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/**********************************************************************
*
* mqmscan.cpp
*
* Copyright (c) 1996-2009 by
* Ritsert C Jansen, Danny Arends, Pjotr Prins and Karl W Broman
*
* initial MQM C code written between 1996-2002 by Ritsert C. Jansen
* improved for the R-language by Danny Arends, Pjotr Prins and Karl W. Broman
*
* Modified by Pjotr Prins and Danny Arends
* last modified December 2009
*
* 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
*
* C functions for the R/qtl package
*
**********************************************************************/
#include "mqm.h"
#include <Rmath.h>
#include <limits>
using namespace std;
inline int mqmmod(int a, int b) {
return a%b;
}
/*
* Helper function for truncate
*/
static double ftruncate(double n, double p = 3){
int sign = 1; // Assume positive sign
if(n < 0) sign = -1; // Test the assumption and change the sign if needed
double val = fabs((pow(10,p)) * n);
val = floor(val);
val /= pow(10,p);
return (double) sign * val;
}
/*
* Truncate a floating point to 3 decimal numbers. This is used for output
* functions, in particular for regression tests - so floating point problems on
* different platforms are eliminated
*/
double ftruncate3(double n){
return ftruncate(n,3);
}
double Lnormal(double residual, double variance) {
//Now using R-library for Lnormal
double result = dnorm(residual,0,sqrt(variance),0);
debug_trace("Lnormal result:%f, residual: %f, variance %f\n",result,residual,variance);
return result;
}
void reorg_pheno(int n_ind, int n_mar, double *pheno, double ***Pheno) {
//reorganisation of doubles into a matrix
int i;
*Pheno = (double **)R_alloc(n_mar, sizeof(double *));
(*Pheno)[0] = pheno;
for (i=1; i< n_mar; i++)
(*Pheno)[i] = (*Pheno)[i-1] + n_ind;
}
void reorg_int(int n_ind, int n_mar, int *pheno, int ***Pheno) {
//reorganisation of integers into a matrix
int i;
*Pheno = (int **)R_alloc(n_mar, sizeof(int *));
(*Pheno)[0] = pheno;
for (i=1; i< n_mar; i++)
(*Pheno)[i] = (*Pheno)[i-1] + n_ind;
}
/*
* analyseF2 - analyse one F2/RIL/BC family
* This is the main controller - called by mqmscan
*
* Returns logL
*/
double analyseF2(int Nind, int *nummark, cvector *cofactor, MQMMarkerMatrix marker,
vector y, int Backwards, double **QTL,vector
*mapdistance, int **Chromo, int Nrun, int RMLorML, double
windowsize, double stepsize, double stepmin, double stepmax,
double alfa, int em, int out_Naug, int **INDlist, char
reestimate, MQMCrossType crosstype, bool dominance, int verbose) {
if (verbose) Rprintf("INFO: Starting C-part of the MQM analysis\n");
int Naug, Nmark = (*nummark), run = 0;
bool useREML = true, fitQTL = false;
bool warned = false;
ivector chr = newivector(Nmark); // The chr vector contains the chromosome number for every marker
for(int i = 0; i < Nmark; i++){ // Rprintf("INFO: Receiving the chromosome matrix from R");
chr[i] = Chromo[0][i];
}
if(RMLorML == 1) useREML=false; // use ML instead
// Create an array of marker positions - and calculate R[f] based on these locations
cvector position = relative_marker_position(Nmark,chr);
vector r = recombination_frequencies(Nmark, position, (*mapdistance));
//Rprintf("INFO: Initialize Frun and informationcontent to 0.0");
const int Nsteps = (int)(chr[Nmark-1]*((stepmax-stepmin)/stepsize+1));
matrix Frun = newmatrix(Nsteps,Nrun+1);
vector informationcontent = newvector(Nsteps);
for (int i = 0; i < (Nrun+1); i++) {
for (int ii = 0; ii < Nsteps; ii++) {
if(i==0) informationcontent[ii] = 0.0;
Frun[ii][i]= 0.0;
}
}
bool dropj = false;
int jj=0;
// Rprintf("any triple of non-segregating markers is considered to be the result of:\n");
// Rprintf("identity-by-descent (IBD) instead of identity-by-state (IBS)\n");
// Rprintf("no (segregating!) cofactors are fitted in such non-segregating IBD regions\n");
for (int j=0; j < Nmark; j++) { // WRONG: (Nmark-1) Should fix the out of bound in mapdistance, it does fix, but created problems for the last marker
dropj = false;
if(j+1 < Nmark){ // Check if we can look ahead
if(((*mapdistance)[j+1]-(*mapdistance)[j])==0.0){ dropj=true; }
}
if (!dropj) {
marker[jj] = marker[j];
(*cofactor)[jj] = (*cofactor)[j];
(*mapdistance)[jj] = (*mapdistance)[j];
chr[jj] = chr[j];
r[jj] = r[j];
position[jj] = position[j];
jj++;
} else{
if (verbose) Rprintf("INFO: Marker %d at chr %d is dropped\n",j,chr[j]);
if ((*cofactor)[j]==MCOF) {
if (verbose) Rprintf("INFO: Cofactor at chr %d is dropped\n",chr[j]);
}
}
}
//if(verbose) Rprintf("INFO: Number of markers: %d -> %d\n",Nmark,jj);
Nmark = jj;
(*nummark) = jj;
// Update the array of marker positions - and calculate R[f] based on these new locations
position = relative_marker_position(Nmark,chr);
r = recombination_frequencies(Nmark, position, (*mapdistance));
debug_trace("After dropping of uninformative cofactors\n");
ivector newind; // calculate Traits mean and variance
vector newy;
MQMMarkerMatrix newmarker;
double ymean = 0.0, yvari = 0.0;
//Rprintf("INFO: Number of individuals: %d Number Aug: %d",Nind,out_Naug);
int cur = -1;
for (int i=0; i < Nind; i++){
if(INDlist[0][i] != cur){
ymean += y[i];
cur = INDlist[0][i];
}
}
ymean/= out_Naug;
for (int i=0; i < Nind; i++){
if(INDlist[0][i] != cur){
yvari += pow(y[i]-ymean, 2);
cur = INDlist[0][i];
}
}
yvari /= (out_Naug-1);
Naug = Nind; // Fix for not doing dataaugmentation, we just copy the current as the augmented and set Naug to Nind
Nind = out_Naug;
newind = newivector(Naug);
newy = newvector(Naug);
newmarker = newMQMMarkerMatrix(Nmark,Naug);
for (int i=0; i<Naug; i++) {
newy[i]= y[i];
newind[i]= INDlist[0][i];
for (int j=0; j<Nmark; j++) {
newmarker[j][i]= marker[j][i];
}
}
// End fix
vector newweight = newvector(Naug);
double max = rmixture(newmarker, newweight, r, position, newind,Nind, Naug, Nmark, mapdistance,reestimate,crosstype,verbose); //Re-estimation of mapdistances if reestimate=TRUE
if(max > stepmax){ fatal("ERROR: Re-estimation of the map put markers at: %f Cm, run the algorithm with a step.max larger than %f Cm", max, max); }
//Check if everything still is correct positions and R[f]
position = relative_marker_position(Nmark,chr);
r = recombination_frequencies(Nmark, position, (*mapdistance));
/* eliminate individuals with missing trait values */
//We can skip this part iirc because R throws out missing phenotypes beforehand
int oldNind = Nind;
for (int i=0; i<oldNind; i++) {
Nind -= ((y[i]==TRAITUNKNOWN) ? 1 : 0);
}
int oldNaug = Naug;
for (int i=0; i<oldNaug; i++) {
Naug -= ((newy[i]==TRAITUNKNOWN) ? 1 : 0);
}
marker = newMQMMarkerMatrix(Nmark+1,Naug);
y = newvector(Naug);
ivector ind = newivector(Naug);
vector weight = newvector(Naug);
int newi = 0;
for (int i=0; i < oldNaug; i++)
if (newy[i]!=TRAITUNKNOWN) {
y[newi]= newy[i];
ind[newi]= newind[i];
weight[newi]= newweight[i];
for (int j=0; j<Nmark; j++) marker[j][newi]= newmarker[j][i];
newi++;
}
int diff;
for (int i=0; i < (Naug-1); i++) {
diff = ind[i+1]-ind[i];
if (diff>1) {
for (int ii=i+1; ii<Naug; ii++){ ind[ii]=ind[ii]-diff+1; }
}
}
//END throwing out missing phenotypes
double variance=-1.0;
cvector selcofactor = newcvector(Nmark); /* selected cofactors */
int dimx = designmatrixdimensions((*cofactor),Nmark,dominance);
double F1 = inverseF(1,Nind-dimx,alfa,verbose);
double F2 = inverseF(2,Nind-dimx,alfa,verbose);
if (verbose) {
Rprintf("INFO: dimX: %d, nInd: %d\n",dimx,Nind);
Rprintf("INFO: F(Threshold, Degrees of freedom 1, Degrees of freedom 2) = Alfa\n");
Rprintf("INFO: F(%.3f, 1, %d) = %f\n",ftruncate3(F1),(Nind-dimx),alfa);
Rprintf("INFO: F(%.3f, 2, %d) = %f\n",ftruncate3(F2),(Nind-dimx),alfa);
}
F2 = 2.0* F2; // 9-6-1998 using threshold x*F(x,df,alfa)
weight[0]= -1.0;
double logL = QTLmixture(marker,(*cofactor),r,position,y,ind,Nind,Naug,Nmark,&variance,em,&weight,useREML,fitQTL,dominance,crosstype, &warned, verbose);
if(verbose){
if (!R_finite(logL)) {
Rprintf("WARNING: Log-likelihood of full model = INFINITE\n");
}else{
if (R_IsNaN(logL)) {
Rprintf("WARNING: Log-likelihood of full model = NOT A NUMBER (NAN)\n");
}else{
Rprintf("INFO: Log-likelihood of full model = %.3f\n",ftruncate3(logL));
}
}
Rprintf("INFO: Residual variance = %.3f\n",ftruncate3(variance));
Rprintf("INFO: Trait mean= %.3f; Trait variation = %.3f\n",ftruncate3(ymean),ftruncate3(yvari));
}
if (R_finite(logL) && !R_IsNaN(logL)) {
if(Backwards==1){ // use only selected cofactors
logL = backward(Nind, Nmark, (*cofactor), marker, y, weight, ind, Naug, logL,variance, F1, F2, &selcofactor, r,
position, &informationcontent, mapdistance,&Frun,run,useREML,fitQTL,dominance, em, windowsize,
stepsize, stepmin, stepmax,crosstype,verbose);
}else{ // use all cofactors
logL = mapQTL(Nind, Nmark, (*cofactor), (*cofactor), marker, position,(*mapdistance), y, r, ind, Naug, variance,
'n', &informationcontent,&Frun,run,useREML,fitQTL,dominance, em, windowsize, stepsize, stepmin,
stepmax,crosstype,verbose); // printout=='n'
}
}
// Write output and/or send it back to R
// Cofactors that made it to the final model
for (int j=0; j<Nmark; j++) {
if (selcofactor[j]==MCOF) {
(*cofactor)[j]=MCOF;
}else{
(*cofactor)[j]=MNOCOF;
}
}
if (verbose) Rprintf("INFO: Number of output datapoints: %d\n", Nsteps); // QTL likelihood for each location
for (int ii=0; ii<Nsteps; ii++) {
//Convert LR to LOD before sending back
QTL[0][ii] = Frun[ii][0] / 4.60517;
QTL[0][Nsteps+ii] = informationcontent[ii];
}
return logL;
}
/**********************************************************************
*
* mqmscan
*
*
**********************************************************************/
void mqmscan(int Nind, int Nmark,int Npheno,int **Geno,int **Chromo, double **Dist, double **Pheno, int **Cofactors, int Backwards, int RMLorML,double Alfa,
int Emiter, double Windowsize,double Steps, double Stepmi,double Stepma,int NRUN,int out_Naug,int **INDlist, double **QTL, int re_estimate,
RqtlCrossType rqtlcrosstype,int domi,int verbose){
int cof_cnt=0;
MQMMarkerMatrix markers = newMQMMarkerMatrix(Nmark+1,Nind);
cvector cofactor = newcvector(Nmark);
vector mapdistance = newvector(Nmark);
MQMCrossType crosstype = determine_MQMCross(Nmark,Nind,(const int **)Geno,rqtlcrosstype);
change_coding(&Nmark, &Nind, Geno, markers, crosstype); // Change all the markers from R/qtl format to MQM internal
for (int i=0; i< Nmark; i++) {
mapdistance[i] = POSITIONUNKNOWN; // Mapdistances
mapdistance[i] = Dist[0][i];
cofactor[i] = MNOCOF; // Cofactors
if (Cofactors[0][i] == 1) {
cofactor[i] = MCOF; // Set cofactor
cof_cnt++;
}
if (Cofactors[0][i] == 2) {
cofactor[i] = MSEX;
cof_cnt++;
}
if (cof_cnt+10 > Nind){ fatal("Setting %d cofactors would leave less than 10 degrees of freedom.\n", cof_cnt); }
}
char reestimate = 'y';
if(re_estimate == 0) reestimate = 'n';
if (crosstype != CF2) { // Determine what kind of cross we have
if (verbose==1) Rprintf("INFO: Dominance setting ignored (setting dominance to 0)\n"); // Update dominance accordingly
domi = 0;
}
bool dominance=false;
if(domi != 0){ dominance=true; }
//WE HAVE EVERYTHING START WITH MAIN SCANNING FUNCTION
analyseF2(Nind, &Nmark, &cofactor, (MQMMarkerMatrix)markers, Pheno[(Npheno-1)], Backwards, QTL, &mapdistance, Chromo, NRUN, RMLorML, Windowsize,
Steps, Stepmi, Stepma, Alfa, Emiter, out_Naug, INDlist, reestimate, crosstype, dominance, verbose);
if (re_estimate) {
if (verbose==1) Rprintf("INFO: Sending back the re-estimated map used during the MQM analysis\n");
for (int i=0; i< Nmark; i++) {
Dist[0][i] = mapdistance[i];
}
}
if (Backwards) {
if (verbose==1) Rprintf("INFO: Sending back the model\n");
for (int i=0; i< Nmark; i++) { Cofactors[0][i] = cofactor[i]; }
}
if(verbose) Rprintf("INFO: All done in C returning to R\n");
#ifndef STANDALONE
R_CheckUserInterrupt(); /* check for ^C */
R_FlushConsole();
#endif
return;
} /* end of function mqmscan */
/**********************************************************************
*
* R_mqmscan
*
**********************************************************************/
void R_mqmscan(int *Nind,int *Nmark,int *Npheno,
int *geno,int *chromo, double *dist, double *pheno,
int *cofactors, int *backwards, int *RMLorML,double *alfa,int *emiter,
double *windowsize,double *steps,double *stepmi,double *stepma,
int *nRun, int *out_Naug, int *indlist, double *qtl, int *reestimate, int *crosstype, int *domi, int *verbose) {
int **Geno;
int **Chromo;
double **Dist;
double **Pheno;
double **QTL;
int **Cofactors;
int **INDlist;
// Reorganise the pointers into arrays, singletons are just cast into the function
reorg_geno(*Nind,*Nmark,geno,&Geno);
reorg_int(*Nmark,1,chromo,&Chromo);
reorg_pheno(*Nmark,1,dist,&Dist);
// Here we have the assumption that step.min is negative this needs to be split in 2
reorg_pheno((int)(2*(*chromo) * (((*stepma)-(*stepmi))/ (*steps))),1,qtl,&QTL);
reorg_pheno(*Nind,*Npheno,pheno,&Pheno);
reorg_int(*Nmark,1,cofactors,&Cofactors);
reorg_int(*out_Naug,1,indlist,&INDlist);
mqmscan(*Nind,*Nmark,*Npheno,Geno,Chromo,Dist,Pheno,Cofactors,*backwards,*RMLorML,*alfa,*emiter,*windowsize,*steps,*stepmi,*stepma,*nRun,*out_Naug,INDlist,QTL, *reestimate,(RqtlCrossType)*crosstype,*domi,*verbose);
}
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