vcfconcat.c

/* The MIT License

   Copyright (c) 2013-2014 Genome Research Ltd.
   Authors:  see http://github.com/samtools/bcftools/blob/master/AUTHORS

   Permission is hereby granted, free of charge, to any person obtaining a copy
   of this software and associated documentation files (the "Software"), to deal
   in the Software without restriction, including without limitation the rights
   to use, copy, modify, merge, publish, distribute, sublicense, and/or sell
   copies of the Software, and to permit persons to whom the Software is
   furnished to do so, subject to the following conditions:

   The above copyright notice and this permission notice shall be included in
   all copies or substantial portions of the Software.

   THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
   IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
   FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE
   AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
   LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,
   OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN
   THE SOFTWARE.

 */

#include <stdio.h>
#include <unistd.h>
#include <getopt.h>
#include <string.h>
#include <errno.h>
#include <math.h>
#include <htslib/vcf.h>
#include <htslib/synced_bcf_reader.h>
#include <htslib/kseq.h>
#include "bcftools.h"

typedef struct _args_t
{
    bcf_srs_t *files;
    htsFile *out_fh;
    int output_type;
    bcf_hdr_t *out_hdr;
    int *seen_seq;

    // phasing
    int *start_pos, start_tid, ifname;
    int *swap_phase, nswap, *nmatch, *nmism;
    bcf1_t **buf;
    int nbuf, mbuf, prev_chr, min_PQ, prev_pos_check;
    int32_t *GTa, *GTb, mGTa, mGTb, *phase_qual, *phase_set;

    char **argv, *file_list, **fnames;
    int argc, nfnames, allow_overlaps, phased_concat;
}
args_t;

static void init_data(args_t *args)
{
    bcf1_t *line = NULL;

    // With phased concat, the chunks overlap and come in the right order.  To
    // avoid opening all files at once, store start positions to recognise need
    // for the next one. This way we can keep only two open chunks at once.
    if ( args->phased_concat )
    {
        args->start_pos = (int*) malloc(sizeof(int)*args->nfnames);
        line = bcf_init();
    }

    kstring_t str = {0,0,0};
    int i, prev_chrid = -1;
    for (i=0; i<args->nfnames; i++)
    {
        htsFile *fp = hts_open(args->fnames[i], "r"); if ( !fp ) error("Failed to open: %s\n", args->fnames[i]);
        bcf_hdr_t *hdr = bcf_hdr_read(fp); if ( !hdr ) error("Failed to parse header: %s\n", args->fnames[i]);
        if ( !args->out_hdr ) 
            args->out_hdr = bcf_hdr_dup(hdr);
        else
        {
            bcf_hdr_combine(args->out_hdr, hdr);

            if ( bcf_hdr_nsamples(hdr) != bcf_hdr_nsamples(args->out_hdr) ) 
                error("Different number of samples in %s. Perhaps \"bcftools merge\" is what you are looking for?\n", args->fnames[i]);

            int j;
            for (j=0; j<bcf_hdr_nsamples(hdr); j++)
                if ( strcmp(args->out_hdr->samples[j],hdr->samples[j]) )
                    error("Different sample names in %s. Perhaps \"bcftools merge\" is what you are looking for?\n", args->fnames[i]);
        }
        if ( args->phased_concat )
        {
            int ret = bcf_read(fp, hdr, line);
            if ( ret!=0 ) args->start_pos[i] = -2;  // empty file
            else
            {
                int chrid = bcf_hdr_id2int(args->out_hdr,BCF_DT_CTG,bcf_seqname(hdr,line));
                args->start_pos[i] = chrid==prev_chrid ? line->pos : -1;
                prev_chrid = chrid;
            }
        }
        bcf_hdr_destroy(hdr);
        hts_close(fp);
    }
    free(str.s);
    if ( line ) bcf_destroy(line);

    args->seen_seq = (int*) calloc(args->out_hdr->n[BCF_DT_CTG],sizeof(int));

    if ( args->phased_concat )
    {
        bcf_hdr_append(args->out_hdr,"##FORMAT=<ID=PQ,Number=1,Type=Integer,Description=\"Phasing Quality (bigger is better)\">");
        bcf_hdr_append(args->out_hdr,"##FORMAT=<ID=PS,Number=1,Type=Integer,Description=\"Phase Set\">");
    }
    bcf_hdr_append_version(args->out_hdr, args->argc, args->argv, "bcftools_concat");
    args->out_fh = hts_open("-",hts_bcf_wmode(args->output_type));
    bcf_hdr_write(args->out_fh, args->out_hdr);

    if ( args->allow_overlaps ) 
    {
        args->files = bcf_sr_init();
        args->files->require_index = 1;
        for (i=0; i<args->nfnames; i++)
            if ( !bcf_sr_add_reader(args->files,args->fnames[i]) ) error("Failed to open, is the file indexed? %s\n", args->fnames[i]);
    }
    else if ( args->phased_concat )
    {
        // Remove empty files from the list
        int nok = 0;
        while (1)
        {
            while ( nok<args->nfnames && args->start_pos[nok]!=-2 ) nok++;
            if ( nok==args->nfnames ) break;

            i = nok;
            while ( i<args->nfnames && args->start_pos[i]==-2 ) i++;
            if ( i==args->nfnames ) break;

            int tmp = args->start_pos[nok]; args->start_pos[nok] = args->start_pos[i]; args->start_pos[i] = tmp;
            char *str = args->fnames[nok]; args->fnames[nok] = args->fnames[i]; args->fnames[i] = str;
        }
        for (i=nok; i<args->nfnames; i++) free(args->fnames[i]);
        args->nfnames = nok;

        for (i=1; i<args->nfnames; i++)
            if ( args->start_pos[i-1]!=-1 && args->start_pos[i]!=-1 && args->start_pos[i]<args->start_pos[i-1] )
                error("The files not in ascending order: %d in %s, %d in %s\n", args->start_pos[i-1]+1,args->fnames[i-1],args->start_pos[i]+1,args->fnames[i]);

        args->prev_chr = -1;
        args->swap_phase = (int*) calloc(bcf_hdr_nsamples(args->out_hdr),sizeof(int));
        args->nmatch = (int*) calloc(bcf_hdr_nsamples(args->out_hdr),sizeof(int));
        args->nmism  = (int*) calloc(bcf_hdr_nsamples(args->out_hdr),sizeof(int));
        args->phase_qual = (int32_t*) malloc(bcf_hdr_nsamples(args->out_hdr)*sizeof(int32_t));
        args->phase_set  = (int32_t*) malloc(bcf_hdr_nsamples(args->out_hdr)*sizeof(int32_t));
        args->files = bcf_sr_init();
        args->files->require_index = 1;
        args->ifname = 0;
    }
}

static void destroy_data(args_t *args)
{
    int i;
    for (i=0; i<args->nfnames; i++) free(args->fnames[i]);
    free(args->fnames);
    if ( args->files ) bcf_sr_destroy(args->files);
    if ( hts_close(args->out_fh)!=0 ) error("hts_close error\n");
    bcf_hdr_destroy(args->out_hdr);
    free(args->seen_seq);
    free(args->start_pos);
    free(args->swap_phase);
    for (i=0; i<args->mbuf; i++) bcf_destroy(args->buf[i]);
    free(args->buf);
    free(args->GTa);
    free(args->GTb);
    free(args->nmatch);
    free(args->nmism);
    free(args->phase_qual);
    free(args->phase_set);
}

int vcf_write_line(htsFile *fp, kstring_t *line);

#define SWAP(type_t, a, b) { type_t t = a; a = b; b = t; }
static void phase_update(args_t *args, bcf_hdr_t *hdr, bcf1_t *rec)
{
    int i, nGTs = bcf_get_genotypes(hdr, rec, &args->GTa, &args->mGTa);
    for (i=0; i<bcf_hdr_nsamples(hdr); i++)
    {
        if ( !args->swap_phase[i] ) continue;
        int *gt = &args->GTa[i*2];
        if ( gt[0]==bcf_gt_missing || gt[1]==bcf_int32_vector_end ) continue;
        SWAP(int, gt[0], gt[1]);
        gt[1] |= 1;
    }
    bcf_update_genotypes(hdr,rec,args->GTa,nGTs);
}

static void phased_flush(args_t *args)
{
    if ( !args->nbuf ) return;

    bcf_hdr_t *ahdr = args->files->readers[0].header;
    bcf_hdr_t *bhdr = args->files->readers[1].header;

    int i, j, nsmpl = bcf_hdr_nsamples(args->out_hdr);

    for (i=0; i<args->nbuf; i+=2)
    {
        bcf1_t *arec = args->buf[i];
        bcf1_t *brec = args->buf[i+1];

        int nGTs = bcf_get_genotypes(ahdr, arec, &args->GTa, &args->mGTa);
        if ( nGTs < 0 ) error("GT is not present at %s:%d\n", bcf_seqname(ahdr,arec), arec->pos+1);
        if ( nGTs != 2*nsmpl ) continue;    // not diploid
        nGTs = bcf_get_genotypes(bhdr, brec, &args->GTb, &args->mGTb);
        if ( nGTs < 0 ) error("GT is not present at %s:%d\n", bcf_seqname(bhdr,brec), brec->pos+1);
        if ( nGTs != 2*nsmpl ) continue;    // not diploid

        for (j=0; j<nsmpl; j++)
        {
            int *gta = &args->GTa[j*2];
            int *gtb = &args->GTb[j*2];
            if ( gta[1]==bcf_int32_vector_end || gtb[1]==bcf_int32_vector_end ) continue;
            if ( gta[0]==bcf_gt_missing || gta[1]==bcf_gt_missing || gtb[0]==bcf_gt_missing || gtb[1]==bcf_gt_missing ) continue;
            if ( !bcf_gt_is_phased(gta[1]) || !bcf_gt_is_phased(gtb[1]) ) continue;
            if ( bcf_gt_allele(gta[0])==bcf_gt_allele(gta[1]) || bcf_gt_allele(gtb[0])==bcf_gt_allele(gtb[1]) ) continue;
            if ( bcf_gt_allele(gta[0])==bcf_gt_allele(gtb[0]) && bcf_gt_allele(gta[1])==bcf_gt_allele(gtb[1]) )
            {
                if ( args->swap_phase[j] ) args->nmism[j]++; else args->nmatch[j]++;
            }
            if ( bcf_gt_allele(gta[0])==bcf_gt_allele(gtb[1]) && bcf_gt_allele(gta[1])==bcf_gt_allele(gtb[0]) )
            {
                if ( args->swap_phase[j] ) args->nmatch[j]++; else args->nmism[j]++;
            }
        }
    }
    for (i=0; i<args->nbuf/2; i+=2)
    {
        bcf1_t *arec = args->buf[i];
        bcf_translate(args->out_hdr, args->files->readers[0].header, arec);
        if ( args->nswap )
            phase_update(args, args->out_hdr, arec);
        bcf_update_format_int32(args->out_hdr,arec,"PS",args->phase_set,nsmpl);
        bcf_write(args->out_fh, args->out_hdr, arec);

        if ( arec->pos < args->prev_pos_check ) error("FIXME, disorder: %s:%d vs %d  [1]\n", bcf_seqname(args->files->readers[0].header,arec),arec->pos+1,args->prev_pos_check+1);
        args->prev_pos_check = arec->pos;
    }
    args->nswap = 0;
    for (j=0; j<nsmpl; j++)
    {
        if ( args->nmatch[j] >= args->nmism[j] )
            args->swap_phase[j] = 0;
        else
        {
            args->swap_phase[j] = 1;
            args->nswap++;
        }
        if ( args->nmatch[j] && args->nmism[j] )
        {
            // Entropy-inspired quality. The factor 0.7 shifts and scales to (0,1)
            double f = (double)args->nmatch[j]/(args->nmatch[j]+args->nmism[j]);
            args->phase_qual[j] = 99*(0.7 + f*log(f) + (1-f)*log(1-f))/0.7;
        }
        else
            args->phase_qual[j] = 99;
        args->nmatch[j] = 0;
        args->nmism[j]  = 0;
    }
    int PQ_printed = 0;
    for (; i<args->nbuf; i+=2)
    {
        bcf1_t *brec = args->buf[i+1];
        bcf_translate(args->out_hdr, args->files->readers[1].header, brec);
        if ( !PQ_printed )
        {
            bcf_update_format_int32(args->out_hdr,brec,"PQ",args->phase_qual,nsmpl);
            PQ_printed = 1;
            for (j=0; j<nsmpl; j++)
                if ( args->phase_qual[j] < args->min_PQ ) args->phase_set[j] = brec->pos+1;
        }
        if ( args->nswap )
            phase_update(args, args->out_hdr, brec);
        bcf_update_format_int32(args->out_hdr,brec,"PS",args->phase_set,nsmpl);
        bcf_write(args->out_fh, args->out_hdr, brec);

        if ( brec->pos < args->prev_pos_check ) error("FIXME, disorder: %s:%d vs %d  [2]\n", bcf_seqname(args->files->readers[1].header,brec),brec->pos+1,args->prev_pos_check+1);
        args->prev_pos_check = brec->pos;
    }
    args->nbuf = 0;
}

static void phased_push(args_t *args, bcf1_t *arec, bcf1_t *brec)
{
    int i, nsmpl = bcf_hdr_nsamples(args->out_hdr);
    int chr_id = bcf_hdr_name2id(args->out_hdr, bcf_seqname(args->files->readers[0].header,arec));
    if ( args->prev_chr<0 || args->prev_chr!=chr_id )
    {
        if ( args->prev_chr>=0 ) phased_flush(args);

        for (i=0; i<nsmpl; i++) 
            args->phase_set[i] = arec->pos+1;

        if ( args->seen_seq[chr_id] ) error("The chromosome block %s is not contiguous\n", bcf_seqname(args->files->readers[0].header,arec));
        args->seen_seq[chr_id] = 1;
        args->prev_chr = chr_id;
        args->prev_pos_check = -1;
    }

    if ( !brec )
    {
        bcf_translate(args->out_hdr, args->files->readers[0].header, arec);
        if ( args->nswap )
            phase_update(args, args->out_hdr, arec);
        bcf_update_format_int32(args->out_hdr,arec,"PS",args->phase_set,nsmpl);
        bcf_write(args->out_fh, args->out_hdr, arec);

        if ( arec->pos < args->prev_pos_check )
            error("FIXME, disorder: %s:%d in %s vs %d written  [3]\n", bcf_seqname(args->files->readers[0].header,arec), arec->pos+1,args->files->readers[0].fname, args->prev_pos_check+1);
        args->prev_pos_check = arec->pos;
        return;
    }

    int m = args->mbuf;
    args->nbuf += 2;
    hts_expand(bcf1_t*,args->nbuf,args->mbuf,args->buf);
    for (i=m; i<args->mbuf; i++)
        args->buf[i] = bcf_init1();

    SWAP(bcf1_t*, args->files->readers[0].buffer[0], args->buf[args->nbuf-2]);
    SWAP(bcf1_t*, args->files->readers[1].buffer[0], args->buf[args->nbuf-1]);
}

static void concat(args_t *args)
{
    int i;
    if ( args->phased_concat )  // phased concat
    {
        // keep only two open files at a time
        while ( args->ifname < args->nfnames )
        {
            int new_file = 0;
            while ( args->files->nreaders < 2 && args->ifname < args->nfnames )
            {
                if ( !bcf_sr_add_reader(args->files,args->fnames[args->ifname]) ) error("Failed to open %s\n", args->fnames[args->ifname]);
                new_file = 1;

                args->ifname++;
                if ( args->start_pos[args->ifname-1]==-1 ) break;   // new chromosome, start with only one file open
                if ( args->ifname < args->nfnames && args->start_pos[args->ifname]==-1 ) break; // next file starts on a different chromosome
            }

            // is there a line from the previous run? Seek the newly opened reader to that position
            int seek_pos = -1;
            int seek_chr = -1;
            if ( bcf_sr_has_line(args->files,0) )
            {
                bcf1_t *line = bcf_sr_get_line(args->files,0);
                bcf_sr_seek(args->files, bcf_seqname(args->files->readers[0].header,line), line->pos);
                seek_pos = line->pos;
                seek_chr = bcf_hdr_name2id(args->out_hdr, bcf_seqname(args->files->readers[0].header,line));
            }
            else if ( new_file ) 
                bcf_sr_seek(args->files,NULL,0);  // set to start

            int nret;
            while ( (nret = bcf_sr_next_line(args->files)) )
            {
                if ( !bcf_sr_has_line(args->files,0) )  // no input from the first reader
                {
                    // We are assuming that there is a perfect overlap, sites which are not present in both files are dropped
                    if ( ! bcf_sr_region_done(args->files,0) ) continue;

                    phased_flush(args);
                    bcf_sr_remove_reader(args->files, 0);
                }

                // Get a line to learn about current position
                for (i=0; i<args->files->nreaders; i++)
                    if ( bcf_sr_has_line(args->files,i) ) break;
                bcf1_t *line = bcf_sr_get_line(args->files,i);

                // This can happen after bcf_sr_seek: indel may start before the coordinate which we seek to.
                if ( seek_chr>=0 && seek_pos>line->pos && seek_chr==bcf_hdr_name2id(args->out_hdr, bcf_seqname(args->files->readers[i].header,line)) ) continue;
                seek_pos = seek_chr = -1;

                //  Check if the position overlaps with the next, yet unopened, reader
                int must_seek = 0;
                while ( args->ifname < args->nfnames && args->start_pos[args->ifname]!=-1 && line->pos >= args->start_pos[args->ifname] )
                {
                    must_seek = 1;
                    bcf_sr_add_reader(args->files,args->fnames[args->ifname]);
                    args->ifname++;
                }
                if ( must_seek )
                {
                    bcf_sr_seek(args->files, bcf_seqname(args->files->readers[i].header,line), line->pos);
                    seek_pos = line->pos;
                    seek_chr = bcf_hdr_name2id(args->out_hdr, bcf_seqname(args->files->readers[i].header,line));
                    continue;
                }

                // We are assuming that there is a perfect overlap, sites which are not present in both files are dropped
                if ( args->files->nreaders>1 && !bcf_sr_has_line(args->files,1) && !bcf_sr_region_done(args->files,1) ) continue;

                phased_push(args, bcf_sr_get_line(args->files,0), args->files->nreaders>1 ? bcf_sr_get_line(args->files,1) : NULL);
            }

            if ( args->files->nreaders )
            {
                phased_flush(args);
                while ( args->files->nreaders )
                    bcf_sr_remove_reader(args->files, 0);
            }
        }
    }
    else if ( args->files )  // combining overlapping files, using synced reader 
    {
        while ( bcf_sr_next_line(args->files) )
        {
            for (i=0; i<args->files->nreaders; i++)
            {
                bcf1_t *line = bcf_sr_get_line(args->files,i);
                if ( !line ) continue;
                bcf_translate(args->out_hdr, args->files->readers[i].header, line);
                bcf_write1(args->out_fh, args->out_hdr, line);
            }
        }
    }
    else    // concatenating
    {
        kstring_t tmp = {0,0,0};
        int prev_chr_id = -1, prev_pos;
        bcf1_t *line = bcf_init();
        for (i=0; i<args->nfnames; i++)
        {
            htsFile *fp = hts_open(args->fnames[i], "r"); if ( !fp ) error("Failed to open: %s\n", args->fnames[i]);
            bcf_hdr_t *hdr = bcf_hdr_read(fp); if ( !hdr ) error("Failed to parse header: %s\n", args->fnames[i]);
            if ( !fp->is_bin && args->output_type&FT_VCF )
            {
                line->max_unpack = BCF_UN_STR;
                // if VCF is on both input and output, avoid VCF to BCF conversion
                while ( hts_getline(fp, KS_SEP_LINE, &fp->line) >=0 )
                {
                    char *str = fp->line.s;
                    while ( *str && *str!='\t' ) str++;
                    tmp.l = 0;
                    kputsn(fp->line.s,str-fp->line.s,&tmp);
                    int chr_id = bcf_hdr_name2id(args->out_hdr, tmp.s);
                    if ( chr_id<0 ) error("FIXME: sequence name %s in %s\n", tmp.s, args->fnames[i]);
                    if ( prev_chr_id!=chr_id ) 
                    {
                        prev_pos = -1;
                        if ( args->seen_seq[chr_id] )
                            error("\nThe chromosome block %s is not contiguous, consider running with -a.\n", tmp.s);
                    }
                    char *end;
                    int pos = strtol(str+1,&end,10) - 1;
                    if ( end==str+1 ) error("Could not parse line: %s\n", fp->line.s);
                    if ( prev_pos > pos )
                        error("The chromosome block %s is not sorted, consider running with -a.\n", tmp.s);
                    args->seen_seq[chr_id] = 1;
                    prev_chr_id = chr_id;

                    if ( vcf_write_line(args->out_fh, &fp->line)!=0 ) error("Failed to write %d bytes\n", fp->line.l);
                }
            }
            else
            {
                // BCF conversion is required
                line->max_unpack = 0;
                while ( bcf_read(fp, hdr, line)==0 )
                {
                    bcf_translate(args->out_hdr, hdr, line);

                    if ( prev_chr_id!=line->rid ) 
                    {
                        prev_pos = -1;
                        if ( args->seen_seq[line->rid] )
                            error("\nThe chromosome block %s is not contiguous, consider running with -a.\n", bcf_seqname(args->out_hdr, line));
                    }
                    if ( prev_pos > line->pos )
                        error("The chromosome block %s is not sorted, consider running with -a.\n", bcf_seqname(args->out_hdr, line));
                    args->seen_seq[line->rid] = 1;
                    prev_chr_id = line->rid;

                    if ( bcf_write(args->out_fh, args->out_hdr, line)!=0 ) error("Failed to write\n");
                }
            }
            bcf_hdr_destroy(hdr);
            hts_close(fp);
        }
        bcf_destroy(line);
        free(tmp.s);
    }
}

static void usage(args_t *args)
{
    fprintf(stderr, "\n");
    fprintf(stderr, "About:   Concatenate or combine VCF/BCF files. All source files must have the same sample\n");
    fprintf(stderr, "         columns appearing in the same order. Can be used, for example, to\n");
    fprintf(stderr, "         concatenate chromosome VCFs into one VCF, or combine a SNP VCF and an indel\n");
    fprintf(stderr, "         VCF into one. The input files must be sorted by chr and position. The files\n");
    fprintf(stderr, "         must be given in the correct order to produce sorted VCF on output unless\n");
    fprintf(stderr, "         the -a, --allow-overlaps option is specified.\n");
    fprintf(stderr, "Usage:   bcftools concat [options] <A.vcf.gz> [<B.vcf.gz> [...]]\n");
    fprintf(stderr, "\n");
    fprintf(stderr, "Options:\n");
	fprintf(stderr, "   -a, --allow-overlaps           First coordinate of the next file can precede last record of the current file.\n");
	fprintf(stderr, "   -f, --file-list <file>         Read the list of files from a file.\n");
	fprintf(stderr, "   -l, --ligate                   Ligate phased VCFs by matching phase at overlapping haplotypes\n");
	fprintf(stderr, "   -q, --min-PQ <int>             Break phase set if phasing quality is lower than <int> [30]\n");
	fprintf(stderr, "   -O, --output-type <b|u|z|v>    b: compressed BCF, u: uncompressed BCF, z: compressed VCF, v: uncompressed VCF [v]\n");
    fprintf(stderr, "\n");
    exit(1);
}

int main_vcfconcat(int argc, char *argv[])
{
    int c;
    args_t *args  = (args_t*) calloc(1,sizeof(args_t));
    args->argc    = argc; args->argv = argv;
    args->output_type = FT_VCF;
    args->min_PQ  = 30;

    static struct option loptions[] = 
    {
        {"allow-overlaps",0,0,'a'},
        {"ligate",0,0,'l'},
        {"output-type",1,0,'O'},
        {"file-list",1,0,'f'},
        {"min-PQ",1,0,'q'},
        {0,0,0,0}
    };
    while ((c = getopt_long(argc, argv, "h:?O:f:alq:",loptions,NULL)) >= 0) 
    {
        switch (c) {
    	    case 'q': args->min_PQ = atoi(optarg); break;
    	    case 'a': args->allow_overlaps = 1; break;
    	    case 'l': args->phased_concat = 1; break;
    	    case 'f': args->file_list = optarg; break;
    	    case 'O': 
                switch (optarg[0]) {
                    case 'b': args->output_type = FT_BCF_GZ; break;
                    case 'u': args->output_type = FT_BCF; break;
                    case 'z': args->output_type = FT_VCF_GZ; break;
                    case 'v': args->output_type = FT_VCF; break;
                    default: error("The output type \"%s\" not recognised\n", optarg);
                };
                break;
            case 'h': 
            case '?': usage(args); break;
            default: error("Unknown argument: %s\n", optarg);
        }
    }
    while ( optind<argc ) 
    { 
        args->nfnames++;
        args->fnames = (char **)realloc(args->fnames,sizeof(char*)*args->nfnames);
        args->fnames[args->nfnames-1] = strdup(argv[optind]);
        optind++;
    }
    if ( args->file_list )
    {
        if ( args->nfnames ) error("Cannot combine -l with file names on command line.\n");
        args->fnames = hts_readlines(args->file_list, &args->nfnames);
    }
    if ( !args->nfnames ) usage(args);
    init_data(args);
    concat(args);
    destroy_data(args);
    free(args);
    return 0;
}