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#' Simulate copy number data for a case-control study.
#'
#' @param n Number of individuals.
#' @param nbSNP Size of the DNA sequence.
#' @param probCas Probability to be a case individual.
#' @param nbSeg Number of causal segments.
#' @param meanSegmentSize The mean size of anormal segment.
#' @param prob A 2*2 matrix containing probabilities:
#'
#' prob[1,1]=probability to have an anomaly to a SNP given the person does not have the disease and the SNP is causal.
#'
#' prob[1,2]=probability to have an anomaly to a SNP given the person does not have the disease and the SNP is not causal.
#'
#' prob[2,1]=probability to have an anomaly to a SNP given the person has the disease and the SNP is causal.
#'
#' prob[2,2]=probability to have an anomaly to a SNP given the person has the disease and the SNP is not causal.
#'
#' @param alpha Parameter of the beta(alpha,alpha).
#' @return a list containing:
#' \item{data}{A matrix of size n*nbSeg, containing values of the copy-number signal.}
#' \item{response}{A vector of size n containing the cas/control status.}
#' \item{causalSNP}{A vector of size nbSeg containing the center of causal segments.}
#' @author Quentin Grimonprez, Serge Iovleff
#' @examples
#' MPA.simul(50,10000,0.4,10,150,matrix(c(0.1,0.8,0.001,0.001),nrow=2))
#' @export
MPA.simul=function(n,nbSNP,probCas,nbSeg,meanSegmentSize,prob,alpha=15)
{
if(missing(n))
stop("n is missing.")
if(missing(nbSNP))
stop("nbSNP is missing.")
if(missing(probCas))
stop("probCas is missing.")
if(missing(nbSeg))
stop("nbSeg is missing.")
if(missing(meanSegmentSize))
stop("meanSegmentSize is missing.")
if(missing(prob))
stop("prob is missing.")
.checkSim(n,nbSNP,probCas,nbSeg,meanSegmentSize,prob,alpha)
#choose the causal SNPs
SNPcaus=sort(sample(1:nbSNP,nbSeg))
#generation of the response
y=rbinom(n,1,probCas)
#initialization of the copy-number signal with a normal signal
X=matrix(rbeta(n*nbSNP,alpha,alpha)+1.5,n,nbSNP)
#decide if the anomaly at a causal SNP is a gain or a loss
anoSNPcaus=2*rbinom(nbSeg,1,0.5)+0.5
anomalie=rep(0,nbSNP)
for(i in 1:n)
{
#where the individuals has an anomaly?
anomalie[SNPcaus]=rbinom(nbSeg,1,prob[y[i]+1,1])
anomalie[-SNPcaus]=rbinom(nbSNP-nbSeg,1,prob[y[i]+1,2])
#size of anomaly
segSize=rpois(which(anomalie==1),meanSegmentSize)
segSize[segSize==0]=1
compteur=1
for(j in which(anomalie==1))
{
sequence=max(1,j-floor(segSize[compteur]/2)):min(nbSNP,j+floor(segSize[compteur]/2))
if(j %in% SNPcaus)
X[i,sequence]=anoSNPcaus[which(SNPcaus==j)]+rbeta(length(sequence),alpha,alpha)
else
X[i,sequence]=2*rbinom(1,1,0.5)+0.5+rbeta(length(sequence),alpha,alpha)
compteur=compteur+1
}
}
return(list(data=X,response=y,causalSNP=SNPcaus))
}
# check arguments from simulation function
.checkSim=function(n,nbSNP,probCas,nbSeg,meanSegmentSize,prob,alpha)
{
## n
if(!.is.wholenumber(n))
stop("n must be a positive integer")
if(n<=0)
stop("n must be a positive integer")
## nbSNP
if(!.is.wholenumber(nbSNP))
stop("nbSNP must be a positive integer")
if(n<=0)
stop("nbSNP must be a positive integer")
## probCas
if(!is.double(probCas))
stop("probCas must be a real between 0 and 1")
if( (probCas<0) || (probCas>1) )
stop("probCas must be a real between 0 and 1")
## nbSeg
if(!.is.wholenumber(nbSeg))
stop("nbSeg must be a positive integer smaller than nbSNP")
if( (nbSeg<0) || (nbSeg> nbSNP) )
stop("nbSeg must be a positive integer smaller than nbSNP")
## meanSegmentSize
if(!.is.wholenumber( meanSegmentSize))
stop(" meanSegmentSize must be a positive integer smaller than nbSNP")
if( (meanSegmentSize<=0) || (meanSegmentSize>nbSNP) )
stop(" meanSegmentSize must be a positive integer smaller than nbSNP")
## prob
if(!is.numeric(prob) || !is.matrix(prob))
stop("prob must be a 2*2 matrix of probability")
if( (ncol(prob)!=2) || (nrow(prob)!=2) || any(prob<0) || any(prob>1) )
stop("prob must be a 2*2 matrix of probability")
## alpha
if(!is.double(alpha))
stop("alpha must be a real greater than 1")
if( alpha<1 )
stop("alpha must be a real greater than 1")
}
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