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dosage.cpp
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//////////////////////////////////////////////////////////////////
// //
// PLINK (c) 2005-2009 Shaun Purcell //
// //
// This file is distributed under the GNU General Public //
// License, Version 2. Please see the file COPYING for more //
// details //
// //
//////////////////////////////////////////////////////////////////
#include <iostream>
#include <iomanip>
#include <string>
#include <cstdlib>
#include <cmath>
#include "options.h"
#include "helper.h"
#include "plink.h"
#include "phase.h"
#include "stats.h"
#include "zed.h"
#include "model.h"
#include "logistic.h"
#include "linear.h"
extern Plink * PP;
class Var {
public:
string snp;
string a1;
bool operator< (const Var & b) const
{
return (snp < b.snp);
}
bool operator== (const Var & b) const
{
return (snp == b.snp && a1 == b.a1 );
}
};
// Helper functions
void setUpQScoring( map<string,double> & ,
vector<double2> &,
vector<string> &);
void Plink::processDosageFile()
{
// For scroring procedure, if used
map<Var, vector<int> > qflag;
map<Var, double> wt;
matrix_t scores;
map<string,double> qscore;
vector<double2> qthresh;
vector<string> qlabel;
if ( par::score_risk )
{
if ( par::score_risk_on_qrange )
setUpQScoring( qscore, qthresh, qlabel);
// Read in score(s)
ZInput zin( par::score_risk_file , compressed( par::score_risk_file ) );
while ( ! zin.endOfFile() )
{
vector<string> tok = zin.tokenizeLine();
if ( tok.size() != 3 )
continue;
Var v;
v.snp = tok[0];
v.a1 = tok[1];
double s;
if ( ! from_string<double>( s, tok[2] , std::dec ) )
continue;
// Store weight
wt.insert(make_pair( v, s ));
// Which scores should we place this in?
if ( par::score_risk_on_qrange )
{
vector<int> qq;
// Can we find a q-score?
map<string,double>::iterator i1 = qscore.find( v.snp );
if ( i1 == qscore.end() )
continue;
double sc = i1->second;
for ( int q = 0 ; q < qthresh.size() ; q++)
{
if ( sc >= qthresh[q].p1 && sc <= qthresh[q].p2 )
qq.push_back(q);
}
qflag.insert(make_pair(v,qq));
}
// Read next score
}
zin.close();
printLOG("Done reading scores\n");
}
printLOG("\nReading dosage information from [ " + par::dosage_file + " ]\n");
// Expect a single file, with header
bool compressed_in = false;
bool compressed_out = false;
bool filelist = false;
bool countOccur = false;
bool header = true;
bool sepHeader = false;
int skip0 = 0;
int skip1 = 0;
int skip2 = 0;
bool dosageScale2 = true;
bool snpBatch = false;
// {skip0} SNP {skip1} A1 A2 {skip2} DATA...
OptionSet * dosage_opt = par::opt.getOptions("DOSAGE");
if ( dosage_opt->isSet("Z") )
compressed_in = compressed_out = true;
if ( dosage_opt->isSet("Zout") )
{
compressed_out = true;
}
if ( dosage_opt->isSet("Zin") )
compressed_in = true;
if ( dosage_opt->isSet("list") )
filelist = true;
if ( dosage_opt->isSet("occur") )
countOccur = true;
if ( dosage_opt->isSet("noheader") )
header = false;
if ( dosage_opt->isSet("sepheader") )
sepHeader = true;
if ( sepHeader && ! filelist )
error("The 'sepheader' option requires the 'list' option to be set");
if ( sepHeader && ! header )
error("Cannot specify both 'sepheader' and 'noheader'");
if ( dosage_opt->getValue("skip0") != "" )
skip0 = atoi( dosage_opt->getValue("skip0").c_str() );
if ( dosage_opt->getValue("skip1") != "" )
skip1 = atoi( dosage_opt->getValue("skip1").c_str() );
if ( dosage_opt->getValue("skip2") != "" )
skip2 = atoi( dosage_opt->getValue("skip2").c_str() );
if ( dosage_opt->isSet("dose1") )
dosageScale2 = false;
// Get relevant columns codes
int snp_field = skip0 + 0;
int a1_field = snp_field + skip1 + 1;
int a2_field = a1_field + 1;
int geno_field = a2_field + skip2 + 1;
int pre_fields = 3 + skip0 + skip1 + skip2;
if ( par::dosage_hasMap )
{
printLOG("A MAP file has been specified: only these markers will be processed\n");
if ( par::dosage_hard_call )
{
printLOG("Going to make hard-calls at "
+ dbl2str( par::dosage_hard_call_thresh ) + " threshold\n");
printLOG("and write remaining dosages to [ " + par::output_file_name
+ ".dosage" );
if ( compressed_out )
printLOG(".gz ]");
else
printLOG(" ]");
printLOG(" if more than " + int2str(par::dosage_hard_call_thresh2) + " non-calls\n");
par::SNP_major = true;
// Consider each new variant
// Space will already have been added
for (int l=0; l<nl_all; l++)
{
// Causal variant, data for all individuals
// default to missing genotype
CSNP * newlocus = SNP[l];
newlocus->one.resize(n,true);
newlocus->two.resize(n,false);
}
}
}
double thresh1_AA = (1-par::dosage_hard_call_thresh)/2.0;
double thresh1_AB = 0.5 - ((1-par::dosage_hard_call_thresh)/2.0);
double thresh2_AB = 0.5 + ((1-par::dosage_hard_call_thresh)/2.0);
double thresh1_BB = 1 - (1-par::dosage_hard_call_thresh)/2.0;
////////////////////////////////////
// Genotype dosage format options
bool oneDose = false;
bool twoProbs = false;
bool threeProbs = false;
if ( dosage_opt->getValue("format") == "1" )
oneDose = true;
else if ( dosage_opt->getValue("format") == "3" )
threeProbs = true;
else
twoProbs = true;
if ( oneDose )
printLOG("Format set to one dosage per genotype\n");
else if ( twoProbs )
printLOG("Format set to two genotype probabilities\n");
else
printLOG("Format set to three genotype probabilities\n");
int step = 1;
if ( twoProbs ) step = 2;
else if ( threeProbs ) step = 3;
// Still assume a single FAM file; but allow for people/SNPs to be
// spread across multiple files
// *** Currently, the order still needs to be similar across files in the
// same SNP batch
vector<string> dosageFilename_all;
vector<string> headerFilename_all;
vector<int> batchName;
set<int> batchNameSet;
if ( ! filelist )
{
dosageFilename_all.push_back( par::dosage_file );
}
else
{
ZInput IN1( par::dosage_file , false );
bool batchModeSet = false;
while ( ! IN1.endOfFile() )
{
vector<string> f = IN1.tokenizeLine();
if ( f.size() == 0 ) break;
// possible formats, if !sepHeader
// dosage-file
// snp-batch dosage-file
// if sepHeader
// dosage-file header-file
// snp-batch dosage-file header-file
if ( batchModeSet )
{
if ( sepHeader && snpBatch && f.size() != 3 )
error("Expecting 3 entries: batch dosage header");
else if ( sepHeader && (!snpBatch) && f.size() != 2 )
error("Expecting 2 entries: dosage header");
else if ( (!sepHeader) && snpBatch && f.size() != 2 )
error("Expecting 2 entries: batch dosage header");
else if ( (!sepHeader) && (!snpBatch) && f.size() != 1 )
error("Expecting 1 entry: dosage");
}
else
{
if (sepHeader)
{
if (f.size() == 3 )
snpBatch = true;
else if (f.size() == 2)
snpBatch = false;
else
error("Problem with dosage file list format");
}
else
{
if ( f.size() == 2 )
snpBatch = true;
else if ( f.size() == 1 )
snpBatch = false;
else
error("Problem with dosage file list format");
}
batchModeSet = true;
}
// Store information
int term = 0;
if ( snpBatch )
{
int nm;
if ( ! from_string<int>( nm, f[term] , std::dec ) )
error("Problem reading SNP batch number");
batchName.push_back( nm );
batchNameSet.insert( nm );
++term;
}
dosageFilename_all.push_back(f[term++]);
if ( sepHeader )
headerFilename_all.push_back(f[term++]);
}
IN1.close();
printLOG("Expecting "
+ int2str( dosageFilename_all.size() )
+ " total files, in " + int2str(batchNameSet.size())
+ " distinct batches of SNPs\n");
}
///////////////////////////////////////////
//
// Set up some basic things, headers, etc
//
///////////////////////////////////////////
map<string,int> msample;
for (int i=0; i<n; i++)
msample.insert(make_pair(sample[i]->fid+"_"+sample[i]->iid,i));
map<string,int> mlocus;
if ( par::dosage_hasMap )
for (int l=0; l<nl_all; l++)
mlocus.insert(make_pair(locus[l]->name,l));
string ext = countOccur
? ".occur.dosage" : par::write_dosage
? ".out.dosage" : ".assoc.dosage";
map<string,int> occur;
ZOutput detout;
if ( par::dosage_hard_call )
{
ext = ".dosage";
detout.open( par::output_file_name + ".dosage.det" , false );
std::ostringstream s2( std::stringstream::out );
s2 << sw("CHR",4)
<< sw("SNP",par::pp_maxsnp)
<< sw("BP", 12)
<< sw("A1", 4)
<< sw("A2", 4)
<< sw("MAF", 8)
<< sw("INFO", 8)
<< sw("ABOVE", 8)
<< sw("BELOW", 8)
<< sw("RATE", 8) << "\n";
detout.write( s2.str() );
printLOG("Writing additional information to [ "
+ par::output_file_name + ".dosage.det ]\n");
}
string tail = compressed_out ? ".gz" : "";
ZOutput zout( par::output_file_name + ext + tail , compressed_out );
if ( ! par::dosage_hard_call )
printLOG("Writing results to [ " + par::output_file_name + ext + tail + " ]\n");
if ( par::dosage_hard_call || par::write_dosage )
{
// Write header to dosage output file
std::ostringstream s2( std::stringstream::out );
s2 << "SNP A1 A2 ";
for (int i=0; i<n; i++)
if ( ! sample[i]->missing )
s2 << sample[i]->fid << " "
<< sample[i]->iid << " ";
s2 << "\n";
zout.write( s2.str() );
}
// Do we need a header?
if ( ! ( countOccur || par::dosage_hard_call || par::write_dosage ) )
{
string es = par::bt ? "OR" : "BETA";
if ( par::dosage_hasMap )
zout << sw("CHR",4)
<< sw("SNP",12)
<< sw("BP",12)
<< sw("A1",4)
<< sw("A2",4)
<< sw("FRQ",8)
<< sw("INFO",8)
<< sw(es,8)
<< sw("SE",8)
<< sw("P",8) << "\n";
else
zout << sw("SNP" ,12)
<< sw("A1" ,4)
<< sw("A2" ,4)
<< sw("FRQ" ,8)
<< sw("INFO" ,8)
<< sw(es ,8)
<< sw("SE",8)
<< sw("P" ,8) << "\n";
}
///////////////////////////////////////////////////
// Set up association model
bool OLD_assoc_glm_without_main_snp = par::assoc_glm_without_main_snp;
bool OLD_clist = par::clist;
par::assoc_glm_without_main_snp = true;
par::clist = true;
// Add an extra covariate slot
++par::clist_number;
clistname.resize( par::clist_number );
clistname[ par::clist_number - 1 ] = "DOSAGE";
for (int i=0; i<n; i++)
sample[i]->clist.resize( par::clist_number );
int term = par::clist_number -1;
int vcount = 0;
///////////////////////////////////////////////////
// Set up scoring procedure
if ( par::score_risk )
{
if ( par::score_risk_on_qrange )
sizeMatrix(scores,n,qthresh.size());
else
sizeMatrix(scores,n,1);
}
///////////////////////////////////////////
//
// Start looping through SNP batches
//
///////////////////////////////////////////
set<int>::iterator bi = batchNameSet.begin();
while (1)
{
// Pull out the relevant set of files
vector<string> dosageFilename;
vector<string> headerFilename;
if ( snpBatch )
{
for (int i=0; i<dosageFilename_all.size(); i++)
{
if ( batchName[i] == *bi )
{
dosageFilename.push_back( dosageFilename_all[i] );
if ( sepHeader )
headerFilename.push_back( headerFilename_all[i] );
}
}
}
else
{
dosageFilename = dosageFilename_all;
headerFilename = headerFilename_all;
}
int nFiles = dosageFilename.size();
vector<int> expected( nFiles );
vector<ZInput*> vzin( nFiles );
vector<ifstream*> vhead( nFiles );
vector< vector<Individual*> > personMap( nFiles);
vector<int> npeople( nFiles );
int found = 0;
int totpeople = 0;
set<Individual*> inDosage;
if ( nFiles > 1 && ! header )
error("Can only specify noheader when reading a single dosage file\n");
for (int f = 0 ; f < vzin.size() ; f++ )
{
ZInput * d = new ZInput( dosageFilename[f] , compressed_in );
vzin[f] = d;
if ( sepHeader )
vhead[f] = new ifstream(headerFilename[f].c_str() , ios::in );
// Read header, or use FAM file
if ( header )
{
vector<string> tok;
if ( ! sepHeader )
tok = vzin[f]->tokenizeLine();
else
{
// read all ID pairs
while (1)
{
string fid, iid;
(*vhead[f]) >> fid >> iid;
if ( fid == "" || vhead[f]->eof() )
break;
tok.push_back(fid);
tok.push_back(iid);
}
}
int firstCol = sepHeader ? 0 : pre_fields ;
if ( tok.size() < firstCol )
error("Bad format fdr dosage file, expecting more columns");
if ( ! sepHeader )
{
if ( tok[snp_field] != "SNP" || tok[a1_field] != "A1" || tok[a2_field] != "A2" )
error("Badly aligned columns for: SNP A1 A2");
}
if ( (tok.size() - firstCol ) % 2 != 0 )
error("Expecting 3 + 2 * N columns in header\n");
// Based on header field, two entries per person (FID, IID)
npeople[f] = (tok.size()- firstCol )/2;
expected[f] = pre_fields + npeople[f] * step;
//////////////////////////////////////////////////////
// Process header row
for (int i=firstCol; i<tok.size(); i+= 2 )
{
string id = tok[i] + "_" + tok[i+1];
map<string,int>::iterator m = msample.find(id);
if ( m == msample.end() )
{
personMap[f].push_back( (Individual*)NULL ) ;
}
else
{
if ( inDosage.find( sample[ m->second ] ) != inDosage.end() )
error("The person appears in >1 dosage file: " + id );
Individual * person = sample[m->second];
personMap[f].push_back( person );
inDosage.insert( person );
++found;
}
}
totpeople += npeople[f];
}
else
{
// If no explicit header given
npeople[f] = n;
expected[f] = pre_fields + npeople[f] * step;
totpeople += npeople[f];
for (int i=0; i<n; i++ )
{
string id = sample[i]->fid+ "_" + sample[i]->iid;
map<string,int>::iterator m = msample.find(id);
if ( m == msample.end() )
{
personMap[f].push_back( (Individual*)NULL ) ;
}
else
{
if ( inDosage.find( sample[ m->second ] ) != inDosage.end() )
error("The person appears in >1 dosage file: " + id );
Individual * person = sample[m->second];
personMap[f].push_back( person );
inDosage.insert( person );
}
}
}
} // next dosage file
if ( ! snpBatch && header )
{
printLOG("Matched to " + int2str(found)
+ " of " + int2str( totpeople ) + " individuals");
if ( filelist )
printLOG(" in " + int2str( nFiles ) + " files\n");
else
printLOG(" in [ " + par::dosage_file + " ]\n");
}
if ( sepHeader )
{
for (int f = 0 ; f < nFiles; f++ )
vhead[f]->close();
}
// Remove missing individuals
if ( ! par::dosage_hard_call )
{
int n_removed = keepIndividuals( inDosage );
if ( n_removed > 0 )
{
printLOG("Removed " + int2str(n_removed)
+ " individuals not in dosage file\n");
// Update person map, given we've removed some people
msample.clear();
for (int i=0; i<n; i++)
msample.insert(make_pair(sample[i]->fid+"_"+sample[i]->iid,i));
}
}
// Create final file column position -> sample # mapping, for each file
vector< vector<int> > personPosition( nFiles );
for (int f = 0 ; f < nFiles; f++ )
{
for (int i = 0; i < personMap[f].size(); i++)
{
Individual * person = personMap[f][i];
if ( person == NULL )
{
personPosition[f].push_back(-1);
}
else
{
string id = person->fid + "_" + person->iid;
map<string,int>::iterator p = msample.find( id );
personPosition[f].push_back( p->second );
}
}
}
/////////////////////////////////////////////////
// Read main dosage data, and analyse SNP by SNP
while ( 1 )
{
bool done = false;
bool skip = false;
string snp_id;
string a1_id;
string a2_id;
int snp_code;
int goodCall = 0;
int badCall = 0;
map<Individual*,double> dose1;
map<Individual*,double> dose2;
for ( int f = 0 ; f < nFiles ; f++ )
{
if ( vzin[f]->endOfFile() )
{
done = true;
break;
}
// Read line from the correct file
vector<string> tok = vzin[f]->tokenizeLine();
if ( tok.size() == 0 )
{
skip = true;
break;
}
if ( tok.size() != expected[f] )
error("Problem with line:\n" + displayLine(tok) );
if ( tok[ snp_field ] == "" )
{
skip = true;
break;
}
if ( f == 0 )
{
snp_id = tok[ snp_field ];
a1_id = tok[ a1_field ];
a2_id = tok[ a2_field ];
}
else
{
if ( snp_id != tok[ snp_field ] )
error("Misaligned SNPs in dosage files");
if ( a1_id != tok[a1_field ] )
error("Misaligned allele codes in dosage file");
}
// If we've loaded a MAP file, then ignore this
// marker if it is not present in the MAP file
if ( par::dosage_hasMap )
{
map<string,int>::iterator mi = mlocus.find( snp_id );
if ( mlocus.find( snp_id ) == mlocus.end() )
{
skip = true;
continue;
}
if ( f==0 )
{
snp_code = mi->second;
locus[ snp_code ]->allele1 = a1_id;
locus[ snp_code ]->allele2 = a2_id;
}
}
// Are we just in the mode in which we simply count
// how many times/files we see this SNP?
if ( countOccur )
{
map<string,int>::iterator o = occur.find( tok[ snp_field ] );
if ( o != occur.end() )
(o->second)++;
else
occur.insert(make_pair( tok[ snp_field ], 1 ));
continue;
}
// Start position for genotype data
int j = pre_fields;
for (int i=0; i<npeople[f]; i++)
{
bool problem = false;
// Skip this individual if not in file
if ( personPosition[f][i] == -1 )
{
j += step;
continue;
}
Individual * person = sample[ personPosition[f][i] ];
double dose, d1, d2, d3;
if ( oneDose )
{
if ( !from_string<double>( dose, tok[j++], std::dec ) )
problem=true;
if ( dosageScale2 )
{
if ( dose < 0 || dose > 2 )
problem = true;
dose /= 2.0;
}
else
{
if ( dose < 0 || dose > 1 )
problem = true;
}
}
else if ( twoProbs )
{
if ( !from_string<double>( d1, tok[j++], std::dec ) )
problem = true;
if ( !from_string<double>( d2, tok[j++], std::dec ) )
problem = true;
if ( d1 < 0 || d1 > 1 )
problem = true;
if ( d2 < 0 || d2 > 1 )
problem = true;
if ( d1 + d2 > 1 )
problem = true;
dose = d1 + d2/2.0;
dose1.insert(make_pair( person , d1 ) );
dose2.insert(make_pair( person , d2 ) );
}
else if ( threeProbs )
{
if ( !from_string<double>( d1, tok[j++], std::dec ) )
problem = true;
if ( !from_string<double>( d2, tok[j++], std::dec ) )
problem = true;
if ( !from_string<double>( d3, tok[j++], std::dec ) )
problem = true;
if ( d1 < 0 || d1 > 1 )
problem = true;
if ( d2 < 0 || d2 > 1 )
problem = true;
// skip sanity check on 3rd
// if ( d1 + d2 > 1 )
// problem = true;
dose = d1 + d2/2.0;
dose1.insert(make_pair( person , d1 ) );
dose2.insert(make_pair( person , d2 ) );
}
// Do we want to make a hard call now, or store
// dosage for analysis?
if ( par::dosage_hard_call )
{
bool s1 = true;
bool s2 = false;
if ( oneDose )
{
if ( dose < thresh1_AA )
{ s1=s2=false; }
else if ( dose > thresh1_AB && dose < thresh2_AB )
{ s1=false; s2=true; }
else if ( dose > thresh1_BB )
{ s1=s2=true; }
}
else
{
if ( d1 > par::dosage_hard_call_thresh )
{ s1=s2=false; }
else if ( d2 > par::dosage_hard_call_thresh )
{ s1=false; s2=true; }
else if ( 1-d1-d2 > par::dosage_hard_call_thresh )
{ s1=s2=true; }
}
if ( s1 && ! s2 )
++badCall;
else
++goodCall;
SNP[snp_code]->one[personPosition[f][i]] = s1;
SNP[snp_code]->two[personPosition[f][i]] = s2;
}
if ( problem )
{
sample[ personPosition[f][i] ]->missing2 = true;
}
else
{
sample[ personPosition[f][i] ]->missing2 = false;
sample[ personPosition[f][i] ]->clist[ term ] = dose;
}
}
} // Next dosage file
// Are we at the end of a file though?
if ( done )
break;
if ( skip )
continue;
// Do we need to bother processing the genotype dosage data?
if ( countOccur )
continue;
++vcount;
if ( ! par::silent )
cerr << "Processed " << vcount << " markers \r";
///////////////////////////////////////////////////
// Set up scoring procedure
if ( par::score_risk )
{
// Does this variant have a score?
Var v;
v.snp = snp_id;
map<Var,double>::iterator i = wt.find( v );
if ( i == wt.end() )
continue;
double weight = i->second;
// Right allele?
bool swapAllele = false;
if ( i->first.a1 == a2_id )
{
// need to swap
swapAllele = true;
}
else
{
if ( i->first.a1 != a1_id )
continue;
}
if ( par::score_risk_on_qrange )
{
map<Var,vector<int> >::iterator i0 = qflag.find(v);
if ( i0 == qflag.end() )
continue;
vector<int> & inQ = i0->second;
for (int q=0; q<inQ.size(); q++)
{
for (int i=0; i<n; i++)
scores[i][ inQ[q] ] += swapAllele ?
weight * ( 1 - sample[i]->clist[ term ] ) :
weight * sample[i]->clist[ term ];
}
}
else
{
for (int i=0; i<n; i++)
{