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//////////////////////////////////////////////////////////////////
// //
// PLINK (c) 2005-2008 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 <fstream>
#include <sstream>
#include <map>
#include <algorithm>
#include <bitset>
#include "plink.h"
#include "options.h"
#include "helper.h"
void Plink::mergeBinaryData()
{
// Function to merge a text file with an exisiting data set
// either SNP-major or individual-major modes
if (!par::merge_list)
{
printLOG( "Using merge mode " + int2str( par::merge_mode ) + " : ");
if (par::merge_mode==1) printLOG("consensus call (default)\n");
else if (par::merge_mode==2) printLOG("overwrite if missing in original\n");
else if (par::merge_mode==3) printLOG("overwrite unless missing in new\n");
else if (par::merge_mode==4) printLOG("overwrite none\n");
else if (par::merge_mode==5) printLOG("overwrite all\n");
else if (par::merge_mode==6) printLOG("diff mode: all differences\n");
else if (par::merge_mode==7) printLOG("diff mode: non-missing differences\n");
diff_overlap = 0;
diff_nonmissing_overlap = 0;
diff_concordant_overlap = 0;
}
// We've already loaded in the first file
// Do not overwrite any existing phenotype information
checkFileExists(par::merge_bedfile);
checkFileExists(par::merge_bimfile);
checkFileExists(par::merge_famfile);
// Make hash of original SNP names
map<string,int> mlocus;
for (int l=0;l<nl_all;l++)
mlocus.insert(make_pair(locus[l]->name,l));
map<string,int>::iterator ilocus;
// A temporary hash for the names of any markers that
// do not match in terms of strand
set<string> misstrand;
map<string,int> misstrand_dummy;
bool fatal_error = false;
///////////////////////////////////////
// .bim
vector<Locus> ordered(0);
map<string,bool> exists;
vector<Locus*> locus2(0);
set<string> flip_alleles;
ifstream MAP(par::merge_bimfile.c_str(), ios::in);
MAP.clear();
int exist_cnt=0;
int c=0;
while(!MAP.eof())
{
Locus * loc = new Locus;
long int inc;
MAP >> loc->chr // will automatically by numeric
>> loc->name
>> loc->pos // will automatically be in M units
>> loc->bp
>> loc->allele1
>> loc->allele2;
inc = loc->bp;
// Use the frequency slot temporarily to
// store order information
loc->freq = c++;
// Check that cM/M specification looks correct, if
// we want to perform a plink-based analysis
if (par::plink && (!par::cm_map) && (loc->pos > 50) )
error("Looks like you need to specify --cm ??");
// Convert cM to M map distances
if (par::cm_map) loc->pos /= 100;
// Including all loci in merge-mode
if (loc->name!="")
{
ilocus = mlocus.find(loc->name);
///////////////////////////////////////////////////
// Check whether or not this Locus already exists?
if (ilocus != mlocus.end())
{
Locus * loc2 = locus[ilocus->second];
// Check same chromosome and positions, etc
if ( loc2->chr != loc->chr )
{
cerr << "Warning: different chromosome for "
<< loc->name << "\n";
loc->chr = loc2->chr;
}
// Check same chromosome and positions, etc
if ( loc2->bp != loc->bp )
{
cerr << "Warning: different physical position for "
<< loc->name << "\n";
loc->bp = loc2->bp;
}
if ( loc2->pos != loc->pos )
{
cerr << "Warning: different genetic position for "
<< loc->name << "\n";
loc->pos = loc2->pos;
}
exists[loc->name] = true;
exist_cnt++;
locus2.push_back(loc2);
// Keep the new file order (would have been in freq)
int t = (int)loc->freq;
if ( loc2->allele1 == "" )
loc2->allele1 = par::missing_genotype;
if ( loc2->allele2 == "" )
loc2->allele2 = par::missing_genotype;
/////////////////////////////////////////
// Add allele names to list, if needed
// and check if allele codes need flipping?
// e.g. if A/C SNP in memory but C/A in file?
// or had one allele missing
// and check that alleles match up correctly
// 0 A A 0 -> 0 A + flip
// 0 0 0 0 -> 0 0
// 0 0 0 A -> {0 A}
// 0 0 A B -> {A B}
// 0 A 0 A -> 0 A
// 0 A 0 B -> {B A} + flip
// 0 A A B -> {B A} + flip
// 0 A B A -> {B A}
// 0 A 0 0 -> 0 A
// A B A B -> A B
// A B B A -> A B + flip
// A B 0 A -> A B + flip
// A B 0 0 -> A B
// 1) Are there any empty slots in the existing allele?
// If so, fill them in with any new alleles
// 2) Do we have a strand problem?
// 3) Or do we need a flip?
// New codes
string one = loc->allele1;
string two = loc->allele2;
// cout << "LOCUS " << loc->name << " OLD, NEW = ["
// << loc2->allele1 << "] ["
// << loc2->allele2 << "] ["
// << one << "] ["
// << two << "]\n";
set<string> alleleCount;
if ( one != par::missing_genotype )
alleleCount.insert( one );
if ( two != par::missing_genotype )
alleleCount.insert( two );
if ( loc2->allele1 != par::missing_genotype )
alleleCount.insert( loc2->allele1 );
if ( loc2->allele2 != par::missing_genotype )
alleleCount.insert( loc2->allele2 );
// More than 2 obseved alleles?
if ( alleleCount.size() > 2 )
{
misstrand.insert(loc2->name);
fatal_error = true;
}
else
{
//////////////////////////////
// 1) Fill in empty slots
// Fill slot 2 first (i.e. 0 A code for monomorphic, not A 0)
// If first new allele is not missing...
if (one!=par::missing_genotype)
{
// ...and not already listed
if (one!=loc2->allele1 && one!=loc2->allele2)
{
// ...then add to first empty slot
if(loc2->allele2=="" || loc2->allele2==par::missing_genotype)
loc2->allele2=one;
else if(loc2->allele1=="" || loc2->allele1==par::missing_genotype)
loc2->allele1=one;
}
}
if (two!=one && two!=par::missing_genotype)
// ...and not already listed
if (two!=loc2->allele1 && two!=loc2->allele2)
{
// ...then add to first empty slot
if(loc2->allele2=="" || loc2->allele2==par::missing_genotype)
loc2->allele2=two;
else if(loc2->allele1=="" || loc2->allele1==par::missing_genotype )
loc2->allele1=two;
}
//////////////////////////////
// 2) Need a flip?
if ( ( one == loc2->allele2 && one != par::missing_genotype ) ||
( two == loc2->allele1 && two != par::missing_genotype ) ||
( one != loc2->allele1 && one != par::missing_genotype && loc2->allele1 != par::missing_genotype ) ||
( two != loc2->allele2 && two != par::missing_genotype && loc2->allele2 != par::missing_genotype ) )
{
if ( one == loc2->allele2 || two == loc2->allele1 )
{
flip_alleles.insert(loc2->name);
}
else
{
//////////////////////////////
// 3) Strand, wrong coding?
misstrand.insert(loc2->name);
fatal_error = true;
}
}
}
// Clean up what we do not need
delete loc;
// Replace with old locus (but swap back in new file position)
loc = loc2;
loc->freq = t;
}
else
{
// Locus does not exist -- add to locus list
exists[loc->name] = false;
locus2.push_back(loc);
}
ordered.push_back(*loc);
}
}
MAP.clear();
MAP.close();
///////////////////////////////////////////////////////
// Did we encounter any fatal errors from flipped SNPs?
if (fatal_error)
{
ofstream MSNP;
string f = par::output_file_name+".missnp";
MSNP.open(f.c_str(), ios::out);
set<string>::iterator ilocus;
for ( ilocus = misstrand.begin() ; ilocus != misstrand.end() ; ilocus++)
{
MSNP << *ilocus << "\n";
}
MSNP.close();
printLOG("\nFound " + int2str(misstrand.size()) + " SNPs that do not match in terms of allele codes\n");
printLOG("Might include strand flips, although flipped A/T and C/G SNPs will be undetected)\n");
printLOG("Writing problem SNPs to [ " + f + " ]\n");
error("Stopping due to mis-matching SNPs -- check +/- strand?");
}
if (!par::merge_list)
{
printLOG("\n" +int2str(locus2.size()) +
" markers to be merged from [ " +par::merge_bimfile + " ]\n");
printLOG("Of these, "+int2str( locus2.size()-exist_cnt ) + " are new, " +
int2str( exist_cnt ) + " already exist in current data\n");
}
///////////////////////////////////////////////
// Build ordered table, so that genotypes can be inserted
// in correct order; then swap locus file over
// Sorting a vector of pointers, so we need this special fix
stable_sort(locus2.begin(),locus2.end(),less<Locus*>());
// Sorting a normal vector
stable_sort(ordered.begin(),ordered.end());
c=0;
for (int i=0; i<ordered.size(); i++)
{
// swap file order into locus position
// and make all same chromosome
ordered[i].bp = (int)ordered[i].freq;
ordered[i].chr = 1;
// keep track of genetic order, but only
// for nonmissing loci
ordered[i].freq = c++;
}
// resort to get lookup table
stable_sort(ordered.begin(),ordered.end());
// i.e. for file position k, the locus position is ordered[k]->freq
// p2 p3 p1 p5 p4 : genetic position
// 0 1 2 3 4 : file order
// sort by cM
// p1 p2 p3 p4 p5 : genetic
// 2 0 1 4 3 : file order
// 0 1 2 : add genetic order: nonmissing...
//
// sort by file order again
// p2 p3 p1 p5 p4 : genetic
// 0 1 2 3 4 : file
// 1 0 2 : position to put in locus[l]
// Add new locus2() to end of locus()
for (int l=0; l<locus2.size(); l++)
{
// need to add a new MAP entry
if (!exists.find(locus2[l]->name)->second )
{
Locus * loc = new Locus;
loc = locus2[l];
locus.push_back(loc);
}
}
///////////////////////////////////////////////
// .fam
// Make new hash of Locus names
mlocus.clear();
for (int l=0;l<locus.size();l++)
{
mlocus.insert(make_pair(locus[l]->name,l));
}
if (mlocus.size() != locus.size() )
{
cerr << "Problem encountered merging files, with the following markers:\n";
mlocus.clear();
for (int l=0;l<locus.size();l++)
{
if (mlocus.find(locus[l]->name) != mlocus.end())
cerr << locus[l]->name << "\n";
mlocus.insert(make_pair(locus[l]->name,l));
}
cerr << "[ dump info: sizes = " << mlocus.size() << " and " << locus.size() << " ]\n";
error("Cannot merge files. Check your MAP files.");
}
// Make hash of existing individuals
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>::iterator isample;
// Resize all existing individuals
// and set new elements to missing genotype (TF)
if (par::SNP_major)
{
// Add space for new SNPs
for (int i=0; i<locus2.size()-exist_cnt; i++)
{
CSNP * newlocus = new CSNP;
newlocus->one.resize(n,true);
newlocus->two.resize(n,false);
SNP.push_back(newlocus);
}
}
else
{
// If using individual-major mode
for (int i=0; i<n; i++)
{
sample[i]->one.resize(locus.size(),true);
sample[i]->two.resize(locus.size(),false);
}
}
// An output file for diff mode
ofstream MERD;
if (par::merge_mode >=6)
{
string f = par::output_file_name+".diff";
MERD.open(f.c_str(), ios::out);
MERD << setw(20) << "SNP" << " "
<< setw(20) << "FID" << " "
<< setw(20) << "IID" << " "
<< setw(8) << "NEW" << " "
<< setw(8) << "OLD" << " " << "\n";
}
int new_person = 0;
int old_person = 0;
///////////////////////////////////////
// Read in FAM/BED file to new merge file
// Initially, assume a binary trait
par::qt = false;
par::bt = true;
ifstream FAM;
FAM.open(par::merge_famfile.c_str());
FAM.clear();
vector<bool> existing_person_list;
int original_sample_size = sample.size();
vector<Individual*> sample2;
c=0;
while(!FAM.eof())
{
Individual * person = new Individual;
// No comments allowed in BED/BIM/FAM files
// First 6 obligatory fields
string phenotype;
FAM >> person->fid
>> person->iid
>> person->pat
>> person->mat
>> person->sexcode
>> phenotype;
// Skip last empty line that gets read
if (person->fid=="") break;
// Check for reserved family ID code
if ( person->fid=="FID" )
error("FID is a reserved ID... please select a different family ID");
// Are we using 0/1 coding?
if (par::coding01)
{
if ( phenotype == "1" )
phenotype = "2";
else if ( phenotype == "0" )
phenotype = "1";
else
phenotype = "0";
}
if (person->sexcode=="1")
person->sex = true; // male
else if (person->sexcode=="2")
person->sex = false; // female (default)
else if (!par::ignore_missing_sex)
{
person->missing = true;
}
// Have we already created this person?
bool already_in = false;
isample = msample.find(person->fid+"_"+person->iid);
int indn = isample->second;
if ( isample != msample.end() )
{
already_in = true;
delete person;
person = sample[isample->second];
old_person++;
}
else
new_person++;
// Only look at phenotype if not already created
if (!already_in)
{
//////////////////
// A non-founder?
person->founder = (person->pat == "0" && person->mat == "0") ? true : false;
/////////////////////////////////////////////////////
// Set missing status; test for quantitative traits?
if (phenotype == par::missing_phenotype)
person->missing = true;
else
{
if ( ! from_string<double>( person->phenotype, phenotype, std::dec ) )
person->missing = true;
else
if (phenotype != "0" &&
phenotype != "1" &&
phenotype != "2" )
{
par::qt = true;
par::bt = false;
}
}
}
///////////////////////////////////////
// Add necessary space for a new person
// Missing genotypes by default
if (!already_in)
{
if (par::SNP_major)
{
// Add a new missing person to each SNP
vector<CSNP*>::iterator s = SNP.begin();
while ( s != SNP.end() )
{
(*s)->one.push_back(true);
(*s)->two.push_back(false);
s++;
}
// And set the individual number
indn = n + new_person - 1;
}
else
{
// Add all new SNPs to this person
person->one.resize(locus.size(),true);
person->two.resize(locus.size(),false);
}
}
// Record whether this individual is new or not
existing_person_list.push_back(already_in);
sample2.push_back(person);
// Add individual to list, if need be
if (!existing_person_list[c])
{
sample.push_back(person);
msample.insert(make_pair( person->fid+"_"+person->iid,
sample.size()-1 ) );
}
// Increase person counter
c++;
}
if (!par::merge_list)
{
printLOG(int2str( existing_person_list.size() )
+ " individuals merged from [ "
+ par::merge_famfile + " ] \n");
printLOG("Of these, " + int2str(new_person)
+ " were new, " + int2str( old_person ) +
" were already in current data\n\n");
}
////////////////////////////////////
// Read genotype information, merge
ifstream BIT;
bool bfile_SNP_major = openBinaryFile( par::merge_bedfile, BIT );
if (bfile_SNP_major != par::SNP_major)
error("BED files must both be SNP-major or both individual-major for merging\n");
if ( (!par::SNP_major) || (!bfile_SNP_major) )
error("Cannot --bmerge individual-major BED files -- convert to SNP-major");
///////////////////////////
// SNP-major mode
if (bfile_SNP_major)
{
// Person look-up table
vector<Individual*>::iterator person = sample2.begin();
vector<int> vindn;
while ( person != sample2.end() )
{
map<string,int>::iterator isample =
msample.find((*person)->fid+"_"+(*person)->iid);
int indn;
if ( isample != msample.end() )
indn = isample->second;
else
error("Internal error in --bmerge... should not happen...\n");
vindn.push_back(indn);
++person;
}
CSNP * snp;
// Outer loop for SNPs
int s=0;
while (s<locus2.size()) // for all SNPs in second file
{
// Look up SNP information
// map<string,int>::iterator ilocus = mlocus.find(locus2[ s ]->name);
// int l2 = ilocus->second;
int k0 = (int)ordered[s].freq;
ilocus = mlocus.find(locus2[k0]->name);
int k = ilocus->second;
bool flipmode = flip_alleles.find( locus2[k0]->name ) != flip_alleles.end();
string snp1 = locus2[ k0 ]->allele1;
string snp2 = locus2[ k0 ]->allele2;
bool existence = exists.find(locus2[k0]->name)->second;
//////////////////////////////////////
// Inner loop for individuals
vector<int>::iterator indn = vindn.begin();
while ( indn != vindn.end() )
{
char ch[1];
BIT.read(ch,1);
bitset<8> b;
b = ch[0];
int c=0;
if (!BIT)
error("Problem with the BED file...has the FAM file been changed?\n");
while (c<7 && indn != vindn.end() )
{
bool s1 = b[c++];
bool s2 = b[c++];
if ( flipmode && s1 == s2 )
{
s1 = !s1;
s2 = !s2;
}
string one = snp1;
string two = snp2;
if (s1 && s2) one=snp2;
else if ( (!s1) && (!s2) ) two=snp1;
else if ( s1 && !s2 ) one=two=par::missing_genotype;
bool already_in = false;
if ( *indn < original_sample_size ) already_in = true;
else already_in = existing_person_list[*indn - original_sample_size];
bool e = reconcileMerge( *indn, k ,
one, two,
already_in,
existence,
MERD, misstrand_dummy);
if (e) fatal_error=true;
// next person
indn++;
}
}
// next SNP
s++;
}
// Set file mode
par::SNP_major = true;
}
////////////////////////////////////
// Individual-major mode
// else
// {
// // Outer loop for individuals
// vector<Individual*>::iterator person = sample.begin();
// while ( person != sample.end() )
// {
// // Inner loop for SNPs
// int s=0;
// while (s<locus.size()) // for all SNPs
// {
// char ch[1];
// BIT.read(ch,1);
// if (!BIT) error("Problem with the BED file... has the FAM file been changed?\n");
// bitset<8> b;
// b = ch[0];
// int c=0;
// while (c<7 && s<locus.size())
// {
// (*person)->one[ s ] = b[c++];
// (*person)->two[ s ] = b[c++];
// s++;
// }
// }
// person++;
// }
// // Set file mode
// par::SNP_major = false;
// }
//////////////
// Close files
FAM.clear();
FAM.close();
BIT.clear();
BIT.close();
// If a binary trait, now make 0 missing also
// i.e. if we never saw other than missing, 0, 1 or 2
if (par::bt)
for (int i=0; i<sample.size(); i++)
if ( sample[i]->phenotype == 0 )
sample[i]->missing = true;
if (par::merge_mode >=6)
{
printLOG("Results from diff ( merge mode "
+ int2str(par::merge_mode) + " ) written to [ " +
par::output_file_name + ".diff ]\n");
MERD.close();
printLOG("Of " + int2str(diff_overlap) + " overlapping SNPs, "
+ int2str( diff_nonmissing_overlap ) + " were both genotyped\nand "
+ int2str( diff_concordant_overlap ) + " were concordant\n");
printLOG("Concordance rate is "
+ dbl2str( (double)diff_concordant_overlap
/ (double)diff_nonmissing_overlap ) + "\n");
shutdown();
}
// Phenotype statistics
if (!par::merge_list)
{
int nm=0;
for (int i=0;i<sample.size();i++)
if(!sample[i]->missing) nm++;
printLOG(int2str( nm ) + " individuals with nonmissing phenotypes\n");
if (par::bt)
{
printLOG("Assuming a disease phenotype (1=unaff, 2=aff, 0=miss)\n");
if (par::missing_phenotype!="0")
printLOG("Missing phenotype value is also " + par::missing_phenotype + "\n");
int ncase = 0;
int ncontrol = 0;
for (int i=0; i<sample.size(); i++)
if ( sample[i]->phenotype == 1 )
ncontrol++;
else if ( sample[i]->phenotype == 2 )
ncase++;
printLOG(int2str(ncase)+" cases and "+int2str(ncontrol)+" controls\n");
}
else
{
printLOG("Assuming a quantitative trait\n");
printLOG("Missing phenotype value is " + par::missing_phenotype + "\n");
}
}
}
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