresults[[i]]$beta
delta.save = llresults[[i]]$delta
LL.save = llresults[[i]]$LL
}
}
}
#--------------------update with the optimum------------------------------------
beta=beta.save
delta=delta.save
LL=LL.save
#--------------------calculating Va and Vem-------------------------------------
#sigma_a1
sigma_a1=0
for(i in 1:length(d)){
one1=matrix(U1TX[i,], ncol=1)
one2=matrix(U1TY[i,], nrow=1)
#sigma_a1_pre=(one2-one1%*%beta)^2/(d[i]+delta)
sigma_a1_pre=(one2-crossprod(one1,beta))^2/(d[i]+delta)
sigma_a1= sigma_a1+sigma_a1_pre
}
### sigma_a2
sigma_a2=0
for(i in 1:nrow(U1)){
one1=matrix(IUX[i,], ncol=1)
one2=matrix(IUY[i,], nrow=1)
#sigma_a2_pre<-(one2-one1%*%beta)^2
sigma_a2_pre<-(one2-crossprod(one1,beta))^2
sigma_a2= sigma_a2+sigma_a2_pre
}
sigma_a2<-sigma_a2/delta
sigma_a<- 1/n*(sigma_a1+sigma_a2)
sigma_e<-delta*sigma_a
return(list(beta=beta, delta=delta, LL=LL, vg=sigma_a, ve=sigma_e))
}
#' FarmCPU.BIN
#'
#' Last update: March 28, 2017
#' Requirement: Y, GDP, and CV must have same taxa order. GDP and GM must have the same order on SNP
#' Requirement: P and GM are in the same order
#' Requirement: No missing data
#'
#' @author Xiaolei Liu and Zhiwu Zhang
#'
#' @param Y a n by 2 matrix, the fist column is taxa id and the second is trait
#' @param GDP genotype, m by n matrix, m is marker size, n is sample size. This is Pure Genotype Data Matrix(GD). THERE IS NO COLUMN FOR TAXA
#' @param GM SNP map information, m by 3 matrix, m is marker size, the three columns are SNP_ID, Chr, and Pos
#' @param CV covariates, n by c matrix, n is sample size, c is number of covariates
#' @param P start p values for all SNPs
#' @param method two options, 'static' or 'FaST-LMM'
#' @param b bin sizes for all iterations, a vector, the bin size is always from large to small
#' @param s number of selected bins in each iteration, a vector
#' @param theLoop iteration number
#' @param bound maximum number of SNPs selected as pseudo QTNs in each iteration
#' @param ncpus number of threads used for parallele computation
#' @param verbose whether to print detail.
#'
#' @return
#' Output: seqQTN - an s by 1 vecter for index of QTNs on GM file
#'
#' @keywords internal
FarmCPU.BIN <-
function(Y=NULL, GDP=NULL, GM=NULL, CV=NULL, P=NULL, method="EMMA", b=c(5e5,5e6,5e7), s=seq(10,100,10), theLoop=NULL, bound=NULL, ncpus=2, verbose=TRUE){
#print("FarmCPU.BIN Started")
if(is.null(P)) return(list(bin=NULL,binmap=NULL,seqQTN=NULL))
#Set upper bound for bin selection to squareroot of sample size
n=nrow(Y)
#bound=round(sqrt(n)/log10(n))
if(is.null(bound)){
bound=round(sqrt(n)/sqrt(log10(n)))
}
s[s>bound]=bound
s=unique(s[s<=bound]) #keep the within bound
optimumable=(length(b)*length(s)>1)
if(!optimumable & method!="optimum"){
method="static"
}
if(optimumable){
s[s>bound]=bound
#print("optimizing possible QTNs...")
#GP=cbind(GM,P,NA,NA,NA)
#mySpecify=FarmCPU.Specify(GI=GM, GP=GP, bin.size=b, inclosure.size=s)
#seqQTN=which(mySpecify$index==TRUE)
}
#Method of static
if(method=="static"&optimumable){
#print("Via static")
if(theLoop==2){
b=b[3]
}else if(theLoop==3){
b=b[2]
}else{
b=b[1]
}
s=bound
s[s>bound]=bound
logging.log("Optimizing Pseudo QTNs...", "\n", verbose = verbose)
GP=cbind(GM,P,NA,NA,NA)
mySpecify=FarmCPU.Specify(GI=GM,GP=GP,bin.size=b,inclosure.size=s)
seqQTN.save=which(mySpecify$index==TRUE)
}
#Method of optimum: FaST-LMM
#============================Optimize by FaST-LMM============================================
if(method=="FaST-LMM"&optimumable){
#print("c(bin.size, bin.selection, -2LL, VG, VE)")
logging.log("Optimizing Pseudo QTNs...", "\n", verbose = verbose)
count=0
for (bin in b){
for (inc in s){
count=count+1
GP=cbind(GM,P,NA,NA,NA)
mySpecify=FarmCPU.Specify(GI=GM,GP=GP,bin.size=bin,inclosure.size=inc)
seqQTN=which(mySpecify$index==TRUE)
GK=t(GDP[seqQTN,])
myBurger=FarmCPU.Burger(Y=Y[,1:2], CV=CV, GK=GK, ncpus=ncpus, method=method)
myREML=myBurger$REMLs
myVG=myBurger$vg #it is unused
myVE=myBurger$ve #it is unused
logging.log(c(bin,inc,myREML,myVG,myVE), "\n", verbose = verbose)
#Recoding the optimum GK
if(count==1){
seqQTN.save=seqQTN
LL.save=myREML
bin.save=bin
inc.save=inc
vg.save=myVG # for genetic variance
ve.save=myVE # for residual variance
}else{
if(myREML<LL.save){
seqQTN.save=seqQTN
LL.save=myREML
bin.save=bin
inc.save=inc
vg.save=myVG # for genetic variance
ve.save=myVE # for residual variance
}
} #end of if(count==1)
}#loop on bin number
}#loop on bin size
#seqQTN=seqQTN.save
}
#Method of optimum: EMMA
#============================Optimize by EMMA============================================
if(method=="EMMA"&optimumable){
#print("c(bin.size, bin.selection, -2LL, VG, VE)")
logging.log("Optimizing Pseudo QTNs...", "\n", verbose = verbose)
m <- length(b)*length(s)
inc.index = rep(c(1:length(s)), length(b))
seqQTN.optimize.parallel <- function(ii){
bin.index = floor((ii-0.1)/length(s)) + 1
bin = b[bin.index]
inc = s[inc.index[ii]]
GP=cbind(GM,P,NA,NA,NA)
mySpecify=FarmCPU.Specify(GI=GM,GP=GP,bin.size=bin,inclosure.size=inc)
seqQTN=which(mySpecify$index==TRUE)
GK=t(GDP[seqQTN,])
myBurger=FarmCPU.Burger(Y=Y[,1:2], CV=CV, GK=GK, ncpus=ncpus, method=method)
myREML=myBurger$REMLs
myVG=myBurger$vg #it is unused
myVE=myBurger$ve #it is unused
logging.log(c(bin,inc,myREML,myVG,myVE), "\n", verbose = verbose)
return(list(seqQTN=seqQTN,myREML=myREML))
}
llresults <- lapply(1:m, seqQTN.optimize.parallel)
for(i in 1:m){
if(i == 1){
seqQTN.save = llresults[[i]]$seqQTN
myREML.save = llresults[[i]]$myREML
}else{
if(llresults[[i]]$myREML < myREML.save){
seqQTN.save = llresults[[i]]$seqQTN
myREML.save = llresults[[i]]$myREML
}
}
}
}
#Method of optimum: GEMMA
#can not be used to provide REML
#============================Optimize by GEMMA============================================
if(method=="GEMMA"&optimumable){
#print("c(bin.size, bin.selection, -2LL, VG, VE)")
logging.log("Optimizing Pseudo QTNs...\n", verbose = verbose)
m <- length(b)*length(s)
seqQTN.optimize.parallel <- function(ii){
bin = floor((ii-0.1)/length(s)) + 1
inc = rep(c(1:length(s)), length(b))
GP=cbind(GM,P,NA,NA,NA)
mySpecify=FarmCPU.Specify(GI=GM,GP=GP,bin.size=bin[ii],inclosure.size=inc[ii])
seqQTN=which(mySpecify$index==TRUE)
GK=t(GDP[seqQTN,])
myBurger=FarmCPU.Burger(Y=Y[,1:2], CV=CV, GK=GK, ncpus=ncpus, method=method)
myREML=myBurger$REMLs
myVG=myBurger$vg #it is unused
myVE=myBurger$ve #it is unused
logging.log(c(bin,inc,myREML,myVG,myVE), "\n", verbose = verbose)
return(list(seqQTN=seqQTN,myREML=myREML))
}
llresults <- lapply(1:m, seqQTN.optimize.parallel)
for(i in 1:m){
if(i == 1){
seqQTN.save = llresults[[i]]$seqQTN
myREML.save = llresults[[i]]$myREML
}else{
if(llresults[[i]]$myREML < myREML.save){
seqQTN.save = llresults[[i]]$seqQTN
myREML.save = llresults[[i]]$myREML
}
}
}
}
return(list(seqQTN=seqQTN.save))
}#The function FarmCPU.BIN ends here
#' To get indicator (TURE or FALSE) for GI based on GP
#'
#' Last update: January 26, 2017
#' Strategy
#' 1.set bins for all snps in GP
#' 2.keep the snp with smallest P value in each bin, record SNP ID
#' 3.Search GI for SNP with SNP ID from above
#' 4.return the position for SNP selected
#'
#' @author Zhiwu Zhang
#'
#' @param GI Data frame with three columns (SNP name, chr and base position)
#' @param GP Data frame with seven columns (SNP name, chr and base position, P, MAF, N, effect)
#' @param bin.size a value of @param b in 'FarmCPU.bin' function
#' @param inclosure.size a value of @param s in 'FarmCPU.bin' function
#' @param MaxBP maximum base pairs for each chromosome
#'
#' @return theIndex: a vector indicating if the SNPs in GI belong to QTN or not
FarmCPU.Specify <-
function(GI=NULL, GP=NULL, bin.size=10000000, inclosure.size=NULL, MaxBP=1e10){
#print("Specification in process...")
if(is.null(GP))return (list(index=NULL,BP=NULL))
#set inclosure bin in GP
#Create SNP ID: position+CHR*MaxBP
ID.GP=as.numeric(as.vector(GP[, 3]))+as.numeric(as.vector(GP[, 2]))*MaxBP
#Creat bin ID
bin.GP=floor(ID.GP/bin.size )
#Create a table with bin ID, SNP ID and p value (set 2nd and 3rd NA temporately)
binP=as.matrix(cbind(bin.GP,NA,NA,ID.GP,as.numeric(as.vector(GP[,4]))) )
n=nrow(binP)
#Sort the table by p value and then bin ID (e.g. sort p within bin ID)
binP=binP[order(as.numeric(as.vector(binP[,5]))),] #sort on P alue
binP=binP[order(as.numeric(as.vector(binP[,1]))),] #sort on bin
#set indicator (use 2nd 3rd columns)
binP[2:n,2]=binP[1:(n-1),1]
binP[1,2]=0 #set the first
binP[,3]= binP[, 1]-binP[, 2]
#Se representives of bins
ID.GP=binP[binP[, 3]>0,]
#Choose the most influencial bins as estimated QTNs
#Handler of single row
if(is.null(dim(ID.GP))) ID.GP=matrix(ID.GP,1,length(ID.GP))
ID.GP=ID.GP[order(as.numeric(as.vector(ID.GP[, 5]))),] #sort on P alue
#Handler of single row (again after reshape)
if(is.null(dim(ID.GP))) ID.GP=matrix(ID.GP,1,length(ID.GP))
index=!is.na(ID.GP[, 4])
ID.GP=ID.GP[index,4] #must have chr and bp information, keep SNP ID only
if(!is.null(inclosure.size) ) {
if(!any(is.na(inclosure.size))){
avaiable=min(inclosure.size,length(ID.GP))
if(avaiable==0){
ID.GP=-1
}else{
ID.GP=ID.GP[1:avaiable] #keep the top ones selected
}
}
}
#create index in GI
theIndex=NULL
if(!is.null(GI)){
ID.GI=as.numeric(as.vector(GI[, 3]))+as.numeric(as.vector(GI[, 2]))*MaxBP
theIndex=ID.GI %in% ID.GP
}
myList=list(index=theIndex,CB=ID.GP)
return (list(index=theIndex,CB=ID.GP))
} #end of FarmCPU.Specify
#' To quickly sovel LM with one variable substitute multiple times
#'
#' Start date: March 1, 2013
#' Last update: March 6, 2013
#' Strategy:
#' 1. Separate constant covariates (w) and dynamic coveriates (x)
#' 2. Build non-x related only once
#' 3. Use apply to iterate x
#' 4. Derive dominance indicate d from additive indicate (x) mathmaticaly
#' 5. When d is not estimable, continue to test x
#'
#' @author Xiaolei Liu and Zhiwu Zhang
#'
#' @param y one column matrix, dependent variable
#' @param w covariates, n by c matrix, n is sample size, c is number of covariates
#' @param GDP genotype, m by n matrix, m is marker size, n is sample size. This is Pure Genotype Data Matrix(GD). THERE IS NO COLUMN FOR TAXA.
#' @param ncpus number of threads used for parallele computation
#' @param npc number of covariates without pseudo QTNs
#' @param verbose whether to print detail.
#'
#' @return
#' Output: P - p-value of each SNP
#' Output: betapred - effects of pseudo QTNs
#' Output: B - effect of each SNP
#'
#' @keywords internal
FarmCPU.LM <-
function(y, w=NULL, GDP, ncpus=2, npc=0, verbose=TRUE){
#print("FarmCPU.LM started")
if(is.null(y)) return(NULL)
if(is.null(GDP)) return(NULL)
#Constant section (non individual marker specific)
#---------------------------------------------------------
#Configration
nd=20 #number of markes for checking A and D dependency
N=length(y) #Total number of taxa, including missing ones
if(!is.null(w)){
w=as.matrix(w,nrow = N)
nf=ncol(w)
w=cbind(rep(1,N),w)
q0=ncol(w)
}else{
w=rep(1,N)
nf=0
q0=1
}
w = as.matrix(w)
logging.log("number of covariates in current loop is:", "\n", verbose = verbose)
logging.log(nf, "\n", verbose = verbose)
n=N
if(nd>n)nd=n #handler of samples less than nd
k=1 #number of genetic effect: 1 and 2 for A and AD respectively
q1=(q0+1) # vecter index for the posistion of genetic effect (a)
q2=(q0+1):(q0+2) # vecter index for the posistion of genetic effect (a and d)
df=n-q0-k #residual df (this should be varied based on validating d)
iXX=matrix(0,q0+k,q0+k) #Reserve the maximum size of inverse of LHS
# ww=crossprodcpp(w)
ww = crossprod(w)
wy = crossprod(w,y)
# yy=crossprodcpp(y)
yy = crossprod(y)
wwi = ginv(ww)
#Statistics on the reduced model without marker
rhs=wy
beta <- crossprod(wwi,rhs)
ve <- (yy - crossprod(beta, rhs)) / df
se <- sqrt(diag(wwi) * ve[1])
if(npc!=0){
betapc = beta[2:(npc+1)]
betapred = beta[-c(1:(npc+1))]
sepred = se[-c(1:(npc+1))]
}else{
betapc = NULL
betapred = beta[-1]
sepred = se[-1]
}
#print(ncpus)
logging.log("scanning...", "\n", verbose = verbose)
# P <- NULL
# B <- NULL
# S <- NULL
# setMKLthreads(10)
# for(i in 1:nrow(GDP)){
# xx <- summary(lm(y~cbind(w,GDP[i, ])))$coeff
# P <- rbind(P, xx[-1,4,drop=TRUE])
# B <- c(B, xx[nrow(xx), 1])
# S <- c(S, xx[nrow(xx), 2])
# }
# if(ncol(w) == 50) write.csv(P, "P.csv")
mkl_env({
results <- glm_c(y=y, X=w, iXX = wwi, GDP@address, verbose=verbose, threads=ncpus)
})
return(list(P=results[ ,-c(1:3), drop=FALSE], betapred=betapred, sepred=sepred, B=results[ , 1, drop=FALSE], S=results[ , 2, drop=FALSE]))
# return(list(P=P, betapred=betapred, B=as.matrix(B), S=S))
} #end of FarmCPU.LM function
#' FarmCPU.Burger
#'
#' Last update: Dec 21, 2016
#' To calculate likelihood, variances and ratio, revised by Xiaolei based on GAPIT.Burger function from GAPIT package
#'
#' @author Xiaolei Liu and Zhiwu Zhang
#'
#' @param Y phenotype, n by t matrix, n is sample size, t is number of phenotypes
#' @param CV covariates, n by c matrix, n is sample size, c is number of covariates
#' @param GK Genotype data in numerical format, taxa goes to row and snp go to columns
#' @param ncpus number of threads used for parallele computation
#' @param method two options for estimating variance components, 'FaST-LMM' or 'EMMA'
#'
#' @return
#' Output: REMLs - maximum log likelihood
#' Output: vg - genetic variance
#' Output: ve - residual variance
#' Output: delta - exp(root)
#'
#' @keywords internal
FarmCPU.Burger <-
function(Y=NULL,CV=NULL,GK=NULL,ncpus=2, method="FaST-LMM"){
if(!is.null(CV)){
CV=as.matrix(CV)#change CV to a matrix when it is a vector
theCV=as.matrix(cbind(matrix(1,nrow(CV),1),CV))
}else{
theCV=matrix(1,nrow(Y),1)
}
#handler of single column GK
n=nrow(GK)
m=ncol(GK)
if(!is.null(GK)){
n=nrow(GK)
m=ncol(GK)
if(m > 2){
theGK = as.matrix(GK)#GK is pure genotype matrix
}else if(m==0){
theGK = NULL
}else{
theGK = matrix(GK,n,1)
}
}else{
theGK=GK
}
if(method=="FaST-LMM"){
myFaSTREML=FarmCPU.FaSTLMM.LL(pheno=matrix(Y[,-1],nrow(Y),1), snp.pool=theGK, X0=theCV, ncpus=ncpus)
REMLs=-2*myFaSTREML$LL
delta=myFaSTREML$delta
vg=myFaSTREML$vg
ve=myFaSTREML$ve
}
if(method=="EMMA"){
K <- MVP.K.VanRaden(M=as.big.matrix(t(theGK)), priority="speed",verbose=FALSE)
myEMMAREML <- MVP.EMMA.Vg.Ve(y=matrix(Y[,-1],nrow(Y),1), X=theCV, K=K)
REMLs=-2*myEMMAREML$REML
delta=myEMMAREML$delta
vg=myEMMAREML$vg
ve=myEMMAREML$ve
}
#print("FarmCPU.Burger succeed!")
return (list(REMLs=REMLs, vg=vg, ve=ve, delta=delta))
} #end of FarmCPU.Burger
#' FarmCPU.SUB
#'
#' Last update: Febuary 26, 2013
#' Requirement: P has row name of SNP. s<=t. covariates of QTNs are next to SNP
#'
#' @author Xiaolei Liu and Zhiwu Zhang
#'
#' @param GM SNP map information, m by 3 matrix, m is marker size, the three columns are SNP_ID, Chr, and Pos
#' @param GLM FarmCPU.GLM object
#' @param QTN s by 3 matrix for SNP name, chromosome and BP
#' @param method options are "penalty", "reward","mean","median",and "onsite"
#'
#' @return
#' Output: GLM$P - Updated p-values by substitution process
#' Output: GLM$B - Updated effects by substitution process
FarmCPU.SUB <-
function(GM=NULL,GLM=NULL,QTN=NULL,method="mean"){
if(is.null(GLM$P)) return(NULL) #P is required
if(is.null(QTN)) return(NULL) #QTN is required
#print("FarmCPU.SUB Started")
#print(length(QTN))
#if(length(QTN)==3){
#QTN=QTN[1]
#}else{
QTN=QTN[ , 1, drop=FALSE]
#}
position=match(QTN, GM[, 1, drop=FALSE], nomatch = 0)
nqtn=length(position)
if(is.numeric(GLM$P)){
GLM$P = as.matrix(GLM$P)
}
GLM$B = as.matrix(GLM$B)
index=(ncol(GLM$P)-nqtn):(ncol(GLM$P)-1)
spot=ncol(GLM$P)
if(ncol(GLM$P)!=1){
if(length(index)>1){
if(method=="penalty") P.QTN=apply(GLM$P[,index],2,max,na.rm=TRUE)
if(method=="reward") P.QTN=apply(GLM$P[,index],2,min,na.rm=TRUE)
if(method=="mean") P.QTN=apply(GLM$P[,index],2,mean,na.rm=TRUE)
if(method=="median") P.QTN=apply(GLM$P[,index],2,median,na.rm=TRUE)
if(method=="onsite") P.QTN=GLM$P0[(length(GLM$P0)-nqtn+1):length(GLM$P0)]
}else{
if(method=="penalty") P.QTN=max(GLM$P[,index, drop=FALSE],na.rm=TRUE)
if(method=="reward") P.QTN=min(GLM$P[,index, drop=FALSE],na.rm=TRUE)
if(method=="mean") P.QTN=mean(GLM$P[,index, drop=FALSE],na.rm=TRUE)
if(method=="median") P.QTN=median(GLM$P[,index, drop=FALSE],median,na.rm=TRUE)
if(method=="onsite") P.QTN=GLM$P0[(length(GLM$P0)-nqtn+1):length(GLM$P0)]
}
#replace SNP pvalues with QTN pvalue
GLM$P[position, spot] = P.QTN
GLM$B[position, ] = GLM$betapred
GLM$S[position, ] = GLM$sepred
}
return(GLM)
}#The function FarmCPU.SUB ends here
#' Remove bins that are highly correlated
#'
#' Last update: March 4, 2013
#' Requirement: GDP and GM have the same order on SNP
#'
#' @author Xiaolei Liu and Zhiwu Zhang
#'
#' @param GDP genotype, m by n matrix, m is marker size, n is sample size. This is Pure Genotype Data Matrix(GD). THERE IS NO COLUMN FOR TAXA
#' @param GM SNP map information, m by 3 matrix, m is marker size, the three columns are SNP_ID, Chr, and Pos
#' @param seqQTN s by 1 vecter for index of QTN on GM
#' @param seqQTN.p p value of each @param seqQTN
#' @param threshold pearson correlation threshold for remove correlated markers
#'
#' @return
#' Output: bin - n by s0 matrix of genotype
#' Output: binmap - s0 by 3 matrix for map of bin
#' Output: seqQTN - s0 by 1 vecter for index of QTN on GM
#' Relationship: bin=GDP[,c(seqQTN)], binmap=GM[seqQTN,], s0<=s
#' @keywords internal
FarmCPU.Remove <-
function(GDP=NULL, GM=NULL, seqQTN=NULL, seqQTN.p=NULL, threshold=.99){
if(is.null(seqQTN))return(list(bin=NULL,binmap=NULL,seqQTN=NULL))
seqQTN=seqQTN[order(seqQTN.p)]
hugeNum=10e10
n=length(seqQTN)
#fielter bins by physical location
binmap=GM[seqQTN, , drop=FALSE]
cb=as.numeric(binmap[, 2, drop=FALSE])*hugeNum+as.numeric(binmap[, 3, drop=FALSE])#create ID for chromosome and bp
cb.unique=unique(cb)
#print("debuge")
#print(cb)
#print(cb.unique)
index=match(cb.unique,cb,nomatch = 0)
seqQTN=seqQTN[index]
#print("Number of bins after chr and bp fillter")
n=length(seqQTN) #update n
#Set sample
ratio=.1
maxNum=100000
m=nrow(GDP) #sample size
s=ncol(GDP) #number of markers
sampled=s
if(sampled>maxNum)sampled=maxNum
#index=sample(s,sampled)
index=1:sampled
#This section has problem of turning big.matrix to R matrix
#It is OK as x is small
if(is.big.matrix(GDP)){
x=t(as.matrix(deepcopy(GDP,rows=seqQTN,cols=index) ))
}else{
x=t(GDP[seqQTN,index] )
}
r=cor(as.matrix(x))
index=abs(r)>threshold
b=r*0
b[index]=1
c=1-b
#The above are replaced by following
c[lower.tri(c)]=1
diag(c)=1
bd <- apply(c,2,prod)
position=(bd==1)
seqQTN=seqQTN[position]
#============================end of optimum============================================
seqQTN=seqQTN[!is.na(seqQTN)]
#This section has problem of turning big.matrix to R matrix
if(is.big.matrix(GDP)){
bin=t(as.matrix(deepcopy(GDP,rows=seqQTN,) ))
}else{
bin=t(GDP[seqQTN, , drop=FALSE] )
}
binmap=GM[seqQTN, , drop=FALSE]
return(list(bin=bin, binmap=binmap, seqQTN=seqQTN))
}#The function FarmCPU.Remove ends here
#' Set prior on existing p value
#'
#' Last update: March 10, 2013
#' Requirement: P and GM are in the same order, Prior is part of GM except P value
#'
#' @author Xiaolei Liu and Zhiwu Zhang
#'
#' @param GM an m by 3 matrix for SNP name, chromosome and BP
#' @param P an m by 1 matrix containing probability
#' @param Prior an s by 4 matrix for SNP name, chromosome, BP and p-value
#'
#' @return
#' Output: P - updated P value by prior information
#'
#' @keywords internal
FarmCPU.Prior <-
function(GM, P=NULL, Prior=NULL){
#print("FarmCPU.Prior Started")
if(is.null(Prior)& is.null(P))return(P)
#get prior position
if(!is.null(Prior)) index=match(Prior[, 1, drop=FALSE],GM[, 1, drop=FALSE],nomatch = 0)
#if(is.null(P)) P=runif(nrow(GM)) #set random p value if not provided (This is not helpful)
#print("debug set prior a")
#Get product with prior if provided
if(!is.null(Prior) & !is.null(P) )P[index]=P[index]*Prior[, 4, drop=FALSE]
return(P)
}#The function FarmCPU.Prior ends here
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Defines functions FarmCPU.Prior FarmCPU.Remove FarmCPU.SUB FarmCPU.Burger FarmCPU.LM FarmCPU.Specify FarmCPU.BIN `FarmCPU.FaSTLMM.LL` `MVP.FarmCPU`
# Licensed under the Apache License, Version 2.0 (the "License");
# you may not use this file except in compliance with the License.
# You may obtain a copy of the License at
#
# http://www.apache.org/licenses/LICENSE-2.0
#
# Unless required by applicable law or agreed to in writing, software
# distributed under the License is distributed on an "AS IS" BASIS,
# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
# See the License for the specific language governing permissions and
# limitations under the License.
#' Perform GWAS using FarmCPU method
#'
#' Date build: Febuary 24, 2013
#' Last update: May 25, 2017
#' Requirement: Y, GD, and CV should have same taxa order. GD and GM should have the same order on SNPs
#'
#' @author Xiaolei Liu and Zhiwu Zhang
#'
#' @param phe phenotype, n by t matrix, n is sample size, t is number of phenotypes
#' @param geno genotype, m by n matrix, m is marker size, n is sample size. This is Pure Genotype Data Matrix(GD). THERE IS NO COLUMN FOR TAXA.
#' @param map SNP map information, m by 3 matrix, m is marker size, the three columns are SNP_ID, Chr, and Pos
#' @param CV covariates, n by c matrix, n is sample size, c is number of covariates
#' @param P start p values for all SNPs
#' @param method.sub method used in substitution process, five options: 'penalty', 'reward', 'mean', 'median', or 'onsite'
#' @param method.sub.final method used in substitution process, five options: 'penalty', 'reward', 'mean', 'median', or 'onsite'
#' @param method.bin method for selecting the most appropriate bins, three options: 'static', 'EMMA' or 'FaST-LMM'
#' @param bin.size bin sizes for all iterations, a vector, the bin size is always from large to small
#' @param bin.selection number of selected bins in each iteration, a vector
#' @param memo a marker on output file name
#' @param Prior prior information, four columns, which are SNP_ID, Chr, Pos, P-value
#' @param ncpus number of threads used for parallele computation
#' @param maxLoop maximum number of iterations
#' @param threshold.output only the GWAS results with p-values lower than threshold.output will be output
#' @param converge a number, 0 to 1, if selected pseudo QTNs in the last and the second last iterations have a certain probality (the probability is converge) of overlap, the loop will stop
#' @param iteration.output whether to output results of all iterations
#' @param p.threshold if all p values generated in the first iteration are bigger than p.threshold, FarmCPU stops
#' @param QTN.threshold in second and later iterations, only SNPs with lower p-values than QTN.threshold have chances to be selected as pseudo QTNs
#' @param bound maximum number of SNPs selected as pseudo QTNs in each iteration
#' @param verbose whether to print detail.
#'
#' @return a m by 4 results matrix, m is marker size, the four columns are SNP_ID, Chr, Pos, and p-value
#' @export
#'
#' @examples
#' \donttest{
#' phePath <- system.file("extdata", "07_other", "mvp.phe", package = "rMVP")
#' phenotype <- read.table(phePath, header=TRUE)
#' idx <- !is.na(phenotype[, 2])
#' phenotype <- phenotype[idx, ]
#' print(dim(phenotype))
#' genoPath <- system.file("extdata", "06_mvp-impute", "mvp.imp.geno.desc", package = "rMVP")
#' genotype <- attach.big.matrix(genoPath)
#' genotype <- deepcopy(genotype, cols=idx)
#' print(dim(genotype))
#' mapPath <- system.file("extdata", "06_mvp-impute", "mvp.imp.geno.map", package = "rMVP")
#' map <- read.table(mapPath , head = TRUE)
#'
#' farmcpu <- MVP.FarmCPU(phe=phenotype,geno=genotype,map=map,maxLoop=2,method.bin="static")
#' str(farmcpu)
#' }
#'
`MVP.FarmCPU` <- function(phe, geno, map, CV=NULL, P=NULL, method.sub="reward", method.sub.final="reward",
method.bin=c("EMMA", "static", "FaST-LMM"), bin.size=c(5e5,5e6,5e7), bin.selection=seq(10,100,10),
memo="MVP.FarmCPU", Prior=NULL, ncpus=2, maxLoop=10,
threshold.output=.01, converge=1, iteration.output=FALSE, p.threshold=NA,
QTN.threshold=0.01, bound=NULL, verbose=TRUE){
#print("--------------------- Welcome to FarmCPU ----------------------------")
if(!is.big.matrix(geno)) stop("genotype should be in 'big.matrix' format.")
if(sum(is.na(phe[, 2])) != 0) stop("NAs are not allowed in phenotype.")
if(nrow(phe) != ncol(geno)) stop("number of individuals not match in phenotype and genotype.")
echo=TRUE
nm=nrow(map)
if(!is.null(CV)){
CV=as.matrix(CV)
CV.index <- apply(CV, 2, function(x) length(table(x)) > 1)
CV <- CV[, CV.index, drop=FALSE]
npc=ncol(CV)
}else{
npc=0
}
method.bin=match.arg(method.bin)
map <- as.matrix(map)
suppressWarnings(max.chr <- max(as.numeric(map[, 2]), na.rm=TRUE))
if(is.infinite(max.chr)) max.chr <- 0
map.xy.index <- which(!as.numeric(map[, 2]) %in% c(0 : max.chr))
if(length(map.xy.index) != 0){
chr.xy <- unique(map[map.xy.index, 2])
for(i in 1:length(chr.xy)){
map[map[, 2] == chr.xy[i], 2] <- max.chr + i
}
}
map[, 1] = 1:nrow(map)
suppressWarnings(map <- matrix(as.numeric(map), nrow(map)))
if(sum(is.na(map[,3]) != 0)) stop("Non-digital characters or NAs are not allowed in map for FarmCPU")
if(!is.na(p.threshold)) QTN.threshold = max(p.threshold, QTN.threshold)
name.of.trait=colnames(phe)[2]
if(!is.null(memo)) name.of.trait=paste(memo,".",name.of.trait,sep="")
theLoop=0
theConverge=0
seqQTN.save=c(0)
seqQTN.pre=c(-1)
isDone=FALSE
name.of.trait2=name.of.trait
while(!isDone) {
theLoop=theLoop+1
logging.log(paste("Current loop: ",theLoop," out of maximum of ", maxLoop, sep=""), "\n", verbose = verbose)
spacer="0"
if(theLoop>9){
spacer=""
}
if(iteration.output){
name.of.trait2=paste("Iteration_",spacer,theLoop,".",name.of.trait,sep="")
}
#Step 2a: Set prior
myPrior=FarmCPU.Prior(GM=map,P=P,Prior=Prior)
#Step 2b: Set bins
if(theLoop<=2){
myBin=FarmCPU.BIN(Y=phe[,c(1,2)],GDP=geno,GM=map,CV=CV,P=myPrior,method=method.bin,b=bin.size,s=bin.selection,theLoop=theLoop,bound=bound,ncpus=ncpus, verbose = verbose)
}else{
myBin=FarmCPU.BIN(Y=phe[,c(1,2)],GDP=geno,GM=map,CV=theCV,P=myPrior,method=method.bin,b=bin.size,s=bin.selection,theLoop=theLoop,ncpus=ncpus, verbose = verbose)
}
#Step 2c: Remove bin dependency
#Remove QTNs in LD
seqQTN=myBin$seqQTN
if(theLoop==2){
if(!is.na(p.threshold)){
if(min(myPrior,na.rm=TRUE)>p.threshold){
seqQTN=NULL
logging.log("Top snps have little effect, set seqQTN to NULL!", "\n", verbose = verbose)
}
}else{
if(min(myPrior,na.rm=TRUE)>0.01/nm){
seqQTN=NULL
logging.log("Top snps have little effect, set seqQTN to NULL!", "\n", verbose = verbose)
}
}
}
#when FarmCPU can not work, make a new QQ plot and manhatthan plot
if(theLoop==2&&is.null(seqQTN)){
#Report
P=myGLM$P[,ncol(myGLM$P)]
P[P==0] <- min(P[P!=0],na.rm=TRUE)*0.01
results = cbind(myGLM$B, myGLM$S, P)
colnames(results) = c("effect", "se", "p")
break
}#force to exit for GLM model while seqQTN=NULL and h2=0
if (!any(is.null(seqQTN.save)) && theLoop > 1) {
if (!(0 %in% seqQTN.save || -1 %in% seqQTN.save) && !is.null(seqQTN)) {
#Force previous QTNs in the model
seqQTN <- union(seqQTN,seqQTN.save)
}
}
if(theLoop!=1){
seqQTN.p=myPrior[seqQTN]
if(theLoop==2){
index.p=seqQTN.p<QTN.threshold
#if(!is.na(p.threshold)){
#index.p=seqQTN.p<p.threshold
#}
seqQTN.p=seqQTN.p[index.p]
seqQTN=seqQTN[index.p]
seqQTN.p=seqQTN.p[!is.na(seqQTN)]
seqQTN=seqQTN[!is.na(seqQTN)]
}else{
index.p=seqQTN.p<QTN.threshold
#if(!is.na(p.threshold)){
#index.p=seqQTN.p<p.threshold
#}
index.p[seqQTN%in%seqQTN.save]=TRUE
seqQTN.p=seqQTN.p[index.p]
seqQTN=seqQTN[index.p]
seqQTN.p=seqQTN.p[!is.na(seqQTN)]
seqQTN=seqQTN[!is.na(seqQTN)]
}
}
myRemove=FarmCPU.Remove(GDP=geno,GM=map,seqQTN=seqQTN,seqQTN.p=seqQTN.p,threshold=.7)
#Recoding QTNs history
seqQTN=myRemove$seqQTN
theConverge=length(intersect(seqQTN,seqQTN.save))/length(union(seqQTN,seqQTN.save))
circle=(length(union(seqQTN,seqQTN.pre))==length(intersect(seqQTN,seqQTN.pre)))
#handler of initial status
if(is.null(seqQTN.pre)){circle=FALSE
}else{
if(seqQTN.pre[1]==0) circle=FALSE
if(seqQTN.pre[1]==-1) circle=FALSE
}
logging.log("seqQTN:", "\n", verbose = verbose)
if(is.null(seqQTN)){
logging.log("NULL", "\n", verbose = verbose)
}else{
logging.log(seqQTN, "\n", verbose = verbose)
}
if(theLoop==maxLoop){
logging.log(paste("Total number of possible QTNs in the model is: ", length(seqQTN),sep=""), "\n", verbose = verbose)
}
isDone=((theLoop>=maxLoop) | (theConverge>=converge) | circle )
seqQTN.pre=seqQTN.save
seqQTN.save=seqQTN
#Step 3: Screen with bins
rm(myBin)
gc()
theCV=CV
if(!is.null(myRemove$bin)){
if(length(myRemove$seqQTN) == 1){
#myRemove$bin = as.matrix(myRemove$bin)
myRemove$bin = t(myRemove$bin)
}
theCV=cbind(CV,myRemove$bin)
}
myGLM=FarmCPU.LM(y=phe[,2],GDP=geno,w=theCV,ncpus=ncpus,npc=npc, verbose=verbose)
if(!is.null(seqQTN)){
if(ncol(myGLM$P) != (npc + length(seqQTN) + 1)) stop("wrong dimensions.")
}
#Step 4: Background unit substitution
if(!isDone){
myGLM=FarmCPU.SUB(GM=map,GLM=myGLM,QTN=map[myRemove$seqQTN, , drop=FALSE],method=method.sub)
}else{
myGLM=FarmCPU.SUB(GM=map,GLM=myGLM,QTN=map[myRemove$seqQTN, , drop=FALSE],method=method.sub.final)
}
P=myGLM$P[,ncol(myGLM$P)]
P[P==0] <- min(P[P!=0], na.rm=TRUE)*0.01
results = cbind(myGLM$B, myGLM$S, P)
colnames(results) = c("effect", "se", "p")
} #end of while loop
#print("****************FarmCPU ACCOMPLISHED****************")
return(results)
}#The MVP.FarmCPU function ends here
#' FarmCPU.FaSTLMM.LL
#' Evaluation of the maximum likelihood using FaST-LMM method
#'
#' Last update: January 11, 2017
#' Requirement: pheno, snp.pool, and X0 must have same taxa order.
#' Requirement: No missing data
#'
#' @author Xiaolei Liu (modified)
#'
#' @param pheno a two-column phenotype matrix
#' @param snp.pool matrix for pseudo QTNs
#' @param X0 covariates matrix
#' @param ncpus number of threads used for parallel computation
#'
#' @return
#' Output: beta - beta effect
#' Output: delta - delta value
#' Output: LL - log-likelihood
#' Output: vg - genetic variance
#' Output: ve - residual variance
#'
`FarmCPU.FaSTLMM.LL` <- function(pheno, snp.pool, X0=NULL, ncpus=2){
y=pheno
p=0
deltaExpStart = -5
deltaExpEnd = 5
snp.pool=snp.pool[,]
if(!is.null(snp.pool)&&any(apply(snp.pool, 2, var)==0)){
deltaExpStart = 100
deltaExpEnd = deltaExpStart
}
if(is.null(X0)) {
X0 = matrix(1, nrow(snp.pool), 1)
}
X=X0
#########SVD of X
K.X.svd <- svd(snp.pool)
d=K.X.svd$d
d=d[d>1e-08]
d=d^2
U1=K.X.svd$u
U1=U1[,1:length(d)]
#handler of single snp
if(is.null(dim(U1))) U1=matrix(U1,ncol=1)
n=nrow(U1)
U1TX=crossprod(U1,X)
U1TY=crossprod(U1,y)
yU1TY <- y-U1%*%U1TY
XU1TX<- X-U1%*%U1TX
IU = -tcrossprod(U1)
diag(IU) = rep(1,n) + diag(IU)
IUX=crossprod(IU,X)
IUY=crossprod(IU,y)
#Iteration on the range of delta (-5 to 5 in glog scale)
delta.range <- seq(deltaExpStart,deltaExpEnd,by=0.1)
m <- length(delta.range)
#for (m in seq(deltaExpStart,deltaExpEnd,by=0.1)){
beta.optimize.parallel <- function(ii){
#p=p+1
delta <- exp(delta.range[ii])
#----------------------------calculate beta-------------------------------------
#######get beta1
beta1=0
for(i in 1:length(d)){
one=matrix(U1TX[i,], nrow=1)
beta=crossprod(one,(one/(d[i]+delta))) #This is not real beta, confusing
beta1= beta1+beta
}
#######get beta2
beta2=0
for(i in 1:nrow(U1)){
one=matrix(IUX[i,], nrow=1)
beta = crossprod(one)
beta2= beta2+beta
}
beta2<-beta2/delta
#######get beta3
beta3=0
for(i in 1:length(d)){
one1=matrix(U1TX[i,], nrow=1)
one2=matrix(U1TY[i,], nrow=1)
beta=crossprod(one1,(one2/(d[i]+delta)))
beta3= beta3+beta
}
###########get beta4
beta4=0
for(i in 1:nrow(U1)){
one1=matrix(IUX[i,], nrow=1)
one2=matrix(IUY[i,], nrow=1)
beta=crossprod(one1,one2)
beta4= beta4+beta
}
beta4<-beta4/delta
#######get final beta
zw1 <- ginv(beta1+beta2)
#zw1 <- try(solve(beta1+beta2))
#if(inherits(zw1, "try-error")){
#zw1 <- ginv(beta1+beta2)
#}
zw2=(beta3+beta4)
beta=crossprod(zw1,zw2)
#----------------------------calculate LL---------------------------------------
####part 1
part11<-n*log(2*3.14)
part12<-0
for(i in 1:length(d)){
part12_pre=log(d[i]+delta)
part12= part12+part12_pre
}
part13<- (nrow(U1)-length(d))*log(delta)
part1<- -1/2*(part11+part12+part13)
###### part2
part21<-nrow(U1)
######part221
part221=0
for(i in 1:length(d)){
one1=U1TX[i,]
one2=U1TY[i,]
part221_pre=(one2-one1%*%beta)^2/(d[i]+delta)
part221 = part221+part221_pre
}
part222=0
for(i in 1:n){
one1=XU1TX[i,]
one2=yU1TY[i,]
part222_pre=((one2-one1%*%beta)^2)/delta
part222= part222+part222_pre
}
part22<-n*log((1/n)*(part221+part222))
part2<- -1/2*(part21+part22)
################# likihood
LL<-part1+part2
part1<-0
part2<-0
return(list(beta=beta,delta=delta,LL=LL))
}
llresults <- lapply(1:m, beta.optimize.parallel)
for(i in 1:m){
if(i == 1){
beta.save = llresults[[i]]$beta
delta.save = llresults[[i]]$delta
LL.save = llresults[[i]]$LL
}else{
if(llresults[[i]]$LL > LL.save){
beta.save = llresults[[i]]$beta
delta.save = llresults[[i]]$delta
LL.save = llresults[[i]]$LL
}
}
}
#--------------------update with the optimum------------------------------------
beta=beta.save
delta=delta.save
LL=LL.save
#--------------------calculating Va and Vem-------------------------------------
#sigma_a1
sigma_a1=0
for(i in 1:length(d)){
one1=matrix(U1TX[i,], ncol=1)
one2=matrix(U1TY[i,], nrow=1)
#sigma_a1_pre=(one2-one1%*%beta)^2/(d[i]+delta)
sigma_a1_pre=(one2-crossprod(one1,beta))^2/(d[i]+delta)
sigma_a1= sigma_a1+sigma_a1_pre
}
### sigma_a2
sigma_a2=0
for(i in 1:nrow(U1)){
one1=matrix(IUX[i,], ncol=1)
one2=matrix(IUY[i,], nrow=1)
#sigma_a2_pre<-(one2-one1%*%beta)^2
sigma_a2_pre<-(one2-crossprod(one1,beta))^2
sigma_a2= sigma_a2+sigma_a2_pre
}
sigma_a2<-sigma_a2/delta
sigma_a<- 1/n*(sigma_a1+sigma_a2)
sigma_e<-delta*sigma_a
return(list(beta=beta, delta=delta, LL=LL, vg=sigma_a, ve=sigma_e))
}
#' FarmCPU.BIN
#'
#' Last update: March 28, 2017
#' Requirement: Y, GDP, and CV must have same taxa order. GDP and GM must have the same order on SNP
#' Requirement: P and GM are in the same order
#' Requirement: No missing data
#'
#' @author Xiaolei Liu and Zhiwu Zhang
#'
#' @param Y a n by 2 matrix, the fist column is taxa id and the second is trait
#' @param GDP genotype, m by n matrix, m is marker size, n is sample size. This is Pure Genotype Data Matrix(GD). THERE IS NO COLUMN FOR TAXA
#' @param GM SNP map information, m by 3 matrix, m is marker size, the three columns are SNP_ID, Chr, and Pos
#' @param CV covariates, n by c matrix, n is sample size, c is number of covariates
#' @param P start p values for all SNPs
#' @param method two options, 'static' or 'FaST-LMM'
#' @param b bin sizes for all iterations, a vector, the bin size is always from large to small
#' @param s number of selected bins in each iteration, a vector
#' @param theLoop iteration number
#' @param bound maximum number of SNPs selected as pseudo QTNs in each iteration
#' @param ncpus number of threads used for parallele computation
#' @param verbose whether to print detail.
#'
#' @return
#' Output: seqQTN - an s by 1 vecter for index of QTNs on GM file
#'
#' @keywords internal
FarmCPU.BIN <-
function(Y=NULL, GDP=NULL, GM=NULL, CV=NULL, P=NULL, method="EMMA", b=c(5e5,5e6,5e7), s=seq(10,100,10), theLoop=NULL, bound=NULL, ncpus=2, verbose=TRUE){
#print("FarmCPU.BIN Started")
if(is.null(P)) return(list(bin=NULL,binmap=NULL,seqQTN=NULL))
#Set upper bound for bin selection to squareroot of sample size
n=nrow(Y)
#bound=round(sqrt(n)/log10(n))
if(is.null(bound)){
bound=round(sqrt(n)/sqrt(log10(n)))
}
s[s>bound]=bound
s=unique(s[s<=bound]) #keep the within bound
optimumable=(length(b)*length(s)>1)
if(!optimumable & method!="optimum"){
method="static"
}
if(optimumable){
s[s>bound]=bound
#print("optimizing possible QTNs...")
#GP=cbind(GM,P,NA,NA,NA)
#mySpecify=FarmCPU.Specify(GI=GM, GP=GP, bin.size=b, inclosure.size=s)
#seqQTN=which(mySpecify$index==TRUE)
}
#Method of static
if(method=="static"&optimumable){
#print("Via static")
if(theLoop==2){
b=b[3]
}else if(theLoop==3){
b=b[2]
}else{
b=b[1]
}
s=bound
s[s>bound]=bound
logging.log("Optimizing Pseudo QTNs...", "\n", verbose = verbose)
GP=cbind(GM,P,NA,NA,NA)
mySpecify=FarmCPU.Specify(GI=GM,GP=GP,bin.size=b,inclosure.size=s)
seqQTN.save=which(mySpecify$index==TRUE)
}
#Method of optimum: FaST-LMM
#============================Optimize by FaST-LMM============================================
if(method=="FaST-LMM"&optimumable){
#print("c(bin.size, bin.selection, -2LL, VG, VE)")
logging.log("Optimizing Pseudo QTNs...", "\n", verbose = verbose)
count=0
for (bin in b){
for (inc in s){
count=count+1
GP=cbind(GM,P,NA,NA,NA)
mySpecify=FarmCPU.Specify(GI=GM,GP=GP,bin.size=bin,inclosure.size=inc)
seqQTN=which(mySpecify$index==TRUE)
GK=t(GDP[seqQTN,])
myBurger=FarmCPU.Burger(Y=Y[,1:2], CV=CV, GK=GK, ncpus=ncpus, method=method)
myREML=myBurger$REMLs
myVG=myBurger$vg #it is unused
myVE=myBurger$ve #it is unused
logging.log(c(bin,inc,myREML,myVG,myVE), "\n", verbose = verbose)
#Recoding the optimum GK
if(count==1){
seqQTN.save=seqQTN
LL.save=myREML
bin.save=bin
inc.save=inc
vg.save=myVG # for genetic variance
ve.save=myVE # for residual variance
}else{
if(myREML<LL.save){
seqQTN.save=seqQTN
LL.save=myREML
bin.save=bin
inc.save=inc
vg.save=myVG # for genetic variance
ve.save=myVE # for residual variance
}
} #end of if(count==1)
}#loop on bin number
}#loop on bin size
#seqQTN=seqQTN.save
}
#Method of optimum: EMMA
#============================Optimize by EMMA============================================
if(method=="EMMA"&optimumable){
#print("c(bin.size, bin.selection, -2LL, VG, VE)")
logging.log("Optimizing Pseudo QTNs...", "\n", verbose = verbose)
m <- length(b)*length(s)
inc.index = rep(c(1:length(s)), length(b))
seqQTN.optimize.parallel <- function(ii){
bin.index = floor((ii-0.1)/length(s)) + 1
bin = b[bin.index]
inc = s[inc.index[ii]]
GP=cbind(GM,P,NA,NA,NA)
mySpecify=FarmCPU.Specify(GI=GM,GP=GP,bin.size=bin,inclosure.size=inc)
seqQTN=which(mySpecify$index==TRUE)
GK=t(GDP[seqQTN,])
myBurger=FarmCPU.Burger(Y=Y[,1:2], CV=CV, GK=GK, ncpus=ncpus, method=method)
myREML=myBurger$REMLs
myVG=myBurger$vg #it is unused
myVE=myBurger$ve #it is unused
logging.log(c(bin,inc,myREML,myVG,myVE), "\n", verbose = verbose)
return(list(seqQTN=seqQTN,myREML=myREML))
}
llresults <- lapply(1:m, seqQTN.optimize.parallel)
for(i in 1:m){
if(i == 1){
seqQTN.save = llresults[[i]]$seqQTN
myREML.save = llresults[[i]]$myREML
}else{
if(llresults[[i]]$myREML < myREML.save){
seqQTN.save = llresults[[i]]$seqQTN
myREML.save = llresults[[i]]$myREML
}
}
}
}
#Method of optimum: GEMMA
#can not be used to provide REML
#============================Optimize by GEMMA============================================
if(method=="GEMMA"&optimumable){
#print("c(bin.size, bin.selection, -2LL, VG, VE)")
logging.log("Optimizing Pseudo QTNs...\n", verbose = verbose)
m <- length(b)*length(s)
seqQTN.optimize.parallel <- function(ii){
bin = floor((ii-0.1)/length(s)) + 1
inc = rep(c(1:length(s)), length(b))
GP=cbind(GM,P,NA,NA,NA)
mySpecify=FarmCPU.Specify(GI=GM,GP=GP,bin.size=bin[ii],inclosure.size=inc[ii])
seqQTN=which(mySpecify$index==TRUE)
GK=t(GDP[seqQTN,])
myBurger=FarmCPU.Burger(Y=Y[,1:2], CV=CV, GK=GK, ncpus=ncpus, method=method)
myREML=myBurger$REMLs
myVG=myBurger$vg #it is unused
myVE=myBurger$ve #it is unused
logging.log(c(bin,inc,myREML,myVG,myVE), "\n", verbose = verbose)
return(list(seqQTN=seqQTN,myREML=myREML))
}
llresults <- lapply(1:m, seqQTN.optimize.parallel)
for(i in 1:m){
if(i == 1){
seqQTN.save = llresults[[i]]$seqQTN
myREML.save = llresults[[i]]$myREML
}else{
if(llresults[[i]]$myREML < myREML.save){
seqQTN.save = llresults[[i]]$seqQTN
myREML.save = llresults[[i]]$myREML
}
}
}
}
return(list(seqQTN=seqQTN.save))
}#The function FarmCPU.BIN ends here
#' To get indicator (TURE or FALSE) for GI based on GP
#'
#' Last update: January 26, 2017
#' Strategy
#' 1.set bins for all snps in GP
#' 2.keep the snp with smallest P value in each bin, record SNP ID
#' 3.Search GI for SNP with SNP ID from above
#' 4.return the position for SNP selected
#'
#' @author Zhiwu Zhang
#'
#' @param GI Data frame with three columns (SNP name, chr and base position)
#' @param GP Data frame with seven columns (SNP name, chr and base position, P, MAF, N, effect)
#' @param bin.size a value of @param b in 'FarmCPU.bin' function
#' @param inclosure.size a value of @param s in 'FarmCPU.bin' function
#' @param MaxBP maximum base pairs for each chromosome
#'
#' @return theIndex: a vector indicating if the SNPs in GI belong to QTN or not
FarmCPU.Specify <-
function(GI=NULL, GP=NULL, bin.size=10000000, inclosure.size=NULL, MaxBP=1e10){
#print("Specification in process...")
if(is.null(GP))return (list(index=NULL,BP=NULL))
#set inclosure bin in GP
#Create SNP ID: position+CHR*MaxBP
ID.GP=as.numeric(as.vector(GP[, 3]))+as.numeric(as.vector(GP[, 2]))*MaxBP
#Creat bin ID
bin.GP=floor(ID.GP/bin.size )
#Create a table with bin ID, SNP ID and p value (set 2nd and 3rd NA temporately)
binP=as.matrix(cbind(bin.GP,NA,NA,ID.GP,as.numeric(as.vector(GP[,4]))) )
n=nrow(binP)
#Sort the table by p value and then bin ID (e.g. sort p within bin ID)
binP=binP[order(as.numeric(as.vector(binP[,5]))),] #sort on P alue
binP=binP[order(as.numeric(as.vector(binP[,1]))),] #sort on bin
#set indicator (use 2nd 3rd columns)
binP[2:n,2]=binP[1:(n-1),1]
binP[1,2]=0 #set the first
binP[,3]= binP[, 1]-binP[, 2]
#Se representives of bins
ID.GP=binP[binP[, 3]>0,]
#Choose the most influencial bins as estimated QTNs
#Handler of single row
if(is.null(dim(ID.GP))) ID.GP=matrix(ID.GP,1,length(ID.GP))
ID.GP=ID.GP[order(as.numeric(as.vector(ID.GP[, 5]))),] #sort on P alue
#Handler of single row (again after reshape)
if(is.null(dim(ID.GP))) ID.GP=matrix(ID.GP,1,length(ID.GP))
index=!is.na(ID.GP[, 4])
ID.GP=ID.GP[index,4] #must have chr and bp information, keep SNP ID only
if(!is.null(inclosure.size) ) {
if(!any(is.na(inclosure.size))){
avaiable=min(inclosure.size,length(ID.GP))
if(avaiable==0){
ID.GP=-1
}else{
ID.GP=ID.GP[1:avaiable] #keep the top ones selected
}
}
}
#create index in GI
theIndex=NULL
if(!is.null(GI)){
ID.GI=as.numeric(as.vector(GI[, 3]))+as.numeric(as.vector(GI[, 2]))*MaxBP
theIndex=ID.GI %in% ID.GP
}
myList=list(index=theIndex,CB=ID.GP)
return (list(index=theIndex,CB=ID.GP))
} #end of FarmCPU.Specify
#' To quickly sovel LM with one variable substitute multiple times
#'
#' Start date: March 1, 2013
#' Last update: March 6, 2013
#' Strategy:
#' 1. Separate constant covariates (w) and dynamic coveriates (x)
#' 2. Build non-x related only once
#' 3. Use apply to iterate x
#' 4. Derive dominance indicate d from additive indicate (x) mathmaticaly
#' 5. When d is not estimable, continue to test x
#'
#' @author Xiaolei Liu and Zhiwu Zhang
#'
#' @param y one column matrix, dependent variable
#' @param w covariates, n by c matrix, n is sample size, c is number of covariates
#' @param GDP genotype, m by n matrix, m is marker size, n is sample size. This is Pure Genotype Data Matrix(GD). THERE IS NO COLUMN FOR TAXA.
#' @param ncpus number of threads used for parallele computation
#' @param npc number of covariates without pseudo QTNs
#' @param verbose whether to print detail.
#'
#' @return
#' Output: P - p-value of each SNP
#' Output: betapred - effects of pseudo QTNs
#' Output: B - effect of each SNP
#'
#' @keywords internal
FarmCPU.LM <-
function(y, w=NULL, GDP, ncpus=2, npc=0, verbose=TRUE){
#print("FarmCPU.LM started")
if(is.null(y)) return(NULL)
if(is.null(GDP)) return(NULL)
#Constant section (non individual marker specific)
#---------------------------------------------------------
#Configration
nd=20 #number of markes for checking A and D dependency
N=length(y) #Total number of taxa, including missing ones
if(!is.null(w)){
w=as.matrix(w,nrow = N)
nf=ncol(w)
w=cbind(rep(1,N),w)
q0=ncol(w)
}else{
w=rep(1,N)
nf=0
q0=1
}
w = as.matrix(w)
logging.log("number of covariates in current loop is:", "\n", verbose = verbose)
logging.log(nf, "\n", verbose = verbose)
n=N
if(nd>n)nd=n #handler of samples less than nd
k=1 #number of genetic effect: 1 and 2 for A and AD respectively
q1=(q0+1) # vecter index for the posistion of genetic effect (a)
q2=(q0+1):(q0+2) # vecter index for the posistion of genetic effect (a and d)
df=n-q0-k #residual df (this should be varied based on validating d)
iXX=matrix(0,q0+k,q0+k) #Reserve the maximum size of inverse of LHS
# ww=crossprodcpp(w)
ww = crossprod(w)
wy = crossprod(w,y)
# yy=crossprodcpp(y)
yy = crossprod(y)
wwi = ginv(ww)
#Statistics on the reduced model without marker
rhs=wy
beta <- crossprod(wwi,rhs)
ve <- (yy - crossprod(beta, rhs)) / df
se <- sqrt(diag(wwi) * ve[1])
if(npc!=0){
betapc = beta[2:(npc+1)]
betapred = beta[-c(1:(npc+1))]
sepred = se[-c(1:(npc+1))]
}else{
betapc = NULL
betapred = beta[-1]
sepred = se[-1]
}
#print(ncpus)
logging.log("scanning...", "\n", verbose = verbose)
# P <- NULL
# B <- NULL
# S <- NULL
# setMKLthreads(10)
# for(i in 1:nrow(GDP)){
# xx <- summary(lm(y~cbind(w,GDP[i, ])))$coeff
# P <- rbind(P, xx[-1,4,drop=TRUE])
# B <- c(B, xx[nrow(xx), 1])
# S <- c(S, xx[nrow(xx), 2])
# }
# if(ncol(w) == 50) write.csv(P, "P.csv")
mkl_env({
results <- glm_c(y=y, X=w, iXX = wwi, GDP@address, verbose=verbose, threads=ncpus)
})
return(list(P=results[ ,-c(1:3), drop=FALSE], betapred=betapred, sepred=sepred, B=results[ , 1, drop=FALSE], S=results[ , 2, drop=FALSE]))
# return(list(P=P, betapred=betapred, B=as.matrix(B), S=S))
} #end of FarmCPU.LM function
#' FarmCPU.Burger
#'
#' Last update: Dec 21, 2016
#' To calculate likelihood, variances and ratio, revised by Xiaolei based on GAPIT.Burger function from GAPIT package
#'
#' @author Xiaolei Liu and Zhiwu Zhang
#'
#' @param Y phenotype, n by t matrix, n is sample size, t is number of phenotypes
#' @param CV covariates, n by c matrix, n is sample size, c is number of covariates
#' @param GK Genotype data in numerical format, taxa goes to row and snp go to columns
#' @param ncpus number of threads used for parallele computation
#' @param method two options for estimating variance components, 'FaST-LMM' or 'EMMA'
#'
#' @return
#' Output: REMLs - maximum log likelihood
#' Output: vg - genetic variance
#' Output: ve - residual variance
#' Output: delta - exp(root)
#'
#' @keywords internal
FarmCPU.Burger <-
function(Y=NULL,CV=NULL,GK=NULL,ncpus=2, method="FaST-LMM"){
if(!is.null(CV)){
CV=as.matrix(CV)#change CV to a matrix when it is a vector
theCV=as.matrix(cbind(matrix(1,nrow(CV),1),CV))
}else{
theCV=matrix(1,nrow(Y),1)
}
#handler of single column GK
n=nrow(GK)
m=ncol(GK)
if(!is.null(GK)){
n=nrow(GK)
m=ncol(GK)
if(m > 2){
theGK = as.matrix(GK)#GK is pure genotype matrix
}else if(m==0){
theGK = NULL
}else{
theGK = matrix(GK,n,1)
}
}else{
theGK=GK
}
if(method=="FaST-LMM"){
myFaSTREML=FarmCPU.FaSTLMM.LL(pheno=matrix(Y[,-1],nrow(Y),1), snp.pool=theGK, X0=theCV, ncpus=ncpus)
REMLs=-2*myFaSTREML$LL
delta=myFaSTREML$delta
vg=myFaSTREML$vg
ve=myFaSTREML$ve
}
if(method=="EMMA"){
K <- MVP.K.VanRaden(M=as.big.matrix(t(theGK)), priority="speed",verbose=FALSE)
myEMMAREML <- MVP.EMMA.Vg.Ve(y=matrix(Y[,-1],nrow(Y),1), X=theCV, K=K)
REMLs=-2*myEMMAREML$REML
delta=myEMMAREML$delta
vg=myEMMAREML$vg
ve=myEMMAREML$ve
}
#print("FarmCPU.Burger succeed!")
return (list(REMLs=REMLs, vg=vg, ve=ve, delta=delta))
} #end of FarmCPU.Burger
#' FarmCPU.SUB
#'
#' Last update: Febuary 26, 2013
#' Requirement: P has row name of SNP. s<=t. covariates of QTNs are next to SNP
#'
#' @author Xiaolei Liu and Zhiwu Zhang
#'
#' @param GM SNP map information, m by 3 matrix, m is marker size, the three columns are SNP_ID, Chr, and Pos
#' @param GLM FarmCPU.GLM object
#' @param QTN s by 3 matrix for SNP name, chromosome and BP
#' @param method options are "penalty", "reward","mean","median",and "onsite"
#'
#' @return
#' Output: GLM$P - Updated p-values by substitution process
#' Output: GLM$B - Updated effects by substitution process
FarmCPU.SUB <-
function(GM=NULL,GLM=NULL,QTN=NULL,method="mean"){
if(is.null(GLM$P)) return(NULL) #P is required
if(is.null(QTN)) return(NULL) #QTN is required
#print("FarmCPU.SUB Started")
#print(length(QTN))
#if(length(QTN)==3){
#QTN=QTN[1]
#}else{
QTN=QTN[ , 1, drop=FALSE]
#}
position=match(QTN, GM[, 1, drop=FALSE], nomatch = 0)
nqtn=length(position)
if(is.numeric(GLM$P)){
GLM$P = as.matrix(GLM$P)
}
GLM$B = as.matrix(GLM$B)
index=(ncol(GLM$P)-nqtn):(ncol(GLM$P)-1)
spot=ncol(GLM$P)
if(ncol(GLM$P)!=1){
if(length(index)>1){
if(method=="penalty") P.QTN=apply(GLM$P[,index],2,max,na.rm=TRUE)
if(method=="reward") P.QTN=apply(GLM$P[,index],2,min,na.rm=TRUE)
if(method=="mean") P.QTN=apply(GLM$P[,index],2,mean,na.rm=TRUE)
if(method=="median") P.QTN=apply(GLM$P[,index],2,median,na.rm=TRUE)
if(method=="onsite") P.QTN=GLM$P0[(length(GLM$P0)-nqtn+1):length(GLM$P0)]
}else{
if(method=="penalty") P.QTN=max(GLM$P[,index, drop=FALSE],na.rm=TRUE)
if(method=="reward") P.QTN=min(GLM$P[,index, drop=FALSE],na.rm=TRUE)
if(method=="mean") P.QTN=mean(GLM$P[,index, drop=FALSE],na.rm=TRUE)
if(method=="median") P.QTN=median(GLM$P[,index, drop=FALSE],median,na.rm=TRUE)
if(method=="onsite") P.QTN=GLM$P0[(length(GLM$P0)-nqtn+1):length(GLM$P0)]
}
#replace SNP pvalues with QTN pvalue
GLM$P[position, spot] = P.QTN
GLM$B[position, ] = GLM$betapred
GLM$S[position, ] = GLM$sepred
}
return(GLM)
}#The function FarmCPU.SUB ends here
#' Remove bins that are highly correlated
#'
#' Last update: March 4, 2013
#' Requirement: GDP and GM have the same order on SNP
#'
#' @author Xiaolei Liu and Zhiwu Zhang
#'
#' @param GDP genotype, m by n matrix, m is marker size, n is sample size. This is Pure Genotype Data Matrix(GD). THERE IS NO COLUMN FOR TAXA
#' @param GM SNP map information, m by 3 matrix, m is marker size, the three columns are SNP_ID, Chr, and Pos
#' @param seqQTN s by 1 vecter for index of QTN on GM
#' @param seqQTN.p p value of each @param seqQTN
#' @param threshold pearson correlation threshold for remove correlated markers
#'
#' @return
#' Output: bin - n by s0 matrix of genotype
#' Output: binmap - s0 by 3 matrix for map of bin
#' Output: seqQTN - s0 by 1 vecter for index of QTN on GM
#' Relationship: bin=GDP[,c(seqQTN)], binmap=GM[seqQTN,], s0<=s
#' @keywords internal
FarmCPU.Remove <-
function(GDP=NULL, GM=NULL, seqQTN=NULL, seqQTN.p=NULL, threshold=.99){
if(is.null(seqQTN))return(list(bin=NULL,binmap=NULL,seqQTN=NULL))
seqQTN=seqQTN[order(seqQTN.p)]
hugeNum=10e10
n=length(seqQTN)
#fielter bins by physical location
binmap=GM[seqQTN, , drop=FALSE]
cb=as.numeric(binmap[, 2, drop=FALSE])*hugeNum+as.numeric(binmap[, 3, drop=FALSE])#create ID for chromosome and bp
cb.unique=unique(cb)
#print("debuge")
#print(cb)
#print(cb.unique)
index=match(cb.unique,cb,nomatch = 0)
seqQTN=seqQTN[index]
#print("Number of bins after chr and bp fillter")
n=length(seqQTN) #update n
#Set sample
ratio=.1
maxNum=100000
m=nrow(GDP) #sample size
s=ncol(GDP) #number of markers
sampled=s
if(sampled>maxNum)sampled=maxNum
#index=sample(s,sampled)
index=1:sampled
#This section has problem of turning big.matrix to R matrix
#It is OK as x is small
if(is.big.matrix(GDP)){
x=t(as.matrix(deepcopy(GDP,rows=seqQTN,cols=index) ))
}else{
x=t(GDP[seqQTN,index] )
}
r=cor(as.matrix(x))
index=abs(r)>threshold
b=r*0
b[index]=1
c=1-b
#The above are replaced by following
c[lower.tri(c)]=1
diag(c)=1
bd <- apply(c,2,prod)
position=(bd==1)
seqQTN=seqQTN[position]
#============================end of optimum============================================
seqQTN=seqQTN[!is.na(seqQTN)]
#This section has problem of turning big.matrix to R matrix
if(is.big.matrix(GDP)){
bin=t(as.matrix(deepcopy(GDP,rows=seqQTN,) ))
}else{
bin=t(GDP[seqQTN, , drop=FALSE] )
}
binmap=GM[seqQTN, , drop=FALSE]
return(list(bin=bin, binmap=binmap, seqQTN=seqQTN))
}#The function FarmCPU.Remove ends here
#' Set prior on existing p value
#'
#' Last update: March 10, 2013
#' Requirement: P and GM are in the same order, Prior is part of GM except P value
#'
#' @author Xiaolei Liu and Zhiwu Zhang
#'
#' @param GM an m by 3 matrix for SNP name, chromosome and BP
#' @param P an m by 1 matrix containing probability
#' @param Prior an s by 4 matrix for SNP name, chromosome, BP and p-value
#'
#' @return
#' Output: P - updated P value by prior information
#'
#' @keywords internal
FarmCPU.Prior <-
function(GM, P=NULL, Prior=NULL){
#print("FarmCPU.Prior Started")
if(is.null(Prior)& is.null(P))return(P)
#get prior position
if(!is.null(Prior)) index=match(Prior[, 1, drop=FALSE],GM[, 1, drop=FALSE],nomatch = 0)
#if(is.null(P)) P=runif(nrow(GM)) #set random p value if not provided (This is not helpful)
#print("debug set prior a")
#Get product with prior if provided
if(!is.null(Prior) & !is.null(P) )P[index]=P[index]*Prior[, 4, drop=FALSE]
return(P)
}#The function FarmCPU.Prior ends here
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