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Diffstat (limited to 'src/io.cpp')
-rw-r--r-- | src/io.cpp | 1396 |
1 files changed, 1396 insertions, 0 deletions
diff --git a/src/io.cpp b/src/io.cpp new file mode 100644 index 0000000..c22f668 --- /dev/null +++ b/src/io.cpp @@ -0,0 +1,1396 @@ +/* + Genome-wide Efficient Mixed Model Association (GEMMA) + Copyright (C) 2011 Xiang Zhou + + This program is free software: you can redistribute it and/or modify + it under the terms of the GNU General Public License as published by + the Free Software Foundation, either version 3 of the License, or + (at your option) any later version. + + This program is distributed in the hope that it will be useful, + but WITHOUT ANY WARRANTY; without even the implied warranty of + MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the + GNU General Public License for more details. + + You should have received a copy of the GNU General Public License + along with this program. If not, see <http://www.gnu.org/licenses/>. +*/ + +#include <iostream> +#include <fstream> +#include <sstream> +#include <string> +#include <iomanip> +#include <bitset> +#include <vector> +#include <map> +#include <set> +#include <cstring> +#include <cmath> +#include <stdio.h> +#include <stdlib.h> + +#include "gsl/gsl_vector.h" +#include "gsl/gsl_matrix.h" +#include "gsl/gsl_linalg.h" +#include "gsl/gsl_blas.h" +#include "gsl/gsl_cdf.h" + +#include "lapack.h" +#include "gzstream.h" +#include "mathfunc.h" + +#ifdef FORCE_FLOAT +#include "io_float.h" +#else +#include "io.h" +#endif + + +using namespace std; + + + +//Print process bar +void ProgressBar (string str, double p, double total) +{ + double progress = (100.0 * p / total); + int barsize = (int) (progress / 2.0); + char bar[51]; + + cout<<str; + for (int i = 0; i <50; i++) { + if (i<barsize) {bar[i] = '=';} + else {bar[i]=' ';} + cout<<bar[i]; + } + cout<<setprecision(2)<<fixed<<progress<<"%\r"<<flush; + + return; +} + + +//Print process bar (with acceptance ratio) +void ProgressBar (string str, double p, double total, double ratio) +{ + double progress = (100.0 * p / total); + int barsize = (int) (progress / 2.0); + char bar[51]; + + cout<<str; + for (int i = 0; i <50; i++) { + if (i<barsize) {bar[i] = '=';} + else {bar[i]=' ';} + cout<<bar[i]; + } + cout<<setprecision(2)<<fixed<<progress<<"% "<<ratio<<"\r"<<flush; + + + return; +} + +// in case files are ended with "\r" or "\r\n" +std::istream& safeGetline(std::istream& is, std::string& t) +{ + t.clear(); + + // The characters in the stream are read one-by-one using a std::streambuf. + // That is faster than reading them one-by-one using the std::istream. + // Code that uses streambuf this way must be guarded by a sentry object. + // The sentry object performs various tasks, + // such as thread synchronization and updating the stream state. + + std::istream::sentry se(is, true); + std::streambuf* sb = is.rdbuf(); + + for(;;) { + int c = sb->sbumpc(); + switch (c) { + case '\n': + return is; + case '\r': + if(sb->sgetc() == '\n') + sb->sbumpc(); + return is; + case EOF: + // Also handle the case when the last line has no line ending + if(t.empty()) + is.setstate(std::ios::eofbit); + return is; + default: + t += (char)c; + } + } +} + +//Read snp file +bool ReadFile_snps (const string &file_snps, set<string> &setSnps) +{ + setSnps.clear(); + + ifstream infile (file_snps.c_str(), ifstream::in); + if (!infile) {cout<<"error! fail to open snps file: "<<file_snps<<endl; return false;} + + string line; + char *ch_ptr; + + while (getline(infile, line)) { + ch_ptr=strtok ((char *)line.c_str(), " , \t"); + setSnps.insert(ch_ptr); + } + + infile.close(); + infile.clear(); + + return true; +} + + +//Read log file +bool ReadFile_log (const string &file_log, double &pheno_mean) +{ + ifstream infile (file_log.c_str(), ifstream::in); + if (!infile) {cout<<"error! fail to open log file: "<<file_log<<endl; return false;} + + string line; + char *ch_ptr; + size_t flag=0; + + while (getline(infile, line)) { + ch_ptr=strtok ((char *)line.c_str(), " , \t"); + ch_ptr=strtok (NULL, " , \t"); + + if (ch_ptr!=NULL && strcmp(ch_ptr, "estimated")==0) { + ch_ptr=strtok (NULL, " , \t"); + if (ch_ptr!=NULL && strcmp(ch_ptr, "mean")==0) { + ch_ptr=strtok (NULL, " , \t"); + if (ch_ptr!=NULL && strcmp(ch_ptr, "=")==0) { + ch_ptr=strtok (NULL, " , \t"); + pheno_mean=atof(ch_ptr); + flag=1; + } + } + } + + if (flag==1) {break;} + } + + infile.close(); + infile.clear(); + + return true; +} + + +//Read bimbam annotation file +bool ReadFile_anno (const string &file_anno, map<string, string> &mapRS2chr, map<string, long int> &mapRS2bp, map<string, double> &mapRS2cM) +{ + mapRS2chr.clear(); + mapRS2bp.clear(); + + ifstream infile (file_anno.c_str(), ifstream::in); + if (!infile) {cout<<"error opening annotation file: "<<file_anno<<endl; return false;} + + string line; + char *ch_ptr; + + string rs; + long int b_pos; + string chr; + double cM; + + while (!safeGetline(infile, line).eof()) { + ch_ptr=strtok ((char *)line.c_str(), " , \t"); + rs=ch_ptr; + ch_ptr=strtok (NULL, " , \t"); + if (strcmp(ch_ptr, "NA")==0) {b_pos=-9;} else {b_pos=atol(ch_ptr);} + ch_ptr=strtok (NULL, " , \t"); + if (ch_ptr==NULL || strcmp(ch_ptr, "NA")==0) {chr="-9";} else {chr=ch_ptr;} + ch_ptr=strtok (NULL, " , \t"); + if (ch_ptr==NULL || strcmp(ch_ptr, "NA")==0) {cM=-9;} else {cM=atof(ch_ptr);} + + mapRS2chr[rs]=chr; + mapRS2bp[rs]=b_pos; + mapRS2cM[rs]=cM; + } + + infile.close(); + infile.clear(); + + return true; +} + +//read one column of phenotype +bool ReadFile_column (const string &file_pheno, vector<int> &indicator_idv, vector<double> &pheno, const int &p_column) +{ + indicator_idv.clear(); + pheno.clear(); + + igzstream infile (file_pheno.c_str(), igzstream::in); +// ifstream infile (file_pheno.c_str(), ifstream::in); + if (!infile) {cout<<"error! fail to open phenotype file: "<<file_pheno<<endl; return false;} + + string line; + char *ch_ptr; + + string id; + double p; + while (!safeGetline(infile, line).eof()) { + ch_ptr=strtok ((char *)line.c_str(), " , \t"); + for (int i=0; i<(p_column-1); ++i) { + ch_ptr=strtok (NULL, " , \t"); + } + if (strcmp(ch_ptr, "NA")==0) {indicator_idv.push_back(0); pheno.push_back(-9);} //pheno is different from pimass2 + else {p=atof(ch_ptr); indicator_idv.push_back(1); pheno.push_back(p);} + } + + infile.close(); + infile.clear(); + + return true; +} + + + +//Read bimbam phenotype file, p_column=1, 2 ... +bool ReadFile_pheno (const string &file_pheno, vector<vector<int> > &indicator_pheno, vector<vector<double> > &pheno, const vector<size_t> &p_column) +{ + indicator_pheno.clear(); + pheno.clear(); + + igzstream infile (file_pheno.c_str(), igzstream::in); +// ifstream infile (file_pheno.c_str(), ifstream::in); + if (!infile) {cout<<"error! fail to open phenotype file: "<<file_pheno<<endl; return false;} + + string line; + char *ch_ptr; + + string id; + double p; + + vector<double> pheno_row; + vector<int> ind_pheno_row; + + size_t p_max=*max_element(p_column.begin(), p_column.end() ); + map<size_t, size_t> mapP2c; + for (size_t i=0; i<p_column.size(); i++) { + mapP2c[p_column[i]]=i; + pheno_row.push_back(-9); + ind_pheno_row.push_back(0); + } + + while (!safeGetline(infile, line).eof()) { + ch_ptr=strtok ((char *)line.c_str(), " , \t"); + + size_t i=0; + while (i<p_max ) { + if (mapP2c.count(i+1)!=0) { + if (strcmp(ch_ptr, "NA")==0) {ind_pheno_row[mapP2c[i+1]]=0; pheno_row[mapP2c[i+1]]=-9;} + else {p=atof(ch_ptr); ind_pheno_row[mapP2c[i+1]]=1; pheno_row[mapP2c[i+1]]=p;} + } + i++; + ch_ptr=strtok (NULL, " , \t"); + } + + indicator_pheno.push_back(ind_pheno_row); + pheno.push_back(pheno_row); + } + + infile.close(); + infile.clear(); + + return true; +} + + +bool ReadFile_cvt (const string &file_cvt, vector<int> &indicator_cvt, vector<vector<double> > &cvt, size_t &n_cvt) +{ + indicator_cvt.clear(); + + ifstream infile (file_cvt.c_str(), ifstream::in); + if (!infile) {cout<<"error! fail to open covariates file: "<<file_cvt<<endl; return false;} + + string line; + char *ch_ptr; + double d; + + int flag_na=0; + + while (!safeGetline(infile, line).eof()) { + vector<double> v_d; flag_na=0; + ch_ptr=strtok ((char *)line.c_str(), " , \t"); + while (ch_ptr!=NULL) { + if (strcmp(ch_ptr, "NA")==0) {flag_na=1; d=-9;} + else {d=atof(ch_ptr);} + + v_d.push_back(d); + ch_ptr=strtok (NULL, " , \t"); + } + if (flag_na==0) {indicator_cvt.push_back(1);} else {indicator_cvt.push_back(0);} + cvt.push_back(v_d); + } + + if (indicator_cvt.empty()) {n_cvt=0;} + else { + flag_na=0; + for (vector<int>::size_type i=0; i<indicator_cvt.size(); ++i) { + if (indicator_cvt[i]==0) {continue;} + + if (flag_na==0) {flag_na=1; n_cvt=cvt[i].size();} + if (flag_na!=0 && n_cvt!=cvt[i].size()) {cout<<"error! number of covariates in row "<<i<<" do not match other rows."<<endl; return false;} + } + } + + infile.close(); + infile.clear(); + + return true; +} + + + +//Read .bim file +bool ReadFile_bim (const string &file_bim, vector<SNPINFO> &snpInfo) +{ + snpInfo.clear(); + + ifstream infile (file_bim.c_str(), ifstream::in); + if (!infile) {cout<<"error opening .bim file: "<<file_bim<<endl; return false;} + + string line; + char *ch_ptr; + + string rs; + long int b_pos; + string chr; + double cM; + string major; + string minor; + + while (getline(infile, line)) { + ch_ptr=strtok ((char *)line.c_str(), " \t"); + chr=ch_ptr; + ch_ptr=strtok (NULL, " \t"); + rs=ch_ptr; + ch_ptr=strtok (NULL, " \t"); + cM=atof(ch_ptr); + ch_ptr=strtok (NULL, " \t"); + b_pos=atol(ch_ptr); + ch_ptr=strtok (NULL, " \t"); + minor=ch_ptr; + ch_ptr=strtok (NULL, " \t"); + major=ch_ptr; + + SNPINFO sInfo={chr, rs, cM, b_pos, minor, major, -9, -9, -9}; + snpInfo.push_back(sInfo); + } + + infile.close(); + infile.clear(); + return true; +} + + +//Read .fam file +bool ReadFile_fam (const string &file_fam, vector<vector<int> > &indicator_pheno, vector<vector<double> > &pheno, map<string, int> &mapID2num, const vector<size_t> &p_column) +{ + indicator_pheno.clear(); + pheno.clear(); + mapID2num.clear(); + + igzstream infile (file_fam.c_str(), igzstream::in); + //ifstream infile (file_fam.c_str(), ifstream::in); + if (!infile) {cout<<"error opening .fam file: "<<file_fam<<endl; return false;} + + string line; + char *ch_ptr; + + string id; + int c=0; + double p; + + vector<double> pheno_row; + vector<int> ind_pheno_row; + + size_t p_max=*max_element(p_column.begin(), p_column.end() ); + map<size_t, size_t> mapP2c; + for (size_t i=0; i<p_column.size(); i++) { + mapP2c[p_column[i]]=i; + pheno_row.push_back(-9); + ind_pheno_row.push_back(0); + } + + while (!safeGetline(infile, line).eof()) { + ch_ptr=strtok ((char *)line.c_str(), " \t"); + ch_ptr=strtok (NULL, " \t"); + id=ch_ptr; + ch_ptr=strtok (NULL, " \t"); + ch_ptr=strtok (NULL, " \t"); + ch_ptr=strtok (NULL, " \t"); + ch_ptr=strtok (NULL, " \t"); + + size_t i=0; + while (i<p_max ) { + if (mapP2c.count(i+1)!=0 ) { + if (strcmp(ch_ptr, "NA")==0) { + ind_pheno_row[mapP2c[i+1]]=0; pheno_row[mapP2c[i+1]]=-9; + } else { + p=atof(ch_ptr); + + if (p==-9) {ind_pheno_row[mapP2c[i+1]]=0; pheno_row[mapP2c[i+1]]=-9;} + else {ind_pheno_row[mapP2c[i+1]]=1; pheno_row[mapP2c[i+1]]=p;} + } + } + i++; + ch_ptr=strtok (NULL, " , \t"); + } + + indicator_pheno.push_back(ind_pheno_row); + pheno.push_back(pheno_row); + + mapID2num[id]=c; c++; + } + + infile.close(); + infile.clear(); + return true; +} + + + + + + +//Read bimbam mean genotype file, the first time, to obtain #SNPs for analysis (ns_test) and total #SNP (ns_total) +bool ReadFile_geno (const string &file_geno, const set<string> &setSnps, const gsl_matrix *W, vector<int> &indicator_idv, vector<int> &indicator_snp, const double &maf_level, const double &miss_level, const double &hwe_level, const double &r2_level, map<string, string> &mapRS2chr, map<string, long int> &mapRS2bp, map<string, double> &mapRS2cM, vector<SNPINFO> &snpInfo, size_t &ns_test) +{ + indicator_snp.clear(); + snpInfo.clear(); + + igzstream infile (file_geno.c_str(), igzstream::in); +// ifstream infile (file_geno.c_str(), ifstream::in); + if (!infile) {cout<<"error reading genotype file:"<<file_geno<<endl; return false;} + + gsl_vector *genotype=gsl_vector_alloc (W->size1); + gsl_vector *genotype_miss=gsl_vector_alloc (W->size1); + gsl_matrix *WtW=gsl_matrix_alloc (W->size2, W->size2); + gsl_matrix *WtWi=gsl_matrix_alloc (W->size2, W->size2); + gsl_vector *Wtx=gsl_vector_alloc (W->size2); + gsl_vector *WtWiWtx=gsl_vector_alloc (W->size2); + gsl_permutation * pmt=gsl_permutation_alloc (W->size2); + + gsl_blas_dgemm(CblasTrans, CblasNoTrans, 1.0, W, W, 0.0, WtW); + int sig; + LUDecomp (WtW, pmt, &sig); + LUInvert (WtW, pmt, WtWi); + + double v_x, v_w; + int c_idv=0; + + string line; + char *ch_ptr; + + string rs; + long int b_pos; + string chr; + string major; + string minor; + double cM; + + double maf, geno, geno_old; + size_t n_miss; + size_t n_0, n_1, n_2; + int flag_poly; + + int ni_total=indicator_idv.size(); + int ni_test=0; + for (int i=0; i<ni_total; ++i) { + ni_test+=indicator_idv[i]; + } + ns_test=0; + + while (!safeGetline(infile, line).eof()) { + ch_ptr=strtok ((char *)line.c_str(), " , \t"); + rs=ch_ptr; + ch_ptr=strtok (NULL, " , \t"); + minor=ch_ptr; + ch_ptr=strtok (NULL, " , \t"); + major=ch_ptr; + + if (setSnps.size()!=0 && setSnps.count(rs)==0) { + SNPINFO sInfo={"-9", rs, -9, -9, minor, major, -9, -9, -9}; + snpInfo.push_back(sInfo); + indicator_snp.push_back(0); + continue; + } + + if (mapRS2bp.count(rs)==0) {chr="-9"; b_pos=-9;cM=-9;} + else {b_pos=mapRS2bp[rs]; chr=mapRS2chr[rs]; cM=mapRS2cM[rs];} + + maf=0; n_miss=0; flag_poly=0; geno_old=-9; + n_0=0; n_1=0; n_2=0; + c_idv=0; gsl_vector_set_zero (genotype_miss); + for (int i=0; i<ni_total; ++i) { + ch_ptr=strtok (NULL, " , \t"); + if (indicator_idv[i]==0) {continue;} + + if (strcmp(ch_ptr, "NA")==0) {gsl_vector_set (genotype_miss, c_idv, 1); n_miss++; c_idv++; continue;} + + geno=atof(ch_ptr); + if (geno>=0 && geno<=0.5) {n_0++;} + if (geno>0.5 && geno<1.5) {n_1++;} + if (geno>=1.5 && geno<=2.0) {n_2++;} + + gsl_vector_set (genotype, c_idv, geno); + +// if (geno<0) {n_miss++; continue;} + + if (flag_poly==0) {geno_old=geno; flag_poly=2;} + if (flag_poly==2 && geno!=geno_old) {flag_poly=1;} + + maf+=geno; + + c_idv++; + } + maf/=2.0*(double)(ni_test-n_miss); + + SNPINFO sInfo={chr, rs, cM, b_pos, minor, major, n_miss, (double)n_miss/(double)ni_test, maf}; + snpInfo.push_back(sInfo); + + if ( (double)n_miss/(double)ni_test > miss_level) {indicator_snp.push_back(0); continue;} + + if ( (maf<maf_level || maf> (1.0-maf_level)) && maf_level!=-1 ) {indicator_snp.push_back(0); continue;} + + if (flag_poly!=1) {indicator_snp.push_back(0); continue;} + + if (hwe_level!=0) { + if (CalcHWE(n_0, n_2, n_1)<hwe_level) {indicator_snp.push_back(0); continue;} + } + + //filter SNP if it is correlated with W + for (size_t i=0; i<genotype->size; ++i) { + if (gsl_vector_get (genotype_miss, i)==1) {geno=maf*2.0; gsl_vector_set (genotype, i, geno);} + } + + gsl_blas_dgemv (CblasTrans, 1.0, W, genotype, 0.0, Wtx); + gsl_blas_dgemv (CblasNoTrans, 1.0, WtWi, Wtx, 0.0, WtWiWtx); + gsl_blas_ddot (genotype, genotype, &v_x); + gsl_blas_ddot (Wtx, WtWiWtx, &v_w); + + if (v_w/v_x >= r2_level) {indicator_snp.push_back(0); continue;} + + indicator_snp.push_back(1); + ns_test++; + } + + gsl_vector_free (genotype); + gsl_vector_free (genotype_miss); + gsl_matrix_free (WtW); + gsl_matrix_free (WtWi); + gsl_vector_free (Wtx); + gsl_vector_free (WtWiWtx); + gsl_permutation_free (pmt); + + infile.close(); + infile.clear(); + + return true; +} + + + + + + +//Read bed file, the first time +bool ReadFile_bed (const string &file_bed, const set<string> &setSnps, const gsl_matrix *W, vector<int> &indicator_idv, vector<int> &indicator_snp, vector<SNPINFO> &snpInfo, const double &maf_level, const double &miss_level, const double &hwe_level, const double &r2_level, size_t &ns_test) +{ + indicator_snp.clear(); + size_t ns_total=snpInfo.size(); + + ifstream infile (file_bed.c_str(), ios::binary); + if (!infile) {cout<<"error reading bed file:"<<file_bed<<endl; return false;} + + gsl_vector *genotype=gsl_vector_alloc (W->size1); + gsl_vector *genotype_miss=gsl_vector_alloc (W->size1); + gsl_matrix *WtW=gsl_matrix_alloc (W->size2, W->size2); + gsl_matrix *WtWi=gsl_matrix_alloc (W->size2, W->size2); + gsl_vector *Wtx=gsl_vector_alloc (W->size2); + gsl_vector *WtWiWtx=gsl_vector_alloc (W->size2); + gsl_permutation * pmt=gsl_permutation_alloc (W->size2); + + gsl_blas_dgemm(CblasTrans, CblasNoTrans, 1.0, W, W, 0.0, WtW); + int sig; + LUDecomp (WtW, pmt, &sig); + LUInvert (WtW, pmt, WtWi); + + double v_x, v_w, geno; + size_t c_idv=0; + + char ch[1]; + bitset<8> b; + + size_t ni_total=indicator_idv.size(); + size_t ni_test=0; + for (size_t i=0; i<ni_total; ++i) { + ni_test+=indicator_idv[i]; + } + ns_test=0; + + //calculate n_bit and c, the number of bit for each snp + size_t n_bit; + if (ni_total%4==0) {n_bit=ni_total/4;} + else {n_bit=ni_total/4+1;} + + //ignore the first three majic numbers + for (int i=0; i<3; ++i) { + infile.read(ch,1); + b=ch[0]; + } + + double maf; + size_t n_miss; + size_t n_0, n_1, n_2, c; + + //start reading snps and doing association test + for (size_t t=0; t<ns_total; ++t) { + infile.seekg(t*n_bit+3); //n_bit, and 3 is the number of magic numbers + + if (setSnps.size()!=0 && setSnps.count(snpInfo[t].rs_number)==0) { + snpInfo[t].n_miss=-9; + snpInfo[t].missingness=-9; + snpInfo[t].maf=-9; + indicator_snp.push_back(0); + continue; + } + + //read genotypes + c=0; maf=0.0; n_miss=0; n_0=0; n_1=0; n_2=0; + c_idv=0; gsl_vector_set_zero (genotype_miss); + for (size_t i=0; i<n_bit; ++i) { + infile.read(ch,1); + b=ch[0]; + for (size_t j=0; j<4; ++j) { //minor allele homozygous: 2.0; major: 0.0; + if ((i==(n_bit-1)) && c==ni_total) {break;} + if (indicator_idv[c]==0) {c++; continue;} + c++; + + if (b[2*j]==0) { + if (b[2*j+1]==0) {gsl_vector_set(genotype, c_idv, 2.0); maf+=2.0; n_2++;} + else {gsl_vector_set(genotype, c_idv, 1.0); maf+=1.0; n_1++;} + } + else { + if (b[2*j+1]==1) {gsl_vector_set(genotype, c_idv, 0.0); maf+=0.0; n_0++;} + else {gsl_vector_set(genotype_miss, c_idv, 1); n_miss++; } + } + c_idv++; + } + } + maf/=2.0*(double)(ni_test-n_miss); + + snpInfo[t].n_miss=n_miss; + snpInfo[t].missingness=(double)n_miss/(double)ni_test; + snpInfo[t].maf=maf; + + if ( (double)n_miss/(double)ni_test > miss_level) {indicator_snp.push_back(0); continue;} + + if ( (maf<maf_level || maf> (1.0-maf_level)) && maf_level!=-1 ) {indicator_snp.push_back(0); continue;} + + if ( (n_0+n_1)==0 || (n_1+n_2)==0 || (n_2+n_0)==0) {indicator_snp.push_back(0); continue;} + + if (hwe_level!=1) { + if (CalcHWE(n_0, n_2, n_1)<hwe_level) {indicator_snp.push_back(0); continue;} + } + + + //filter SNP if it is correlated with W + for (size_t i=0; i<genotype->size; ++i) { + if (gsl_vector_get (genotype_miss, i)==1) {geno=maf*2.0; gsl_vector_set (genotype, i, geno);} + } + + gsl_blas_dgemv (CblasTrans, 1.0, W, genotype, 0.0, Wtx); + gsl_blas_dgemv (CblasNoTrans, 1.0, WtWi, Wtx, 0.0, WtWiWtx); + gsl_blas_ddot (genotype, genotype, &v_x); + gsl_blas_ddot (Wtx, WtWiWtx, &v_w); + + if (v_w/v_x > r2_level) {indicator_snp.push_back(0); continue;} + + indicator_snp.push_back(1); + ns_test++; + } + + gsl_vector_free (genotype); + gsl_vector_free (genotype_miss); + gsl_matrix_free (WtW); + gsl_matrix_free (WtWi); + gsl_vector_free (Wtx); + gsl_vector_free (WtWiWtx); + gsl_permutation_free (pmt); + + infile.close(); + infile.clear(); + + return true; +} + + + +void ReadFile_kin (const string &file_kin, vector<int> &indicator_idv, map<string, int> &mapID2num, const size_t k_mode, bool &error, gsl_matrix *G) +{ + igzstream infile (file_kin.c_str(), igzstream::in); +// ifstream infile (file_kin.c_str(), ifstream::in); + if (!infile) {cout<<"error! fail to open kinship file: "<<file_kin<<endl; error=true; return;} + + size_t ni_total=indicator_idv.size(); + + gsl_matrix_set_zero (G); + + string line; + char *ch_ptr; + double d; + + if (k_mode==1) { + size_t i_test=0, i_total=0, j_test=0, j_total=0; + while (getline(infile, line)) { + if (i_total==ni_total) {cout<<"error! number of rows in the kinship file is larger than the number of phentypes."<<endl; error=true;} + + if (indicator_idv[i_total]==0) {i_total++; continue;} + + j_total=0; j_test=0; + ch_ptr=strtok ((char *)line.c_str(), " , \t"); + while (ch_ptr!=NULL) { + if (j_total==ni_total) {cout<<"error! number of columns in the kinship file is larger than the number of phentypes for row = "<<i_total<<endl; error=true;} + + d=atof(ch_ptr); + if (indicator_idv[j_total]==1) {gsl_matrix_set (G, i_test, j_test, d); j_test++;} + j_total++; + + ch_ptr=strtok (NULL, " , \t"); + } + if (j_total!=ni_total) {cout<<"error! number of columns in the kinship file do not match the number of phentypes for row = "<<i_total<<endl; error=true;} + i_total++; i_test++; + } + if (i_total!=ni_total) {cout<<"error! number of rows in the kinship file do not match the number of phentypes."<<endl; error=true;} + } + else { + map<size_t, size_t> mapID2ID; + size_t c=0; + for (size_t i=0; i<indicator_idv.size(); i++) { + if (indicator_idv[i]==1) {mapID2ID[i]=c; c++;} + } + + string id1, id2; + double Cov_d; + size_t n_id1, n_id2; + + while (getline(infile, line)) { + ch_ptr=strtok ((char *)line.c_str(), " , \t"); + id1=ch_ptr; + ch_ptr=strtok (NULL, " , \t"); + id2=ch_ptr; + ch_ptr=strtok (NULL, " , \t"); + d=atof(ch_ptr); + if (mapID2num.count(id1)==0 || mapID2num.count(id2)==0) {continue;} + if (indicator_idv[mapID2num[id1]]==0 || indicator_idv[mapID2num[id2]]==0) {continue;} + + n_id1=mapID2ID[mapID2num[id1]]; + n_id2=mapID2ID[mapID2num[id2]]; + + Cov_d=gsl_matrix_get(G, n_id1, n_id2); + if (Cov_d!=0 && Cov_d!=d) {cout<<"error! redundant and unequal terms in the kinship file, for id1 = "<<id1<<" and id2 = "<<id2<<endl;} + else { + gsl_matrix_set(G, n_id1, n_id2, d); + gsl_matrix_set(G, n_id2, n_id1, d); + } + } + } + + infile.close(); + infile.clear(); + + return; +} + + +void ReadFile_mk (const string &file_mk, vector<int> &indicator_idv, map<string, int> &mapID2num, const size_t k_mode, bool &error, gsl_matrix *G) +{ + igzstream infile (file_mk.c_str(), igzstream::in); + if (!infile) {cout<<"error! fail to open file: "<<file_mk<<endl; error=true; return;} + + string file_kin, line; + + size_t i=0; + while (getline(infile, line)) { + file_kin=line.c_str(); + gsl_matrix_view G_sub=gsl_matrix_submatrix(G, 0, i*G->size1, G->size1, G->size1); + ReadFile_kin (file_kin, indicator_idv, mapID2num, k_mode, error, &G_sub.matrix); + i++; + } + + infile.close(); + infile.clear(); + return; +} + + +void ReadFile_eigenU (const string &file_ku, bool &error, gsl_matrix *U) +{ + igzstream infile (file_ku.c_str(), igzstream::in); +// ifstream infile (file_ku.c_str(), ifstream::in); + if (!infile) {cout<<"error! fail to open the U file: "<<file_ku<<endl; error=true; return;} + + size_t n_row=U->size1, n_col=U->size2, i_row=0, i_col=0; + + gsl_matrix_set_zero (U); + + string line; + char *ch_ptr; + double d; + + while (getline(infile, line)) { + if (i_row==n_row) {cout<<"error! number of rows in the U file is larger than expected."<<endl; error=true;} + + i_col=0; + ch_ptr=strtok ((char *)line.c_str(), " , \t"); + while (ch_ptr!=NULL) { + if (i_col==n_col) {cout<<"error! number of columns in the U file is larger than expected, for row = "<<i_row<<endl; error=true;} + + d=atof(ch_ptr); + gsl_matrix_set (U, i_row, i_col, d); + i_col++; + + ch_ptr=strtok (NULL, " , \t"); + } + + i_row++; + } + + infile.close(); + infile.clear(); + + return; +} + + + + +void ReadFile_eigenD (const string &file_kd, bool &error, gsl_vector *eval) +{ + igzstream infile (file_kd.c_str(), igzstream::in); +// ifstream infile (file_kd.c_str(), ifstream::in); + if (!infile) {cout<<"error! fail to open the D file: "<<file_kd<<endl; error=true; return;} + + size_t n_row=eval->size, i_row=0; + + gsl_vector_set_zero (eval); + + string line; + char *ch_ptr; + double d; + + while (getline(infile, line)) { + if (i_row==n_row) {cout<<"error! number of rows in the D file is larger than expected."<<endl; error=true;} + + ch_ptr=strtok ((char *)line.c_str(), " , \t"); + d=atof(ch_ptr); + + ch_ptr=strtok (NULL, " , \t"); + if (ch_ptr!=NULL) {cout<<"error! number of columns in the D file is larger than expected, for row = "<<i_row<<endl; error=true;} + + gsl_vector_set (eval, i_row, d); + + i_row++; + } + + infile.close(); + infile.clear(); + + return; +} + + + +//read bimbam mean genotype file and calculate kinship matrix +bool BimbamKin (const string &file_geno, vector<int> &indicator_snp, const int k_mode, const int display_pace, gsl_matrix *matrix_kin) +{ + igzstream infile (file_geno.c_str(), igzstream::in); + //ifstream infile (file_geno.c_str(), ifstream::in); + if (!infile) {cout<<"error reading genotype file:"<<file_geno<<endl; return false;} + + string line; + char *ch_ptr; + + size_t n_miss; + double d, geno_mean, geno_var; + + size_t ni_total=matrix_kin->size1; + gsl_vector *geno=gsl_vector_alloc (ni_total); + gsl_vector *geno_miss=gsl_vector_alloc (ni_total); + + size_t ns_test=0; + for (size_t t=0; t<indicator_snp.size(); ++t) { + !safeGetline(infile, line).eof(); + if (t%display_pace==0 || t==(indicator_snp.size()-1)) {ProgressBar ("Reading SNPs ", t, indicator_snp.size()-1);} + if (indicator_snp[t]==0) {continue;} + + ch_ptr=strtok ((char *)line.c_str(), " , \t"); + ch_ptr=strtok (NULL, " , \t"); + ch_ptr=strtok (NULL, " , \t"); + + geno_mean=0.0; n_miss=0; geno_var=0.0; + gsl_vector_set_all(geno_miss, 0); + for (size_t i=0; i<ni_total; ++i) { + ch_ptr=strtok (NULL, " , \t"); + if (strcmp(ch_ptr, "NA")==0) {gsl_vector_set(geno_miss, i, 0); n_miss++;} + else { + d=atof(ch_ptr); + gsl_vector_set (geno, i, d); + gsl_vector_set (geno_miss, i, 1); + geno_mean+=d; + geno_var+=d*d; + } + } + + geno_mean/=(double)(ni_total-n_miss); + geno_var+=geno_mean*geno_mean*(double)n_miss; + geno_var/=(double)ni_total; + geno_var-=geno_mean*geno_mean; +// geno_var=geno_mean*(1-geno_mean*0.5); + + for (size_t i=0; i<ni_total; ++i) { + if (gsl_vector_get (geno_miss, i)==0) {gsl_vector_set(geno, i, geno_mean);} + } + + gsl_vector_add_constant (geno, -1.0*geno_mean); + + if (geno_var!=0) { + if (k_mode==1) {gsl_blas_dsyr (CblasUpper, 1.0, geno, matrix_kin);} + else if (k_mode==2) {gsl_blas_dsyr (CblasUpper, 1.0/geno_var, geno, matrix_kin);} + else {cout<<"Unknown kinship mode."<<endl;} + } + + ns_test++; + } + cout<<endl; + + gsl_matrix_scale (matrix_kin, 1.0/(double)ns_test); + + for (size_t i=0; i<ni_total; ++i) { + for (size_t j=0; j<i; ++j) { + d=gsl_matrix_get (matrix_kin, j, i); + gsl_matrix_set (matrix_kin, i, j, d); + } + } + + gsl_vector_free (geno); + gsl_vector_free (geno_miss); + + infile.close(); + infile.clear(); + + return true; +} + + + + + + + +bool PlinkKin (const string &file_bed, vector<int> &indicator_snp, const int k_mode, const int display_pace, gsl_matrix *matrix_kin) +{ + ifstream infile (file_bed.c_str(), ios::binary); + if (!infile) {cout<<"error reading bed file:"<<file_bed<<endl; return false;} + + char ch[1]; + bitset<8> b; + + size_t n_miss, ci_total; + double d, geno_mean, geno_var; + + size_t ni_total=matrix_kin->size1; + gsl_vector *geno=gsl_vector_alloc (ni_total); + + size_t ns_test=0; + int n_bit; + + //calculate n_bit and c, the number of bit for each snp + if (ni_total%4==0) {n_bit=ni_total/4;} + else {n_bit=ni_total/4+1; } + + //print the first three majic numbers + for (int i=0; i<3; ++i) { + infile.read(ch,1); + b=ch[0]; + } + + for (size_t t=0; t<indicator_snp.size(); ++t) { + if (t%display_pace==0 || t==(indicator_snp.size()-1)) {ProgressBar ("Reading SNPs ", t, indicator_snp.size()-1);} + if (indicator_snp[t]==0) {continue;} + + infile.seekg(t*n_bit+3); //n_bit, and 3 is the number of magic numbers + + //read genotypes + geno_mean=0.0; n_miss=0; ci_total=0; geno_var=0.0; + for (int i=0; i<n_bit; ++i) { + infile.read(ch,1); + b=ch[0]; + for (size_t j=0; j<4; ++j) { //minor allele homozygous: 2.0; major: 0.0; + if ((i==(n_bit-1)) && ci_total==ni_total) {break;} + + if (b[2*j]==0) { + if (b[2*j+1]==0) {gsl_vector_set(geno, ci_total, 2.0); geno_mean+=2.0; geno_var+=4.0; } + else {gsl_vector_set(geno, ci_total, 1.0); geno_mean+=1.0; geno_var+=1.0;} + } + else { + if (b[2*j+1]==1) {gsl_vector_set(geno, ci_total, 0.0); } + else {gsl_vector_set(geno, ci_total, -9.0); n_miss++; } + } + + ci_total++; + } + } + + geno_mean/=(double)(ni_total-n_miss); + geno_var+=geno_mean*geno_mean*(double)n_miss; + geno_var/=(double)ni_total; + geno_var-=geno_mean*geno_mean; +// geno_var=geno_mean*(1-geno_mean*0.5); + + for (size_t i=0; i<ni_total; ++i) { + d=gsl_vector_get(geno,i); + if (d==-9.0) {gsl_vector_set(geno, i, geno_mean);} + } + + gsl_vector_add_constant (geno, -1.0*geno_mean); + + if (geno_var!=0) { + if (k_mode==1) {gsl_blas_dsyr (CblasUpper, 1.0, geno, matrix_kin);} + else if (k_mode==2) {gsl_blas_dsyr (CblasUpper, 1.0/geno_var, geno, matrix_kin);} + else {cout<<"Unknown kinship mode."<<endl;} + } + + ns_test++; + } + cout<<endl; + + gsl_matrix_scale (matrix_kin, 1.0/(double)ns_test); + + for (size_t i=0; i<ni_total; ++i) { + for (size_t j=0; j<i; ++j) { + d=gsl_matrix_get (matrix_kin, j, i); + gsl_matrix_set (matrix_kin, i, j, d); + } + } + + gsl_vector_free (geno); + + infile.close(); + infile.clear(); + + return true; +} + + + + + +//Read bimbam mean genotype file, the second time, recode "mean" genotype and calculate K +bool ReadFile_geno (const string &file_geno, vector<int> &indicator_idv, vector<int> &indicator_snp, gsl_matrix *UtX, gsl_matrix *K, const bool calc_K) +{ + igzstream infile (file_geno.c_str(), igzstream::in); +// ifstream infile (file_geno.c_str(), ifstream::in); + if (!infile) {cout<<"error reading genotype file:"<<file_geno<<endl; return false;} + + string line; + char *ch_ptr; + + if (calc_K==true) {gsl_matrix_set_zero (K);} + + gsl_vector *genotype=gsl_vector_alloc (UtX->size1); + gsl_vector *genotype_miss=gsl_vector_alloc (UtX->size1); + double geno, geno_mean; + size_t n_miss; + + int ni_total=(int)indicator_idv.size(); + int ns_total=(int)indicator_snp.size(); + int ni_test=UtX->size1; + int ns_test=UtX->size2; + + int c_idv=0, c_snp=0; + + for (int i=0; i<ns_total; ++i) { + !safeGetline(infile, line).eof(); + if (indicator_snp[i]==0) {continue;} + + ch_ptr=strtok ((char *)line.c_str(), " , \t"); + ch_ptr=strtok (NULL, " , \t"); + ch_ptr=strtok (NULL, " , \t"); + + c_idv=0; geno_mean=0; n_miss=0; + gsl_vector_set_zero (genotype_miss); + for (int j=0; j<ni_total; ++j) { + ch_ptr=strtok (NULL, " , \t"); + if (indicator_idv[j]==0) {continue;} + + if (strcmp(ch_ptr, "NA")==0) {gsl_vector_set (genotype_miss, c_idv, 1); n_miss++;} + else { + geno=atof(ch_ptr); + gsl_vector_set (genotype, c_idv, geno); + geno_mean+=geno; + } + c_idv++; + } + + geno_mean/=(double)(ni_test-n_miss); + + for (size_t i=0; i<genotype->size; ++i) { + if (gsl_vector_get (genotype_miss, i)==1) {geno=0;} + else {geno=gsl_vector_get (genotype, i); geno-=geno_mean;} + + gsl_vector_set (genotype, i, geno); + gsl_matrix_set (UtX, i, c_snp, geno); + } + + if (calc_K==true) {gsl_blas_dsyr (CblasUpper, 1.0, genotype, K);} + + c_snp++; + } + + if (calc_K==true) { + gsl_matrix_scale (K, 1.0/(double)ns_test); + + for (size_t i=0; i<genotype->size; ++i) { + for (size_t j=0; j<i; ++j) { + geno=gsl_matrix_get (K, j, i); + gsl_matrix_set (K, i, j, geno); + } + } + } + + gsl_vector_free (genotype); + gsl_vector_free (genotype_miss); + + infile.clear(); + infile.close(); + + return true; +} + + + + + + + +//Read bimbam mean genotype file, the second time, recode "mean" genotype and calculate K +bool ReadFile_bed (const string &file_bed, vector<int> &indicator_idv, vector<int> &indicator_snp, gsl_matrix *UtX, gsl_matrix *K, const bool calc_K) +{ + ifstream infile (file_bed.c_str(), ios::binary); + if (!infile) {cout<<"error reading bed file:"<<file_bed<<endl; return false;} + + char ch[1]; + bitset<8> b; + + int ni_total=(int)indicator_idv.size(); + int ns_total=(int)indicator_snp.size(); + int ni_test=UtX->size1; + int ns_test=UtX->size2; + int n_bit; + + if (ni_total%4==0) {n_bit=ni_total/4;} + else {n_bit=ni_total/4+1;} + + //print the first three majic numbers + for (int i=0; i<3; ++i) { + infile.read(ch,1); + b=ch[0]; + } + + if (calc_K==true) {gsl_matrix_set_zero (K);} + + gsl_vector *genotype=gsl_vector_alloc (UtX->size1); + + double geno, geno_mean; + size_t n_miss; + int c_idv=0, c_snp=0, c=0; + + //start reading snps and doing association test + for (int t=0; t<ns_total; ++t) { + if (indicator_snp[t]==0) {continue;} + infile.seekg(t*n_bit+3); //n_bit, and 3 is the number of magic numbers + + //read genotypes + c_idv=0; geno_mean=0.0; n_miss=0; c=0; + for (int i=0; i<n_bit; ++i) { + infile.read(ch,1); + b=ch[0]; + for (size_t j=0; j<4; ++j) { //minor allele homozygous: 2.0; major: 0.0; + if ((i==(n_bit-1)) && c==ni_total) {break;} + if (indicator_idv[c]==0) {c++; continue;} + c++; + + if (b[2*j]==0) { + if (b[2*j+1]==0) {gsl_vector_set(genotype, c_idv, 2.0); geno_mean+=2.0;} + else {gsl_vector_set(genotype, c_idv, 1.0); geno_mean+=1.0;} + } + else { + if (b[2*j+1]==1) {gsl_vector_set(genotype, c_idv, 0.0); geno_mean+=0.0;} + else {gsl_vector_set(genotype, c_idv, -9.0); n_miss++;} + } + c_idv++; + } + } + + geno_mean/=(double)(ni_test-n_miss); + + for (size_t i=0; i<genotype->size; ++i) { + geno=gsl_vector_get (genotype, i); + if (geno==-9) {geno=0;} + else {geno-=geno_mean;} + + gsl_vector_set (genotype, i, geno); + gsl_matrix_set (UtX, i, c_snp, geno); + } + + if (calc_K==true) {gsl_blas_dsyr (CblasUpper, 1.0, genotype, K);} + + c_snp++; + } + + if (calc_K==true) { + gsl_matrix_scale (K, 1.0/(double)ns_test); + + for (size_t i=0; i<genotype->size; ++i) { + for (size_t j=0; j<i; ++j) { + geno=gsl_matrix_get (K, j, i); + gsl_matrix_set (K, i, j, geno); + } + } + } + + gsl_vector_free (genotype); + infile.clear(); + infile.close(); + + return true; +} + + + + + +bool ReadFile_est (const string &file_est, const vector<size_t> &est_column, map<string, double> &mapRS2est) +{ + mapRS2est.clear(); + + ifstream infile (file_est.c_str(), ifstream::in); + if (!infile) {cout<<"error opening estimated parameter file: "<<file_est<<endl; return false;} + + string line; + char *ch_ptr; + + string rs; + double alpha, beta, gamma, d; + + //header + getline(infile, line); + + size_t n=*max_element(est_column.begin(), est_column.end()); + + while (getline(infile, line)) { + ch_ptr=strtok ((char *)line.c_str(), " \t"); + + alpha=0.0; beta=0.0; gamma=1.0; + for (size_t i=0; i<n+1; ++i) { + if (i==est_column[0]-1) {rs=ch_ptr;} + if (i==est_column[1]-1) {alpha=atof(ch_ptr);} + if (i==est_column[2]-1) {beta=atof(ch_ptr);} + if (i==est_column[3]-1) {gamma=atof(ch_ptr);} + if (i<n) {ch_ptr=strtok (NULL, " \t");} + } + + d=alpha+beta*gamma; + + if (mapRS2est.count(rs)==0) { + mapRS2est[rs]=d; + } + else { + cout<<"the same SNP occurs more than once in estimated parameter file: "<<rs<<endl; return false; + } + } + + infile.clear(); + infile.close(); + return true; +} + + + +bool CountFileLines (const string &file_input, size_t &n_lines) +{ + igzstream infile (file_input.c_str(), igzstream::in); + //ifstream infile (file_input.c_str(), ifstream::in); + if (!infile) {cout<<"error! fail to open file: "<<file_input<<endl; return false;} + + n_lines=count(istreambuf_iterator<char>(infile), istreambuf_iterator<char>(), '\n'); + infile.seekg (0, ios::beg); + + return true; +} + + + +//Read gene expression file +bool ReadFile_gene (const string &file_gene, vector<double> &vec_read, vector<SNPINFO> &snpInfo, size_t &ng_total) +{ + vec_read.clear(); + ng_total=0; + + ifstream infile (file_gene.c_str(), ifstream::in); + if (!infile) {cout<<"error! fail to open gene expression file: "<<file_gene<<endl; return false;} + + string line; + char *ch_ptr; + string rs; + + size_t n_idv=0, t=0; + + //header + getline(infile, line); + + while (getline(infile, line)) { + ch_ptr=strtok ((char *)line.c_str(), " , \t"); + rs=ch_ptr; + + ch_ptr=strtok (NULL, " , \t"); + + t=0; + while (ch_ptr!=NULL) { + if (ng_total==0) { + vec_read.push_back(0); + t++; + n_idv++; + } else { + vec_read[t]+=atof(ch_ptr); + t++; + } + + ch_ptr=strtok (NULL, " , \t"); + } + + if (t!=n_idv) {cout<<"error! number of columns doesn't match in row: "<<ng_total<<endl; return false;} + + SNPINFO sInfo={"-9", rs, -9, -9, "-9", "-9", -9, -9, -9}; + snpInfo.push_back(sInfo); + + ng_total++; + } + + infile.close(); + infile.clear(); + + return true; +} + + |