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Main.cpp
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#include "BaseQualityHelper.h"
#include "GlfLikelihoods.h"
#include "StringArray.h"
#include "StringAlias.h"
#include "Parameters.h"
#include "Pedigree.h"
#include "Error.h"
#include "pFile.h"
#include <math.h>
#include <time.h>
#include <limits.h>
#include <map>
#include <string>
#include <vector>
#include <fstream>
FILE * baseCalls = NULL;
class snpKey {
public:
int pos0;
unsigned char ref;
unsigned char alts[3];
int priorACs[3];
int priorAN;
static int char2int(char c) {
switch(c) {
case 'a': case 'A':
return 1;
case 'c': case 'C':
return 2;
case 'g': case 'G':
return 3;
case 't': case 'T':
return 4;
default:
return 0;
}
}
snpKey(int _pos1) : pos0(_pos1-1), priorAN(0) {
priorACs[0] = priorACs[1] = priorACs[2] = 0;
ref = alts[0] = alts[1] = alts[2] = 0;
}
snpKey(int _pos1, const char* _ref, const char* _alt, const char* _info) {
pos0 = _pos1-1;
ref = char2int(_ref[0]);
alts[0] = alts[1] = alts[2] = 0;
alts[0] = char2int(_alt[0]);
priorAN = 0;
priorACs[0] = priorACs[1] = priorACs[2] = 0;
if ( _info != NULL ) {
const char* pch = strstr(_info,"AC=");
if ( pch != NULL ) {
priorACs[0] = atoi(pch+3);
const char* psemi = strchr(_info,';');
if ( psemi == NULL )
psemi = pch + strlen(pch);
pch = strchr(pch,',');
if ( ( pch != NULL ) && ( pch < psemi ) ) {
priorACs[1] = atoi(pch+1);
pch = strchr(pch+1,',');
if ( ( pch != NULL ) && ( pch < psemi ) ) {
priorACs[2] = atoi(pch+1);
}
}
}
pch = strstr(_info,"AN=");
if ( pch != NULL )
priorAN = atoi(pch+3);
}
if ( priorAN < priorACs[0] + priorACs[1] + priorACs[2] )
error("priorAN = %d, priorACs = %d, %d, %d",priorAN, priorACs[0], priorACs[1], priorACs[2]);
if ( _alt[1] == '\0' ) return;
else if ( _alt[1] == ',' ) alts[1] = char2int(_alt[2]);
else {
error("Cannot recognize alternate allele %s at pos0=%d",_alt,pos0);
}
if ( _alt[3] == '\0' ) return;
else if ( _alt[3] == ',' ) alts[2] = char2int(_alt[4]);
else {
error("Cannot recognize alternate allele %s at pos0=%d",_alt,pos0);
}
}
};
void ReportDate(FILE * output) {
if (output == NULL) return;
time_t systemTime;
time(&systemTime);
tm * digestedTime;
digestedTime = gmtime(&systemTime);
fprintf(output, "##filedate=%04d%02d%02d\n", digestedTime->tm_year + 1900,
digestedTime->tm_mon + 1,
digestedTime->tm_mday);
}
void DumpDetails(glfHandler * glf, int n, int position, int refBase) {
char alleles[] = { 0, 'A', 'C', 'G', 'T' };
int firstGlf = 0;
while (glf[firstGlf].isStub)
firstGlf++;
printf("Dump for section %s, position %d [%c]\n",
(const char *) glf[firstGlf].label, position, alleles[refBase]);
printf("Depth");
for (int i = 0; i < n; i++)
printf("\t%d", glf[i].GetDepth(position));
printf("\n");
printf("MapQ");
for (int i = 0; i < n; i++)
printf("\t%d", glf[i].GetMapQuality(position));
printf("\n");
for (int i = 1, index = 0; i <= 4; i++)
for (int j = i; j <= 4; j++, index++)
{
printf("%c/%c", alleles[i], alleles[j]);
for (int k = 0; k < n; k++)
printf("\t%d", glf[k].GetLogLikelihoods(position)[index]);
printf("\n");
}
}
int GetBestGenotype(const double likelihoods[], const double priors[])
{
int best = 0;
for (int i = 1; i < 10; i++)
if (likelihoods[i] * priors[i] > likelihoods[best] * priors[best])
best = i;
return best;
}
const char * GetBestGenotypeLabel(const double likelihoods[], const double priors[])
{
const char * genotypeLabel[10] = {"A/A", "A/C", "A/G", "A/T", "C/C", "C/G", "C/T", "G/G", "G/T", "T/T"};
return genotypeLabel[GetBestGenotype(likelihoods, priors)];
}
int GetBestRatio(const double likelihoods[], const double priors[])
{
double sum = 0.0;
int best = 0;
for (int i = 1; i < 10; i++)
if (likelihoods[i] * priors[i] > likelihoods[best] * priors[best])
best = i;
for (int i = 0; i < 10; i++)
sum += likelihoods[i] * priors[i];
if (sum <= 0.0)
return 0;
double error = 1.0 - likelihoods[best] * priors[best]/sum;
if (error < 0.0000000001)
return 100;
return int (-log10(error) * 10 + 0.5);
}
void ReportGenotypes(FullLikelihood & lk, glfHandler * glf, int n,
int position, int refAllele, int *altBases,
String & info, String & genotypes)
{
info.Clear();
genotypes.Clear();
int ns = 0;
//int ac[4] = {0, 0, 0, 0};
double Acount = 0.5;
double ABcount = 1.0;
int allele1s[10] = {1, 1, 1, 1, 2, 2, 2, 3, 3, 4};
int allele2s[10] = {1, 2, 3, 4, 2, 3, 4, 3, 4, 4};
//int alleleMap[5] = {99,99,99,99,99};
//alleleMap[refAllele] = 0;
//alleleMap[altBases[0]] = 1;
//if ( altBases[1] > 0 ) alleleMap[altBases[1]] = 2;
//if ( altBases[2] > 0 ) alleleMap[altBases[2]] = 3;
int ploidies[2];
int acs[5] = {0,0,0,0,0};
int an = 0;
if (lk.chromosomeType == CT_AUTOSOME) {
ploidies[0] = 2;
ploidies[1] = 2;
}
if (lk.chromosomeType == CT_CHRX) {
ploidies[0] = 1;
ploidies[1] = 2;
}
else if ( lk.chromosomeType == CT_CHRY) {
ploidies[0] = 1;
ploidies[1] = 0;
}
else if (lk.chromosomeType == CT_MITO)
ploidies[0] = ploidies[1] = 1;
// determine genotype index for each possible genotypes 0/0, 0/1, ...
int gIdx[10] = {-1,-1,-1,-1,-1,-1,-1,-1,-1,-1};
int best2idx[10] = {-1,-1,-1,-1,-1,-1,-1,-1,-1};
gIdx[0] = glfHandler::GenotypeIndex(refAllele,refAllele);
gIdx[1] = glfHandler::GenotypeIndex(refAllele,altBases[0]);
gIdx[2] = glfHandler::GenotypeIndex(altBases[0],altBases[0]);
best2idx[gIdx[0]] = 0;
best2idx[gIdx[1]] = 1;
best2idx[gIdx[2]] = 2;
if ( altBases[1] > 0 ) {
gIdx[3] = glfHandler::GenotypeIndex(refAllele,altBases[1]);
gIdx[4] = glfHandler::GenotypeIndex(altBases[0],altBases[1]);
gIdx[5] = glfHandler::GenotypeIndex(altBases[1],altBases[1]);
best2idx[gIdx[3]] = 3;
best2idx[gIdx[4]] = 4;
best2idx[gIdx[5]] = 5;
}
if ( altBases[2] > 0 ) {
gIdx[6] = glfHandler::GenotypeIndex(refAllele,altBases[2]);
gIdx[7] = glfHandler::GenotypeIndex(altBases[0],altBases[2]);
gIdx[8] = glfHandler::GenotypeIndex(altBases[1],altBases[2]);
gIdx[9] = glfHandler::GenotypeIndex(altBases[2],altBases[2]);
best2idx[gIdx[6]] = 6;
best2idx[gIdx[7]] = 7;
best2idx[gIdx[8]] = 8;
best2idx[gIdx[9]] = 9;
}
const char* labels[10] = {"0/0","0/1","1/1","0/2","1/2","2/2","0/3","1/3","2/3","3/3"};
const char* labelsH[10] = {"0",".","1",".",".","2",".",".",".","3"};
// allows mapping from 0-9 genotype index to this
for (int i = 0; i < n; i++) {
int sex = lk.sexes[i] == SEX_MALE ? 1 : 0;
const unsigned char * llks = glf[i].GetLogLikelihoods(position);
int quality = lk.qualGenotypes[i];
int best = lk.bestGenotypes[i];
int depth = glf[i].GetDepth(position);
if ( best2idx[best] < 0 ) {
error("ref = %d, alt = %d, best = %d, best2idx[best] = %d, GPs=%.6lg,%.6lg,%.6lg,%.6lg,%.6lg,%.6lg,%.6lg,%.6lg,%.6lg,%.6lg",refAllele,altBases[0],best,best2idx[best],lk.GPs[i*10+0],lk.GPs[i*10+1],lk.GPs[i*10+2],lk.GPs[i*10+3],lk.GPs[i*10+4],lk.GPs[i*10+5],lk.GPs[i*10+6],lk.GPs[i*10+7],lk.GPs[i*10+8],lk.GPs[i*10+9]);
}
if ( ploidies[sex] == 2 ) {
genotypes.catprintf("\t%s:%d:%d",labels[best2idx[best]],depth,quality);
++acs[allele1s[best]];
++acs[allele2s[best]];
if ( depth > 0 ) {
an += 2;
++ns;
}
}
else if ( ploidies[sex] == 1 ) {
genotypes.catprintf("\t%s:%d:%d",labelsH[best2idx[best]],depth,quality);
++acs[allele1s[best]];
if ( depth > 0 ) {
++an;
++ns;
}
}
else {
genotypes.catprintf("\t.:%d:0",depth);
}
double pHet = 0;
if ( altBases[1] == 0 ) { // biallelic
genotypes.catprintf(":%d,%d,%d",llks[gIdx[0]], llks[gIdx[1]], llks[gIdx[2]]);
pHet = lk.GPs[10*i+gIdx[1]]/lk.sumPs[i];
}
else if ( altBases[2] == 0 ) { // triallelic
genotypes.catprintf(":%d,%d,%d,%d,%d,%d",llks[gIdx[0]], llks[gIdx[1]], llks[gIdx[2]], llks[gIdx[3]], llks[gIdx[4]], llks[gIdx[5]]);
pHet = lk.GPs[10*i+gIdx[1]]/(lk.GPs[10*i+gIdx[0]]+lk.GPs[10*i+gIdx[1]]+lk.GPs[10*i+gIdx[2]]+1e-30);
}
else { // four alleles
genotypes.catprintf(":%d,%d,%d,%d,%d,%d",llks[gIdx[0]], llks[gIdx[1]], llks[gIdx[2]], llks[gIdx[3]], llks[gIdx[4]], llks[gIdx[5]], llks[gIdx[6]], llks[gIdx[7]], llks[gIdx[8]], llks[gIdx[9]]);
pHet = lk.GPs[10*i+gIdx[1]]/(lk.GPs[10*i+gIdx[0]]+lk.GPs[10*i+gIdx[1]]+lk.GPs[10*i+gIdx[2]]+1e-30);
}
if ( ( depth > 0 ) && ( pHet > 1e-5 ) ) {
int scale = llks[gIdx[2]] + llks[gIdx[0]] - 2 * llks[gIdx[1]] + 6 * depth;
int minimum = abs(llks[gIdx[2]] - llks[gIdx[0]]);
if (scale < 4) scale = 4;
if (scale < minimum) scale = minimum;
double delta = (llks[gIdx[2]] - llks[gIdx[0]])
/ (scale + 1e-30);
double nref = 0.5 * depth * (1.0 + delta);
Acount += pHet * nref;
ABcount += pHet * depth;
}
}
info.catprintf("NS=%d", ns);
info.catprintf(";AN=%d", an);
info.catprintf(";AC=%d", acs[altBases[0]]);
if ( altBases[1] != 0 ) {
info.catprintf(",%d", acs[altBases[1]]);
if ( altBases[2] != 0 ) {
info.catprintf(",%d", acs[altBases[2]]);
}
}
info.catprintf(";AF=%.6lf", lk.freqs[altBases[0]]);
if ( altBases[1] != 0 ) {
info.catprintf(",%.6lf", lk.freqs[altBases[1]]);
if ( altBases[2] != 0 ) {
info.catprintf(",%.6lf", lk.freqs[altBases[2]]);
}
}
double AB = Acount / (ABcount + 1e-30);
double AZ = (Acount - 0.5*ABcount)/sqrt(ABcount*0.25 + 1e-30);
info.catprintf(";AB=%.4lf;AZ=%.4lf", AB, AZ);
double inbreedingCoeff = lk.inbreedingCoeff();
double signedLRT = (inbreedingCoeff > 0 ? 1 : -1) * lk.hwdLRT();
info.catprintf(";FIC=%.4lf;SLRT=%.4lf", inbreedingCoeff, signedLRT );
//info.catprintf(";HWDGF=%.6lf,%.6lf,%.6lf", lk.dfreqs[gIdx[0]], lk.dfreqs[gIdx[1]], lk.dfreqs[gIdx[2]] );
}
void ReportSNP(FullLikelihood & lk,
int n, int position,
int refBase, int* altBases,
const char * filter,
int totalCoverage, int rmsMapQuality, double log10post) {
if (baseCalls == NULL) return;
char alleles[] = { 0, 'A', 'C', 'G', 'T' };
glfHandler * glf = lk.glf;
// Find the location of the first non-stub glf
int firstGlf = 0;
while (glf[firstGlf].isStub)
firstGlf++;
// #Chrom Pos Id
fprintf(baseCalls, "%s\t%d\t.\t", (const char *) glf[firstGlf].label, position + 1);
// Reference allele
fprintf(baseCalls, "%c\t", alleles[refBase]);
if ( altBases[0] != 0 )
fprintf(baseCalls, "%c", alleles[altBases[0]]);
else
fprintf(baseCalls, ".");
if ( altBases[1] != 0 )
fprintf(baseCalls, ",%c", alleles[altBases[1]]);
if ( altBases[2] != 0 )
fprintf(baseCalls, ",%c", alleles[altBases[2]]);
fprintf(baseCalls, "\t");
double quality = (-10.0 * log10post);//posterior > 0.9999999999 ? 100 : (int)(-10 * log10(1.0 - posterior));
//double log10post = 0-log10( prior * exp(lFull-lRef) + 1.0 );
//int quality = (int)(10.0 * log10( prior * exp(0-lk.min-lRef) + 1.0 ));
// Quality for this call
//fprintf(baseCalls, "%lf,%lf\t", lRef, 0-lk.min);
fprintf(baseCalls, "%.3lf\t", quality);
// Filter for this call
fprintf(baseCalls, "%s\t", filter == NULL || filter[0] == 0 ? "PASS" : filter);
String info, genotypes;
ReportGenotypes(lk, glf, n, position, refBase, altBases, info, genotypes);
// Information for this call
fprintf(baseCalls, "DP=%d;MQ=%d;", totalCoverage, rmsMapQuality);
fprintf(baseCalls, "%s\t", (const char *) info);
// Format for this call
fprintf(baseCalls, "GT:DP:GQ:PL");
fprintf(baseCalls, "%s\n", (const char *) genotypes);
}
double FilteringLikelihood
(FilterLikelihood & lk, int n, int position, int refAllele)
{
lk.SetReferenceAllele(refAllele);
lk.OptimizeFrequency();
return -lk.fmin;
}
double PolymorphismLikelihood
(GenotypeLikelihood & lk, int n, int position, int refAllele, int mutAllele)
{
lk.SetAlleles(refAllele, mutAllele);
lk.OptimizeFrequency();
return -lk.fmin;
}
double SinkLikelihood
(glfHandler * glf, int n, int position)
{
double lk = 0.0;
double scale = -log(10.0) / 10;
for (int r = 1; r <= 4; r++)
for (int m = r + 1; m <= 4; m++)
{
int geno = glfHandler::GenotypeIndex(r, m);
double partial = log(1.0 / 6.0);
for (int i = 0; i < n; i++)
partial += glf[i].GetLogLikelihoods(position)[geno] * scale;
if (lk == 0.0)
{
lk = partial;
continue;
}
double max = partial > lk ? partial : lk;
double min = partial > lk ? lk : partial;
if (max - min > 50)
lk = max;
else
lk = log(exp(partial - min) + exp(lk - min)) + min;
}
return lk;
}
void getRegionInfo(const String& region, String& regionChr,
int& regionStart, int& regionEnd)
{
regionChr.Clear();
regionStart = 0;
regionEnd = -1;
if(!region.IsEmpty())
{
// Only process a specific region.
int chrStrEnd = region.FastFindChar(':',1);
if(chrStrEnd < 1)
{
regionChr = region;
printf("Processing only Chromosome %s\n", regionChr.c_str());
}
else
{
regionChr = region.Left(chrStrEnd);
// get the start region position.
int startStrEnd = region.FastFindChar('-',chrStrEnd);
String startStr;
if(startStrEnd < chrStrEnd)
{
startStr = region.SubStr(chrStrEnd+1);
}
else
{
startStr = region.Mid(chrStrEnd+1, startStrEnd-1);
}
// Convert the start string to an integer
if(!startStr.AsInteger(regionStart))
{
String errorStr = "Error: Invalid --region string, '";
errorStr += region;
errorStr += "', the start position, '";
errorStr += startStr;
errorStr += "', is not an integer.";
error(errorStr.c_str());
}
if(startStrEnd < chrStrEnd)
{
// No end position.
printf("Processing only Chromosome %s, starting from %d\n",
regionChr.c_str(), regionStart);
}
else
{
String endStr = region.SubStr(startStrEnd+1);
// Convert to integer.
if(!endStr.AsInteger(regionEnd))
{
String errorStr = "Error: Invalid --region string, '";
errorStr += region;
errorStr += "', the end position, '";
errorStr += endStr;
errorStr += "', is not an integer.";
error(errorStr.c_str());
}
printf("Processing only Chromosome %s, positions %d - %d\n",
regionChr.c_str(), regionStart, regionEnd);
}
}
}
}
int main(int argc, char ** argv) {
printf("glfMultiples -- SNP calls based on .glf or .glz files\n");
printf("(c) 2008-2014 Goncalo Abecasis, Sebastian Zoellner, Yun Li, Hyun Min Kang, and Mary Kate Trost\n\n");
String pedfile;
String positionfile;
String callfile;
String glfAliases;
String region;
String sfsfile; // custom site frequency spectrum
bool afprior = false; // use AF prior from site vcf
bool skipDetect = false; // skip variant detection
bool printMono = true; // print monomorphic variants
bool glfsingle = false; // use glfsingle model
ParameterList pl;
bool uniformTsTv = false;
double theta = 0.001;
double posterior = 0.50;
int minMapQuality = 0;
int minTotalDepth = 1;
int maxTotalDepth = INT_MAX;
bool verbose = false;
bool mapQualityStrict = false;
bool hardFilter = false;
bool smartFilter = false;
bool softFilter = true;
//bool vcfPosFilter = true;
String xLabel("X"), yLabel("Y"), mitoLabel("MT");
int xStart = 2699520, xStop = 154931044;
BEGIN_LONG_PARAMETERS(longParameters)
LONG_PARAMETER_GROUP("Pedigree File")
LONG_STRINGPARAMETER("ped", &pedfile)
LONG_PARAMETER_GROUP("Model")
LONG_PARAMETER("uniformTsTv", &uniformTsTv)
LONG_DOUBLEPARAMETER("heterozygosity", &theta)
LONG_STRINGPARAMETER("sfs",&sfsfile)
LONG_PARAMETER("glfsingle", &glfsingle)
LONG_PARAMETER_GROUP("Map Quality Filter")
LONG_INTPARAMETER("minMapQuality", &minMapQuality)
LONG_PARAMETER("strict", &mapQualityStrict)
LONG_PARAMETER_GROUP("Total Depth Filter")
LONG_INTPARAMETER("minDepth", &minTotalDepth)
LONG_INTPARAMETER("maxDepth", &maxTotalDepth)
LONG_PARAMETER_GROUP("Position Filter")
LONG_STRINGPARAMETER("positionFile", &positionfile)
LONG_PARAMETER("skipDetect",&skipDetect)
// LONG_PARAMETER("printMono",&printMono)
LONG_PARAMETER("afPrior",&afprior)
LONG_PARAMETER_GROUP("Chromosome Labels")
LONG_STRINGPARAMETER("xChr", &xLabel)
LONG_STRINGPARAMETER("yChr", &yLabel)
LONG_STRINGPARAMETER("mito", &mitoLabel)
LONG_INTPARAMETER("xStart", &xStart)
LONG_INTPARAMETER("xStop", &xStop)
LONG_PARAMETER_GROUP("Filtering Options")
EXCLUSIVE_PARAMETER("hardFilter", &hardFilter)
EXCLUSIVE_PARAMETER("smartFilter", &smartFilter)
EXCLUSIVE_PARAMETER("softFilter", &softFilter)
LONG_PARAMETER_GROUP("Region(optional)")
LONG_STRINGPARAMETER("region", ®ion)
LONG_PARAMETER_GROUP("Output")
LONG_PARAMETER("verbose", &verbose)
LONG_PARAMETER_GROUP("Sample Names")
LONG_STRINGPARAMETER("glfAliases", &glfAliases)
END_LONG_PARAMETERS();
pl.Add(new StringParameter('b', "Base Call File", callfile));
pl.Add(new DoubleParameter('p', "Posterior Threshold", posterior));
pl.Add(new LongParameters("Additional Options", longParameters));
int argstart = pl.ReadWithTrailer(argc, argv) + 1;
pl.Status();
if (posterior < 0)
error("Posterior threshold for genotype calls (-p option) must be > 0.");
time_t t;
time(&t);
printf("Analysis started on %s\n", ctime(&t));
fflush(stdout);
int n = argc - argstart;
argv += argstart;
Pedigree ped;
if (!pedfile.IsEmpty())
{
ped.pd.AddStringColumn("glfFile");
ped.Load(pedfile);
n = ped.count;
}
else
if (n == 0)
error("No pedigree file present and no glf files listed at the end of command line\n");
// Determine if only a subset of the regions are being processed.
String regionChr;
int regionStart = 0;
int regionEnd = -1;
getRegionInfo(region, regionChr, regionStart, regionEnd);
// Prior for finding difference from the reference at a particular site
double prior = 0.0;
double * sfs = new double[ n + n + 1 ];
if ( sfsfile.IsEmpty() ) {
double sum = 0;
for (int i = 1; i <= 2 * n; ++i) {
sfs[i] = 1.0 / i;
sum += sfs[i];
}
for (int i = 1; i <= 2 * n; ++i) {
sfs[i] /= sum;
}
}
else {
StringArray buf, tok;
buf.Read(sfsfile);
double sum = 0;
for (int i = 1; i <= 2 * n; ++i) {
sfs[i] = 0;
}
for(int i=0; i < buf.Length(); ++i) {
tok.ReplaceTokens(buf[i], " \t");
if ( tok.Length() != 2 )
error("Site frequency spectrum file %s must have two columns",(const char*)sfsfile);
int ac = tok[0].AsInteger();
if ( ( ac < 0 ) || ( ac > 2 * n ) ) {
error("Allele count %d is beyond the interval [%d, %d]", ac, 0, 2 * n);
}
if ( sfs[ac] > 0 ) {
error("Allele count %d appears twice in %s", ac, (const char*)sfsfile);
}
sfs[ ac ] = tok[1].AsDouble();
sum += sfs[ac];
}
for (int i = 1; i <= 2 * n; ++i) {
sfs[i] /= sum;
}
}
// now, the prior needs to be normalized
prior = 0.0;
for(int i = 1; i <= 2 * n; ++i) {
prior += (double)(i*(2*n-i))/(double)(n*(2*n-1))*sfs[i]; // this quantifies heterozygosity per site
}
prior = theta / prior;
printf("Pairwise heterozogosity : %.6lf\nProportion of polymorphic site : %.6lf\n", theta, prior );
glfHandler * glf = new glfHandler[n];
int firstGlf = n;
if (ped.count) {
bool warn = false;
bool anyOpened = false;
for (int i = n - 1; i >= 0; i--)
if (!glf[i].Open(ped[i].strings[0])) {
printf("Failed to open genotype likelihood file [%s] for individual %s:%s\n",
(const char *) ped[i].strings[0],
(const char *) ped[i].famid,
(const char *) ped[i].pid);
glf[i].OpenStub();
}
else {
anyOpened = true;
if(ifeof(glf[i].handle) != 0) {
// Empty GLF (just header).
// Close it and open a stub.
warning("GLF file '%s' appears empty ...\n",
ped.count ? (const char *) ped[i].strings[0] : argv[i]);
glf[i].Close();
glf[i].OpenStub();
}
else {
firstGlf = i;
}
}
if (warn)
printf("\n");
if ((firstGlf == n) && (!anyOpened))
error("No genotype likelihood files could be opened");
}
else
for (int i = n - 1; i >= 0; i--)
if (!glf[i].Open(argv[i]))
error("Failed to open genotype likelihood file [%s]\n", argv[i]);
else
firstGlf = i;
StringAlias aliases;
aliases.ReadFromFile(glfAliases);
printf("Calling genotypes for files ...\n");
for (int i = 0; i < n; i++)
printf("%s\n", ped.count ? (const char *) ped[i].strings[0] : argv[i]);
printf("\n");
baseCalls = fopen(callfile, "wt");
if (baseCalls != NULL) {
fprintf(baseCalls, "##fileformat=VCFv4.1\n");
ReportDate(baseCalls);
fprintf(baseCalls, "##source=glfMultiples\n");
fprintf(baseCalls, "##minDepth=%d\n", minTotalDepth);
if (maxTotalDepth != INT_MAX) fprintf(baseCalls, "##maxDepth=%d\n", maxTotalDepth);
fprintf(baseCalls, "##minMapQuality=%d\n", minMapQuality);
fprintf(baseCalls, "##minPosterior=%.4f\n", posterior);
fprintf(baseCalls, "##INFO=<ID=DP,Number=1,Type=Integer,Description=\"Total Depth at Site\">\n");
fprintf(baseCalls, "##INFO=<ID=MQ,Number=1,Type=Integer,Description=\"Root Mean Squared Mapping Quality\">\n");
fprintf(baseCalls, "##INFO=<ID=NS,Number=1,Type=Integer,Description=\"Number of Samples With Coverage\">\n");
fprintf(baseCalls, "##INFO=<ID=AN,Number=1,Type=Integer,Description=\"Number of Alleles in Samples with Coverage\">\n");
fprintf(baseCalls, "##INFO=<ID=AC,Number=.,Type=Integer,Description=\"Alternate Allele Counts in Samples with Coverage\">\n");
fprintf(baseCalls, "##INFO=<ID=AF,Number=.,Type=Float,Description=\"Alternate Allele Frequencies\">\n");
fprintf(baseCalls, "##INFO=<ID=AB,Number=1,Type=Float,Description=\"Allele Balance in Heterozygotes\">\n");
fprintf(baseCalls, "##FILTER=<ID=mq%d,Description=\"Mapping Quality Below %d\">\n", minMapQuality, minMapQuality);
fprintf(baseCalls, "##FILTER=<ID=dp%d,Description=\"Total Read Depth Below %d\">\n", minTotalDepth, minTotalDepth);
if (maxTotalDepth != INT_MAX)
fprintf(baseCalls, "##FILTER=<ID=DP%d,Description=\"Total Read Depth Above %d\">\n", maxTotalDepth, maxTotalDepth);
fprintf(baseCalls, "##FORMAT=<ID=GT,Number=1,Type=String,Description=\"Most Likely Genotype\">\n");
fprintf(baseCalls, "##FORMAT=<ID=GQ,Number=1,Type=Integer,Description=\"Genotype Call Quality\">\n");
fprintf(baseCalls, "##FORMAT=<ID=DP,Number=1,Type=Integer,Description=\"Read Depth\">\n");
fprintf(baseCalls, "##FORMAT=<ID=PL,Number=.,Type=Integer,Description=\"Genotype Likelihoods for Genotypes in Phred Scale, for 0/0, 0/1, 1/1, 0/2, 1/2, 2/2, ...\">\n");
fprintf(baseCalls, "#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\tFORMAT");
for (int i = 0; i < n; i++) {
fprintf(baseCalls, "\t%s", ped.count ?
( (ped[i].famid.Compare(ped[i].pid) == 0) ?
(const char*)(ped[i].pid) :
(const char *) (ped[i].famid + ":" + ped[i].pid) )
: (const char *) aliases.GetAlias(argv[i]));
}
fprintf(baseCalls, "\n");
}
// Prepare an array of filters. Positions are stored as strings, in the
// format chr:position or as VCF input files
// The input position map must be stored
// * if position file is specified, no allele information will be stored
// * if VCF is specified, allele information will be known to be assumed
// * with --afprior, AF information will be added to it
String buffer;
//StringArray tokens, tokens2, vcfTokens;
std::map<std::string, std::vector<snpKey> > pos;
if ( !positionfile.IsEmpty() ) {
int nkeys = 0;
pFile posFile;
// check whether indexfile exists
std::ifstream f((const char*)(positionfile + ".tbi"));
if (f.good()) {
f.close();
posFile.load(positionfile, region.IsEmpty() ? NULL : (const char*)region);
} else {
f.close();
posFile.load(positionfile, NULL);
}
const char* line = NULL;
std::vector<std::string> tokens, tokens2;
int pos1;
while( ( line = posFile.getLine() ) != NULL ) {
if ( line[0] == '#' ) continue;
pFile::tokenizeLine(line, " \t\r\n", tokens);
if (tokens.size() < 2) {
pFile::tokenizeLine(tokens[0].c_str(),":",tokens2);
if ( tokens2.size() < 2 )
warning("Line %s was not recognized and skipped in %s",tokens[0].c_str(), (const char*)positionfile);
else {
pos1 = atoi(tokens2[1].c_str());
if ( !regionChr.IsEmpty() ) {
if ( tokens2[0].compare((const char*)regionChr) != 0 )
continue;
if ( ( pos1 < regionStart ) || ( pos1 > regionEnd ) )
continue;
}
pos[tokens2[0]].push_back( snpKey(pos1) );
}
}
else if ( tokens.size() < 5 ) { // VCF-like [CHROM] [POS] [ID] [REF] [ALT]
pos1 = atoi(tokens[1].c_str());
if ( !regionChr.IsEmpty() ) {
if ( tokens[0].compare((const char*)regionChr) != 0 )
continue;
if ( ( pos1 < regionStart ) || ( pos1 > regionEnd ) )
continue;
}
pos[tokens[0]].push_back( snpKey(pos1) );
}
else {
pos1 = atoi(tokens[1].c_str());
// check if the variant is SNP
bool isSNP = true;
if ( tokens[3].size() != 1 ) {
isSNP = false;
}
else {
for(int i=0; i < (int)tokens[4].size(); ++i) {
switch(tokens[4][i]) {
case 'a': case 'A': case 'c': case 'C': case 'g': case 'G': case 't': case 'T':
if ( i % 2 != 0 ) {
isSNP = false;
}
break;
case ',':
if ( i % 2 != 1 ) {
isSNP = false;
}
break;
default:
isSNP = false;
}
}
if ( tokens[4].size() > 5 ) {
isSNP = false;
}
}
if ( !isSNP ) {
fprintf(stderr,"%s:%s_%s/%s in %s is not a SNP.. Skipping..\n",tokens[0].c_str(),tokens[1].c_str(),tokens[3].c_str(),tokens[4].c_str(),positionfile.c_str());
continue;
}
//fprintf(stderr,"%d\n",pos1);
pos[tokens[0]].push_back( snpKey(pos1, tokens[3].c_str(), tokens[4].c_str(), (tokens.size() >=8 && afprior ) ? tokens[7].c_str() : NULL ) );
++nkeys;
}
}
printf("Finished loading %d SNPs for unconditional genotyping\n",nkeys);
}
else if ( skipDetect ) {
error("--skipDetect option requires to specify --positionFile option");
}
// Prepare GenotypeLikelihood calculator, which will use sex information,
// if available
GenotypeLikelihood lkGeno(n, glf);
FilterLikelihood lkFilter(n, glf);
FullLikelihood lkFull(n, glf);
lkGeno.glf = lkFilter.glf = lkFull.glf = glf;
lkGeno.n = lkFilter.n = lkFull.n = n;
/*
IFILE vcfFile = sitevcf.IsEmpty() ? NULL : ifopen(sitevcf,"rb");
int vcfPos;
if ( vcfFile != NULL ) {
while( buffer.ReadLine(vcfFile) > 0 ) {
}
vcfTokens.ReplaceColumns(buffer, '\t');
if ( vcfTokens.Length() < 8 )
error("Input VCF file needs to have at least 8 columns");
vcfPos = vcfTokens[1].AsInteger();
}
*/
if (ped.count)
for (int i = 0; i < ped.count; i++)
lkGeno.sexes[i] = lkFilter.sexes[i] = ped[i].sex == SEX_MALE ? SEX_MALE : SEX_FEMALE;
int chromosomeType = 0;
// Main loop, which iterates through chromosomes and then positions
while((firstGlf != n) && (glf[firstGlf].NextSection())) {
// synchronize the base position between glf files
for (int i = firstGlf + 1; i < n; i++) {
if (glf[i].isStub) continue;
if ( !glf[i].NextSection() ) {
warning("GLF file '%s' appears empty ...\n",
//" File '%s' section %s with %d entries ...\n",
ped.count ? (const char *) ped[i].strings[0] : argv[i],
ped.count ? (const char *) ped[i].strings[0] : argv[i],
(const char *) glf[i].label, glf[i].maxPosition);
glf[i].isStub = true;
glf[i].position = glf[i].maxPosition = glf[firstGlf].maxPosition;
continue;
}
if (glf[firstGlf].maxPosition != glf[i].maxPosition || glf[firstGlf].label != glf[i].label) {
error("Genotype files '%s' and '%s' are not compatible ...\n"
" File '%s' has section %s with %d entries ...\n"
" File '%s' section %s with %d entries ...\n",
ped.count ? (const char *) ped[firstGlf].strings[0] : argv[firstGlf],
ped.count ? (const char *) ped[i].strings[0] : argv[i],
ped.count ? (const char *) ped[firstGlf].strings[0] : argv[firstGlf],
(const char *) glf[firstGlf].label, glf[firstGlf].maxPosition,
ped.count ? (const char *) ped[i].strings[0] : argv[i],
(const char *) glf[i].label, glf[i].maxPosition);
}
}
// If the region is specified, continue if this is not the correct chromosome.
if(!region.IsEmpty()) {
if(glf[firstGlf].label != regionChr)
continue;
}
std::vector<snpKey>& keys = pos[(const char*)glf[firstGlf].label];
chromosomeType = CT_AUTOSOME;
if (ped.count) {
if (glf[firstGlf].label == xLabel) chromosomeType = CT_CHRX;
if (glf[firstGlf].label == yLabel) chromosomeType = CT_CHRY;
if (glf[firstGlf].label == mitoLabel) chromosomeType = CT_MITO;
}
int endPos = glf[firstGlf].maxPosition;
if((regionEnd != -1) && (regionEnd < endPos)) {
endPos = regionEnd;
}
int numEntries = endPos - regionStart;
printf("Processing section %s with %d entries\n",
(const char *) glf[firstGlf].label, numEntries);
int refBase = 0;
int mapQualityFilter = 0;
int depthFilter = 0;
int homozygousReference = 0;
//int transitions = 0;
//int transversions = 0;
//int otherPolymorphisms = 0;
int sinkFilter = 0;
int smartFilterHits = 0;
int baseCounts[5] = {0, 0, 0, 0, 0};
String filter;
int keyCursor = 0; // current index
int newPos0 = -1;
int altBases[3];
//int quality;
if ( regionStart > 0 ) {
while( keyCursor < (int)keys.size() && keys[keyCursor].pos0 < regionStart-1 )
++keyCursor;
}
while (true) {
if (newPos0 > 0) {
// Check whether we have reached the end of the current chromosome
bool done = true;
for (int i = 0; i < n; i++)