float estimate_gt() {
int i,j,count=0,g;
float den,af=af_start,old_af=100;
dosage=(float *)realloc(dosage,n*sizeof(float));
prior[0] = (1-af)*(1-af);
prior[1] = 2 * af * (1-af);
prior[2] = af * af;
for( i=0;i<n;i++)
if(bcf_float_is_missing(gl[i*3]) || bcf_float_is_missing(gl[i*3+1]) || bcf_float_is_missing(gl[i*3+2]) )
for( j=0;j<3;j++) gl[i*3+j]=1.;
//Expectation-Maximisation to estimate AF
while(1) {
af = 0.;
for(i=0;i<n;i++) {
dosage[i]=0.;
den = 0.;
for(j=0;j<3;j++) {
tmp_gl[j] = prior[j] *pow(10.,gl[i*3 + j]);
den += tmp_gl[j];
}
for(j=0;j<3;j++) tmp_gl[j]/=den;
for(j=1;j<3;j++) dosage[i] += j * tmp_gl[j];
af+=dosage[i];
}
af /= (2.*n);
prior[2] = af * af;
prior[1] = 2 * af * (1-af);
prior[0] = (1. - af)*(1. - af);
// assert(af>=0 && af<=1);
// fprintf(stderr,"count=%d af=%.5f old_af=%.5f %.5f\n",count,af,old_af,fabs(af-old_af));
if( (count>0 && fabs(af-old_af)<.000001) || count>100)
break;
else
old_af=af;
count++;
// fprintf(stderr,"%d\n",count);
}
//dosage -> GT
for(i=0;i<n;i++) {
g = roundf(dosage[i]);
if(g==0) {
gt[i*2] = bcf_gt_unphased(0);
gt[i*2+1] = bcf_gt_unphased(0);
}
else if(g==1) {
gt[i*2] = bcf_gt_unphased(0);
gt[i*2+1] = bcf_gt_unphased(1);
}
else {
gt[i*2] = bcf_gt_unphased(1);
gt[i*2+1] = bcf_gt_unphased(1);
}
}
return(af);
}
static void filters_set_qual(bcf1_t *line, token_t *tok)
{
float *ptr = &line->qual;
if ( bcf_float_is_missing(*ptr) )
tok->missing_value = 1;
else
tok->num_value = line->qual;
}
bcf1_t *process(bcf1_t *rec)
{
int i, n;
if ( mode==GP_TO_GL )
{
n = bcf_get_format_float(in_hdr,rec,"GP",&farr,&mfarr);
for (i=0; i<n; i++)
{
if ( bcf_float_is_missing(farr[i]) || bcf_float_is_vector_end(farr[i]) ) continue;
farr[i] = farr[i] ? log(farr[i]) : -99;
}
bcf_update_format_float(out_hdr,rec,"GL",farr,n);
if ( drop_source_tag )
bcf_update_format_float(out_hdr,rec,"GP",NULL,0);
}
return rec;
}
static void init_data(args_t *args)
{
bcf_srs_t *files = bcf_sr_init();
if ( args->regions_list )
{
if ( bcf_sr_set_regions(files, args->regions_list, args->regions_is_file)<0 )
error("Failed to read the regions: %s\n", args->regions_list);
}
if ( args->targets_list )
{
if ( bcf_sr_set_targets(files, args->targets_list, args->targets_is_file, 0)<0 )
error("Failed to read the targets: %s\n", args->targets_list);
}
if ( !bcf_sr_add_reader(files, args->fname) ) error("Failed to open %s: %s\n", args->fname,bcf_sr_strerror(files->errnum));
bcf_hdr_t *hdr = files->readers[0].header;
if ( !args->sample )
{
if ( bcf_hdr_nsamples(hdr)>1 ) error("Missing the option -s, --sample\n");
args->sample = hdr->samples[0];
}
else if ( bcf_hdr_id2int(hdr,BCF_DT_SAMPLE,args->sample)<0 ) error("No such sample: %s\n", args->sample);
int ret = bcf_hdr_set_samples(hdr, args->sample, 0);
if ( ret<0 ) error("Error setting the sample: %s\n", args->sample);
if ( !bcf_hdr_idinfo_exists(hdr,BCF_HL_FMT,bcf_hdr_id2int(hdr,BCF_DT_ID,"BAF")) )
error("The tag FORMAT/BAF is not present in the VCF: %s\n", args->fname);
int i;
args->xvals = (double*) calloc(args->nbins,sizeof(double));
for (i=0; i<args->nbins; i++) args->xvals[i] = 1.0*i/(args->nbins-1);
// collect BAF distributions for all chromosomes
int idist = -1, nbaf = 0, nprocessed = 0, ntotal = 0, prev_chr = -1;
float *baf = NULL;
while ( bcf_sr_next_line(files) )
{
ntotal++;
bcf1_t *line = bcf_sr_get_line(files,0);
if ( bcf_get_format_float(hdr,line,"BAF",&baf,&nbaf) != 1 ) continue;
if ( bcf_float_is_missing(baf[0]) ) continue;
nprocessed++;
if ( prev_chr==-1 || prev_chr!=line->rid )
{
// new chromosome
idist = args->ndist++;
args->dist = (dist_t*) realloc(args->dist, sizeof(dist_t)*args->ndist);
memset(&args->dist[idist],0,sizeof(dist_t));
args->dist[idist].chr = strdup(bcf_seqname(hdr,line));
args->dist[idist].yvals = (double*) calloc(args->nbins,sizeof(double));
args->dist[idist].xvals = args->xvals;
args->dist[idist].nvals = args->nbins;
prev_chr = line->rid;
}
int bin = baf[0]*(args->nbins-1);
args->dist[idist].yvals[bin]++; // the distribution
}
free(baf);
bcf_sr_destroy(files);
for (idist=0; idist<args->ndist; idist++)
{
#if 0
int j;
for (j=0; j<args->nbins; j++)
{
double x = args->dist[idist].xvals[j];
args->dist[idist].yvals[j] = exp(-(x-0.5)*(x-0.5)/1e-3);
}
#endif
init_dist(args, &args->dist[idist],args->verbose);
}
args->dat_fp = open_file(&args->dat_fname,"w","%s/dist.dat", args->output_dir);
fprintf(args->dat_fp, "# This file was produced by: bcftools polysomy(%s+htslib-%s), the command line was:\n", bcftools_version(),hts_version());
fprintf(args->dat_fp, "# \t bcftools %s ", args->argv[0]);
for (i=1; i<args->argc; i++)
fprintf(args->dat_fp, " %s",args->argv[i]);
fprintf(args->dat_fp,"\n#\n");
fprintf(args->dat_fp,"# DIST\t[2]Chrom\t[3]BAF\t[4]Normalized Count\n");
fprintf(args->dat_fp,"# FIT\t[2]Goodness of Fit\t[3]iFrom\t[4]iTo\t[5]The Fitted Function\n");
fprintf(args->dat_fp,"# CN\t[2]Chrom\t[3]Estimated Copy Number\t[4]Absolute fit deviation\n");
char *fname = NULL;
FILE *fp = open_file(&fname,"w","%s/dist.py", args->output_dir);
//-------- matplotlib script --------------
fprintf(fp,
"#!/usr/bin/env python\n"
"#\n"
"import matplotlib as mpl\n"
"mpl.use('Agg')\n"
"import matplotlib.pyplot as plt\n"
"import csv,sys,argparse\n"
"from math import exp\n"
"\n"
"outdir = '%s'\n"
"\n"
"def read_dat(dat,fit,cn):\n"
" csv.register_dialect('tab', delimiter='\t', quoting=csv.QUOTE_NONE)\n"
" with open(outdir+'/dist.dat', 'rb') as f:\n"
" reader = csv.reader(f, 'tab')\n"
" for row in reader:\n"
" if row[0][0]=='#': continue\n"
" type = row[0]\n"
" chr = row[1]\n"
" if type=='DIST':\n"
" if chr not in dat: dat[chr] = []\n"
" dat[chr].append(row)\n"
" elif type=='FIT':\n"
" if chr not in fit: fit[chr] = []\n"
" fit[chr].append(row)\n"
" elif type=='CN':\n"
" cn[chr] = row[2]\n"
"\n"
"def plot_dist(dat,fit,chr):\n"
" fig, ax = plt.subplots(1, 1, figsize=(7,5))\n"
" ax.plot([x[2] for x in dat[chr]],[x[3] for x in dat[chr]],'k-',label='Distribution')\n"
" if chr in fit:\n"
" for i in range(len(fit[chr])):\n"
" pfit = fit[chr][i]\n"
" exec('def xfit(x): return '+pfit[5])\n"
" istart = int(pfit[3])\n"
" iend = int(pfit[4])+1\n"
" vals = dat[chr][istart:iend]\n"
" args = {}\n"
" if i==0: args = {'label':'Target to Fit'}\n"
" ax.plot([x[2] for x in vals],[x[3] for x in vals],'r-',**args)\n"
" if i==0: args = {'label':'Best Fit'}\n"
" ax.plot([x[2] for x in vals],[xfit(float(x[2])) for x in vals],'g-',**args)\n"
" ax.set_title('BAF distribution, chr'+chr)\n"
" ax.set_xlabel('BAF')\n"
" ax.set_ylabel('Frequency')\n"
" ax.legend(loc='best',prop={'size':7},frameon=False)\n"
" plt.savefig(outdir+'/dist.chr'+chr+'.png')\n"
" plt.close()\n"
"\n"
"def plot_copy_number(cn):\n"
" fig, ax = plt.subplots(1, 1, figsize=(7,5))\n"
" xlabels = sorted(cn.keys())\n"
" xvals = range(len(xlabels))\n"
" yvals = [float(cn[x]) for x in xlabels]\n"
" ax.plot(xvals,yvals,'o',color='red')\n"
" for i in range(len(xvals)):\n"
" if yvals[i]==-1: ax.annotate('?', xy=(xvals[i],0.5),va='center',ha='center',color='red',fontweight='bold')\n"
" ax.tick_params(axis='both', which='major', labelsize=9)\n"
" ax.set_xticks(xvals)\n"
" ax.set_xticklabels(xlabels,rotation=45)\n"
" ax.set_xlim(-1,len(xlabels))\n"
" ax.set_ylim(0,5.0)\n"
" ax.set_yticks([1.0,2.0,3.0,4.0])\n"
" ax.set_xlabel('Chromosome')\n"
" ax.set_ylabel('Copy Number')\n"
" plt.savefig(outdir+'/copy-number.png')\n"
" plt.close()\n"
"\n"
"class myParser(argparse.ArgumentParser):\n"
" def error(self, message):\n"
" self.print_help()\n"
" sys.stderr.write('error: %%s\\n' %% message)\n"
" sys.exit(2)\n"
"\n"
"def main():\n"
" parser = myParser()\n"
" parser.add_argument('-a', '--all', action='store_true', help='Create all plots')\n"
" parser.add_argument('-c', '--copy-number', action='store_true', help='Create copy-number plot')\n"
" parser.add_argument('-d', '--distrib', metavar='CHR', help='Plot BAF distribution of a single chromosome')\n"
" args = parser.parse_args()\n"
" dat = {}; fit = {}; cn = {}\n"
" read_dat(dat,fit,cn)\n"
" if args.distrib!=None:\n"
" plot_dist(dat,fit,args.distrib)\n"
" if args.all:\n"
" for chr in dat: plot_dist(dat,fit,chr)\n"
" plot_copy_number(cn)\n"
" elif args.copy_number:\n"
" plot_copy_number(cn)\n"
" else:\n"
" for chr in dat: plot_dist(dat,fit,chr)\n"
"\n"
"if __name__ == '__main__':\n"
" main()\n",
args->output_dir);
//---------------------------------------
chmod(fname, S_IWUSR|S_IRUSR|S_IRGRP|S_IROTH|S_IXUSR|S_IXGRP|S_IXOTH);
free(fname);
fclose(fp);
}
