static void print_chain(args_t *args)
{
/*
Example chain format (see: https://genome.ucsc.edu/goldenPath/help/chain.html):
chain 1 500 + 480 500 1 501 + 480 501 1
12 3 1
1 0 3
484
chain line is:
- chain
- score (sum of the length of ungapped block in this case)
- ref_seqname (from the fasta header, parsed by htslib)
- ref_seqlength (from the fasta header)
- ref_strand (+ or -; always + for bcf-consensus)
- ref_start (as defined in the fasta header)
- ref_end (as defined in the fasta header)
- alt_seqname (same as ref_seqname as bcf-consensus only considers SNPs and indels)
- alt_seqlength (adjusted to match the length of the alt sequence)
- alt_strand (+ or -; always + for bcf-consensus)
- alt_start (same as ref_start, as no edits are recorded/applied before that position)
- alt_end (adjusted to match the length of the alt sequence)
- chain_num (just an auto-increment id)
the other (sorted) lines are:
- length of the ungapped alignment block
- gap on the ref sequence between this and the next block (all but the last line)
- gap on the alt sequence between this and the next block (all but the last line)
*/
chain_t *chain = args->chain;
int n = chain->num;
int ref_end_pos = args->fa_length + chain->ori_pos;
int last_block_size = ref_end_pos - chain->ref_last_block_ori;
int alt_end_pos = chain->alt_last_block_ori + last_block_size;
int score = 0;
for (n=0; n<chain->num; n++) {
score += chain->block_lengths[n];
}
score += last_block_size;
fprintf(args->fp_chain, "chain %d %s %d + %d %d %s %d + %d %d %d\n", score, bcf_hdr_id2name(args->hdr,args->rid), ref_end_pos, chain->ori_pos, ref_end_pos, bcf_hdr_id2name(args->hdr,args->rid), alt_end_pos, chain->ori_pos, alt_end_pos, ++args->chain_id);
for (n=0; n<chain->num; n++) {
fprintf(args->fp_chain, "%d %d %d\n", chain->block_lengths[n], chain->ref_gaps[n], chain->alt_gaps[n]);
}
fprintf(args->fp_chain, "%d\n\n", last_block_size);
}
static void mask_region(args_t *args, char *seq, int len)
{
char *chr = (char*)bcf_hdr_id2name(args->hdr,args->rid);
int start = args->fa_src_pos - len;
int end = args->fa_src_pos;
regitr_t itr;
if ( !regidx_overlap(args->mask, chr,start,end, &itr) ) return;
int idx_start, idx_end, i;
while ( REGITR_OVERLAP(itr,start,end) )
{
idx_start = REGITR_START(itr) - start;
idx_end = REGITR_END(itr) - start;
if ( idx_start < 0 ) idx_start = 0;
if ( idx_end >= len ) idx_end = len - 1;
for (i=idx_start; i<=idx_end; i++) seq[i] = 'N';
itr.i++;
}
}
static void apply_variant(args_t *args, bcf1_t *rec)
{
if ( rec->n_allele==1 ) return;
if ( rec->pos <= args->fa_frz_pos )
{
fprintf(pysamerr,"The site %s:%d overlaps with another variant, skipping...\n", bcf_seqname(args->hdr,rec),rec->pos+1);
return;
}
if ( args->mask )
{
char *chr = (char*)bcf_hdr_id2name(args->hdr,args->rid);
int start = rec->pos;
int end = rec->pos + rec->rlen - 1;
if ( regidx_overlap(args->mask, chr,start,end,NULL) ) return;
}
int i, ialt = 1;
if ( args->isample >= 0 )
{
bcf_fmt_t *fmt = bcf_get_fmt(args->hdr, rec, "GT");
if ( !fmt ) return;
if ( args->haplotype )
{
if ( args->haplotype > fmt->n ) error("Can't apply %d-th haplotype at %s:%d\n", args->haplotype,bcf_seqname(args->hdr,rec),rec->pos+1);
uint8_t *ignore, *ptr = fmt->p + fmt->size*args->isample + args->haplotype - 1;
ialt = bcf_dec_int1(ptr, fmt->type, &ignore);
if ( bcf_gt_is_missing(ialt) || ialt==bcf_int32_vector_end ) return;
ialt = bcf_gt_allele(ialt);
}
else if ( args->output_iupac )
{
uint8_t *ignore, *ptr = fmt->p + fmt->size*args->isample;
ialt = bcf_dec_int1(ptr, fmt->type, &ignore);
if ( bcf_gt_is_missing(ialt) || ialt==bcf_int32_vector_end ) return;
ialt = bcf_gt_allele(ialt);
int jalt;
if ( fmt->n>1 )
{
ptr = fmt->p + fmt->size*args->isample + 1;
jalt = bcf_dec_int1(ptr, fmt->type, &ignore);
if ( bcf_gt_is_missing(jalt) || jalt==bcf_int32_vector_end ) jalt = ialt;
else jalt = bcf_gt_allele(jalt);
}
else jalt = ialt;
if ( rec->n_allele <= ialt || rec->n_allele <= jalt ) error("Broken VCF, too few alts at %s:%d\n", bcf_seqname(args->hdr,rec),rec->pos+1);
if ( ialt!=jalt && !rec->d.allele[ialt][1] && !rec->d.allele[jalt][1] ) // is this a het snp?
{
char ial = rec->d.allele[ialt][0];
char jal = rec->d.allele[jalt][0];
rec->d.allele[ialt][0] = gt2iupac(ial,jal);
}
}
else
{
for (i=0; i<fmt->n; i++)
{
uint8_t *ignore, *ptr = fmt->p + fmt->size*args->isample + i;
ialt = bcf_dec_int1(ptr, fmt->type, &ignore);
if ( bcf_gt_is_missing(ialt) || ialt==bcf_int32_vector_end ) return;
ialt = bcf_gt_allele(ialt);
if ( ialt ) break;
}
}
if ( !ialt ) return; // ref allele
if ( rec->n_allele <= ialt ) error("Broken VCF, too few alts at %s:%d\n", bcf_seqname(args->hdr,rec),rec->pos+1);
}
else if ( args->output_iupac && !rec->d.allele[0][1] && !rec->d.allele[1][1] )
{
char ial = rec->d.allele[0][0];
char jal = rec->d.allele[1][0];
rec->d.allele[1][0] = gt2iupac(ial,jal);
}
int idx = rec->pos - args->fa_ori_pos + args->fa_mod_off;
if ( idx<0 || idx>=args->fa_buf.l )
error("FIXME: %s:%d .. idx=%d, ori_pos=%d, len=%d, off=%d\n",bcf_seqname(args->hdr,rec),rec->pos+1,idx,args->fa_ori_pos,args->fa_buf.l,args->fa_mod_off);
// sanity check the reference base
int len_diff = 0, alen = 0;
if ( rec->d.allele[ialt][0]=='<' )
{
if ( strcasecmp(rec->d.allele[ialt], "<DEL>") )
error("Symbolic alleles other than <DEL> are currently not supported: %s at %s:%d\n",rec->d.allele[ialt],bcf_seqname(args->hdr,rec),rec->pos+1);
assert( rec->d.allele[0][1]==0 ); // todo: for now expecting strlen(REF) = 1
len_diff = 1-rec->rlen;
rec->d.allele[ialt] = rec->d.allele[0]; // according to VCF spec, REF must precede the event
alen = strlen(rec->d.allele[ialt]);
}
else if ( strncasecmp(rec->d.allele[0],args->fa_buf.s+idx,rec->rlen) )
{
// fprintf(pysamerr,"%d .. [%s], idx=%d ori=%d off=%d\n",args->fa_ori_pos,args->fa_buf.s,idx,args->fa_ori_pos,args->fa_mod_off);
char tmp = 0;
if ( args->fa_buf.l - idx > rec->rlen )
{
tmp = args->fa_buf.s[idx+rec->rlen];
args->fa_buf.s[idx+rec->rlen] = 0;
}
error(
"The fasta sequence does not match the REF allele at %s:%d:\n"
" .vcf: [%s]\n"
" .vcf: [%s] <- (ALT)\n"
" .fa: [%s]%c%s\n",
bcf_seqname(args->hdr,rec),rec->pos+1, rec->d.allele[0], rec->d.allele[ialt], args->fa_buf.s+idx,
tmp?tmp:' ',tmp?args->fa_buf.s+idx+rec->rlen+1:""
);
}
else
{
alen = strlen(rec->d.allele[ialt]);
len_diff = alen - rec->rlen;
}
if ( args->fa_case )
for (i=0; i<alen; i++) rec->d.allele[ialt][i] = toupper(rec->d.allele[ialt][i]);
else
for (i=0; i<alen; i++) rec->d.allele[ialt][i] = tolower(rec->d.allele[ialt][i]);
if ( len_diff <= 0 )
{
// deletion or same size event
for (i=0; i<alen; i++)
args->fa_buf.s[idx+i] = rec->d.allele[ialt][i];
if ( len_diff )
memmove(args->fa_buf.s+idx+alen,args->fa_buf.s+idx+rec->rlen,args->fa_buf.l-idx-rec->rlen);
}
else
{
// insertion
ks_resize(&args->fa_buf, args->fa_buf.l + len_diff);
memmove(args->fa_buf.s + idx + rec->rlen + len_diff, args->fa_buf.s + idx + rec->rlen, args->fa_buf.l - idx - rec->rlen);
for (i=0; i<alen; i++)
args->fa_buf.s[idx+i] = rec->d.allele[ialt][i];
}
if (args->chain && len_diff != 0)
{
// If first nucleotide of both REF and ALT are the same... (indels typically include the nucleotide before the variant)
if ( strncasecmp(rec->d.allele[0],rec->d.allele[ialt],1) == 0)
{
// ...extend the block by 1 bp: start is 1 bp further and alleles are 1 bp shorter
push_chain_gap(args->chain, rec->pos + 1, rec->rlen - 1, rec->pos + 1 + args->fa_mod_off, alen - 1);
}
else
{
// otherwise, just the coordinates of the variant as given
push_chain_gap(args->chain, rec->pos, rec->rlen, rec->pos + args->fa_mod_off, alen);
}
}
args->fa_buf.l += len_diff;
args->fa_mod_off += len_diff;
args->fa_frz_pos = rec->pos + rec->rlen - 1;
}
void union_data::readGenotypesVCF(string fvcf,string region) {
int n_includedG = 0;
int n_excludedG_mult = 0;
int n_excludedG_void = 0;
int n_excludedG_user = 0;
int n_includedS = 0;
vector < int > mappingS;
genotype_id.clear();
genotype_chr.clear();
genotype_start.clear();
genotype_end.clear();
genotype_val.clear();
genotype_count=0;
genotype_id_to_idx.clear();
//Opening files
bcf_srs_t * sr = bcf_sr_init();
//vrb.bullet("target region [" + regionGenotype.get() + "]");
//if (bcf_sr_set_regions(sr, regionGenotype.get().c_str(), 0) == -1) vrb.error("Cannot jump to region!");
bcf_sr_set_regions(sr, region.c_str(), 0);
if(!(bcf_sr_add_reader (sr, fvcf.c_str()))) {
switch (sr->errnum) {
case not_bgzf: vrb.error("File not compressed with bgzip!");
case idx_load_failed: vrb.error("Impossible to load index file!");
case file_type_error: vrb.error("File format not detected by htslib!");
default : vrb.error("Unknown error!");
}
}
//Sample processing
int n_samples = bcf_hdr_nsamples(sr->readers[0].header);
for (int i0 = 0 ; i0 < n_samples ; i0 ++) {
mappingS.push_back(findSample(string(sr->readers[0].header->samples[i0])));
if (mappingS.back() >= 0) n_includedS++;
}
//Read genotype data
int ngt, ngt_arr = 0, nds, nds_arr = 0, * gt_arr = NULL, nsl, nsl_arr = 0, * sl_arr = NULL;
float * ds_arr = NULL;
bcf1_t * line;
unsigned int linecount = 0;
while(bcf_sr_next_line (sr)) {
linecount ++;
if (linecount % 100000 == 0) vrb.bullet("Read " + stb.str(linecount) + " lines");
line = bcf_sr_get_line(sr, 0);
if (line->n_allele == 2) {
ngt = bcf_get_genotypes(sr->readers[0].header, line, >_arr, &ngt_arr);
nds = bcf_get_format_float(sr->readers[0].header, line,"DS", &ds_arr, &nds_arr);
if (nds == n_samples || ngt == 2*n_samples) {
bcf_unpack(line, BCF_UN_STR);
string sid = string(line->d.id);
if (filter_genotype.check(sid)) {
genotype_id.push_back(sid);
genotype_chr.push_back(string(bcf_hdr_id2name(sr->readers[0].header, line->rid)));
string genotype_ref = string(line->d.allele[0]);
genotype_start.push_back(line->pos + 1);
nsl = bcf_get_info_int32(sr->readers[0].header, line, "END", &sl_arr, &nsl_arr);
if (nsl >= 0 && nsl_arr == 1) genotype_end.push_back(sl_arr[0]);
else genotype_end.push_back(genotype_start.back() + genotype_ref.size() - 1);
genotype_val.push_back(vector < float > (sample_count, 0.0));
for(int i = 0 ; i < n_samples ; i ++) {
if (mappingS[i] >= 0) {
if (nds > 0) genotype_val.back()[mappingS[i]] = ds_arr[i];
else {
if (gt_arr[2*i+0] == bcf_gt_missing || gt_arr[2*i+1] == bcf_gt_missing) genotype_val.back()[mappingS[i]] = bcf_float_missing;
else genotype_val.back()[mappingS[i]] = bcf_gt_allele(gt_arr[2*i+0]) + bcf_gt_allele(gt_arr[2*i+1]);
}
}
}
pair < string, int > temp (sid,n_includedG);
genotype_id_to_idx.insert(temp);
n_includedG++;
} else n_excludedG_user ++;
} else n_excludedG_void ++;
} else n_excludedG_mult ++;
}
//Finalize
free(gt_arr);
free(ds_arr);
bcf_sr_destroy(sr);
genotype_count = n_includedG;
//vrb.bullet(stb.str(n_includedG) + " variants included");
//if (n_excludedG_user > 0) vrb.bullet(stb.str(n_excludedG_user) + " variants excluded by user");
//if (n_excludedG_mult > 0) vrb.bullet(stb.str(n_excludedG_mult) + " multi-allelic variants excluded");
//if (n_excludedG_void > 0) vrb.bullet(stb.str(n_excludedG_void) + " uninformative variants excluded [no GT/DS]");
//if (genotype_count == 0) vrb.leave("Cannot find genotypes in target region!");
}
int main(int argc, char **argv)
{
if (argc < 3) {
fprintf(stderr,"%s <bcf file> <num vars>\n", argv[0]);
return 1;
}
char *fname = argv[1];
uint32_t num_vars = atoi(argv[2]);
htsFile *fp = hts_open(fname,"rb");
bcf_hdr_t *hdr = bcf_hdr_read(fp);
bcf1_t *line = bcf_init1();
int32_t *gt_p = NULL;
uint32_t num_inds = bcf_hdr_nsamples(hdr);
int32_t i, j, k, ntmp = 0, int_i = 0, two_bit_i = 0, sum, t_sum = 0;
uint32_t num_ind_ints = 1 + ((num_inds - 1) / 16);
pri_queue q = priq_new(0);
priority p;
uint32_t *packed_ints = (uint32_t *) calloc(num_ind_ints,
sizeof(uint32_t));
FILE *gt_of = fopen("gt.tmp.packed","wb");
FILE *md_of = fopen("md.tmp.packed","w");
uint32_t *md_index = (uint32_t *) malloc(num_vars * sizeof(uint32_t));
uint32_t md_i = 0;
unsigned long t_bcf_read = 0,
t_bcf_dup = 0,
t_bcf_unpack = 0,
t_bcf_get_genotypes = 0,
t_bcf_hdr_nsamples = 0,
t_q = 0,
t_write = 0,
t_get_md = 0,
t_md_write = 0,
t_pack = 0;
for (i = 0; i < num_vars; ++i) {
sum = 0;
int_i = 0;
two_bit_i = 0;
int r = bcf_read(fp, hdr, line);
// Copy
bcf1_t *t_line = bcf_dup(line);
// Unpack
bcf_unpack(t_line, BCF_UN_ALL);
// Get metadata
size_t len = strlen(bcf_hdr_id2name(hdr, t_line->rid)) +
10 + // max length of pos
strlen(t_line->d.id) +
strlen(t_line->d.allele[0]) +
strlen(t_line->d.allele[1]) +
4; //tabs
char *md = (char *) malloc(len * sizeof(char));
sprintf(md, "%s\t%d\t%s\t%s\t%s",
bcf_hdr_id2name(hdr, t_line->rid),
t_line->pos + 1,
t_line->d.id,
t_line->d.allele[0],
t_line->d.allele[1]);
// Write metadata
md_i += strlen(md);
md_index[i] = md_i;
fprintf(md_of, "%s", md);
// Get gentotypes
uint32_t num_gts_per_sample = bcf_get_genotypes(hdr,
t_line,
>_p,
&ntmp);
num_gts_per_sample /= num_inds;
int32_t *gt_i = gt_p;
// Pack genotypes
for (j = 0; j < num_inds; ++j) {
uint32_t gt = 0;
for (k = 0; k < num_gts_per_sample; ++k) {
gt += bcf_gt_allele(gt_i[k]);
}
packed_ints[int_i] += gt << (30 - 2*two_bit_i);
two_bit_i += 1;
if (two_bit_i == 16) {
two_bit_i = 0;
int_i += 1;
}
sum += gt;
gt_i += num_gts_per_sample;
}
// Get a priority for the variant based on the sum and number of
// leading zeros
p.sum = sum;
uint32_t prefix_len = 0;
j = 0;
while ((j < num_ind_ints) && (packed_ints[j] == 0)){
prefix_len += 32;
j += 1;
}
if (j < num_ind_ints)
prefix_len += nlz1(packed_ints[j]);
// Push it into the q
p.len = prefix_len;
int *j = (int *) malloc (sizeof(int));
j[0] = i;
priq_push(q, j, p);
// Write to file
fwrite(packed_ints, sizeof(uint32_t), num_ind_ints,gt_of);
memset(packed_ints, 0, num_ind_ints*sizeof(uint32_t));
t_sum += sum;
bcf_destroy(t_line);
free(md);
}
fclose(gt_of);
fclose(md_of);
md_of = fopen("md.tmp.packed","r");
FILE *md_out = fopen("md.bim","w");
gt_of = fopen("gt.tmp.packed","rb");
FILE *s_gt_of = fopen("s.gt.tmp.packed","wb");
// Get variants in order and rewrite a variant-major sorted matrix
while ( priq_top(q, &p) != NULL ) {
int *d = priq_pop(q, &p);
uint32_t start = 0;
if (*d != 0)
start = md_index[*d - 1];
uint32_t len = md_index[*d] - start;
fseek(md_of, start*sizeof(char), SEEK_SET);
char buf[len+1];
fread(buf, sizeof(char), len, md_of);
buf[len] = '\0';
fseek(gt_of, (*d)*num_ind_ints*sizeof(uint32_t), SEEK_SET);
fread(packed_ints, sizeof(uint32_t), num_ind_ints, gt_of);
fwrite(packed_ints, sizeof(uint32_t), num_ind_ints,s_gt_of);
fprintf(md_out, "%s\n", buf);
}
fclose(md_out);
fclose(md_of);
fclose(gt_of);
fclose(s_gt_of);
/*
* In a packed-int variant-major matrix there will be a num_vars
* number of rows, and a num_inds number of values packed into
* num_inds_ints number of intergers. For examples, 16 rows of 16 values
* will be 16 ints, where each int encodes 16 values.
*
*/
uint32_t num_var_ints = 1 + ((num_vars - 1) / 16);
uint32_t *I_data = (uint32_t *)calloc(num_var_ints*16,sizeof(uint32_t));
uint32_t **I = (uint32_t **)malloc(16*sizeof(uint32_t*));
for (i = 0; i < 16; ++i)
I[i] = I_data + i*num_var_ints;
uint32_t I_i = 0, I_int_i = 0;
uint32_t v;
s_gt_of = fopen("s.gt.tmp.packed","rb");
FILE *rs_gt_of = fopen("r.s.gt.tmp.packed","wb");
// Write these to values to that this is a well-formed uncompressed
// packed int binary file (ubin) file
fwrite(&num_vars, sizeof(uint32_t), 1, rs_gt_of);
fwrite(&num_inds, sizeof(uint32_t), 1, rs_gt_of);
/*
* we need to loop over the columns in the v-major file.
* There are num_vars rows, and num_ind_ints 16-ind packed columns
*
* In this loop :
* i: cols in var-major form, rows in ind-major form
* j: rows in var-major form, cols in ind-major form
*/
uint32_t num_inds_to_write = num_inds;
for (i = 0; i < num_ind_ints; ++i) { // loop over each int col
for (j = 0; j < num_vars; ++j) { // loop over head row in that col
// skip to the value at the row/col
fseek(s_gt_of,
j*num_ind_ints*sizeof(uint32_t) + //row
i*sizeof(uint32_t), //col
SEEK_SET);
fread(&v, sizeof(uint32_t), 1, s_gt_of);
// one int corresponds to a col of 16 two-bit values
// two_bit_i will move across the cols
for (two_bit_i = 0; two_bit_i < 16; ++two_bit_i) {
I[two_bit_i][I_i] += ((v >> (30 - 2*two_bit_i)) & 3) <<
(30 - 2*I_int_i);
}
I_int_i += 1;
if (I_int_i == 16) {
I_i += 1;
I_int_i = 0;
}
}
// When we are at the end of the file, and the number of lines
// is not a factor of 16, only write out the lines that contain values
if (num_inds_to_write >= 16) {
fwrite(I_data,
sizeof(uint32_t),
num_var_ints*16,
rs_gt_of);
num_inds_to_write -= 16;
} else {
fwrite(I_data,
sizeof(uint32_t),
num_var_ints*num_inds_to_write,
rs_gt_of);
}
memset(I_data, 0, num_var_ints*16*sizeof(uint32_t));
I_int_i = 0;
I_i = 0;
}
fclose(s_gt_of);
fclose(rs_gt_of);
free(md_index);
free(packed_ints);
}
static void flush_viterbi(args_t *args)
{
int i,j;
if ( !args->nsites ) return;
if ( !args->vi_training )
{
// single viterbi pass, one chromsome
hmm_run_viterbi(args->hmm, args->nsites, args->eprob, args->sites);
hmm_run_fwd_bwd(args->hmm, args->nsites, args->eprob, args->sites);
double *fwd = hmm_get_fwd_bwd_prob(args->hmm);
const char *chr = bcf_hdr_id2name(args->hdr,args->prev_rid);
uint8_t *vpath = hmm_get_viterbi_path(args->hmm);
for (i=0; i<args->nsites; i++)
{
int state = vpath[i*2]==STATE_AZ ? 1 : 0;
double *pval = fwd + i*2;
printf("%s\t%d\t%d\t%.1f\n", chr,args->sites[i]+1, state, phred_score(1.0-pval[state]));
}
return;
}
// viterbi training, multiple chromosomes
double t2az_prev, t2hw_prev;
double deltaz, delthw;
int niter = 0;
do
{
double *tprob_arr = hmm_get_tprob(args->hmm);
t2az_prev = MAT(tprob_arr,2,1,0); //args->t2AZ;
t2hw_prev = MAT(tprob_arr,2,0,1); //args->t2HW;
double tcounts[] = { 0,0,0,0 };
for (i=0; i<args->nrids; i++)
{
// run viterbi for each chromosomes. eprob and sites contain
// multiple chromosomes, rid_offs mark the boundaries
int ioff = args->rid_offs[i];
int nsites = (i+1==args->nrids ? args->nsites : args->rid_offs[i+1]) - ioff;
hmm_run_viterbi(args->hmm, nsites, args->eprob+ioff*2, args->sites+ioff);
// what transitions were observed: add to the total counts
uint8_t *vpath = hmm_get_viterbi_path(args->hmm);
for (j=1; j<nsites; j++)
{
// count the number of transitions
int prev_state = vpath[2*(j-1)];
int curr_state = vpath[2*j];
MAT(tcounts,2,curr_state,prev_state) += 1;
}
}
// update the transition matrix tprob
for (i=0; i<2; i++)
{
int n = 0;
for (j=0; j<2; j++) n += MAT(tcounts,2,i,j);
if ( !n) error("fixme: state %d not observed\n", i+1);
for (j=0; j<2; j++) MAT(tcounts,2,i,j) /= n;
}
if ( args->genmap_fname || args->rec_rate > 0 )
hmm_set_tprob(args->hmm, tcounts, 0);
else
hmm_set_tprob(args->hmm, tcounts, 10000);
tprob_arr = hmm_get_tprob(args->hmm);
deltaz = fabs(MAT(tprob_arr,2,1,0)-t2az_prev);
delthw = fabs(MAT(tprob_arr,2,0,1)-t2hw_prev);
niter++;
fprintf(pysamerr,"%d: %f %f\n", niter,deltaz,delthw);
}
while ( deltaz > 0.0 || delthw > 0.0 );
fprintf(pysamerr, "Viterbi training converged in %d iterations to", niter);
double *tprob_arr = hmm_get_tprob(args->hmm);
for (i=0; i<2; i++) for (j=0; j<2; j++) fprintf(pysamerr, " %f", MAT(tprob_arr,2,i,j));
fprintf(pysamerr, "\n");
// output the results
for (i=0; i<args->nrids; i++)
{
int ioff = args->rid_offs[i];
int nsites = (i+1==args->nrids ? args->nsites : args->rid_offs[i+1]) - ioff;
hmm_run_viterbi(args->hmm, nsites, args->eprob+ioff*2, args->sites+ioff);
uint8_t *vpath = hmm_get_viterbi_path(args->hmm);
const char *chr = bcf_hdr_id2name(args->hdr,args->rids[i]);
for (j=0; j<nsites; j++)
{
printf("%s\t%d\t%d\t..\n", chr,args->sites[ioff+j]+1,vpath[j*2]==STATE_AZ ? 1 : 0);
}
}
}
void flush_viterbi(args_t *args)
{
const char *s1, *s2, *s3 = NULL;
if ( args->mode==C_UNRL )
{
s1 = bcf_hdr_int2id(args->hdr,BCF_DT_SAMPLE,args->isample);
s2 = bcf_hdr_int2id(args->hdr,BCF_DT_SAMPLE,args->jsample);
}
else if ( args->mode==C_TRIO )
{
s1 = bcf_hdr_int2id(args->hdr,BCF_DT_SAMPLE,args->imother);
s3 = bcf_hdr_int2id(args->hdr,BCF_DT_SAMPLE,args->ifather);
s2 = bcf_hdr_int2id(args->hdr,BCF_DT_SAMPLE,args->ichild);
}
if ( !args->fp )
{
kstring_t str = {0,0,0};
kputs(args->prefix, &str);
kputs(".dat", &str);
args->fp = fopen(str.s,"w");
if ( !args->fp ) error("%s: %s\n", str.s,strerror(errno));
free(str.s);
fprintf(args->fp,"# SG, shared segment\t[2]Chromosome\t[3]Start\t[4]End\t[5]%s:1\t[6]%s:2\n",s2,s2);
fprintf(args->fp,"# SW, number of switches\t[3]Sample\t[4]Chromosome\t[5]nHets\t[5]nSwitches\t[6]switch rate\n");
}
hmm_run_viterbi(args->hmm,args->nsites,args->eprob,args->sites);
uint8_t *vpath = hmm_get_viterbi_path(args->hmm);
int i, iprev = -1, prev_state = -1, nstates = hmm_get_nstates(args->hmm);
int nswitch_mother = 0, nswitch_father = 0;
for (i=0; i<args->nsites; i++)
{
int state = vpath[i*nstates];
if ( state!=prev_state || i+1==args->nsites )
{
uint32_t start = iprev>=0 ? args->sites[iprev]+1 : 1, end = i>0 ? args->sites[i-1] : 1;
const char *chr = bcf_hdr_id2name(args->hdr,args->prev_rid);
if ( args->mode==C_UNRL )
{
switch (prev_state)
{
case UNRL_0x0x:
fprintf(args->fp,"SG\t%s\t%d\t%d\t%s:1\t-\n", chr,start,end,s1); break;
case UNRL_0xx0:
fprintf(args->fp,"SG\t%s\t%d\t%d\t-\t%s:1\n", chr,start,end,s1); break;
case UNRL_x00x:
fprintf(args->fp,"SG\t%s\t%d\t%d\t%s:2\t-\n", chr,start,end,s1); break;
case UNRL_x0x0:
fprintf(args->fp,"SG\t%s\t%d\t%d\t-\t%s:2\n", chr,start,end,s1); break;
case UNRL_0101:
fprintf(args->fp,"SG\t%s\t%d\t%d\t%s:1\t%s:2\n", chr,start,end,s1,s1); break;
case UNRL_0110:
fprintf(args->fp,"SG\t%s\t%d\t%d\t%s:2\t%s:1\n", chr,start,end,s1,s1); break;
}
}
else if ( args->mode==C_TRIO )
{
switch (prev_state)
{
case TRIO_AC:
fprintf(args->fp,"SG\t%s\t%d\t%d\t%s:1\t%s:1\n", chr,start,end,s1,s3); break;
case TRIO_AD:
fprintf(args->fp,"SG\t%s\t%d\t%d\t%s:1\t%s:2\n", chr,start,end,s1,s3); break;
case TRIO_BC:
fprintf(args->fp,"SG\t%s\t%d\t%d\t%s:2\t%s:1\n", chr,start,end,s1,s3); break;
case TRIO_BD:
fprintf(args->fp,"SG\t%s\t%d\t%d\t%s:2\t%s:2\n", chr,start,end,s1,s3); break;
case TRIO_CA:
fprintf(args->fp,"SG\t%s\t%d\t%d\t%s:1\t%s:1\n", chr,start,end,s3,s1); break;
case TRIO_DA:
fprintf(args->fp,"SG\t%s\t%d\t%d\t%s:2\t%s:1\n", chr,start,end,s3,s1); break;
case TRIO_CB:
fprintf(args->fp,"SG\t%s\t%d\t%d\t%s:1\t%s:2\n", chr,start,end,s3,s1); break;
case TRIO_DB:
fprintf(args->fp,"SG\t%s\t%d\t%d\t%s:2\t%s:2\n", chr,start,end,s3,s1); break;
}
if ( hap_switch[state][prev_state] & SW_MOTHER ) nswitch_mother++;
if ( hap_switch[state][prev_state] & SW_FATHER ) nswitch_father++;
}
iprev = i-1;
}
prev_state = state;
}
float mrate = args->nhet_mother>1 ? (float)nswitch_mother/(args->nhet_mother-1) : 0;
float frate = args->nhet_father>1 ? (float)nswitch_father/(args->nhet_father-1) : 0;
fprintf(args->fp,"SW\t%s\t%s\t%d\t%d\t%f\n", s1,bcf_hdr_id2name(args->hdr,args->prev_rid),args->nhet_mother,nswitch_mother,mrate);
fprintf(args->fp,"SW\t%s\t%s\t%d\t%d\t%f\n", s3,bcf_hdr_id2name(args->hdr,args->prev_rid),args->nhet_father,nswitch_father,frate);
args->nsites = 0;
args->nhet_father = args->nhet_mother = 0;
}
void genrich_data::readReferenceGenotypes(string fvcf) {
vector < int > mappingS;
//Opening files
vrb.title("Reading variant list in [" + fvcf + "] MAF=" + stb.str(threshold_maf));
bcf_srs_t * sr = bcf_sr_init();
if(!(bcf_sr_add_reader (sr, fvcf.c_str()))) {
switch (sr->errnum) {
case not_bgzf: vrb.error("File not compressed with bgzip!");
case idx_load_failed: vrb.error("Impossible to load index file!");
case file_type_error: vrb.error("File format not detected by htslib!");
default : vrb.error("Unknown error!");
}
}
//Sample processing
int included_sample = 0;
int n_samples = bcf_hdr_nsamples(sr->readers[0].header);
for (int i = 0 ; i < n_samples ; i ++) {
mappingS.push_back(findSample(string(sr->readers[0].header->samples[i])));
if (mappingS.back() >= 0) included_sample ++;
}
vrb.bullet("#samples = " + stb.str(included_sample));
//Variant processing
unsigned int n_excludedV_mult = 0, n_excludedV_void = 0, n_excludedV_rare = 0, n_excludedV_uchr = 0, n_line = 0, n_excludedV_toofar = 0;
int ngt, ngt_arr = 0, *gt_arr = NULL;
bcf1_t * line;
while(bcf_sr_next_line (sr)) {
line = bcf_sr_get_line(sr, 0);
if (line->n_allele == 2) {
bcf_unpack(line, BCF_UN_STR);
string sid = string(line->d.id);
string chr = string(bcf_hdr_id2name(sr->readers[0].header, line->rid));
int chr_idx = findCHR(chr);
if (chr_idx >= 0) {
unsigned int pos = line->pos + 1;
ngt = bcf_get_genotypes(sr->readers[0].header, line, >_arr, &ngt_arr);
if (ngt == 2*n_samples) {
double freq = 0.0, tot = 0.0;
for(int i = 0 ; i < n_samples ; i ++) {
assert(gt_arr[2*i+0] != bcf_gt_missing && gt_arr[2*i+1] != bcf_gt_missing);
if (mappingS[i] >= 0) {
freq += bcf_gt_allele(gt_arr[2*i+0]) + bcf_gt_allele(gt_arr[2*i+1]);
tot += 2.0;
}
}
double maf = freq / tot;
if (maf > 0.5) maf = 1.0 - maf;
if (maf >= threshold_maf) {
int dist_tss = getDistance(chr_idx, pos);
if (dist_tss < 1e6) {
string tmp_id = chr + "_" + stb.str(pos);
genotype_uuid.insert(pair < string, unsigned int > (tmp_id, genotype_pos.size()));
genotype_chr.push_back(chr_idx);
genotype_pos.push_back(pos);
genotype_maf.push_back(maf);
genotype_dist.push_back(dist_tss);
genotype_haps.push_back(vector < bool > (2 * included_sample, false));
for(int i = 0 ; i < n_samples ; i ++) {
if (mappingS[i] >= 0) {
genotype_haps.back()[2 * mappingS[i] + 0] = bcf_gt_allele(gt_arr[2 * i + 0]);
genotype_haps.back()[2 * mappingS[i] + 1] = bcf_gt_allele(gt_arr[2 * i + 1]);
}
}
} else n_excludedV_toofar++;
} else n_excludedV_rare ++;
} else n_excludedV_void ++;
} else n_excludedV_uchr ++;
} else n_excludedV_mult ++;
if (n_line % 100000 == 0) vrb.bullet("#lines = " + stb.str(n_line));
n_line ++;
}
genotype_qtl = vector < bool > (genotype_pos.size(), false);
genotype_gwas = vector < bool > (genotype_pos.size(), false);
genotype_bin = vector < int > (genotype_pos.size(), -1);
//Finalize
bcf_sr_destroy(sr);
vrb.bullet(stb.str(genotype_pos.size()) + " variants included");
if (n_excludedV_mult > 0) vrb.bullet(stb.str(n_excludedV_mult) + " multi-allelic variants excluded");
if (n_excludedV_uchr > 0) vrb.bullet(stb.str(n_excludedV_uchr) + " variants with unreferenced chromosome in --tss");
if (n_excludedV_rare > 0) vrb.bullet(stb.str(n_excludedV_rare) + " maf filtered variants");
if (n_excludedV_toofar > 0) vrb.bullet(stb.str(n_excludedV_toofar) + " too far variants");
}
