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/* The MIT License
Copyright (c) 2013 Adrian Tan <atks@umich.edu>
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 "normalize.h"
namespace
{
class Igor : Program
{
public:
///////////
//options//
///////////
std::string input_vcf_file;
std::string output_vcf_file;
std::vector<GenomeInterval> intervals;
std::string ref_fasta_file;
int32_t window_size;
// 0 - do not fail at all
// 1 - fail on unmasked consistencies
// 2 - fail on all consistencies
int32_t strict_level;
bool print;
bool debug;
///////
//i/o//
///////
BCFOrderedReader *odr;
BCFOrderedWriter *odw;
bcf1_t *v;
//////////
//filter//
//////////
std::string fexp;
Filter filter;
bool filter_exists;
/////////
//stats//
/////////
uint32_t no_variants;
uint32_t no_refs;
uint32_t no_lt; //# left trimmed
uint32_t no_rt; //# right trimmed
uint32_t no_lt_rt; //# left trimmed and right trimmed
uint32_t no_rt_la; //# right trimmed and left aligned
uint32_t no_la; //# left aligned
uint32_t no_multi_lt; //# left trimmed
uint32_t no_multi_rt; //# right trimmed
uint32_t no_multi_lt_rt; //# left trimmed and right trimmed
uint32_t no_multi_rt_la; //# right trimmed and left aligned
uint32_t no_multi_la; //# left aligned
/////////
//tools//
/////////
VariantManip *vm;
Igor(int argc, char **argv)
{
version = "0.5";
//////////////////////////
//options initialization//
//////////////////////////
try
{
std::string desc = "normalizes variants in a VCF file. \n";
TCLAP::CmdLine cmd(desc, ' ', version);
VTOutput my; cmd.setOutput(&my);
TCLAP::ValueArg<std::string> arg_ref_fasta_file("r", "r", "reference sequence fasta file []", true, "", "str", cmd);
TCLAP::ValueArg<std::string> arg_intervals("i", "i", "intervals []", false, "", "str", cmd);
TCLAP::ValueArg<std::string> arg_interval_list("I", "I", "file containing list of intervals []", false, "", "file", cmd);
TCLAP::ValueArg<int32_t> arg_window_size("w", "w", "window size for local sorting of variants [10000]", false, 10000, "integer", cmd);
TCLAP::ValueArg<std::string> arg_fexp("f", "f", "filter expression []", false, "", "str", cmd);
TCLAP::SwitchArg arg_warn_only("n", "n", "warns but does not exit when REF is inconsistent\n"
" with reference sequence for non SNPs [false]", cmd, false);
TCLAP::SwitchArg arg_warn_for_masked_only("m", "m", "warns but does not exit when REF is inconsistent\n"
" with masked reference sequence for non SNPs.\n"
" This overrides the -n option [false]", cmd, false);
TCLAP::SwitchArg arg_quiet("q", "q", "do not print options and summary [false]", cmd, false);
TCLAP::SwitchArg arg_debug("d", "d", "debug [false]", cmd, false);
TCLAP::ValueArg<std::string> arg_output_vcf_file("o", "o", "output VCF file [-]", false, "-", "str", cmd);
TCLAP::UnlabeledValueArg<std::string> arg_input_vcf_file("<in.vcf>", "input VCF file", true, "","file", cmd);
cmd.parse(argc, argv);
input_vcf_file = arg_input_vcf_file.getValue();
output_vcf_file = arg_output_vcf_file.getValue();
parse_intervals(intervals, arg_interval_list.getValue(), arg_intervals.getValue());
fexp = arg_fexp.getValue();
print = !arg_quiet.getValue();
strict_level = arg_warn_only.getValue() ? 0 : 2;
strict_level = arg_warn_for_masked_only.getValue() ? 1 : strict_level;
debug = arg_debug.getValue();
window_size = arg_window_size.getValue();
ref_fasta_file = arg_ref_fasta_file.getValue();
}
catch (TCLAP::ArgException &e)
{
std::cerr << "error: " << e.error() << " for arg " << e.argId() << "\n";
abort();
}
};
void initialize()
{
//////////////////////
//i/o initialization//
//////////////////////
odr = new BCFOrderedReader(input_vcf_file, intervals);
odw = new BCFOrderedWriter(output_vcf_file, window_size);
odw->link_hdr(odr->hdr);
bcf_hdr_append(odw->hdr, "##INFO=<ID=OLD_VARIANT,Number=.,Type=String,Description=\"Original chr:pos:ref:alt encoding\">\n");
odw->write_hdr();
/////////////////////////
//filter initialization//
/////////////////////////
filter.parse(fexp.c_str(), false);
filter_exists = fexp=="" ? false : true;
////////////////////////
//stats initialization//
////////////////////////
no_variants = 0;
no_refs = 0;
no_lt = 0;
no_rt = 0;
no_lt_rt = 0;
no_rt_la = 0;
no_la = 0;
no_multi_lt = 0;
no_multi_rt = 0;
no_multi_lt_rt = 0;
no_multi_rt_la = 0;
no_multi_la = 0;
////////////////////////
//tools initialization//
////////////////////////
vm = new VariantManip(ref_fasta_file);
}
void normalize()
{
int32_t left_extended = 0;
int32_t left_trimmed = 0;
int32_t right_trimmed = 0;
kstring_t old_alleles = {0,0,0};
kstring_t new_alleles = {0,0,0};
v = odw->get_bcf1_from_pool();
Variant variant;
bcf_hdr_t *h = odr->hdr;
while (odr->read(v))
{
bcf_unpack(v, BCF_UN_INFO);
if (debug) bcf_print_liten(odr->hdr, v);
int32_t type = vm->classify_variant(odw->hdr, v, variant);
if (filter_exists)
{
if (!filter.apply(h, v, &variant, false))
{
continue;
}
}
int32_t is_not_ref_consistent = 0;
if (type!=VT_SNP && (is_not_ref_consistent = vm->is_not_ref_consistent(h,v)))
{
if (is_not_ref_consistent > (2-strict_level))
{
fprintf(stderr, "[%s:%d %s] Normalization not performed due to inconsistent reference sequences. (use -n or -m option to relax this)\n", __FILE__, __LINE__, __FUNCTION__);
exit(1);
}
else
{
fprintf(stderr, "[%s:%d %s] Normalization skipped due to inconsistent reference sequences\n", __FILE__, __LINE__, __FUNCTION__);
}
}
if (!is_not_ref_consistent && !(type&VT_SV) && !(type&VT_VNTR) && !vm->is_normalized(v))
{
const char* chrom = odr->get_seqname(v);
int32_t pos1 = bcf_get_pos1(v);
std::vector<std::string> alleles;
for (size_t i=0; i<bcf_get_n_allele(v); ++i)
{
char *s = bcf_get_alt(v, i);
while (*s)
{
*s = toupper(*s);
++s;
}
alleles.push_back(std::string(bcf_get_alt(v, i)));
}
left_extended = left_trimmed = right_trimmed = 0;
vm->right_trim_or_left_extend(alleles, pos1, chrom, left_extended, right_trimmed);
vm->left_trim(alleles, pos1, left_trimmed);
if (left_trimmed || left_extended || right_trimmed)
{
old_alleles.l = 0;
bcf_variant2string(odw->hdr, v, &old_alleles);
bcf_update_info_string(odw->hdr, v, "OLD_VARIANT", old_alleles.s);
bcf_set_pos1(v, pos1);
new_alleles.l = 0;
for (size_t i=0; i<alleles.size(); ++i)
{
if (i) kputc(',', &new_alleles);
kputs(alleles[i].c_str(), &new_alleles);
}
bcf_update_alleles_str(odw->hdr, v, new_alleles.s);
if (bcf_get_n_allele(v)==2)
{
if (left_extended)
{
if (right_trimmed>left_extended)
{
++no_rt_la;
}
else
{
++no_la;
}
}
else
{
if (left_trimmed && right_trimmed>left_extended)
{
++no_lt_rt;
}
else if (left_trimmed)
{
++no_lt;
}
else if (right_trimmed>left_extended)
{
++no_rt;
}
}
}
else
{
if (left_extended)
{
if (right_trimmed>left_extended)
{
++no_multi_rt_la;
}
else
{
++no_multi_la;
}
}
else
{
if (left_trimmed && right_trimmed>left_extended)
{
++no_multi_lt_rt;
}
else if (left_trimmed)
{
++no_multi_lt;
}
else if (right_trimmed>left_extended)
{
++no_multi_rt;
}
}
}
}
}
if (type==VT_REF)
{
++no_refs;
}
else
{
++no_variants;
}
odw->write(v);
v = odw->get_bcf1_from_pool();
}
odw->close();
odr->close();
};
void print_options()
{
if (!print) return;
std::clog << "normalize v" << version << "\n";
std::clog << "\n";
std::clog << "options: input VCF file " << input_vcf_file << "\n";
std::clog << " [o] output VCF file " << output_vcf_file << "\n";
std::clog << " [w] sorting window size " << window_size << "\n";
print_str_op(" [f] filter ", fexp);
std::clog << " [m] no fail on masked reference inconsistency " << (strict_level==1 ? "true" : "false") << "\n";
std::clog << " [n] no fail on reference inconsistency " << (strict_level==0 ? "true" : "false") << "\n";
std::clog << " [q] quiet " << (!print ? "true" : "false") << "\n";
std::clog << " [d] debug " << (debug ? "true" : "false") << "\n";
std::clog << " [r] reference FASTA file " << ref_fasta_file << "\n";
print_int_op(" [i] intervals ", intervals);
std::clog << "\n";
}
void print_stats()
{
if (!print) return;
int32_t no_biallelic_normalized = no_lt+no_rt+no_lt_rt+no_rt_la+no_la;
int32_t no_multiallelic_normalized = no_multi_lt+no_multi_rt+no_multi_lt_rt+no_multi_rt_la+no_multi_la;
int32_t no_normalized = no_biallelic_normalized + no_multiallelic_normalized;
std::clog << "\n";
std::clog << "stats: biallelic\n";
std::clog << " no. left trimmed : " << no_lt << "\n";
std::clog << " no. right trimmed : " << no_rt << "\n";
std::clog << " no. left and right trimmed : " << no_lt_rt << "\n";
std::clog << " no. right trimmed and left aligned : " << no_rt_la << "\n";
std::clog << " no. left aligned : " << no_la << "\n";
std::clog << "\n";
std::clog << " total no. biallelic normalized : " << no_biallelic_normalized << "\n";
std::clog << "\n";
std::clog << " multiallelic\n";
std::clog << " no. left trimmed : " << no_multi_lt << "\n";
std::clog << " no. right trimmed : " << no_multi_rt << "\n";
std::clog << " no. left and right trimmed : " << no_multi_lt_rt << "\n";
std::clog << " no. right trimmed and left aligned : " << no_multi_rt_la << "\n";
std::clog << " no. left aligned : " << no_multi_la << "\n";
std::clog << "\n";
std::clog << " total no. multiallelic normalized : " << no_multiallelic_normalized << "\n";
std::clog << "\n";
std::clog << " total no. variants normalized : " << no_normalized << "\n";
std::clog << " total no. variants observed : " << no_variants << "\n";
std::clog << " total no. reference observed : " << no_refs << "\n";
std::clog << "\n";
};
~Igor() {};
private:
};
}
bool normalize(int argc, char ** argv)
{
Igor igor(argc, argv);
igor.print_options();
igor.initialize();
igor.normalize();
igor.print_stats();
return igor.print;
};
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