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abcFreq.cpp
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/*
thorfinn@binf.ku.dk
part of angsd.
gnu license, mit, bsd whatever free license
BUGS:
phat doesn't put data into freq->freq. Maybe this should be fixed, in either case, nobody is using the phat estimator
*/
#include <cassert>
#include <cmath>
#include <zlib.h>
#include <htslib/kstring.h>
#include <htslib/bgzf.h>
#include "abcFreq.h"
#include "abcSaf.h"
#include "abcFilter.h"
int abcFreq::emIter = EM_NITER;
double abcFreq::EM_start = EM_START;
double *abcFreq::indF = NULL;
double abcFreq::to_pval(Chisqdist *chisq,double f){
return f<0?1:1-chisq->cdf(f);
}
//simple phat estimator from the 200danes article, one site function
double phatFun(suint *counts,int nFiles,double eps,char major,char minor) {
double pis[nFiles];
double wis[nFiles];
if(major==minor)
return 0.0;
//if the site is variable
for(int i=0;i<nFiles;i++){
int ni = counts[i*4+minor];
int nt= counts[i*4+minor] + counts[i*4+major];
if(nt==0){//if we dont have any reads for individual 'i'
pis[i] = 0;
wis[i] = 0;
continue;
}
pis[i] = (ni-eps*nt)/(nt*(1-2*eps));
wis[i] = 2.0*nt/(nt+1.0);
}
double tmp=0;
for(int i=0;i<nFiles;i++)
tmp+= (pis[i]*wis[i]);
double phatV = std::max(0.0,tmp/angsd::sum<double>(wis,nFiles));
return phatV;
}
//simple phat estimator will loop over all sites in the pars
void phatLoop(funkyPars *pars,double eps,double nInd,freqStruct *freqs){
freqs->phat = new double[pars->numSites];
freqs->freq = new double[pars->numSites];
for(int s=0;s<pars->numSites;s++)
if(pars->keepSites[s]){
freqs->phat[s] = phatFun(pars->counts[s],nInd,eps,pars->major[s],pars->minor[s]);
freqs->freq[s] = freqs->phat[s];
}
}
void abcFreq::printArg(FILE *argFile){
fprintf(argFile,"------------------------\n%s:\n",__FILE__);
fprintf(argFile,"-doMaf\t%d (Calculate persite frequencies \'.mafs.gz\')\n",doMaf);
fprintf(argFile,"\t1: Frequency (fixed major and minor)\n");
fprintf(argFile,"\t2: Frequency (fixed major unknown minor)\n");
fprintf(argFile,"\t4: Frequency from genotype probabilities\n");
fprintf(argFile,"\t8: AlleleCounts based method (known major minor)\n");
fprintf(argFile,"\tNB. Filedumping is supressed if value is negative\n");
fprintf(argFile,"-doPost\t%d\t(Calculate posterior prob 3xgprob)\n",doPost);
fprintf(argFile,"\t1: Using frequency as prior\n");
fprintf(argFile,"\t2: Using uniform prior\n");
fprintf(argFile,"\t3: Using SFS as prior (still in development)\n");
fprintf(argFile,"\t4: Using reference panel as prior (still in development), requires a site file with chr pos major minor af ac an\n");
fprintf(argFile,"Filters:\n");
fprintf(argFile,"\t-minMaf \t%f\t(Remove sites with MAF below)\n",minMaf);
fprintf(argFile,"\t-SNP_pval\t%f\t(Remove sites with a pvalue larger)\n",SNP_pval);
fprintf(argFile,"\t-rmTriallelic\t%f\t(Remove sites with a pvalue lower)\n",rmTriallelic);
fprintf(argFile,"Extras:\n");
fprintf(argFile,"\t-ref\t%s\t(Filename for fasta reference)\n",refName);
fprintf(argFile,"\t-anc\t%s\t(Filename for fasta ancestral)\n",ancName);
fprintf(argFile,"\t-eps\t%f [Only used for -doMaf &8]\n",eps);
fprintf(argFile,"\t-beagleProb\t%d (Dump beagle style postprobs)\n",beagleProb);
fprintf(argFile,"\t-indFname\t%s (file containing individual inbreedcoeficients)\n",indFname);
fprintf(argFile,"\t-underFlowProtect\t%d (file containing individual inbreedcoeficients)\n",underflowprotect);
fprintf(argFile,"NB These frequency estimators requires major/minor -doMajorMinor\n");
}
//fancy little function
int isPowerOfTwo (unsigned int x)
{
return ((x != 0) && ((x & (~x + 1)) == x));
}
void abcFreq::getOptions(argStruct *arguments){
int inputtype = arguments->inputtype;
doMaf=angsd::getArg("-doMaf",doMaf,arguments);
doPost=angsd::getArg("-doPost",doPost,arguments);
if(doMaf==0 && doPost ==0)
return;
rmTriallelic=angsd::getArg("-rmTriallelic",rmTriallelic,arguments);
GL=angsd::getArg("-GL",GL,arguments);
if(inputtype!=INPUT_VCF_GL && inputtype!=INPUT_GLF && inputtype!=INPUT_GLF3 && doPost && GL==0){
fprintf(stderr,"\t-> Potential problem: You are required to choose a genotype likelihood model (-GL) for estimating genotypes posteriors.\n");
exit(0);
}
doMajorMinor=angsd::getArg("-doMajorMinor",doMajorMinor,arguments);
// fprintf(stderr,"%d %d\n",inputtype,INPUT_VCF_GL);
if((doPost||doMaf) &&doMajorMinor==0 &&inputtype!=INPUT_VCF_GL){
if(doMaf!=4){
fprintf(stderr,"\t-> Potential problem: You are required to choose a major/minor estimator (-doMajorMinor)\n");
exit(0);
}
}
if(doPost==1 &&doMaf==0){
fprintf(stderr,"\t-> Potential problem: You are required to choose a maf estimator (-doMaf) with -doPost 1\n");
exit(0);
}
indFname = angsd::getArg("-indF",indFname,arguments);
if(indFname !=NULL)
indF = angsd::readDouble(indFname,arguments->nInd);
if(doMaf==0 )//&& doPost==0?
return;
underflowprotect=angsd::getArg("-underFlowProtect",underflowprotect,arguments);
chisq1 = new Chisqdist(1);
chisq2 = new Chisqdist(2);
chisq3 = new Chisqdist(3);
minMaf=angsd::getArg("-minMaf",minMaf,arguments);
// assert(minMaf<=1&&minMaf>=0);
double tmp=-1;
tmp=angsd::getArg("-SNP_pval",tmp,arguments);
if(tmp!=-1){
SNP_pval = tmp;
double pre = SNP_pval;
// fprintf(stderr,"ind:%f :%p: \t",SNP_pval,chisq3);
if(SNP_pval <=1){
if(abs(doMaf) ==2)
SNP_pval = chisq1->invcdf(1-SNP_pval);
if(abs(doMaf) ==1)
SNP_pval = chisq1->invcdf(1-SNP_pval);
}
doSNP =1 ;
fprintf(stderr,"\t-> SNP-filter using a pvalue: %e correspond to %f likelihood units\n",pre,SNP_pval);
}
if(rmTriallelic)
SNP_pval_tri = chisq2->invcdf(1-rmTriallelic);
refName = angsd::getArg("-ref",refName,arguments);
ancName = angsd::getArg("-anc",ancName,arguments);
if(abs(doMaf)&& !isPowerOfTwo((unsigned int) abs(doMaf))){
fprintf(stderr,"\n[%s] You have selected filters for maf/lrt\n",__FILE__);
fprintf(stderr,"If you have selected more than one MAF estimator we will choose in following order\n");
fprintf(stderr,"\t1. knownminor EM\n");
fprintf(stderr,"\t2. unknownminor EM\n");
fprintf(stderr,"\t3. Posterior maf\n");
}
if(doSNP&&abs(doMaf)==0){
fprintf(stderr,"You've selected SNP-calling but no maf estimator please select -doMaf INT\n");
exit(0);
}
if(doSNP==1 && abs(doMaf)==0){
fprintf(stderr,"You've selected SNP_pval threshold please also select -doMaf \n");
exit(0);
}
if(minMaf>0.0 &&(abs(doMaf)==0)){
fprintf(stderr,"\nYou've selected minMaf but no MAF estimator, choose -doMaf\n\n");
exit(0);
}
if(rmTriallelic>0.0 &&(abs(doMaf)!=1)){
fprintf(stderr,"\n rmTriallelic only works with -doMaf 1 \n\n");
exit(0);
}
int doCounts =0;
doCounts=angsd::getArg("-doCounts",doCounts,arguments);
beagleProb=angsd::getArg("-beagleProb",beagleProb,arguments);
minInd=angsd::getArg("-minInd",minInd,arguments);
if(abs(doMaf)==0 &&doPost==0)
return;
if(inputtype!=INPUT_VCF_GP&&inputtype!=INPUT_BEAGLE&&inputtype!=0&&doMajorMinor==0&&inputtype!=INPUT_VCF_GL){
fprintf(stderr,"You must specify \'-doMajorMinor\' to infer major/minor \n");
exit(0);
}
if(inputtype==INPUT_BEAGLE&&abs(doMaf)!=4){
fprintf(stderr,"Only \'-doMaf 4\' can not be performed on posterior input\n");
exit(0);
}
if(inputtype!=INPUT_BEAGLE&&inputtype!=INPUT_VCF_GP&&abs(doMaf)==4){
fprintf(stderr,"\t \'-doMaf 4\' can only be performed on genotype probabilities provided by the user (-beagle).\n");
exit(0);
}
if((inputtype==INPUT_BAM || inputtype==INPUT_PILEUP )&& GL==0 &&doMaf!=8){
fprintf(stderr,"Error: For sequence data (BAM,pileups) likehoods (-GL) must be specified for frequency estimation\n");
exit(0);
}
if(doSNP&&abs(doMaf) &4){
fprintf(stderr,"Error: -doMaf 4 cannot be used for a likelihood ratio test (doSNP) \n");
exit(0);
}
if(inputtype==INPUT_BEAGLE&&doPost){
fprintf(stderr,"Error: Cannot estimate post (doPost) based on posterior probabilites\n");
exit(0);
}
if(abs(doMaf)&8&&doCounts==0){
fprintf(stderr,"Must supply -doCounts for MAF estimator based on counts\n");
exit(0);
}
if(beagleProb && doPost==0 &&inputtype!=INPUT_VCF_GP){
fprintf(stderr,"Must supply -doPost 1 to write beaglestyle postprobs\n");
exit(0);
}
if(doPost!=0 && doMajorMinor==0 &&INPUT_VCF_GL!=inputtype){
fprintf(stderr,"Do post requires major and minor: supply -doMajorMinor \n");
exit(0);
}
}
//constructor
abcFreq::abcFreq(const char *outfiles,argStruct *arguments,int inputtype){
underflowprotect =0;
minInd = 0;
chisq1=chisq2=chisq3=NULL;
inputIsBeagle =0;
beagleProb = 0; //<-output for beagleprobs
minMaf =-1.0;
SNP_pval = 1;
nInd = arguments->nInd;
eps = 0.001;
outfileZ2 = NULL;
outfileZ = NULL;
indFname = NULL;
doMaf=0;
rmTriallelic=0;
GL=0;
doSNP=0;
doPost=0;
bufstr.s=NULL;bufstr.l=bufstr.m=0;
//emIter=EM_NITER; //these are static see top of this file
//EM_start = EM_START; //these are static see top of this file
doMajorMinor=0;
refName = NULL;
ancName = NULL;
if(arguments->argc==2){
if(!strcasecmp(arguments->argv[1],"-doMaf")||!strcasecmp(arguments->argv[1],"-doPost")){
printArg(stdout);
exit(0);
}else
return;
}
getOptions(arguments);
if(doMaf==0 && doPost==0){
shouldRun[index]=0;
return;
}
printArg(arguments->argumentFile);
if(doMaf>0){
//make output files
const char* postfix;
postfix=".mafs.gz";
outfileZ = aio::openFileBG(outfiles,postfix);
if(beagleProb){
postfix=".beagle.gprobs.gz";
outfileZ2 = aio::openFileBG(outfiles,postfix);
}
}else
doMaf=abs(doMaf);
//print header
kputs("chromo\tposition\tmajor\tminor\t",&bufstr);
if(refName!=NULL||arguments->inputtype==INPUT_PILEUP)
kputs("ref\t",&bufstr);
if(ancName)
kputs("anc\t",&bufstr);
if(doMaf &1)
kputs("knownEM\t",&bufstr);
if(doMaf &2)
kputs("unknownEM\t",&bufstr);
if(doMaf &4)
kputs("PPmaf\t",&bufstr);
if(doMaf &8)
kputs("phat\t",&bufstr);
if(doSNP){
if(doMaf &1)
kputs("pK-EM\t",&bufstr);
if(doMaf &2)
kputs("pu-EM\t",&bufstr);
}
kputs("nInd\n",&bufstr);
aio::bgzf_write(outfileZ,bufstr.s,bufstr.l);
bufstr.l=0;
if(beagleProb){
kputs("marker\tallele1\tallele2",&bufstr);
for(int i=0;i<arguments->nInd;i++){
kputs("\tInd",&bufstr);
kputw(i,&bufstr);
kputs("\tInd",&bufstr);
kputw(i,&bufstr);
kputs("\tInd",&bufstr);
kputw(i,&bufstr);
}
kputc('\n',&bufstr);
aio::bgzf_write(outfileZ2,bufstr.s,bufstr.l);
bufstr.l=0;
}
}
abcFreq::~abcFreq(){
if(outfileZ!=NULL){
bgzf_close(outfileZ);
}
if(outfileZ2!=NULL){
bgzf_close(outfileZ2);
}
free(refName);
free(ancName);
delete [] indF;
delete chisq1;
delete chisq2;
delete chisq3;
free(bufstr.s);
}
void abcFreq::print(funkyPars *pars) {
if(outfileZ==NULL&&outfileZ2==NULL)
return;
freqStruct *freq =(freqStruct *) pars->extras[index];
for(int s=0;s<pars->numSites;s++) {
if(pars->keepSites[s]==0)
continue;
//plugin chr,pos,major,minor
kputs(header->target_name[pars->refId],&bufstr);kputc('\t',&bufstr);
kputw(pars->posi[s]+1,&bufstr);kputc('\t',&bufstr);
kputc(intToRef[pars->major[s]],&bufstr);kputc('\t',&bufstr);
kputc(intToRef[pars->minor[s]],&bufstr);kputc('\t',&bufstr);
//plugin ref, anc if exists
if(pars->ref!=NULL)
{kputc(intToRef[pars->ref[s]],&bufstr);kputc('\t',&bufstr);}
if(pars->anc!=NULL)
{kputc(intToRef[pars->anc[s]],&bufstr);kputc('\t',&bufstr);}
if(doMaf &1)
ksprintf(&bufstr,"%f\t",freq->freq_EM[s]);
if(doMaf &2)
ksprintf(&bufstr,"%f\t",freq->freq_EM_unknown[s]);
if(doMaf &4)
ksprintf(&bufstr,"%f\t",freq->freq[s]);
if(doMaf &8)
ksprintf(&bufstr,"%f\t",freq->phat[s]);
if(doSNP){
if(doMaf &1)
ksprintf(&bufstr,"%e\t",to_pval(chisq1,freq->lrt_EM[s]));
if(doMaf &2)
ksprintf(&bufstr,"%e\t",to_pval(chisq1,freq->lrt_EM_unknown[s]));
}
kputw(pars->keepSites[s],&bufstr);kputc('\n',&bufstr);
}
aio::bgzf_write(outfileZ,bufstr.s,bufstr.l);
bufstr.l=0;
if(beagleProb){
//beagle format
for(int s=0;s<pars->numSites;s++) {
if(pars->keepSites[s]==0)
continue;
// fprintf(stderr,"keepsites=%d\n",pars->keepSites[s]);
kputs(header->target_name[pars->refId],&bufstr);
kputc('_',&bufstr);
kputw(pars->posi[s]+1,&bufstr);
kputc('\t',&bufstr);
kputw(pars->major[s],&bufstr);
kputc('\t',&bufstr);
kputw(pars->minor[s],&bufstr);
int major = pars->major[s];
int minor = pars->minor[s];
assert(major!=4&&minor!=4);
for(int i=0;i<3*pars->nInd;i++) {
ksprintf(&bufstr, "\t%f",pars->post[s][i]);
}
kputc('\n',&bufstr);
}
//valgrind on osx complains here check if prob on unix
int ret=aio::bgzf_write(outfileZ2,bufstr.s,bufstr.l);
bufstr.l=0;
//fprintf(stderr,"ret.l:%d bufstr.l:%zu\n",ret,bufstr.l);
}
}
void abcFreq::clean(funkyPars *pars) {
if(doMaf==0&&doPost==0)
return;
freqStruct *freq =(freqStruct *) pars->extras[index];
//cleaning
delete [] freq->freq;
delete [] freq->lrt;//maybe in doSNP
delete [] freq->freq_EM;
delete [] freq->freq_EM_unknown;
delete [] freq->lrt_tri;
delete [] freq->lrt_EM;
delete [] freq->lrt_EM_unknown;
delete [] freq->phat;
delete freq;
if(pars->post!=NULL){
for(int i=0;i<pars->numSites;i++)
delete [] pars->post[i];
delete [] pars->post;
pars->post =NULL;
}
}
freqStruct *allocFreqStruct(){
freqStruct *freq = new freqStruct;
freq->freq_EM=NULL;
freq->freq_EM_unknown= NULL;
freq->lrt_tri=NULL;
freq->lrt_EM=NULL;
freq->lrt_EM_unknown=NULL;
freq->freq = NULL;
freq->lrt = NULL;
freq->phat = NULL;
return freq;
}
//filipes
void make_post_F(double *like,double *post,double freqEst,int nInd){
//fprintf(stderr,"[%s]\n",__FUNCTION__);
double *indF = abcFreq::indF;
for(int i=0;i<nInd;i++){
post[i*3+2]=like[i*3+2] + log(pow(freqEst,2) + (1-freqEst)*freqEst*indF[i]);
post[i*3+1]=like[i*3+1] + log(2*(1-freqEst)*freqEst - 2*(1-freqEst)*freqEst*indF[i]);
post[i*3+0]=like[i*3+0] + log(pow(1-freqEst,2) + (1-freqEst)*freqEst*indF[i]);
double norm = angsd::addProtect3(post[i*3+0],post[i*3+1],post[i*3+2]);
post[i*3+0]=exp(post[i*3+0]-norm);
post[i*3+1]=exp(post[i*3+1]-norm);
post[i*3+2]=exp(post[i*3+2]-norm);
}
//
}
void make_post(double *like,double *post,double freqEst,int nInd){
if(abcFreq::indF!=NULL){
make_post_F(like,post,freqEst,nInd);
return;
}
for(int i=0;i<nInd;i++){
// fprintf(stderr,"[%d]\nlik= %f %f %f\n",i,like[0][i*3+0],like[0][i*3+1],like[0][i*3+2]);
post[i*3+2]=like[i*3+2]+2*log(freqEst);
post[i*3+1]=like[i*3+1]+log(2)+log(1-freqEst)+log(freqEst);
post[i*3+0]=like[i*3+0]+2*log(1-freqEst);
// fprintf(stderr,"likmod= %f %f %f\n",post[0][i*3+0],post[0][i*3+1],post[0][i*3+2]);
double norm = angsd::addProtect3(post[i*3+0],post[i*3+1],post[i*3+2]);
post[i*3+0]=exp(post[i*3+0]-norm);
post[i*3+1]=exp(post[i*3+1]-norm);
post[i*3+2]=exp(post[i*3+2]-norm);
// fprintf(stderr,"%f %f %f\n",post[0][i*3+0],post[0][i*3+1],post[0][i*3+2]);
}
}
void abcFreq::run(funkyPars *pars) {
if(doMaf==0&&doPost==0)
return;
freqStruct *freq = allocFreqStruct();
pars->extras[index] = freq;
extern abc **allMethods;
// abcFilter *abcf=(abcFilter *) allMethods[0];
filt *fl = ((abcFilter *) allMethods[0])->fl;
if(doMaf!=0) {
if(doMaf&8)
phatLoop(pars,eps,nInd,freq);
if(doMaf&4)
postFreq(pars,freq);
if(doMaf % 4){ // doMaf =1 or doMaf 2
likeFreq(pars,freq);
}
assert(freq->freq!=NULL);
for(int s=0;s<pars->numSites;s++){
if(pars->keepSites[s]==0)
continue;
if(freq->freq[s] < minMaf)
pars->keepSites[s]=0;
else if(freq->freq[s] > 1 - minMaf)
pars->keepSites[s]=0;
if(doSNP && (freq->lrt[s] < SNP_pval))
pars->keepSites[s]=0;
if(rmTriallelic && (freq->lrt_tri[s] > SNP_pval_tri))
pars->keepSites[s]=0;
if(minInd>0&&pars->keepSites[s]<minInd)
pars->keepSites[s] = 0;
}
}
if(doPost) {
assert(pars->likes!=NULL);
double **post = new double*[pars->numSites];
double **like=angsd::get3likes(pars);
for(int s=0;s<pars->numSites;s++){
post[s] = new double [3*pars->nInd];
if(pars->keepSites[s]==0){
delete [] like[s];
continue;
}
if(doPost==1) //maf prior
make_post(like[s],post[s],freq->freq[s],pars->nInd);
else if(doPost==2) {//uniform prior
for(int i=0;i<pars->nInd;i++){
double norm = angsd::addProtect3(like[s][i*3+0],like[s][i*3+1],like[s][i*3+2]);
for(int g=0;g<3;g++)
post[s][i*3+g]=exp(like[s][i*3+g]-norm);
}
}
else if(doPost==3){//uniform prior
if(algoGeno(pars->likes[s],refToInt[pars->major[s]],refToInt[pars->minor[s]],pars->nInd,underflowprotect,abcSaf::prior,post[s]))
fprintf(stderr,"\t-> Problem calling genotypes at: (%s,%d)\n",header->target_name[pars->refId],pars->posi[s]+1);
}
else if(doPost==4){
assert(fl!=NULL);
//af for this pos: fl->af[pars->posi[s]]
//an for this pos: fl->an[pars->posi[s]]
//ac for this pos: fl->ac[pars->posi[s]]
// fprintf(stderr,"chr: %s pos: %d freq:%f\n",header->target_name[pars->refId],pars->posi[s]+1,fl->af[pars->posi[s]]);
if(fl->keeps[pars->posi[s]]==0)
make_post(like[s],post[s],freq->freq[s],pars->nInd);
else{
double exp_obs_allels_in_ngs= freq->freq[s]*pars->keepSites[s];
// fprintf(stderr,"pars->keepSite:%d\n",pars->k)
double aac = fl->ac[pars->posi[s]];
double aan = fl->an[pars->posi[s]];
double af = (aac+exp_obs_allels_in_ngs)/(1.0*(aan+pars->keepSites[s]));
fprintf(stderr,"aac:%f aan:%f nal_in_ngs:%f af:%f\n",aac,aan,exp_obs_allels_in_ngs,af);
make_post(like[s],post[s],af,pars->nInd);
}
}
else{
fprintf(stderr,"[%s] doPost must be 1 or 2 \n",__FUNCTION__);
exit(0);
}
delete [] like[s];
}
pars->post = post;
delete[] like;
}
}
/*
Estimate the allele frequency from the posterior probabilities
*/
void abcFreq::postFreq(funkyPars *pars,freqStruct *freq){
if(freq->freq==NULL)
freq->freq = new double[pars->numSites];
for(int s=0;s<pars->numSites;s++){
freq->freq[s]=0;
for(int i=0;i<pars->nInd;i++){
freq->freq[s] += pars->post[s][i*3+1]+2*pars->post[s][i*3+2];
}
freq->freq[s] = freq->freq[s]/(pars->nInd*2);
}
}
void abcFreq::likeFreq(funkyPars *pars,freqStruct *freq){//method=1: bfgs_known ;method=2 em;method=4 bfgs_unknown
//here only the likelihoods for the three genotypes are used.
double **loglike = NULL;
if(inputIsBeagle==1)
loglike= pars->likes;
else
loglike=angsd::get3likesRescale(pars);
assert(loglike!=NULL);
if(freq->freq == NULL)
freq->freq = new double[pars->numSites];
if(doSNP)
freq->lrt = new double[pars->numSites];
if(rmTriallelic)
freq->lrt_tri = new double[pars->numSites];
if(doMaf &1){
freq->freq_EM = new double[pars->numSites];
if(doSNP)
freq->lrt_EM = new double[pars->numSites];
}
if(doMaf &2){
freq->freq_EM_unknown =new double[pars->numSites];
if(doSNP)
freq->lrt_EM_unknown =new double[pars->numSites];
}
// number of individuals with data
int *keepInd = pars->keepSites;
int keepList[pars->nInd];
//loop though all sites and check if we have data.
for(int s=0;s<pars->numSites;s++) {
if(keepInd[s]==0)//if we dont have any information
continue;
keepInd[s]=0;//
for(int i=0 ; i<pars->nInd ;i++) {//DRAGON CHECK THIS
keepList[i]=1;
//also discard if all gls are the same
if(loglike[s][i*3+0]+loglike[s][i*3+1]+loglike[s][i*3+2]>-0.0001||((loglike[s][i*3]==loglike[s][i*3+1] )&& (loglike[s][i*3]==loglike[s][i*3+2]))){
keepList[i]=0;
}
else{
keepInd[s]++;
}
}
if(keepInd[s]==0)//if we dont have any information
continue;
if(doMaf &1) {
double mstart = EM_start;
if(freq->phat!=NULL)
mstart = freq->phat[s];
freq->freq_EM[s]=emFrequency(loglike[s],pars->nInd,emIter,mstart,keepList,keepInd[s]);
if(doSNP){
freq->lrt_EM[s]= 2*likeFixedMinor(0.0,loglike[s],pars->nInd)-2*likeFixedMinor(freq->freq_EM[s],loglike[s],pars->nInd);
if(freq->lrt_EM[s]<0)
freq->lrt_EM[s]=0;
}
}
if( doMaf &2) {
double mstart = EM_start;
if(freq->phat!=NULL)
mstart = freq->phat[s];
freq->freq_EM_unknown[s]=emFrequencyNoFixed(pars->likes[s],pars->nInd,emIter,mstart,keepList,keepInd[s],pars->major[s],pars->posi[s]);
if(doSNP){
freq->lrt_EM_unknown[s] = 2*likeNoFixedMinor(0.0,pars->likes[s],pars->nInd,pars->major[s])-2*likeNoFixedMinor(freq->freq_EM_unknown[s],pars->likes[s],pars->nInd,pars->major[s]);
if(freq->lrt_EM_unknown[s]<0)
freq->lrt_EM_unknown[s]=0;
}
}
if(rmTriallelic!=0){
double lrtTri=0;
if(freq->freq_EM[s]>0.0001)
lrtTri=isMultiAllelic(pars->likes[s],pars->nInd,emIter,freq->freq_EM[s],keepList,keepInd[s],pars->major[s],pars->minor[s]);
freq->lrt_tri[s] = lrtTri;
}
}
if(inputIsBeagle!=1){
for(int i=0;i<pars->numSites;i++)
delete [] loglike[i];
delete [] loglike;
}
for(int s=0;s<pars->numSites;s++){
if(doMaf &2 )
freq->freq[s]=freq->freq_EM_unknown[s];
else if(doMaf &1 )
freq->freq[s]=freq->freq_EM[s];
}
//thorfinn april 16 2012
for(int s=0;s<pars->numSites;s++){
if((doMaf &2) && doSNP )
freq->lrt[s]=freq->lrt_EM_unknown[s];
else if((doMaf &1) && doSNP)
freq->lrt[s]=freq->lrt_EM[s];
}
}
double abcFreq::emFrequencyNoFixed_ext(double *loglike,int numInds,int *keep,int keepInd,int major,int posi){
return emFrequencyNoFixed(loglike,numInds, emIter,EM_start, keep,keepInd,major,posi);
}
double abcFreq::emFrequencyNoFixed_F(double *loglike,int numInds, int iter,double start,int *keep,int keepInd,int major,int posi){
int iMinor[3];
int n=0;
for(int i=0;i<4;i++){
if(i!=major){
iMinor[n]=i;
n++;
}
}
double **loglikeGeno;
loglikeGeno =new double*[3];
for(int j=0;j<3;j++){
loglikeGeno[j] = new double[numInds*3];
for(int i=0;i<numInds;i++){
loglikeGeno[j][i*3+0]=loglike[i*10+angsd::majorminor[major][major]];
loglikeGeno[j][i*3+1]=loglike[i*10+angsd::majorminor[major][iMinor[j]]];
loglikeGeno[j][i*3+2]=loglike[i*10+angsd::majorminor[iMinor[j]][iMinor[j]]];
}
}
float W0[3];
float W1[3];
float W2[3];
start=0.4;
float p=(float)start;
float temp_p=(float)start;
double accu=0.00001;
double accu2=0;
float sum;
int it=0;
float weight[3];
float normWeight[3];
float norm;
int correctInd;
for(it=0;it<iter;it++){
for(int j=0;j<3;j++)
weight[j]=-likeFixedMinor(p,loglikeGeno[j],keepInd);
norm=angsd::addProtect3(weight[0],weight[1],weight[2]);
for(int j=0;j<3;j++)
normWeight[j]=exp(weight[j]-norm);
sum=0;
correctInd=keepInd;
for(int i=0;i<numInds;i++){
if(keep[i]==0)
continue;
for(int j=0;j<3;j++){
W0[j]=exp(loglike[i*10+angsd::majorminor[major][major]]) * (pow(1-p,2) + (1-p)*p*indF[i]);
W1[j]=exp(loglike[i*10+angsd::majorminor[major][iMinor[j]]]) * (2*(1-p)*p - 2*(1-p)*p*indF[i]);
W2[j]=exp(loglike[i*10+angsd::majorminor[iMinor[j]][iMinor[j]]]) * (pow(p,2) + (1-p)*p*indF[i]);
if(W0[j]+W1[j]+W2[j]<0.0000001)
continue;
}
}
p=sum/correctInd;
if((p-temp_p<accu&&temp_p-p<accu)||(p/temp_p<1+accu2&&p/temp_p>1-accu2))
break;
temp_p=p;
if(std::isnan(p)){
fprintf(stderr,"[%s] caught nan at position: %d\n",__FUNCTION__,posi);
for(int j=0;j<3;j++)
fprintf(stderr,"w%d %f ",j,weight[j]);
fflush(stderr);
for(int i=0;i<numInds;i++){
for(int j=0;j<10;j++){
if(keep[i]==0)
continue;
fprintf(stderr,"%f\t",loglike[i*10+j]);
}
fprintf(stderr,"\n");
}
fprintf(stderr,"%f | %f %f %f |%f | %d | \n",p, normWeight[0], normWeight[1], normWeight[2],angsd::addProtect3(weight[0],weight[1],weight[2]),major);
}
}
for(int j=0;j<3;j++)
delete[] loglikeGeno[j];
delete[] loglikeGeno;
return(p);
}
double abcFreq::emFrequencyNoFixed(double *loglike,int numInds, int iter,double start,int *keep,int keepInd,int major,int posi){
if(indF!=NULL)
return emFrequencyNoFixed_F(loglike,numInds,iter,start,keep,keepInd,major,posi);
int iMinor[3];
int n=0;
for(int i=0;i<4;i++){
if(i!=major){
iMinor[n]=i;
n++;
}
}
double **loglikeGeno;
loglikeGeno =new double*[3];
for(int j=0;j<3;j++){
loglikeGeno[j] = new double[numInds*3];
for(int i=0;i<numInds;i++){
loglikeGeno[j][i*3+0]=loglike[i*10+angsd::majorminor[major][major]];
loglikeGeno[j][i*3+1]=loglike[i*10+angsd::majorminor[major][iMinor[j]]];
loglikeGeno[j][i*3+2]=loglike[i*10+angsd::majorminor[iMinor[j]][iMinor[j]]];
}
}
float W0[3];
float W1[3];
float W2[3];
start=0.4;
float p=(float)start;
float temp_p=(float)start;
double accu=0.00001;
double accu2=0;
float sum;
int it=0;
float weight[3];
float normWeight[3];
float norm;
int correctInd;
for(it=0;it<iter;it++){
for(int j=0;j<3;j++)
weight[j]=-likeFixedMinor(p,loglikeGeno[j],keepInd);
norm=angsd::addProtect3(weight[0],weight[1],weight[2]);
for(int j=0;j<3;j++)
normWeight[j]=exp(weight[j]-norm);
sum=0;
correctInd=keepInd;
for(int i=0;i<numInds;i++){
if(keep!=NULL && keep[i]==0)
continue;
for(int j=0;j<3;j++){
W0[j]=exp(loglike[i*10+angsd::majorminor[major][major]])*pow(1-p,2);
W1[j]=exp(loglike[i*10+angsd::majorminor[major][iMinor[j]]])*2*p*(1-p);
W2[j]=exp(loglike[i*10+angsd::majorminor[iMinor[j]][iMinor[j]]])*(pow(p,2));
if(W0[j]+W1[j]+W2[j]<0.0000001)
continue;
sum+=(W1[j]+2*W2[j])/(2*(W0[j]+W1[j]+W2[j]))*normWeight[j];
}
}
p=sum/correctInd;
if((p-temp_p<accu&&temp_p-p<accu)||(p/temp_p<1+accu2&&p/temp_p>1-accu2))
break;
temp_p=p;
if(std::isnan(p)){
fprintf(stderr,"[%s] caught nan at position: %d will exit\n",__FUNCTION__,posi+1);
for(int j=0;j<3;j++)
fprintf(stderr,"w%d %f ",j,weight[j]);
fflush(stderr);
for(int i=0;i<numInds;i++){
for(int j=0;j<10;j++){
if(keep[i]==0)
continue;
fprintf(stderr,"%f\t",loglike[i*10+j]);
}
fprintf(stderr,"\n");
}
fprintf(stderr,"%f | %f %f %f |%f | %d | \n",p, normWeight[0], normWeight[1], normWeight[2],angsd::addProtect3(weight[0],weight[1],weight[2]),major);
}
}
for(int j=0;j<3;j++)
delete[] loglikeGeno[j];
delete[] loglikeGeno;
return(p);
}
///////////////////////////////////////////////
double abcFreq::isMultiAllelic(double *loglike,int numInds, int iter,double freqStandard,int *keep,int keepInd,int major,int minor){
double freq[4];
double temp_freq[4];
double W[10];
float sum[4];
for(int j=0;j<4;j++)
freq[j] = 0.25;
double accu=0.00001;
int it=0;
float norm;
/* for(int i=0;i<numInds;i++){
if(keep!=NULL && keep[i]==0)
continue;
for(int j=0;j<10;j++)
fprintf(stderr,"%f ", loglike[i*10+j]);
fprintf(stderr,"\n");
}
*/
for(it=0;it<iter;it++){
for(int j=0;j<4;j++){
temp_freq[j] = freq[j] ;
sum[j]=0;
}
for(int i=0;i<numInds;i++){
if(keep!=NULL && keep[i]==0)
continue;
W[0] = exp(loglike[i*10+0]) * pow(freq[0],2); //AA 0
W[1] = exp(loglike[i*10+1]) * 2*freq[0]*freq[1]; //AC 1
W[2] = exp(loglike[i*10+2]) * 2*freq[0]*freq[2]; //AG 2
W[3] = exp(loglike[i*10+3]) * 2*freq[0]*freq[3]; //AT 3
W[4] = exp(loglike[i*10+4]) * pow(freq[1],2); //CC 4
W[5] = exp(loglike[i*10+5]) * 2*freq[1]*freq[2]; //CG 5
W[6] = exp(loglike[i*10+6]) * 2*freq[1]*freq[3]; //CT 6
W[7] = exp(loglike[i*10+7]) * pow(freq[2],2); //GG 7
W[8] = exp(loglike[i*10+8]) * 2*freq[2]*freq[3]; //GT 8
W[9] = exp(loglike[i*10+9]) * pow(freq[3],2); //TT 9
norm=0;