######################################################################
#
# scanqtl.R
#
# copyright (c) 2002-2019, Hao Wu and Karl W. Broman
# last modified Dec, 2019
# first written Apr, 2002
#
# This program is free software; you can redistribute it and/or
# modify it under the terms of the GNU General Public License,
# version 3, as published by the Free Software Foundation.
#
# This program is distributed in the hope that it will be useful,
# but without any warranty; without even the implied warranty of
# merchantability or fitness for a particular purpose. See the GNU
# General Public License, version 3, for more details.
#
# A copy of the GNU General Public License, version 3, is available
# at http://www.r-project.org/Licenses/GPL-3
#
# Part of the R/qtl package
# Contains: scanqtl
#
######################################################################
scanqtl <-
function(cross, pheno.col=1, chr, pos, covar=NULL, formula,
method=c("imp", "hk"), model=c("normal", "binary"),
incl.markers=FALSE, verbose=TRUE, tol=1e-4, maxit=1000,
forceXcovar=FALSE)
{
if(!inherits(cross, "cross"))
stop("Input should have class \"cross\".")
if(!is.null(covar) && !is.data.frame(covar)) {
if(is.matrix(covar) && is.numeric(covar))
covar <- as.data.frame(covar, stringsAsFactors=TRUE)
else stop("covar should be a data.frame")
}
if(LikePheVector(pheno.col, nind(cross), nphe(cross))) {
cross$pheno <- cbind(pheno.col, cross$pheno)
pheno.col <- 1
}
if(length(pheno.col) > 1) {
pheno.col <- pheno.col[1]
warning("scanqtl can take just one phenotype; only the first will be used")
}
if(is.character(pheno.col)) {
num <- find.pheno(cross, pheno.col)
if(is.na(num))
stop("Couldn't identify phenotype \"", pheno.col, "\"")
pheno.col <- num
}
if(pheno.col < 1 | pheno.col > nphe(cross))
stop("pheno.col values should be between 1 and the no. phenotypes")
pheno <- cross$pheno[,pheno.col]
if(!is.null(covar) && nrow(covar) != length(pheno))
stop("nrow(covar) != no. individuals in cross.")
method <- match.arg(method)
model <- match.arg(model)
# allow formula to be a character string
if(!missing(formula) && is.character(formula))
formula <- as.formula(formula)
if(method=="imp") {
if(!("draws" %in% names(cross$geno[[1]]))) {
if("prob" %in% names(cross$geno[[1]])) {
warning("The cross doesn't contain imputations; using method=\"hk\".")
method <- "hk"
}
else
stop("You need to first run sim.geno.")
}
}
else {
if(!("prob" %in% names(cross$geno[[1]]))) {
if("draws" %in% names(cross$geno[[1]])) {
warning("The cross doesn't contain QTL genotype probabilities; using method=\"imp\".")
method <- "imp"
}
else
stop("You need to first run calc.genoprob.")
}
}
if(method=="imp") {
if("stepwidth" %in% names(attributes(cross$geno[[1]]$draws)) &&
attr(cross$geno[[1]]$draws, "stepwidth") != "fixed") {
stepwidth.var <- TRUE
incl.markers <- TRUE
}
else stepwidth.var <- FALSE
}
else {
if("stepwidth" %in% names(attributes(cross$geno[[1]]$prob)) &&
attr(cross$geno[[1]]$prob, "stepwidth") != "fixed") {
stepwidth.var <- TRUE
incl.markers <- TRUE
}
else stepwidth.var <- FALSE
}
type <- crosstype(cross)
chr_type <- sapply(cross$geno, chrtype)
# input data checking
if( length(chr) != length(pos))
stop("Input chr and pos must have the same length")
# note that input chr is a vector and pos is a list
method <- match.arg(method)
ichr <- match(chr, names(cross$geno))
if(any(is.na(ichr)))
stop("There's no chromosome number ", chr[is.na(ichr)],
" in input cross object")
# if formula is missing, make one.
# All QTLs and covariates will be additive by default
n.qtl <- length(chr)
n.covar <- length(covar)
if(missing(formula)) {
tmp.Q <- paste("Q", 1:n.qtl, sep="") # QTL term names
formula <- "y~Q1"
if(n.qtl > 1)
for (i in 2:n.qtl)
formula <- paste(formula, tmp.Q[i], sep="+")
if (n.covar) { # if covariate is not empty
tmp.C <- names(covar) # covariate term names
for(i in 1:n.covar)
formula <- paste(formula, tmp.C[i], sep="+")
}
formula <- as.formula(formula)
}
else {
# include all input QTLs and covariates in the formula additively
formula.str <- deparseQTLformula(formula) # deparse formula as a string
for(i in 1:n.qtl) { # loop thru the QTLs
qtl.term <- paste("Q", i, sep="")
if( length(grep(qtl.term, formula.str, ignore.case=TRUE))==0 )
# this term is not in the formula
# add it to the formula
formula.str <- paste(formula.str, qtl.term, sep="+")
}
if(n.covar) { # covariate is not empty
for(i in 1:n.covar) {
covar.term <- names(covar)[i]
if( length(grep(covar.term, formula.str, ignore.case=TRUE))==0 )
# this term is not in the formula
# add it to the formula
formula.str <- paste(formula.str, covar.term, sep="+")
}
}
formula <- as.formula(formula.str)
}
# check the formula
formula <- checkformula(formula, paste("Q", 1:length(chr), sep=""),
colnames(covar))
# drop covariates that are not in the formula
if(!is.null(covar)) {
theterms <- rownames(attr(terms(formula), "factors"))
m <- match(colnames(covar), theterms)
if(all(is.na(m))) covar <- NULL
else covar <- covar[,!is.na(m),drop=FALSE]
}
# check phenotypes and covariates; drop ind'ls with missing values
if(!is.null(covar)) phcovar <- cbind(pheno, covar)
else phcovar <- cbind(pheno)
if(any(is.na(phcovar))) {
if(ncol(phcovar)==1) hasmissing <- is.na(phcovar)
else hasmissing <- apply(phcovar, 1, function(a) any(is.na(a)))
if(all(hasmissing))
stop("All individuals are missing phenotypes or covariates.")
if(any(hasmissing)) {
warning("Dropping ", sum(hasmissing), " individuals with missing phenotypes.\n")
cross <- subset(cross, ind=!hasmissing)
pheno <- pheno[!hasmissing]
if(!is.null(covar)) covar <- covar[!hasmissing,,drop=FALSE]
}
}
sexpgm <- getsex(cross)
# find the chromosome with multiple QTLs
# indices for chromosomes with multiple QTLs
idx.varied <- NULL
indices <- pos ## added by Karl 8/23/05
for(i in 1:length(pos)) {
l <- length(pos[[i]] )
if( l >= 2 ) {
# if there're more than two elements in pos, issue warning message
if(l > 2) {
msg <- "There are more than two elements in "
msg <- paste(msg, i, "th input pos.")
msg <- paste(msg, "The first two are taken as starting and ending position.")
warning(msg)
}
# user specified a range
# find all markers in this range
idx.varied <- c(idx.varied, i)
# make the genetic map on this chromosome
# make genetic map
if(method=="imp") {
if("map" %in% names(attributes(cross$geno[[ichr[i]]]$draws)))
map <- attr(cross$geno[[ichr[i]]]$draws,"map")
else {
stp <- attr(cross$geno[[ichr[i]]]$draws, "step")
oe <- attr(cross$geno[[ichr[i]]]$draws, "off.end")
if("stepwidth" %in% names(attributes(cross$geno[[ichr[i]]]$draws)))
stpw <- attr(cross$geno[[ichr[i]]]$draws, "stepwidth")
else stpw <- "fixed"
map <- create.map(cross$geno[[ichr[i]]]$map,stp,oe,stpw)
}
}
else {
if("map" %in% names(attributes(cross$geno[[ichr[i]]]$prob)))
map <- attr(cross$geno[[ichr[i]]]$prob,"map")
else {
stp <- attr(cross$geno[[ichr[i]]]$prob, "step")
oe <- attr(cross$geno[[ichr[i]]]$prob, "off.end")
if("stepwidth" %in% names(attributes(cross$geno[[ichr[i]]]$prob)))
stpw <- attr(cross$geno[[ichr[i]]]$prob, "stepwidth")
else stpw <- "fixed"
map <- create.map(cross$geno[[ichr[i]]]$map,stp,oe,stpw)
}
}
# pull out the female map if there are sex-specific maps
if(is.matrix(map)) map <- map[1,]
indices[[i]] <- seq(along=map)
if(method=="imp")
step <- attr(cross$geno[[ichr[i]]]$draws,"step")
else
step <- attr(cross$geno[[ichr[i]]]$prob,"step")
if(!incl.markers && step>0) { # equally spaced positions
eq.sp.pos <- seq(min(map), max(map), by=step)
wh.eq.pos <- match(eq.sp.pos, map)
map <- map[wh.eq.pos]
indices[[i]] <- indices[[i]][wh.eq.pos]
}
# locate the markers given starting and ending postion
# we should do this before or after incl.markers?
start <- pos[[i]][1]
end <- pos[[i]][2]
# replace pos[[i]] (a range) by the marker positions within the range
# extend the position to the nearest markers outside the ranges
tmp <- which( (map - start)<=0 )
if(length(tmp) != 0) # starting position is after the first marker
start <- map[max(tmp)]
tmp <- which( (end-map) <= 0 )
if(length(tmp) != 0) # ending position is before the last marker
end <- map[min(tmp)]
pos[[i]] <- as.vector( map[(map>=start)&(map<=end)] )
indices[[i]] <- indices[[i]][(map>=start)&(map<=end)]
}
}
# Now, pos contains all the marker positions for all chromosomes
#########################
# Now start general scan
#########################
# There might be several chromosomes with multiple QTLs
# Use one loop
sexpgm <- getsex(cross)
cross.attr <- attributes(cross)
# number of chromosomes with multiple positions to be scanned
n.idx.varied <- length(idx.varied)
n.loop <- 1 # total number of loops
if(n.idx.varied != 0) { # there IS some chromosomes with multiple QTL
# vector to indicate the positions indices for those chromosomes
idx.pos <- rep(0, n.idx.varied)
l.varied <- NULL
for(i in 1:n.idx.varied) {
l.varied[i] <- length(pos[[idx.varied[i]]])
n.loop <- n.loop * l.varied[i]
}
# initialize output variable
result <- array(rep(0, n.loop), rev(l.varied))
matrix.rank <- matrix.ncol <- array(rep(0, n.loop), rev(l.varied))
}
else { # fixed QTL model (no scanning)
if(method=="imp")
qtl <- makeqtl(cross, chr=chr, pos=unlist(pos), what="draws")
else
qtl <- makeqtl(cross, chr=chr, pos=unlist(pos), what="prob")
result <- fitqtlengine(pheno=pheno, qtl=qtl, covar=covar,
formula=formula, method=method, model=model, dropone=FALSE,
get.ests=FALSE, run.checks=FALSE, cross.attr=cross.attr,
crosstype=crosstype(cross),
sexpgm=sexpgm, tol=tol, maxit=maxit, forceXcovar=forceXcovar)
matrix.rank <- attr(result, "matrix.rank")
matrix.ncol <- attr(result, "matrix.ncol")
result <- result[[1]][1,4]
names(result) <- "LOD"
class(result) <- "scanqtl"
attr(result, "method") <- method
attr(result, "formula") <- deparseQTLformula(formula)
attr(result, "matrix.rank") <- matrix.rank
attr(result, "matrix.ncol") <- matrix.ncol
return(result)
}
# loop thru all varied QTLs
if(verbose) {
cat(" ",n.loop, "models to fit\n")
n.prnt <- floor(n.loop/20)
if(n.prnt < 1) n.prnt <- 1
}
current.pos <- NULL ## added by Karl 8/23/05
for(i in 1:n.loop) {
# find the indices for positions
remain <- i
if(n.idx.varied > 1) {
for(j in 1:(n.idx.varied-1)) {
ns <- 1
for( k in (j+1):n.idx.varied )
ns <- ns * length(pos[[idx.varied[k]]])
idx.pos[j] <- floor(remain / ns) + 1
remain <- remain - (idx.pos[j]-1) * ns
# remain cannot be zero
if(remain == 0) {
idx.pos[j] <- idx.pos[j] - 1
remain <- remain + ns
}
}
}
idx.pos[n.idx.varied] <- remain
# make an QTL object
pos.tmp <- NULL
for(j in 1:length(pos)) {
if(j %in% idx.varied) {
idx.tmp <- which(j==idx.varied)
pos.tmp <- c(pos.tmp, pos[[j]][idx.pos[idx.tmp]])
}
else
pos.tmp <- c(pos.tmp, pos[[j]])
}
# this bit revised by Karl 8/23/05; now we make the qtl object
# once, and copy stuff over otherwise
if(is.null(current.pos)) {
if(method=="imp")
qtl.obj <- makeqtl(cross, chr, pos.tmp, what="draws")
else
qtl.obj <- makeqtl(cross, chr, pos.tmp, what="prob")
current.pos <- pos.tmp
}
else {
thew <- rep(NA, length(pos.tmp)) ####
for(kk in seq(along=pos.tmp)) {
if(pos.tmp[kk] != current.pos[kk]) {
u <- abs(pos.tmp[kk]-pos[[kk]])
w <- indices[[kk]][u==min(u)]
if(length(w) > 1) {
warning("Confused about QTL positions. You should probably run jittermap to ensure that no two markers conincide.")
w <- sample(w, 1)
}
if(method=="imp")
qtl.obj$geno[,kk,] <- cross$geno[[ichr[kk]]]$draws[,w,]
else
qtl.obj$prob[[kk]] <- cross$geno[[ichr[kk]]]$prob[,w,]
thew[kk] <- w ####
if(chr_type[ichr[kk]]=="X" && (type=="bc" || type=="f2")) {
if(method=="imp")
qtl.obj$geno[,kk,] <-
reviseXdata(type,"full",sexpgm,draws=qtl.obj$geno[,kk,,drop=FALSE],
cross.attr=attributes(cross))
else {
temp <- qtl.obj$prob[[kk]]
temp <- array(temp, dim=c(nrow(temp),1,ncol(temp)))
dimnames(temp) <- list(NULL,"loc", 1:ncol(qtl.obj$prob[[kk]]))
qtl.obj$prob[[kk]] <- reviseXdata(type,"full",sexpgm,prob=temp,
cross.attr=attributes(cross))[,1,]
}
}
current.pos[kk] <- pos.tmp[kk]
}
}
}
# end of Karl's 8/23/05 addition
# fit QTL, don't do drop one at a time
fit <- fitqtlengine(pheno=pheno, qtl=qtl.obj, covar=covar,
formula=formula, method=method, model=model, dropone=FALSE,
get.ests=FALSE, run.checks=FALSE,
cross.attr=cross.attr, crosstype=crosstype(cross),
sexpgm=sexpgm, tol=tol, maxit=maxit,
forceXcovar=forceXcovar)
matrix.rank[i] <- attr(fit, "matrix.rank")
matrix.ncol[i] <- attr(fit, "matrix.ncol")
if(verbose && ((i-1) %% n.prnt) == 0)
cat(" ", i,"/", n.loop, "\n")
# assign to result matrix
# Note: [[1]][1,4] picks out the LOD score
result[i] <- fit[[1]][1,4]
}
# make the row and column names for the result matrix
dnames <- list(NULL)
for(i in 1:n.idx.varied) {
i.chr <- chr[idx.varied[n.idx.varied-i+1]]
i.pos <- pos[[idx.varied[n.idx.varied-i+1]]]
dnames[[i]] <- paste( paste("Chr", i.chr,sep=""),
i.pos, sep="@")
}
dimnames(result) <- dnames
class(result) <- "scanqtl"
attr(result, "method") <- method
attr(result, "formula") <- deparseQTLformula(formula)
attr(result, "matrix.rank") <- matrix.rank
attr(result, "matrix.ncol") <- matrix.ncol
result
}
#summary.scanqtl <- function(object, ...)
#{
#}
#print.summary.qtl <- function(x, ...)
#{
#}
# end of scanqtl.R
Add the following code to your website.
For more information on customizing the embed code, read Embedding Snippets.