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main.cpp
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main.cpp
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#include "main.hpp"
#include "CmdLineArgs.hpp"
#include "common.hpp"
#include "grouping.hpp"
#include "iohts.hpp"
#include "version.h"
#include "htslib/bgzf.h"
#include "htslib/faidx.h"
#include "htslib/synced_bcf_reader.h"
#include <chrono>
#include <ctime>
#include <future>
#include <thread>
#include <tuple>
#if !defined(USE_STDLIB_THREAD)
#include "omp.h"
#endif
void
xfree(void *ptr) {
if (NULL != ptr) { free(ptr); }
}
template <bool TIsInputCompressed>
int
clearstring(BGZF * bgzip_file, const std::string & outstring_allp, bool is_output_to_stdout = false, bool flush = !TIsInputCompressed) {
if (is_output_to_stdout) {
std::cout << outstring_allp;
return outstring_allp.size();
}
if (NULL == bgzip_file) { return -1; }
int ret = 0;
if (TIsInputCompressed) {
ret = bgzf_raw_write(bgzip_file, outstring_allp.c_str(), outstring_allp.size());
LOG(logINFO) << "Written " << ret << " bytes of compressed data from " << outstring_allp.size() << " bytes of compressed data.";
} else {
ret = bgzf_write(bgzip_file, outstring_allp.c_str(), outstring_allp.size());
LOG(logINFO) << "Written " << ret << " bytes of compressed data from " << outstring_allp.size() << " bytes of raw data.";
}
if (flush) {
int flushret = bgzf_flush(bgzip_file);
if (flushret != 0) {
return flushret;
}
}
return ret;
};
std::string
load_refstring(const faidx_t *ref_faidx, uvc1_refgpos_t tid, uvc1_refgpos_t incbeg, uvc1_refgpos_t excend) {
assertUVC(incbeg < excend);
if (NULL == ref_faidx) {
return std::string(excend - incbeg, 'n');
}
const char *tname = faidx_iseq(ref_faidx, tid);
int regionlen;
char *fetchedseq = faidx_fetch_seq(ref_faidx, tname, incbeg, excend - 1, ®ionlen);
assertUVC (regionlen == (excend - incbeg) || !fprintf(stderr, "%d == %u - %u failed for %s:%d-%d\n", regionlen, excend, incbeg, tname, incbeg, excend));
std::string ret(fetchedseq);
for (size_t i = 0; i < ret.size(); i++) {
ret[i] = toupper(ret[i]);
}
free(fetchedseq);
return ret;
};
template <class TKey, class TVal>
std::vector<std::pair<TKey, TVal>>
map2vector(const std::map<TKey, TVal> & key2val4map) {
std::vector<std::pair<TKey, TVal>> ret;
for (auto kv : key2val4map) {
ret.push_back(kv);
}
return ret;
};
std::map<std::pair<uvc1_refgpos_t, AlignmentSymbol>, std::set<size_t>>
mutform2count4vec_to_simplemut2indices(
std::vector<HapLink> mutform2count4vec) {
std::map<std::pair<uvc1_refgpos_t, AlignmentSymbol>, std::set<size_t>> simplemut2indices;
for (size_t i = 0; i < mutform2count4vec.size(); i++) {
auto counts = mutform2count4vec[i].fr_cnts;
if (counts[0] + counts[1] < 2) { continue; }
std::basic_string<std::pair<uvc1_refgpos_t, AlignmentSymbol>> mutset = mutform2count4vec[i].pos_symb_string;
for (auto simplemut : mutset) {
simplemut2indices.insert(std::make_pair(simplemut, std::set<size_t>()));
simplemut2indices[simplemut].insert(i);
}
}
return simplemut2indices;
};
int
bgzip_string(std::string & compressed_outstring, const std::string & uncompressed_outstring) {
char *compressed_outstr = (char*)malloc(uncompressed_outstring.size() * sizeof(char));
if (NULL == compressed_outstr) {
fprintf(stderr, "The library function malloc failed at line %d in file %s!\n", __LINE__, __FILE__);
exit(-1);
}
size_t compressed_capacity = uncompressed_outstring.size();
size_t compressed_totlen = 0;
size_t uncompress_totlen = 0;
do {
if (compressed_totlen + BGZF_BLOCK_SIZE >= compressed_capacity) {
char *compressed_outstr_tmp = (char*)realloc(compressed_outstr, (compressed_capacity * 2 + BGZF_BLOCK_SIZE) * sizeof(char));
if (NULL == compressed_outstr_tmp) {
fprintf(stderr, "The library function realloc failed at line %d in file %s!\n", __LINE__, __FILE__);
exit(-2);
}
compressed_outstr = compressed_outstr_tmp;
compressed_capacity = compressed_capacity * 2 + BGZF_BLOCK_SIZE;
}
size_t block_len = MIN(uncompressed_outstring.size() - uncompress_totlen, (size_t)BGZF_BLOCK_SIZE);
if (0 == block_len) { break; }
size_t compressed_len = 0;
bgzf_compress(compressed_outstr + compressed_totlen, &compressed_len, uncompressed_outstring.c_str() + uncompress_totlen, block_len, 5);
uncompress_totlen += block_len;
compressed_totlen += compressed_len;
} while (uncompress_totlen < uncompressed_outstring.size());
compressed_outstring += std::string(compressed_outstr, compressed_totlen);
free(compressed_outstr);
return 0;
}
struct BatchArg {
std::array<std::string, NUM_FQLIKE_CON_OUT_FILES> outstring3fastq; // outstring_fastq;
std::string outstring_allp;
std::string outstring_pass;
int thread_id;
samFile *samfile;
hts_idx_t *hts_idx;
faidx_t *ref_faidx;
bcf_hdr_t *bcf_hdr;
bcf_srs_t *sr;
BedLine prev_bedline;
BedLine bedline;
std::tuple<std::string, uint32_t> tname_tseqlen_tuple;
size_t regionbatch_ordinal;
size_t regionbatch_tot_num;
const CommandLineArgs paramset;
const std::string UMI_STRUCT_STRING;
const bool is_vcf_out_pass_to_stdout;
};
std::string
als_to_string(const char *const* const allele, uint32_t n_allele) {
std::string ret;
ret.reserve(n_allele*2);
for (uint32_t i = 0; i < n_allele; i++) {
if (0 == i) {
ret += allele[i];
} else if (1 == i) {
ret += std::string("\t") + allele[i];
} else {
ret += std::string(",") + allele[i];
}
}
return ret;
}
#define assertAlways(x) assert((x));
#define BCF_GET_FORMAT_INT32_WITH_CHECK(v) \
ndst_val = 0; \
valsize = bcf_get_format_int32(bcf_hdr, line, v, &bcfints, &ndst_val); \
assertAlways((2 == ndst_val && 2 == valsize) || !fprintf(stderr, "2 == %d && 2 == %d failed for %s and line %ld!\n", ndst_val, valsize, v, line->pos));
#define BCF_GET_FORMAT_INT32B_WITH_CHECK(k,v) \
ndst_val = 0; \
valsize = bcf_get_format_int32(bcf_hdr, line, v, &bcfints, &ndst_val); \
assertAlways((2 == ndst_val && 2 == valsize) || !fprintf(stderr, "2 == %d && 2 == %d failed for %s and line %ld!\n", ndst_val, valsize, v, line->pos)); \
(k) = (bcfints[0] + bcfints[1]);
template <class T1, class T2, class T3>
const std::map<std::tuple<uvc1_refgpos_t, uvc1_refgpos_t, AlignmentSymbol>, std::vector<TumorKeyInfo>>
rescue_variants_from_vcf(
const T1 & bedlines,
const T2 & tid_to_tname_tlen_tuple_vec,
const std::string & vcf_tumor_fname,
const T3 *bcf_hdr,
const bool is_tumor_format_retrieved) {
std::map<std::tuple<uvc1_refgpos_t, uvc1_refgpos_t, AlignmentSymbol>, std::vector<TumorKeyInfo>> ret;
if (ISNT_PROVIDED(vcf_tumor_fname)) {
return ret;
}
std::string regionstring;
std::string targetstring;
int64_t prev_tid = -1;
int64_t prev_beg = -1;
int64_t prev_end = -1;
for (const auto & bedline : bedlines) {
if (prev_tid != bedline.tid) {
if (prev_tid != -1) {
if (0 < regionstring.size()) { regionstring += std::string(","); }
regionstring += (std::get<0>(tid_to_tname_tlen_tuple_vec[prev_tid]) + ":" + std::to_string(prev_beg+1) + "-" + std::to_string(prev_end+1-1));
}
prev_tid = bedline.tid;
prev_beg = bedline.beg_pos;
}
const uvc1_refgpos_t tid = bedline.tid; // std::get<0>(tid_beg_end_e2e);
const uvc1_refgpos_t rpos_inclu_beg = bedline.beg_pos; // std::get<1>(tid_beg_end_e2e);
const uvc1_refgpos_t rpos_exclu_end = bedline.end_pos; // std::get<2>(tid_beg_end_e2e);
const auto & tname_tseqlen_tuple = tid_to_tname_tlen_tuple_vec[tid];
if (0 < targetstring.size()) { targetstring += std::string(","); }
std::string targetspec = (std::get<0>(tname_tseqlen_tuple) + ":" + std::to_string(rpos_inclu_beg+1) + "-" + std::to_string(rpos_exclu_end+1-1));
targetstring += targetspec;
prev_end = bedline.end_pos;
}
if (prev_tid != -1) {
if (0 < regionstring.size()) { regionstring += std::string(","); }
regionstring += (std::get<0>(tid_to_tname_tlen_tuple_vec[prev_tid]) + ":" + std::to_string(prev_beg+1) + "-" + std::to_string(prev_end+1-1));
}
{
LOG(logINFO) << "BCF region is " << regionstring;
LOG(logINFO) << "BCF target is " << targetstring;
}
if (targetstring.size() == 0) {
return ret;
}
bcf_srs_t *const sr = bcf_sr_init();
if (NULL == sr) {
LOG(logCRITICAL) << "Failed to initialize bcf sr";
exit(-6);
}
bcf_sr_set_regions(sr, regionstring.c_str(), false);
bcf_sr_set_targets(sr, targetstring.c_str(), false, 0);
int sr_set_opt_retval = bcf_sr_set_opt(sr, BCF_SR_REQUIRE_IDX);
if (sr_set_opt_retval < 0) {
LOG(logCRITICAL) << "The validation of the index file for the tumor vcf " << vcf_tumor_fname << " failed with return code " << sr_set_opt_retval;
exit(-8);
}
int sr_add_reader_retval = bcf_sr_add_reader(sr, vcf_tumor_fname.c_str());
if (sr_add_reader_retval != 1) {
LOG(logCRITICAL) << "Failed to synchronize-read the tumor vcf " << vcf_tumor_fname << " with return code " << sr_add_reader_retval;
exit(-9);
}
int valsize = 0;
int ndst_val = 0;
char *bcfstring = NULL;
float *bcffloats = NULL;
int32_t *bcfints = NULL;
while (bcf_sr_next_line(sr)) {
bcf1_t *line = bcf_sr_get_line(sr, 0);
bcf_unpack(line, BCF_UN_ALL);
// skip over all symbolic alleles except MGVCF_SYMBOL and ADDITIONAL_INDEL_CANDIDATE_SYMBOL
bool should_continue = false;
for (uint32_t i = 1; i < line->n_allele; i++) {
if ('<' == line->d.allele[i][0] && ((strcmp("<NON_REF>", line->d.allele[i]) && strcmp("<ADDITIONAL_INDEL_CANDIDATE>", line->d.allele[i])) || !is_tumor_format_retrieved)) {
should_continue = true;
}
}
if (should_continue) { continue; }
ndst_val = 0;
valsize = bcf_get_format_int32(bcf_hdr, line, "VTI", &bcfints, &ndst_val);
if (valsize <= 0) { continue; }
assertUVC((2 == ndst_val && 2 == valsize) || !fprintf(stderr, "2 == %d && 2 == %d failed for VTI and line %ld!\n", ndst_val, valsize, line->pos));
assertUVC((2 == line->n_allele) || !fprintf(stderr, "Bcf line %ld has %d alleles!\n", line->pos, line->n_allele));
const AlignmentSymbol symbol = AlignmentSymbol(bcfints[1]);
auto symbolpos = ((isSymbolSubstitution(symbol) || MGVCF_SYMBOL == symbol || ADDITIONAL_INDEL_CANDIDATE_SYMBOL == symbol) ? (line->pos) : (line->pos + 1));
TumorKeyInfo tki;
tki.VTI = bcfints[1];
if (MGVCF_SYMBOL == symbol) {
LOG(logINFO) << "gVCFblock with pos " << symbolpos << " was retrieved";
}
if (ADDITIONAL_INDEL_CANDIDATE_SYMBOL == symbol) {
LOG(logINFO) << "ADDITIONAL_INDEL_CANDIDATE symbol with pos " << symbolpos << " was retrieved";
}
if (MGVCF_SYMBOL != symbol && ADDITIONAL_INDEL_CANDIDATE_SYMBOL != symbol) {
BCF_GET_FORMAT_INT32B_WITH_CHECK(tki.BDP, "BDPb");
/*
ndst_val = 0;
valsize = bcf_get_format_int32(bcf_hdr, line, "BDPf", &bcfints, &ndst_val);
assertAlways((2 == ndst_val && 2 == valsize) || !fprintf(stderr, "2 == %d && 2 == %d failed for BDPf and line %ld!\n", ndst_val, valsize, line->pos));
tki.BDP = bcfints[0];
ndst_val = 0;
valsize = bcf_get_format_int32(bcf_hdr, line, "BDPr", &bcfints, &ndst_val);
assertAlways((2 == ndst_val && 2 == valsize) || !fprintf(stderr, "2 == %d && 2 == %d failed for BDPr and line %ld!\n", ndst_val, valsize, line->pos));
tki.BDP += bcfints[0];
*/
ndst_val = 0;
valsize = bcf_get_format_int32(bcf_hdr, line, "bDPf", &bcfints, &ndst_val);
assertAlways((2 == ndst_val && 2 == valsize) || !fprintf(stderr, "2 == %d && 2 == %d failed for bDPf and line %ld!\n", ndst_val, valsize, line->pos));
tki.bDP = bcfints[1];
ndst_val = 0;
valsize = bcf_get_format_int32(bcf_hdr, line, "bDPr", &bcfints, &ndst_val);
assertAlways((2 == ndst_val && 2 == valsize) || !fprintf(stderr, "2 == %d && 2 == %d failed for bDPr and line %ld!\n", ndst_val, valsize, line->pos));
tki.bDP += bcfints[1];
ndst_val = 0;
valsize = bcf_get_format_int32(bcf_hdr, line, "CDP1x", &bcfints, &ndst_val);
assertAlways((2 == ndst_val && 2 == valsize) || !fprintf(stderr, "2 == %d && 2 == %d failed for CDP1x and line %ld!\n", ndst_val, valsize, line->pos));
tki.CDP1x = bcfints[0];
ndst_val = 0;
valsize = bcf_get_format_int32(bcf_hdr, line, "cDP1x", &bcfints, &ndst_val);
assertAlways((2 == ndst_val && 2 == valsize) || !fprintf(stderr, "2 == %d && 2 == %d failed for cDP1x and line %ld!\n", ndst_val, valsize, line->pos));
tki.cDP1x = bcfints[1];
ndst_val = 0;
valsize = bcf_get_format_int32(bcf_hdr, line, "cVQ1", &bcfints, &ndst_val);
assertAlways((2 == ndst_val && 2 == valsize) || !fprintf(stderr, "2 == %d && 2 == %d failed for cVQ1 and line %ld!\n", ndst_val, valsize, line->pos));
tki.cVQ1 = bcfints[1];
ndst_val = 0;
valsize = bcf_get_format_int32(bcf_hdr, line, "cPCQ1", &bcfints, &ndst_val);
assertAlways((2 == ndst_val && 2 == valsize) || !fprintf(stderr, "2 == %d && 2 == %d failed for cPCQ1 and line %ld!\n", ndst_val, valsize, line->pos));
tki.cPCQ1 = bcfints[1];
ndst_val = 0;
valsize = bcf_get_format_int32(bcf_hdr, line, "CDP2x", &bcfints, &ndst_val);
assertAlways((2 == ndst_val && 2 == valsize) || !fprintf(stderr, "2 == %d && 2 == %d failed for CDP2x and line %ld!\n", ndst_val, valsize, line->pos));
tki.CDP2x = bcfints[0];
ndst_val = 0;
valsize = bcf_get_format_int32(bcf_hdr, line, "cDP2x", &bcfints, &ndst_val);
assertAlways((2 == ndst_val && 2 == valsize) || !fprintf(stderr, "2 == %d && 2 == %d failed for cDP2x and line %ld!\n", ndst_val, valsize, line->pos));
tki.cDP2x = bcfints[1];
ndst_val = 0;
valsize = bcf_get_format_int32(bcf_hdr, line, "cVQ2", &bcfints, &ndst_val);
assertAlways((2 == ndst_val && 2 == valsize) || !fprintf(stderr, "2 == %d && 2 == %d failed for cVQ2 and line %ld!\n", ndst_val, valsize, line->pos));
tki.cVQ2 = bcfints[1];
ndst_val = 0;
valsize = bcf_get_format_int32(bcf_hdr, line, "cPCQ2", &bcfints, &ndst_val);
assertAlways((2 == ndst_val && 2 == valsize) || !fprintf(stderr, "2 == %d && 2 == %d failed for cPCQ2 and line %ld!\n", ndst_val, valsize, line->pos));
tki.cPCQ2 = bcfints[1];
ndst_val = 0;
valsize = bcf_get_format_int32(bcf_hdr, line, "bNMQ", &bcfints, &ndst_val);
assertAlways((2 == ndst_val && 2 == valsize) || !fprintf(stderr, "2 == %d && 2 == %d failed for bNMQ and line %ld!\n", ndst_val, valsize, line->pos));
tki.bNMQ = bcfints[1];
ndst_val = 0;
valsize = bcf_get_format_int32(bcf_hdr, line, "vHGQ", &bcfints, &ndst_val);
assertAlways((1 == ndst_val && 1 == valsize) || !fprintf(stderr, "1 == %d && 1 == %d failed for vHGQ and line %ld!\n", ndst_val, valsize, line->pos));
tki.vHGQ = bcfints[0];
// extra code for backward compatibility
BCF_GET_FORMAT_INT32B_WITH_CHECK(tki.tDP, "CDP1b");
BCF_GET_FORMAT_INT32_WITH_CHECK("cDP1f");
tki.tADR = {{ bcfints[0], bcfints[1] }};
BCF_GET_FORMAT_INT32_WITH_CHECK("cDP1r");
for (int i = 0; i < 2; i++) { tki.tADR[i] += bcfints[i]; }
BCF_GET_FORMAT_INT32B_WITH_CHECK(tki.tDPC, "CDP2b");
BCF_GET_FORMAT_INT32_WITH_CHECK("cDP2f");
tki.tADCR = {{ bcfints[0], bcfints[1] }};
BCF_GET_FORMAT_INT32_WITH_CHECK("cDP2r");
for (int i = 0; i < 2; i++) { tki.tADCR[i] += bcfints[i]; }
}
tki.pos = line->pos;
tki.ref_alt = als_to_string(line->d.allele, line->n_allele);
if (is_tumor_format_retrieved) {
tki.bcf1_record = bcf_dup(line);
}
ndst_val = 0;
valsize = bcf_get_format_char(bcf_hdr, line, "_C2XP", &bcfstring, &ndst_val);
tki.enable_tier2_consensus_format_tags = (valsize > 0);
const auto retkey = std::make_tuple(line->rid, symbolpos, symbol);
ret.insert(std::make_pair(retkey, std::vector<TumorKeyInfo>()));
ret[retkey].push_back(tki);
}
xfree(bcfstring);
xfree(bcfints);
xfree(bcffloats);
bcf_sr_destroy(sr);
return ret;
}
template <bool TIsAnyTandemRepeat = false>
CoveredRegion<uvc1_qual_big_t>
region_repeatvec_to_baq_offsetarr(
const std::vector<RegionalTandemRepeat> & region_repeatvec,
uvc1_refgpos_t tid,
uvc1_refgpos_t extended_inclu_beg_pos,
uvc1_refgpos_t extended_exclu_end_pos,
const CommandLineArgs & paramset) {
auto ret = CoveredRegion<uvc1_qual_big_t>(tid, extended_inclu_beg_pos, extended_exclu_end_pos);
uvc1_qual_big_t baq_prefixsum = 0;
for (auto i = extended_inclu_beg_pos; i < extended_exclu_end_pos; i++) {
auto rtr_idx = i - extended_inclu_beg_pos;
const auto & rtr = region_repeatvec[rtr_idx];
const auto tracklen2 = (TIsAnyTandemRepeat ? rtr.anyTR_tracklen : rtr.tracklen);
assertUVC (rtr.begpos <= rtr_idx);
assertUVC (rtr.unitlen > 0);
assertUVC (tracklen2 >= rtr.unitlen);
if (tracklen2 / rtr.unitlen >= 3 || (tracklen2 / rtr.unitlen >= 2 && tracklen2 >= (uvc1_readpos_t)round(paramset.indel_polymerase_size))) {
baq_prefixsum += (paramset.indel_str_phred_per_region * 10) / (tracklen2) + 1;
ret.getRefByPos(i) = baq_prefixsum;
} else {
baq_prefixsum += paramset.indel_nonSTR_phred_per_base * 10;
ret.getRefByPos(i) = baq_prefixsum;
}
}
for (auto i = extended_inclu_beg_pos; i < extended_exclu_end_pos; i++) {
ret.getRefByPos(i) /= 10;
}
return ret;
}
bool
are_depths_diff(uvc1_readnum_t currDP, uvc1_readnum_t prevDP, uvc1_readnum_t mul_perc_ratio, uvc1_readnum_t add_num_ratio) {
const uvc1_readnum_t minDP = MIN(currDP, prevDP);
const uvc1_readnum_t maxDP = MAX(currDP, prevDP);
if (minDP * mul_perc_ratio >= maxDP * 100) {
return false;
}
if (minDP + add_num_ratio >= maxDP) {
return false;
}
return true;
}
void
umi_strand_readset_uvc_destroy(auto & umi_strand_readset) {
for (auto strand_readset : umi_strand_readset) {
for (int strand = 0; strand < 2; strand++) {
auto readset = strand_readset.first[strand];
for (auto read : readset) {
for (bam1_t *b : read) {
bam_destroy1(b);
}
}
}
}
}
template <class T>
int
process_batch(
std::string & uncompressed_vcf_string,
std::array<std::string, NUM_FQLIKE_CON_OUT_FILES> & uncompressed_3fastq_string,
BatchArg & arg,
const T & tid_pos_symb_to_tkis) {
const faidx_t *const ref_faidx = arg.ref_faidx;
const bcf_hdr_t *const bcf_hdr = arg.bcf_hdr;
const CommandLineArgs & paramset = arg.paramset;
const std::string UMI_STRUCT_STRING = arg.UMI_STRUCT_STRING;
const BedLine bedline = arg.bedline;
const std::tuple<std::string, uvc1_refgpos_t> tname_tseqlen_tuple = arg.tname_tseqlen_tuple;
const auto regionbatch_ordinal = arg.regionbatch_ordinal;
const auto regionbatch_tot_num = arg.regionbatch_tot_num;
const auto thread_id = arg.thread_id;
bool is_loginfo_enabled = (ispowerof2(regionbatch_ordinal + 1) || ispowerof2(regionbatch_tot_num - regionbatch_ordinal) || paramset.always_log);
std::string raw_out_string;
std::string raw_out_string_pass;
auto tid = bedline.tid;
const auto incluBegPosition = bedline.beg_pos;
const auto excluEndPosition = bedline.end_pos;
bool end2end = (bedline.region_flag & BED_END_TO_END_BIT);
std::map<MolecularBarcode, std::pair<std::array<std::map<uvc1_hash_t, std::vector<bam1_t *>>, 2>, MolecularBarcode>> umi_to_strand_to_reads;
uvc1_refgpos_t bam_inclu_beg_pos, bam_exclu_end_pos;
std::vector<std::pair<std::array<std::vector<std::vector<bam1_t *>>, 2>, MolecularBarcode>> umi_strand_readset;
if (is_loginfo_enabled) { LOG(logINFO) << "Thread " << thread_id << " starts bamfname_to_strand_to_familyuid_to_reads with pair_end_merge = " << paramset.pair_end_merge; }
std::array<uvc1_readnum_big_t, 3> passed_pcrpassed_umipassed = bamfname_to_strand_to_familyuid_to_reads(
umi_to_strand_to_reads,
bam_inclu_beg_pos,
bam_exclu_end_pos,
tid,
incluBegPosition,
excluEndPosition,
end2end,
regionbatch_ordinal,
regionbatch_tot_num,
UMI_STRUCT_STRING,
arg.samfile,
arg.hts_idx,
thread_id,
paramset,
0);
const auto num_passed_reads = passed_pcrpassed_umipassed[0]; // -1 means that min read depth is not satisfied.
const auto num_pcrpassed_reads = passed_pcrpassed_umipassed[1];
const bool is_by_capture = ((num_pcrpassed_reads) * 2 <= num_passed_reads);
const AssayType inferred_assay_type = ((ASSAY_TYPE_AUTO == paramset.assay_type) ? (is_by_capture ? ASSAY_TYPE_CAPTURE : ASSAY_TYPE_AMPLICON) : (paramset.assay_type));
if (is_loginfo_enabled) { LOG(logINFO) << "Thread " << thread_id << " starts converting umi_to_strand_to_reads with is_by_capture = " << is_by_capture << " " ;}
fill_strand_umi_readset_with_strand_to_umi_to_reads(
umi_strand_readset,
umi_to_strand_to_reads,
paramset,
0); // bigger region
if ((0 == num_passed_reads) || (-1 == num_passed_reads)) {
umi_strand_readset_uvc_destroy(umi_strand_readset);
return -1;
};
const uvc1_qual_t minABQ_snv = ((ASSAY_TYPE_AMPLICON == inferred_assay_type) ? paramset.syserr_minABQ_pcr_snv : paramset.syserr_minABQ_cap_snv);
const uvc1_qual_t minABQ_indel = ((ASSAY_TYPE_AMPLICON == inferred_assay_type) ? paramset.syserr_minABQ_pcr_indel : paramset.syserr_minABQ_cap_indel);
const uvc1_refgpos_t rpos_inclu_beg = MAX(incluBegPosition, bam_inclu_beg_pos);
const uvc1_refgpos_t rpos_exclu_end = MIN(excluEndPosition, bam_exclu_end_pos);
const uvc1_refgpos_t extended_inclu_beg_pos = MAX(0, non_neg_minus(MIN(incluBegPosition, bam_inclu_beg_pos), MAX_STR_N_BASES));
const uvc1_refgpos_t extended_exclu_end_pos = MIN(std::get<1>(tname_tseqlen_tuple), MAX(excluEndPosition, bam_exclu_end_pos) + MAX_STR_N_BASES);
const auto tkis_beg = tid_pos_symb_to_tkis.lower_bound(std::make_tuple(tid, extended_inclu_beg_pos , AlignmentSymbol(0)));
const auto tkis_end = tid_pos_symb_to_tkis.upper_bound(std::make_tuple(tid, extended_exclu_end_pos + 1, AlignmentSymbol(0)));
std::vector<bool> extended_posidx_to_is_rescued(extended_exclu_end_pos - extended_inclu_beg_pos + 1, false);
int num_rescued = 0;
for (auto tkis_it = tkis_beg; tkis_it != tkis_end; tkis_it++) {
auto symbolpos = std::get<1>(tkis_it->first);
extended_posidx_to_is_rescued[symbolpos - extended_inclu_beg_pos] = true;
num_rescued++;
if (is_loginfo_enabled) {
// The short deletion at 22:17946835 in NA12878-NA24385 mixture is overwhelmed by the false positve long del spanning the true positive short del.
// Due to the VCF specs and left alignment as best practice, the symmetry between left and right alignments are broken.
// Thus, this variant is true positive if using left alignemnt but false positive if using right alignment.
// TODO: modifications to the VCF specs or somatic-variant definitions, which is beyond the scope of this program.
LOG(logDEBUG4) << "Thread " << thread_id << " iterated over symbolpos " << symbolpos << " and symbol " << std::get<2>(tkis_it->first) << " as a rescued var";
}
} // bigger region
if (is_loginfo_enabled) { LOG(logINFO) << "Thread " << thread_id << " deals with " << num_rescued << " tumor-sample variants in region " << extended_inclu_beg_pos << " to " << extended_exclu_end_pos + 1 ;}
if (is_loginfo_enabled) { LOG(logINFO) << "Thread " << thread_id << " starts constructing symbolToCountCoverageSet12 with " << extended_inclu_beg_pos << (" , ") << extended_exclu_end_pos; }
// + 1 accounts for insertion at the end of the region, this should happen rarely for only re-aligned reads at around once per one billion base pairs
if (is_loginfo_enabled) { LOG(logINFO)<< "Thread " << thread_id << " starts updateByRegion3Aln with " << umi_strand_readset.size() << " families"; }
const std::string refstring = load_refstring(ref_faidx, tid, extended_inclu_beg_pos, extended_exclu_end_pos);
std::vector<RegionalTandemRepeat> region_repeatvec = refstring2repeatvec(
refstring,
paramset.indel_str_repeatsize_max,
paramset.indel_vntr_repeatsize_max, // https://en.wikipedia.org/wiki/Variable_number_tandem_repeat
paramset.indel_BQ_max,
paramset.indel_polymerase_slip_rate,
paramset.indel_del_to_ins_err_ratio,
0);
const auto & baq_offsetarr = region_repeatvec_to_baq_offsetarr(region_repeatvec, tid, extended_inclu_beg_pos, extended_exclu_end_pos + 1, paramset);
const auto & baq_offsetarr2 = region_repeatvec_to_baq_offsetarr<true>(region_repeatvec, tid, extended_inclu_beg_pos, extended_exclu_end_pos + 1, paramset);
assertUVC(((baq_offsetarr.getExcluEndPosition() - baq_offsetarr.getIncluBegPosition()) == UNSIGN2SIGN(region_repeatvec.size()))
|| !fprintf(stderr, "%d - %d == %lu failed (baq == repeat in size)!\n", baq_offsetarr.getExcluEndPosition(), baq_offsetarr.getIncluBegPosition(), region_repeatvec.size()));
// begin of smaller regions
Symbol2CountCoverageSet symbolToCountCoverageSet12(tid, extended_inclu_beg_pos, extended_exclu_end_pos + 1);
std::vector<HapLink> mutform2count4vec_bq;
std::vector<HapLink> mutform2count4vec_fq;
std::vector<HapLink> mutform2count4vec_f2q;
std::array<std::string, NUM_FQLIKE_CON_OUT_FILES> fqdata3;
symbolToCountCoverageSet12.updateByRegion3Aln(
fqdata3,
mutform2count4vec_bq,
mutform2count4vec_fq,
mutform2count4vec_f2q,
umi_strand_readset,
refstring,
region_repeatvec,
baq_offsetarr,
baq_offsetarr2,
arg.prev_bedline,
arg.bedline,
paramset,
0);
std::string buf_out_string_pass;
if (paramset.inferred_is_vcf_generated) {
if (is_loginfo_enabled) { LOG(logINFO) << "Thread " << thread_id << " starts analyzing phasing info"; }
auto simplemut2indices_bq = mutform2count4vec_to_simplemut2indices(mutform2count4vec_bq);
auto simplemut2indices_fq = mutform2count4vec_to_simplemut2indices(mutform2count4vec_fq);
auto simplemut2indices_f2q = mutform2count4vec_to_simplemut2indices(mutform2count4vec_f2q);
if (is_loginfo_enabled) { LOG(logINFO) << "Thread " << thread_id << " starts generating block gzipped vcf"; }
const std::set<size_t> empty_size_t_set;
uvc1_readpos_t prev_tracklen = 0;
uvc1_readpos_t curr_tracklen = 0;
for (uvc1_refgpos_t zerobased_pos = rpos_inclu_beg; zerobased_pos <= rpos_exclu_end; zerobased_pos++, prev_tracklen = curr_tracklen) {
std::string repeatunit;
uvc1_readpos_t repeatnum = 0;
uvc1_rp_diff_t rridx = zerobased_pos - extended_inclu_beg_pos;
indelpos_to_context(repeatunit, repeatnum, refstring, rridx, paramset.indel_str_repeatsize_max);
curr_tracklen = repeatnum * UNSIGN2SIGN(repeatunit.size());
const std::array<AlignmentSymbol, 2> symboltype_to_refsymbol = {{
((UNSIGN2SIGN(refstring.size()) == ((zerobased_pos - 1) - extended_inclu_beg_pos) || (-1 == ((zerobased_pos - 1) - extended_inclu_beg_pos)))
? BASE_NN : CHAR_TO_SYMBOL.data.at(refstring.at((zerobased_pos - 1) - extended_inclu_beg_pos))),
LINK_M,
}};
const auto refsize = UNSIGN2SIGN(refstring.size());
const auto refidx = zerobased_pos - extended_inclu_beg_pos;
const AlignmentSymbol prev_base1 = ((refidx >= 2 ) ? CHAR_TO_SYMBOL.data.at(refstring.at((refidx - 2))) : BASE_NN);
const AlignmentSymbol prev_base2 = ((refidx >= 3 ) ? CHAR_TO_SYMBOL.data.at(refstring.at((refidx - 3))) : BASE_NN);
const AlignmentSymbol next_base1 = ((refidx < refsize) ? CHAR_TO_SYMBOL.data.at(refstring.at((refidx))) : BASE_NN);
const AlignmentSymbol next_base2 = ((refidx + 1 < refsize) ? CHAR_TO_SYMBOL.data.at(refstring.at((refidx + 1))) : BASE_NN);
std::array<bcfrec::BcfFormat, 2> st_to_init_fmt = {{bcfrec::BcfFormat(), bcfrec::BcfFormat()}};
std::array<std::vector<std::tuple<bcfrec::BcfFormat, TumorKeyInfo>>, NUM_SYMBOL_TYPES> st_to_fmt_tki_tup_vec;
uvc1_readnum_t ins_bdepth = 0;
uvc1_readnum_t del_bdepth = 0;
uvc1_readnum_t ins_cdepth = 0;
uvc1_readnum_t del_cdepth = 0;
uvc1_readnum_t ins1_bdepth = 0;
uvc1_readnum_t del1_bdepth = 0;
uvc1_readnum_t ins1_cdepth = 0;
uvc1_readnum_t del1_cdepth = 0;
for (const SymbolType symboltype : SYMBOL_TYPE_ARR)
{
if (zerobased_pos == rpos_inclu_beg && BASE_SYMBOL == symboltype) { continue; }
const uvc1_refgpos_t refpos = (BASE_SYMBOL == symboltype ? (zerobased_pos - 1) : zerobased_pos);
TumorKeyInfo THE_DUMMY_TUMOR_KEY_INFO;
const AlignmentSymbol refsymbol = symboltype_to_refsymbol[symboltype];
std::array<uvc1_readnum_t, 2> bDPcDP = BcfFormat_symboltype_init(
st_to_init_fmt[symboltype],
symbolToCountCoverageSet12,
refpos,
symboltype,
refsymbol,
0);
if ((paramset.outvar_flag & OUTVAR_MGVCF) && ((((refpos) % MGVCF_REGION_MAX_SIZE) == 0)
|| (refpos == incluBegPosition)) && (SYMBOL_TYPE_ARR[0] == symboltype)) {
const auto & frag_format_depth_sets = symbolToCountCoverageSet12.symbol_to_frag_format_depth_sets;
const auto & fam_format_depth_sets = symbolToCountCoverageSet12.symbol_to_fam_format_depth_sets_2strand;
const uvc1_qual_t init_refQ = (INT_MAX / 2 + 1);
uvc1_readnum_t prev_tot_bdepth = 0;
uvc1_readnum_t prev_tot_cdepth = 0;
uvc1_readnum_t prev_tot_cdep12 = 0;
uvc1_qual_t prev_refQ = init_refQ;
std::vector<uvc1_rp_diff_t> pos_stype_BDP_CDP_refQ_1dvec;
const auto rp2end = MIN(refpos + MGVCF_REGION_MAX_SIZE + 1, symbolToCountCoverageSet12.getUnifiedExcluEndPosition());
for (uvc1_refgpos_t rp2 = refpos; rp2 < rp2end; rp2++) {
for (SymbolType stype : SYMBOL_TYPES_IN_VCF_ORDER) {
const uvc1_rp_diff_t refstring_offset = rp2 - extended_inclu_beg_pos;
if (refstring_offset > UNSIGN2SIGN(refstring.size())) {
fprintf(stderr, "The refstring offset %d at tid %d pos %d is invalid!\n\n", refstring_offset, tid, refpos);
abort();
}
const AlignmentSymbol base_m = ((refstring_offset < UNSIGN2SIGN(refstring.size()))
? CHAR_TO_SYMBOL.data[refstring.substr(refstring_offset, 1)[0]]
: BASE_N);
const auto refsymbol = ((BASE_SYMBOL == stype) ? (base_m) : (LINK_M));
uvc1_readnum_t curr_tot_bdepth = 0;
uvc1_readnum_t curr_tot_cdepth = 0;
uvc1_readnum_t curr_tot_cdep12 = 0;
for (int strand = 0; strand < 2; strand++) {
curr_tot_bdepth += formatSumBySymbolType(frag_format_depth_sets[strand].getByPos(rp2), stype, FRAG_bDP);
curr_tot_cdepth += formatSumBySymbolType(fam_format_depth_sets[strand].getByPos(rp2), stype, FAM_cDP1);
curr_tot_cdep12 += formatSumBySymbolType(fam_format_depth_sets[strand].getByPos(rp2), stype, FAM_cDP12);
}
const auto ref_cdepth =
fam_format_depth_sets[0].getByPos(rp2)[refsymbol][FAM_cDP12] +
fam_format_depth_sets[1].getByPos(rp2)[refsymbol][FAM_cDP12];
const auto nonref_cdepth = curr_tot_cdep12 - ref_cdepth;
// contam, lower nonref-FA -> close to zero qual
const auto ref_like_binom = -calc_binom_10log10_likeratio(paramset.contam_any_mul_frac, nonref_cdepth + 0.5, curr_tot_cdepth + 1.0);
const auto ref_like_powlaw = -MAX(0, paramset.powlaw_exponent * (10/log(10))
* logit2((nonref_cdepth + 0.5) / (curr_tot_cdepth + 1.0), paramset.contam_any_mul_frac));
// hetero, higher nonref-FA (lower ref-FA) -> close to zero qual
const auto nonref_like_binom = -calc_binom_10log10_likeratio(paramset.germ_hetero_FA, ref_cdepth + 0.5, curr_tot_cdepth + 1.0);
const auto nonref_like_powlaw = -MAX(0, paramset.powlaw_exponent * (10/log(10))
* logit2((ref_cdepth + 0.5) / (curr_tot_cdepth + 1.0), paramset.germ_hetero_FA));
const uvc1_qual_t curr_refQ = paramset.germ_phred_hetero_snp
+ (uvc1_qual_t)round(MAX(ref_like_binom, ref_like_powlaw)
- (uvc1_qual_t)round(MAX(nonref_like_binom, nonref_like_powlaw)));
if ((init_refQ == prev_refQ) || (abs(curr_refQ - prev_refQ) > 10)
|| are_depths_diff(curr_tot_bdepth, prev_tot_bdepth, 100 + 30, 3)
|| are_depths_diff(curr_tot_cdepth, prev_tot_cdepth, 100 + 30, 3)
|| are_depths_diff(curr_tot_cdep12, prev_tot_cdep12, 100 + 30, 3)) {
pos_stype_BDP_CDP_refQ_1dvec.push_back(rp2 + ((BASE_SYMBOL == stype) ? (1) : (0)));
pos_stype_BDP_CDP_refQ_1dvec.push_back(1+(int32_t)stype);
pos_stype_BDP_CDP_refQ_1dvec.push_back(INT32_MIN);
pos_stype_BDP_CDP_refQ_1dvec.push_back(curr_tot_bdepth);
pos_stype_BDP_CDP_refQ_1dvec.push_back(curr_tot_cdepth);
pos_stype_BDP_CDP_refQ_1dvec.push_back(curr_tot_cdep12);
pos_stype_BDP_CDP_refQ_1dvec.push_back(curr_refQ);
pos_stype_BDP_CDP_refQ_1dvec.push_back(INT32_MIN);
prev_tot_bdepth = curr_tot_bdepth;
prev_tot_cdepth = curr_tot_cdepth;
prev_tot_cdep12 = curr_tot_cdep12;
prev_refQ = curr_refQ;
}
}
}
const auto vcfREF = refstring.substr(refpos - extended_inclu_beg_pos, 1);
const AlignmentSymbol match_refsymbol = CHAR_TO_SYMBOL.data[vcfREF[0]];
const std::string gvcf_blockline = string_join(std::vector<std::string>{{
std::get<0>(tname_tseqlen_tuple),
std::to_string(refpos + 1),
std::string("."),
vcfREF,
std::string("<NON_REF>"),
std::string("."),
std::string("."),
std::string("MGVCF_BLOCK"),
std::string("GT:VTI:POS_VT_BDP_CDP_HomRefQ"),
std::string(".") + ":" + std::to_string(match_refsymbol) + "," + std::to_string(MGVCF_SYMBOL) + ":"
+ int32t_join(pos_stype_BDP_CDP_refQ_1dvec, ",") + "," + std::to_string(rp2end),
}}, "\t");
std::string tumor_gvcf_format = "";
if (paramset.is_tumor_format_retrieved && IS_PROVIDED(paramset.vcf_tumor_fname)) {
const auto tkis_it = tid_pos_symb_to_tkis.find(std::make_tuple(tid, refpos, MGVCF_SYMBOL));
if (tkis_it != tid_pos_symb_to_tkis.end()) {
const auto & tkis = tid_pos_symb_to_tkis.find(std::make_tuple(tid, refpos, MGVCF_SYMBOL))->second;
if (tkis.size() == 1) {
tumor_gvcf_format = bcf1_to_string(bcf_hdr, tkis[0].bcf1_record);
LOG(logDEBUG4) << "gVCFblock at " << refpos << " is indeed found, tumor_gvcf_format == " << tumor_gvcf_format;
} else {
tumor_gvcf_format = std::string("\t.:.,.:-1");
LOG(logDEBUG4) << "gVCFblock at " << refpos << " is not found, tkis.size() == " << tkis.size();
}
} else {
tumor_gvcf_format = std::string("\t.:.,.:.");
LOG(logDEBUG4) << "gVCFblock at " << refpos << " is not found at all.";
}
}
buf_out_string_pass += gvcf_blockline + tumor_gvcf_format + "\n";
}
const auto aCDP = symbolToCountCoverageSet12.seg_format_prep_sets.getByPos(refpos).segprep_a_near_long_clip_dp;
const auto ADP = symbolToCountCoverageSet12.seg_format_prep_sets.getByPos(refpos).segprep_a_dp;
const bool is_in_long_track = (curr_tracklen > MAX(paramset.microadjust_alignment_tracklen_min - 1, prev_tracklen));
const bool is_in_clip_region = ((aCDP >= paramset.microadjust_alignment_clip_min_count)
&& (aCDP >= ADP * (paramset.microadjust_alignment_clip_min_frac - DBL_EPSILON)));
if ((OUTVAR_ADDITIONAL_INDEL_CANDIDATE & paramset.outvar_flag)
&& (SYMBOL_TYPE_ARR[0] == symboltype)
&& (is_in_long_track || is_in_clip_region)
&& (ADP >= 2 * paramset.microadjust_alignment_clip_min_count)) {
const auto vcfREF = refstring.substr(refpos - extended_inclu_beg_pos, 1);
const AlignmentSymbol match_refsymbol = CHAR_TO_SYMBOL.data[vcfREF[0]];
const std::string vcfline = string_join(std::vector<std::string>{{
std::get<0>(tname_tseqlen_tuple), // chrom
std::to_string(refpos + 1), // pos
std::string("."), // id
vcfREF, // ref
SYMBOL_TO_DESC_ARR[ADDITIONAL_INDEL_CANDIDATE_SYMBOL], // alt
std::string("."), // qual
std::string("."), // filter
(std::string("ADDITIONAL_INDEL_CANDIDATE;RU=") + repeatunit + ";RC=" + std::to_string(repeatnum)), // info
std::string("GT:VTI:clipDP"), // format
std::string(".") + ":" + std::to_string(match_refsymbol) + "," + std::to_string(ADDITIONAL_INDEL_CANDIDATE_SYMBOL)
+ ":" + std::to_string(ADP) + "," + std::to_string(aCDP) // format values
}}, "\t");
std::string tumor_format = "";
if (paramset.is_tumor_format_retrieved && IS_PROVIDED(paramset.vcf_tumor_fname)) {
const auto tkis_it = tid_pos_symb_to_tkis.find(std::make_tuple(tid, refpos, ADDITIONAL_INDEL_CANDIDATE_SYMBOL));
if (tkis_it != tid_pos_symb_to_tkis.end()) {
const auto & tkis = tid_pos_symb_to_tkis.find(std::make_tuple(tid, refpos, ADDITIONAL_INDEL_CANDIDATE_SYMBOL))->second;
if (tkis.size() == 1) {
tumor_format = bcf1_to_string(bcf_hdr, tkis[0].bcf1_record);
} else {
tumor_format = std::string("\t.:-1,-1:-1,-1");
}
} else {
tumor_format = std::string("\t.:.,.:.,.");
}
}
buf_out_string_pass += vcfline + tumor_format + "\n";
}
const auto ref_bdepth =
symbolToCountCoverageSet12.symbol_to_frag_format_depth_sets[0].getByPos(refpos)[refsymbol][FRAG_bDP]
+ symbolToCountCoverageSet12.symbol_to_frag_format_depth_sets[1].getByPos(refpos)[refsymbol][FRAG_bDP];
for (AlignmentSymbol symbol : SYMBOL_TYPE_TO_SYMBOLS[symboltype])
{
const bool is_pos_rescued = (IS_PROVIDED(paramset.vcf_tumor_fname) && (extended_posidx_to_is_rescued[refpos - extended_inclu_beg_pos]));
const bool is_var_rescued = (is_pos_rescued && (tid_pos_symb_to_tkis.end() != tid_pos_symb_to_tkis.find(std::make_tuple(tid, refpos, symbol))));
const auto bdepth =
symbolToCountCoverageSet12.symbol_to_frag_format_depth_sets[0].getByPos(refpos)[symbol][FRAG_bDP]
+ symbolToCountCoverageSet12.symbol_to_frag_format_depth_sets[1].getByPos(refpos)[symbol][FRAG_bDP];
const auto cdepth =
MAX(symbolToCountCoverageSet12.symbol_to_fam_format_depth_sets_2strand[0].getByPos(refpos)[symbol][FAM_cDP1],
symbolToCountCoverageSet12.symbol_to_fam_format_depth_sets_2strand[0].getByPos(refpos)[symbol][FAM_cDP12])
+ MAX(symbolToCountCoverageSet12.symbol_to_fam_format_depth_sets_2strand[1].getByPos(refpos)[symbol][FAM_cDP1],
symbolToCountCoverageSet12.symbol_to_fam_format_depth_sets_2strand[1].getByPos(refpos)[symbol][FAM_cDP12]);
if (isSymbolIns(symbol)) {
ins_bdepth += bdepth;
ins_cdepth += cdepth;
if (LINK_I1 == symbol) {
ins1_bdepth += bdepth;
ins1_cdepth += cdepth;
}
} else if (isSymbolDel(symbol)) {
del_bdepth += bdepth;
del_cdepth += cdepth;
if (LINK_D1 == symbol) {
del1_bdepth += bdepth;
del1_cdepth += cdepth;
}
}
if ((ISNT_PROVIDED(paramset.vcf_tumor_fname))
&& (((refsymbol != symbol) && (bdepth < paramset.min_altdp_thres))
|| ((refsymbol == symbol) && (bDPcDP[0] - ref_bdepth < paramset.min_altdp_thres)))
&& (!paramset.should_output_all)) {
continue;
}
if (IS_PROVIDED(paramset.vcf_tumor_fname) && (!is_pos_rescued)) {
continue;
}
const auto simplemut = std::make_pair(refpos, symbol);
const auto indices_bq = (simplemut2indices_bq.find(simplemut) != simplemut2indices_bq.end() ? simplemut2indices_bq[simplemut] : empty_size_t_set);
const auto indices_fq = (simplemut2indices_fq.find(simplemut) != simplemut2indices_fq.end() ? simplemut2indices_fq[simplemut] : empty_size_t_set);
const auto indices_f2q = (simplemut2indices_f2q.find(simplemut) != simplemut2indices_f2q.end() ? simplemut2indices_f2q[simplemut] : empty_size_t_set);
std::vector<TumorKeyInfo> tkis;
if (is_var_rescued) {
tkis = tid_pos_symb_to_tkis.find(std::make_tuple(tid, refpos, symbol))->second;
}
auto fmt = st_to_init_fmt[symboltype];
int tkiidx = 0;
std::vector<std::tuple<uvc1_readnum_t, uvc1_readnum_t, std::string, TumorKeyInfo>> bcad0a_indelstring_tki_vec;
if (isSymbolIns(symbol) || isSymbolDel(symbol)) {
for (int strand = 0; strand < 2; strand++) {
if (0 < symbolToCountCoverageSet12.symbol_to_frag_format_depth_sets[strand].getByPos(refpos)[symbol][FRAG_bDP]) {
fill_by_indel_info(
fmt,
symbolToCountCoverageSet12,
strand,
refpos,
symbol,
refstring,
0);
}
}
if (is_var_rescued) {
for (const auto & tki : tkis) {
const auto tabpos = tki.ref_alt.find("\t");
const auto & vcfref = tki.ref_alt.substr(0, tabpos);
const auto & vcfalt = tki.ref_alt.substr(tabpos + 1);
std::string indelstring;
if (vcfref.size() > vcfalt.size()) {
indelstring = vcfref.substr(vcfalt.size());
} else {
assertUVC (vcfref.size() < vcfalt.size());
indelstring = vcfalt.substr(vcfref.size());
}
bcad0a_indelstring_tki_vec.push_back(std::make_tuple(bdepth, cdepth, indelstring, tki));
tkiidx++;
}
} else {
const auto bcad0a_arr_indelstring_pairvec = indel_get_majority(
fmt,
std::get<0>(tname_tseqlen_tuple).c_str(),
refpos,
symbol,
(IS_PROVIDED(paramset.vcf_tumor_fname)),
0);
for (const auto & bcad0a_arr_indelstring_pair : bcad0a_arr_indelstring_pairvec) {
bcad0a_indelstring_tki_vec.push_back(std::make_tuple(
bcad0a_arr_indelstring_pair.first[0],
bcad0a_arr_indelstring_pair.first[1],
bcad0a_arr_indelstring_pair.second,
THE_DUMMY_TUMOR_KEY_INFO));
}
}
} else if (is_var_rescued) {
for (const auto & tki : tkis) {
bcad0a_indelstring_tki_vec.push_back(std::make_tuple(bdepth, cdepth, std::string(""), tki));
}
} else {
bcad0a_indelstring_tki_vec.push_back(std::make_tuple(bdepth, cdepth, std::string(""), THE_DUMMY_TUMOR_KEY_INFO));
}
for (const auto & bcad0a_indelstring_tki : bcad0a_indelstring_tki_vec) {
const auto & indelstring = std::get<2>(bcad0a_indelstring_tki);
const auto & tki = std::get<3>(bcad0a_indelstring_tki);
const bool is_homopol_1bp = (prev_base1 == refsymbol && next_base1 == refsymbol);
const bool is_homopol_2bp = (prev_base2 == refsymbol && next_base2 == refsymbol);
BcfFormat_symbol_init(
fmt,
symbolToCountCoverageSet12,
refpos,
symbol,
mutform2count4vec_bq,
indices_bq,
mutform2count4vec_fq,
indices_fq,
mutform2count4vec_f2q,
indices_f2q,
std::get<0>(bcad0a_indelstring_tki),
std::get<1>(bcad0a_indelstring_tki),
indelstring,
(isSymbolSubstitution(symbol)
? non_neg_minus(minABQ_snv, (is_homopol_1bp ? (is_homopol_2bp ? 20 : 10) : 0))
: minABQ_indel),
paramset,
0);
BcfFormat_symbol_calc_DPv(
fmt,
region_repeatvec[MAX(refpos - extended_inclu_beg_pos, 3) - 3],
region_repeatvec[MIN(refpos - extended_inclu_beg_pos + 3, UNSIGN2SIGN(region_repeatvec.size()) - 1)],
((is_var_rescued && (tki.VTI == LAST(fmt.VTI))) ? ((double)(tki.cDP1x + 1) / (double)(tki.CDP1x + 2)) : -1.0), /* tpfa */
tki,
refsymbol,
symbolToCountCoverageSet12,
refpos,
paramset,
0);
st_to_fmt_tki_tup_vec[symboltype].push_back(std::make_tuple(fmt, std::get<3>(bcad0a_indelstring_tki)));
}
}
} // end of iterations within symboltype
const size_t string_pass_old_size = buf_out_string_pass.size();
auto st_to_nlodq_fmtptr1_fmtptr2_tup = std::array<std::tuple<uvc1_qual_t, bcfrec::BcfFormat*, bcfrec::BcfFormat*>, NUM_SYMBOL_TYPES>();
std::array<int32_t, NUM_SYMBOL_TYPES> curr_vAC = {{ 0 }};
for (SymbolType symboltype : SYMBOL_TYPE_ARR) {
if (zerobased_pos == rpos_inclu_beg && BASE_SYMBOL == symboltype) { continue; }
const uvc1_refgpos_t refpos = (BASE_SYMBOL == symboltype ? (zerobased_pos - 1) : zerobased_pos);
const AlignmentSymbol refsymbol = symboltype_to_refsymbol[symboltype];
auto & fmt_tki_tup_vec = st_to_fmt_tki_tup_vec[symboltype];
if (fmt_tki_tup_vec.size() == 0) { continue; }
BcfFormat_symbol_sum_DPv(fmt_tki_tup_vec);
std::vector<std::tuple<uvc1_qual_t, uvc1_qual_t, uvc1_qual_t, AlignmentSymbol, std::string>> maxVQ_VQ1_VQ2_symbol_indelstr_tup_vec;
for (auto & fmt_tki_tup : fmt_tki_tup_vec)
{
const auto VTI = LAST(std::get<0>(fmt_tki_tup).VTI);
assertUVC((VTI >= 0 && VTI <= END_ALIGNMENT_SYMBOLS) || !fprintf(stderr, "VTI %d at pos %d is invalid!\n", VTI, refpos));
AlignmentSymbol symbol = (VTI >= 0 ? AlignmentSymbol(VTI) : END_ALIGNMENT_SYMBOLS);
auto & fmt = std::get<0>(fmt_tki_tup);
const auto & tki = std::get<1>(fmt_tki_tup);
BcfFormat_symbol_calc_qual(
fmt,
ins_cdepth,
del_cdepth,
ins1_cdepth,
del1_cdepth,
repeatunit,
repeatnum,
IS_PROVIDED(paramset.vcf_tumor_fname),
region_repeatvec.at(MAX(refpos - extended_inclu_beg_pos, 3) - 3),
region_repeatvec.at(MIN(refpos - extended_inclu_beg_pos + 3, UNSIGN2SIGN(region_repeatvec.size()) - 1)),
tid,
refpos,
refsymbol,
((IS_PROVIDED(paramset.vcf_tumor_fname) && (tki.VTI == LAST(fmt.VTI))) ?
((double)(tki.bDP + 0.5) / (double)(tki.BDP + 1.0)) : -1.0),
symbolToCountCoverageSet12,
paramset,
0);
if (refsymbol != symbol) {
uvc1_qual_t cVQ1 = LAST(std::get<0>(fmt_tki_tup).cVQ1);
uvc1_qual_t cVQ2 = LAST(std::get<0>(fmt_tki_tup).cVQ2);
maxVQ_VQ1_VQ2_symbol_indelstr_tup_vec.push_back(std::make_tuple(MAX(cVQ1, cVQ2), cVQ1, cVQ2, symbol, LAST(std::get<0>(fmt_tki_tup).gapSa)));
const uvc1_qual_t germ_phred_het3al = ((BASE_SYMBOL == symboltype) ? paramset.germ_phred_het3al_snp : paramset.germ_phred_het3al_indel);
if (MAX(cVQ1, cVQ2) >= germ_phred_het3al) {
curr_vAC[symboltype] += 1;
}
}
}
std::sort(maxVQ_VQ1_VQ2_symbol_indelstr_tup_vec.rbegin(), maxVQ_VQ1_VQ2_symbol_indelstr_tup_vec.rend());