void PlinkOutputFile::writeBED(SimpleMatrix* mat, int nPeople, int nMarker){
/* int nPeople = mat->cols; */
/* int nMarker = mat->rows; */
unsigned char c = 0;
int offset;
for (int m = 0; m < nMarker; m++){
for (int i = 0; i < nPeople ; i ++) {
offset = i & (4 - 1);
int geno = (int)( (*mat)[m][i]);
switch(geno){
case HOM_REF:
setGenotype(&c, offset, HET); // het: 0b01
break;
case HET:
setGenotype(&c, offset, HET); // het: 0b01
break;
case HOM_ALT:
setGenotype(&c, offset, HOM_ALT); // hom alt: 0b11
break;
default:
setGenotype(&c, offset, MISSING); // missing
break;
}
}
if ( offset == 3) { // 3: 4 - 1, so every 4 genotype we will flush
fwrite(&c, sizeof(char), 1, this->fpBed);
c = 0;
}
};
if (nPeople % 4 != 0 )
fwrite(&c, sizeof(char), 1, this->fpBed);
};
int PlinkOutputFile::extractBED(PlinkInputFile& pin,
const std::vector<int>& sampleIdx,
const std::vector<int>& snpIdx) {
const int M = snpIdx.size();
const int N = sampleIdx.size();
unsigned char c = 0;
int offset = 0;
for (int i = 0; i < M; ++i) { // assume SNP-major
for (int j = 0; j < N; ++j) {
offset = j & (4 - 1);
setGenotype(&c, offset, pin.get2BitGenotype(sampleIdx[j], snpIdx[i]));
if (offset == 3) { // 3: 4 - 1, so every 4 genotype we will flush
fwrite(&c, sizeof(char), 1, this->fpBed);
c = 0;
}
} // end for j
if (N % 4 != 0) { // remaining some bits
fwrite(&c, sizeof(char), 1, this->fpBed);
c = 0;
}
} // end for i
return 0;
}
GenMatrixBinary::GenMatrixBinary(const char* vcfFile, bool siteOnly, std::vector<std::string>& subsetInds, double minAF, double minCallRate) {
// open a VCF file
VcfFile vcf;
VcfMarker* pMarker;
std::vector<int> indIndices;
vcf.bSiteOnly = siteOnly;
if ( !siteOnly ) {
vcf.bParseGenotypes = true;
vcf.bParseDosages = false;
vcf.bParseValues = false;
}
vcf.openForRead(vcfFile);
// match the individual IDs;
if ( siteOnly ) {
if ( subsetInds.size() > 0 ) {
Logger::gLogger->warning("--siteOnly option is turned on with subset of individuals information provided. subset information will be ignored");
}
}
else {
if ( subsetInds.size() == 0 ) {
for(int i=0; i < (int)vcf.vpVcfInds.size(); ++i) {
indids.push_back(vcf.vpVcfInds[i]->sIndID.c_str());
indIndices.push_back(i);
}
}
else {
for(int i=0; i < (int)vcf.vpVcfInds.size(); ++i) {
for(int j=0; j < (int)subsetInds.size(); ++j) {
if ( vcf.vpVcfInds[i]->sIndID.Compare( subsetInds[j].c_str() ) == 0 ) {
indids.push_back(vcf.vpVcfInds[i]->sIndID.c_str());
indIndices.push_back(i);
break;
}
}
}
Logger::gLogger->writeLog("Total of %d out of %d individuals successfully matched IDs",(int)indids.size(),(int)subsetInds.size());
}
}
// set bytesPerMarker attribute
if ( siteOnly ) {
bytesPerMarker = 0;
}
else {
bytesPerMarker = (indids.size() + 3)/4;
}
int numNonAutoWarn = 0;
int afWarn = 0;
int callRateWarn = 0;
// read each marker and stores genotype
while( vcf.iterateMarker() ) {
// set per-marker level information
if ( vcf.nNumMarkers % 10000 == 0 ) {
Logger::gLogger->writeLog("Reading %d markers from VCF file",vcf.nNumMarkers);
}
pMarker = vcf.getLastMarker();
// Non-autosomal chromosomes must be discarded
if ( !VcfHelper::isAutosome(pMarker->sChrom.c_str()) ) {
if(++numNonAutoWarn <= 5)
{
Logger::gLogger->warning("Skipping no-autosomal marker %s:%d",pMarker->sChrom.c_str(),pMarker->nPos);
}
continue;
}
// get allele frequency information from VCF file
// if site-only is set
// -- use INFO
// else if subset is set
// -- use subset genotypes
// else
// -- use INFO if available
// -- otherwise, use all genotypes
double AF = -1;
double callRate = 1.;
// if site-only is set use INFO only
if ( siteOnly ) {
// use AC and AN first to estimate AF
const char* sAC = pMarker->getInfoValue("AC");
const char* sAN = pMarker->getInfoValue("AN");
int AC = (sAC == NULL) ? -1 : atoi(sAC);
int AN = (sAN == NULL) ? -1 : atoi(sAN);
if ( ( AC > 0 ) && ( AN > 0 ) ) {
AF = (double)AC/(double)AN;
if ( vcf.vpVcfInds.size() > 0 ) {
callRate = AN / 2. / vcf.vpVcfInds.size();
}
}
if ( AF < 0 ) {
const char* sAF = pMarker->getInfoValue("AF");
AF = (sAF == NULL) ? -1. : atof(sAF);
}
}
// if subset is set, do not use INFO and use genotypes
else if ( indIndices.size() > 1 ) { // if not self-only option
std::pair<int,int> alleleCounts = pMarker->computeAlleleCounts(indIndices);
AF = (double)alleleCounts.first/(double)(alleleCounts.second+1e-6);
callRate = (double)alleleCounts.second / 2. / subsetInds.size();
}
// if selfOnly or use-all, use INFO first and genotypes later
else if ( vcf.vpVcfInds.size() >= 0 ) {
// use AC and AN first to estimate AF
const char* sAC = pMarker->getInfoValue("AC");
const char* sAN = pMarker->getInfoValue("AN");
int AC = (sAC == NULL) ? -1 : atoi(sAC);
int AN = (sAN == NULL) ? -1 : atoi(sAN);
if ( ( AC > 0 ) && ( AN > 0 ) ) {
AF = (double)AC/(double)AN;
if ( vcf.vpVcfInds.size() > 0 ) {
callRate = AN / 2. / vcf.vpVcfInds.size();
}
}
if ( AF < 0 ) {
const char* sAF = pMarker->getInfoValue("AF");
AF = (sAF == NULL) ? -1. : atof(sAF);
}
// use all genotype if INFO field does not have AF, AC, AN
if ( AF < 0 ) {
std::pair<int,int> alleleCounts = pMarker->computeAlleleCounts();
AF = (double)alleleCounts.first/(double)(alleleCounts.second+1e-6);
callRate = (double)alleleCounts.second / 2. / vcf.vpVcfInds.size();
}
}
if ( AF < 0 ) {
Logger::gLogger->warning("Cannot obtain allele frequency information at %s:%d",pMarker->sChrom.c_str(),pMarker->nPos);
}
// skip by AF or callRate
if ( AF < minAF )
{
if(++afWarn < 5)
{
Logger::gLogger->warning("Skipping marker where AF (%lf) is < minAF (%lf)", AF, minAF);
}
continue;
}
if ( callRate < minCallRate )
{
if(++callRateWarn < 5)
{
Logger::gLogger->warning("Skipping marker where callRate (%lf) is < minCallRate (%lf)", callRate, minCallRate);
}
continue;
}
// skip non-bi-allelic marker
if ( pMarker->asAlts.Length() > 1 ) {
Logger::gLogger->warning("Skipping marker %s:%d with multiple alternative alleles",pMarker->sChrom.c_str(),pMarker->nPos);
continue;
}
// add marker information
addMarker(pMarker->sChrom.c_str(), pMarker->nPos, pMarker->sRef[0], pMarker->asAlts[0][0], AF);
// set genotypes
if ( siteOnly ) {
// no genotypes can be stored, skip them
}
else {
for(int i=0; i < (int)indIndices.size(); ++i) {
setGenotype( pMarker->vnSampleGenotypes[indIndices[i]], i );
}
}
}
Logger::gLogger->writeLog("Finished reading %d markers from VCF file",vcf.nNumMarkers);
Logger::gLogger->writeLog("Total of %d informative markers passed after AF >= %lf and callRate >= %lf threshold",(int)chroms.size(),minAF,minCallRate);
if(afWarn > 0)
{
Logger::gLogger->warning("Skipped %d markers where AF was less than minAF (%lf)",afWarn,minAF);
}
if(callRateWarn > 0)
{
Logger::gLogger->warning("Skipped %d markers where callRate was less than minCallRate (%lf)",callRateWarn,minCallRate);
}
if ( chroms.size() == 0 ) {
Logger::gLogger->error("No informative markers were found. Does the VCF have individual genotypes or either AF entry or AC & AN entries included in the INFO field?");
}
}
int PlinkOutputFile::writeRecord(VCFRecord* r) {
// write BIM
if (isMultiAllelic(r->getRef()) || isMultiAllelic(r->getAlt())) {
fprintf(stdout, "%s:%d Skip with ref = [ %s ] and alt= [ %s ]\n", __FILE__,
__LINE__, r->getRef(), r->getAlt());
return -1;
}
this->writeBIM(r->getChrom(), r->getID(), 0, r->getPos(), r->getRef(),
r->getAlt());
// write BED
int GTidx = r->getFormatIndex("GT");
VCFPeople& people = r->getPeople();
unsigned char c = 0;
VCFIndividual* indv;
int offset;
for (unsigned int i = 0; i < people.size(); i++) {
indv = people[i];
offset = i & (4 - 1);
if (indv->justGet(GTidx).isHaploid()) { // 0: index of GT
int a1 = indv->justGet(GTidx).getAllele1();
if (a1 == 0)
setGenotype(&c, offset, HOM_REF);
else if (a1 == 1)
setGenotype(&c, offset, HET);
else
setGenotype(&c, offset, MISSING);
} else {
int a1 = indv->justGet(GTidx).getAllele1();
int a2 = indv->justGet(GTidx).getAllele2();
if (a1 == 0) {
if (a2 == 0) {
// h**o ref: 0b00
} else if (a2 == 1) {
setGenotype(&c, offset, HET); // het: 0b01
} else {
setGenotype(&c, offset, MISSING); // missing 0b10
}
} else if (a1 == 1) {
if (a2 == 0) {
setGenotype(&c, offset, HET); // het: 0b01
} else if (a2 == 1) {
setGenotype(&c, offset, HOM_ALT); // hom alt: 0b11
} else {
setGenotype(&c, offset, MISSING); // missing
}
} else {
// NOTE: Plink does not support tri-allelic
// so have to set genotype as missing.
setGenotype(&c, offset, MISSING); // missing
}
}
if (offset == 3) { // 3: 4 - 1, so every 4 genotype we will flush
fwrite(&c, sizeof(char), 1, this->fpBed);
c = 0;
}
}
if (people.size() % 4 != 0) { // remaining some bits
fwrite(&c, sizeof(char), 1, this->fpBed);
}
return 0;
}
