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VcfUtils.cpp
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VcfUtils.cpp
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#include "VcfUtils.h"
#include <sstream>
#include <stdio.h>
#include <string.h>
#include <vector>
namespace VcfUtils{
/**
* Loads all correct markers in file_name into Pedigree.
*
* A correct marker :
* Is a SNP with 1 alternative allele and with no missing base in the reference or alt allele.
* Has no missing or unphased genotypes.
*
*
* Throws error if unphased or missing genotypes present in any sample.
*/
void LoadReferenceMarkers(const String &file_name){
// printf("Loading markers from file %s \n", file_name.c_str());
VcfFileReader reader;
VcfHeader header;
reader.open(file_name, header);
const char * marker_name;
VcfRecord record;
while(reader.readRecord(record)){
//A marker's name in the pedigree is its chromosome and position.
//So they can be identified as same when originating from different files
std::stringstream ss;
ss << record.getChromStr() << ":" << record.get1BasedPosition();
std::string markerstring = ss.str();
ss.clear();
marker_name = markerstring.c_str();
if(!record.allPhased()) {
//TODO throw error.
printf("ERROR: NOT ALL PHASED! at %s \n", marker_name);
printf("all phased = %d \n", record.allPhased());
printf("all genotypes = %d \n", record.hasAllGenotypeAlleles());
}
// if marker is a monomorphic SNP with no missing bases
if(record.getNumRefBases() == 1 && record.getNumAlts() == 1 && strcmp(record.getRefStr(),"N") != 0 && strlen(record.getRefStr()) == 1 && strlen(record.getAltStr()) == 1) {
int marker_id = Pedigree::GetMarkerID(marker_name);
String ref_base = String(record.getRefStr()[0]);
String alt_base = String(record.getAltStr()[0]);
// printf("ref base = %s \n", ref_base.c_str());
// printf("alt base = %s \n", alt_base.c_str());
//TODO perform check on ref and alt values?
int ref = Pedigree::LoadAllele(marker_id, ref_base);
int alt = Pedigree::LoadAllele(marker_id, alt_base);
//printf("ref str = %s num = %d \n", ref_base.c_str(), ref);
//printf("alt str = %s num = %d \n", alt_base.c_str(), alt);
}
}
unphased_marker_subset.resize(Pedigree::markerCount,0);
reader.close();
};
/**
* Add individuals from ref_file to the pedigree ped.
*
*/
void LoadReferenceIndividuals(Pedigree &ped, const String &ref_file) {
VcfFileReader reader;
VcfHeader header;
reader.open(ref_file, header);
int num_samples = header.getNumSamples();
// printf("Num reference inds : %d \n", num_samples);
if(num_samples == 0) {
//TODO add exceptions
// printf("ERROR: No reference individuals in file");
}
for(int i = 0; i < num_samples; i++) {
ped.AddPerson(header.getSampleName(i), header.getSampleName(i), "0", "0", 0, 1);
}
reader.close();
};
void writeVectorToCSV(const char * file_name, const std::vector<vector<double>>& v, const char* opentype){
FILE * csvout = fopen(file_name, opentype);
for(const auto& vector : v) {
for (auto elem : vector) {
std::string s = std::to_string(elem);
fwrite(s.c_str(), sizeof(char), s.length(), csvout);
putc(',', csvout);
}
putc('\n',csvout);
fflush(csvout);
}
fclose(csvout);
};
/**
* Add individual sample_index from sample_file to pedigree.
*
*/
void LoadSampleIndividual(Pedigree &ped, const String &sample_file, int sample_index) {
VcfFileReader reader;
VcfHeader header;
reader.open(sample_file, header);
ped.AddPerson(header.getSampleName(sample_index), header.getSampleName(sample_index), "0", "0", 0, 1);
reader.close();
};
/**
* Initialize the haplotypes of the samples to 0.
*
* index indicates the first index that contains a sample haplotype
*
*/
void FillSampleHaplotypes(const Pedigree &ped, MatrixXc & haplotypes, int index) {
for (int hap = index; hap < ped.count*2; hap++) {
for (int m = 0; m < ped.markerCount; m++) {
haplotypes(hap,m) = 0;
}
}
};
/**
* Load all alleles from file_name at markers present in pedigree into haplotypes.
*
* Assumes the file only contains samples that are phased at all markers, have no missing reference of alternative alleles,
* and that the pedigree only contains monomorphic SNPs.
*
*/
void LoadHaplotypes(const String &file_name, const Pedigree &ped, char** haplotypes) {
VcfFileReader reader;
VcfHeader header;
reader.open(file_name, header);
const char * marker_name;
VcfRecord record;
while(reader.readRecord(record)){
std::stringstream ss;
ss << record.getChromStr() << ":" << record.get1BasedPosition();
marker_name = ss.str().c_str();
int marker_id = Pedigree::LookupMarker(marker_name);
if(marker_id >= 0){
for (int ind = 0; ind < ped.count; ind++) {
int i0 = record.getGT(ind,0);
int i1 = record.getGT(ind,1);
haplotypes[ind*2][marker_id] = i0;
haplotypes[ind*2 + 1][marker_id] = i1;
}
}
}
reader.close();
// printf("Done \n");
};
/**
* Load all alleles from file_name at markers present in pedigree into haplotypes.
*
* Assumes the file only contains samples that are phased at all markers, have no missing reference of alternative alleles,
* and that the pedigree only contains monomorphic SNPs.
*
*/
void LoadHaplotypes(const String &file_name, const Pedigree &ped, MatrixXc & haplotypes ) {
VcfFileReader reader;
VcfHeader header;
reader.open(file_name, header);
const char * marker_name;
VcfRecord record;
while(reader.readRecord(record)){
std::stringstream ss;
ss << record.getChromStr() << ":" << record.get1BasedPosition();
std::string markers = ss.str();
marker_name = markers.c_str();
int marker_id = Pedigree::LookupMarker(marker_name);
if(marker_id >= 0){
for (int ind = 0; ind < ped.count; ind++) {
int i0 = record.getGT(ind,0);
int i1 = record.getGT(ind,1);
haplotypes(ind*2,marker_id) = i0;
haplotypes(ind*2 + 1,marker_id) = i1;
}
}
}
reader.close();
// printf("Done \n");
};
/**
* Load genotypes of individual sample_index_file from file_name into last row of genotypes.
* Markers present in pedigree but not in file_name are given genotype phreds 0.
*
* temproary: fill all other genotypes with 0
*/
void LoadGenotypeLikelihoods(const String &file_name, const Pedigree &ped, vector<double> & sample_gls, int sample_index_file) {
const char * marker_name;
// int pl_00, pl_01, pl_11;
int num_common_markers = 0;
int num_total_markers = 0;
// std::string sub00, sub01, sub11;
VcfFileReader reader;
VcfHeader header;
reader.open(file_name, header);
VcfRecord record;
while(reader.readRecord(record)){
num_total_markers += 1;
// TODO: This pattern could be factored out...
std::stringstream ss;
ss << record.getChromStr() << ":" << record.get1BasedPosition();
std::string markers = ss.str();
marker_name = markers.c_str();
int marker_id = Pedigree::LookupMarker(marker_name);
if(marker_id >= 0){
// if marker is a monomorphic SNP with no missing bases
if(record.getNumRefBases() != 1 || record.getNumAlts() != 1) {
//TODO throw error
printf("ERROR: Sample marker is not monomorphic SNP\n");
continue;
}
String sample_ref_base = String(record.getRefStr()[0]);
String sample_alt_base = String(record.getAltStr()[0]);
MarkerInfo * mi = Pedigree::GetMarkerInfo(marker_id);
String phased_ref_base = mi->GetAlleleLabel(1);
String phased_alt_base = mi->GetAlleleLabel(2);
if(sample_ref_base != phased_ref_base || sample_alt_base != phased_alt_base){
//TODO throw error or warning
printf("ERROR: Sample alleles do not match phased reference's alles\n");
continue;
}
vector<double> gls = get_GL(header, record, sample_index_file);
// OBS GL SHOULD BE log10(likelihood, so thould be this)
sample_gls[marker_id*3] = pow(10,gls[0]);
sample_gls[marker_id*3+1] = pow(10,gls[1]);
sample_gls[marker_id*3+2] = pow(10,gls[2]);
unphased_marker_subset[marker_id] = 1;
num_common_markers += 1;
}
}
reader.close();
for(int marker_id = 0; marker_id < ped.markerCount; marker_id++){
if(!unphased_marker_subset[marker_id]){
sample_gls[marker_id*3] = 0.3333;
sample_gls[marker_id*3+1] = 0.3333;
sample_gls[marker_id*3+2] = 0.3333;
}
}
// printf("Num reference markers : %d, Num sample markers: %d, %d of which are also in reference. \n", ped.markerCount, num_total_markers, num_common_markers);
};
int GetMarkerPos(int marker_id){
std::string marker_name = Pedigree::GetMarkerInfo(marker_id)->name.c_str();
std::size_t delim = marker_name.find(":");
return std::stoi(marker_name.substr(delim+1));
}
/**
* Get the format of genotype likelihoods specified in header.
* Return forst occurrence of "GL" or "PL" found.
* Assumes at most one specified.
* Returns "" if neither specified.
*/
std::string get_likelihood_format(VcfHeader& header) {
std::string line;
int index;
int lines = header.getNumMetaLines();
for(int i = 0; i < lines; i++) {
line = header.getMetaLine(i);
index = line.find("ID=GL,");
if(index > -1) {
return "GL";
}
index = line.find("ID=PL,");
if(index > -1) {
return "PL";
}
}
return "";
};
vector<double> get_GL(VcfHeader& header, VcfRecord& record, int sample) {
vector<double> gl_vals;
string lformat = get_likelihood_format(header);
std::string sub00, sub01, sub11;
const string * likelihood = record.getGenotypeInfo().getString(lformat,sample);
if(*likelihood == "" || *likelihood == ".") {
//TODO throw error or handle somehow
printf("ERROR: INDIVIDUAL WITH NO LIKELIHOOD FOUND \n");
}
std::istringstream iss(*likelihood);
double gl_00;
double gl_01;
double gl_11;
std::getline(iss, sub00, ',');
std::getline(iss, sub01, ',');
std::getline(iss, sub11, ',');
gl_00 = (lformat == "PL") ? atof(sub00.c_str())/-10.0 : atof(sub00.c_str());
gl_01 = (lformat == "PL") ? atof(sub01.c_str())/-10.0 : atof(sub01.c_str());
gl_11 = (lformat == "PL") ? atof(sub11.c_str())/-10.0 : atof(sub11.c_str());
gl_vals.push_back(gl_00);
gl_vals.push_back(gl_01);
gl_vals.push_back(gl_11);
return gl_vals;
}
/**
* Fill distances with crossover probabilities so that
* distances[m] = prob of crossover happening in interval between m-1 and m.
*
*
*/
void LoadGeneticMap(const char *file_name, const Pedigree &ped, vector<double> &distances) {
int ped_pos;
int map_pos;
double dist;
double prev_dist;
char marker_name [256];
int result;
//TODO dont hardcode Ne
// double pop_const = 4*11418;
FILE * mapstream = fopen(file_name, "r");
map_pos = -1;
prev_dist = 0.0;
result = 3;
for (int i = 0; i < Pedigree::markerCount && result == 3; i++) {
ped_pos = GetMarkerPos(i);
while(map_pos < ped_pos && result == 3) {
result = fscanf(mapstream, "%255s %d %lf", marker_name, &map_pos, &dist);
}
if(map_pos == ped_pos) {
distances[i] = (dist - prev_dist > 0.0000000000001) ? (dist - prev_dist) : 0.01;
prev_dist = dist;
}
else{
distances[i] = distances[i-1];
printf("WARNING: Marker %d is not present in crossover file. \n", GetMarkerPos(i));
continue;
}
}
distances[0] = 0.01;
};
//////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////
int max_pl = 255;
std::vector<int> unphased_marker_subset;
}