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/* The MIT License
Copyright (c) 2014 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 "annotate_vntrs.h"
namespace
{
class Igor : Program
{
public:
std::string version;
///////////
//options//
///////////
std::string input_vcf_file;
std::string ref_fasta_file;
std::string output_vcf_file;
std::vector<GenomeInterval> intervals;
std::string interval_list;
bool debug;
std::string method; //methods of detection
std::string vntr_annotation_mode; //modes of annotation
int32_t vntr_classification; //vntr classification schemas
bool override_tag;
bool add_vntr_record;
bool add_flank_annotation; //add flank annotation
//motif related
std::string END;
std::string MOTIF;
std::string MLEN;
std::string RU;
std::string BASIS;
std::string BLEN;
//exact alignment related statistics
std::string REPEAT_TRACT;
std::string COMP;
std::string ENTROPY;
std::string ENTROPY2;
std::string RL;
std::string RU_COUNTS;
std::string SCORE;
std::string TRF_SCORE;
std::string FLANKSEQ;
//////////
//filter//
//////////
std::string fexp;
Filter filter;
bool filter_exists;
///////
//i/o//
///////
BCFOrderedReader *odr;
BCFOrderedWriter *odw;
/////////
//stats//
/////////
int32_t no_vntrs_annotated;
////////////////
//common tools//
////////////////
VariantManip* vm;
VNTRAnnotator* va;
ReferenceSequence* rs;
Igor(int argc, char **argv)
{
version = "0.5";
//////////////////////////
//options initialization//
//////////////////////////
try
{
std::string desc = "annotates indels with VNTR information and adds a VNTR record.";
TCLAP::CmdLine cmd(desc, ' ', version);
VTOutput my; cmd.setOutput(&my);
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, "", "str", cmd);
TCLAP::ValueArg<std::string> arg_output_vcf_file("o", "o", "output VCF file [-]", false, "-", "str", cmd);
TCLAP::ValueArg<std::string> arg_ref_fasta_file("r", "r", "reference sequence fasta file []", true, "", "str", cmd);
TCLAP::SwitchArg arg_debug("d", "d", "debug [false]", cmd, false);
TCLAP::UnlabeledValueArg<std::string> arg_input_vcf_file("<in.vcf>", "input VCF file", true, "","file", cmd);
TCLAP::ValueArg<std::string> arg_fexp("f", "f", "filter expression []", false, "", "str", cmd);
TCLAP::SwitchArg arg_override_tag("x", "x", "override tags [false]", cmd, false);
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();
debug = arg_debug.getValue();
ref_fasta_file = arg_ref_fasta_file.getValue();
}
catch (TCLAP::ArgException &e)
{
std::cerr << "error: " << e.error() << " for arg " << e.argId() << std::endl;
abort();
}
};
~Igor()
{
};
void initialize()
{
/////////////////////////
//filter initialization//
/////////////////////////
filter.parse(fexp.c_str(), false);
filter_exists = fexp=="" ? false : true;
//////////////////////
//i/o initialization//
//////////////////////
odr = new BCFOrderedReader(input_vcf_file, intervals);
odw = new BCFOrderedWriter(output_vcf_file, 10000);
odw->link_hdr(odr->hdr);
//////////////////////////////
//INFO header adding for VCF//
//////////////////////////////
bool rename = false;
//motif related
END = bcf_hdr_append_info_with_backup_naming(odw->hdr, "END", "1", "Integer", "End position of the variant.", rename);
MOTIF = bcf_hdr_append_info_with_backup_naming(odw->hdr, "MOTIF", "1", "String", "Canonical motif in a VNTR.", rename);
RU = bcf_hdr_append_info_with_backup_naming(odw->hdr, "RU", "1", "String", "Repeat unit in the reference sequence.", rename);
BASIS = bcf_hdr_append_info_with_backup_naming(odw->hdr, "BASIS", "1", "String", "Basis nucleotides in the motif.", rename);
MLEN = bcf_hdr_append_info_with_backup_naming(odw->hdr, "MLEN", "1", "Integer", "Motif length.", rename);
BLEN = bcf_hdr_append_info_with_backup_naming(odw->hdr, "BLEN", "1", "Integer", "Basis length.", rename);
//exact alignment related statisitcs
REPEAT_TRACT = bcf_hdr_append_info_with_backup_naming(odw->hdr, "REPEAT_TRACT", "2", "Integer", "Boundary of the repeat tract detected by exact alignment.", rename);
COMP = bcf_hdr_append_info_with_backup_naming(odw->hdr, "COMP", "4", "Integer", "Composition(%) of bases in an exact repeat tract.", rename);
ENTROPY = bcf_hdr_append_info_with_backup_naming(odw->hdr, "ENTROPY", "1", "Float", "Entropy measure of an exact repeat tract (0-2).", rename);
ENTROPY2 = bcf_hdr_append_info_with_backup_naming(odw->hdr, "ENTROPY2", "1", "Float", "Dinucloetide Entropy measure of an exact repeat tract (0-2).", rename);
RL = bcf_hdr_append_info_with_backup_naming(odw->hdr, "RL", "1", "Integer", "Reference exact repeat tract length in bases.", rename);
RU_COUNTS = bcf_hdr_append_info_with_backup_naming(odw->hdr, "RU_COUNTS", "2", "Integer", "Number of exact repeat units and total number of repeat units in exact repeat tract.", rename);
SCORE = bcf_hdr_append_info_with_backup_naming(odw->hdr, "SCORE", "1", "Float", "Score of repeat unit in exact repeat tract.", rename);
TRF_SCORE = bcf_hdr_append_info_with_backup_naming(odw->hdr, "TRF_SCORE", "1", "Integer", "TRF Score for M/I/D as 2/-7/-7 in exact repeat tract.", rename);
FLANKSEQ = bcf_hdr_append_info_with_backup_naming(odw->hdr, "FLANKSEQ", "1", "String", "Flanking sequence 10bp on either side of REF.", rename);
////////////////////////
//stats initialization//
////////////////////////
no_vntrs_annotated = 0;
////////////////////////
//tools initialization//
////////////////////////
vm = new VariantManip(ref_fasta_file);
va = new VNTRAnnotator(ref_fasta_file, debug);
rs = new ReferenceSequence(ref_fasta_file);
}
void print_options()
{
std::clog << "annotate_vntrs v" << version << "\n";
std::clog << "\n";
std::clog << "options: input VCF file(s) " << input_vcf_file << "\n";
std::clog << " [o] output VCF file " << output_vcf_file << "\n";
std::clog << " [v] add VNTR records " << (add_vntr_record ? "true" : "false") << "\n";
std::clog << " [k] add_flank_annotation " << (add_flank_annotation ? "true" : "false") << "\n";
print_boo_op(" [d] debug ", debug);
print_ref_op(" [r] ref FASTA file ", ref_fasta_file);
print_boo_op(" [x] override tag ", override_tag);
print_int_op(" [i] intervals ", intervals);
std::clog << "\n";
}
void print_stats()
{
std::clog << "\n";
std::cerr << "stats: no. of VNTRs annotated " << no_vntrs_annotated << "\n";
std::clog << "\n";
}
/**
* Updates the FLANKSEQ INFO field.
*/
void update_flankseq(bcf_hdr_t* h, bcf1_t *v, const char* chrom, int32_t lflank_beg1, int32_t lflank_end1, int32_t rflank_beg1, int32_t rflank_end1)
{
std::string flanks;
char* seq = rs->fetch_seq(chrom, lflank_beg1, lflank_end1);
flanks.assign(seq);
if (seq) free(seq);
flanks.append(1, '[');
seq = rs->fetch_seq(chrom, lflank_end1+1, rflank_beg1-1);
flanks.append(seq);
if (seq) free(seq);
flanks.append(1, ']');
seq = rs->fetch_seq(chrom, rflank_beg1, rflank_end1);
flanks.append(seq);
if (seq) free(seq);
bcf_update_info_string(h, v, "FLANKSEQ", flanks.c_str());
}
void annotate_vntrs()
{
odw->write_hdr();
bcf1_t *v = odw->get_bcf1_from_pool();
bcf_hdr_t *h = odw->hdr;
Variant variant;
while (odr->read(v))
{
int32_t vtype = vm->classify_variant(odr->hdr, v, variant);
if (filter_exists)
{
if (!filter.apply(h, v, &variant, false))
{
continue;
}
}
//variants with N crashes the alignment models!!!!!! :(
if (vm->contains_N(v))
{
std::string var = variant.get_variant_string();
fprintf(stderr, "[%s:%d %s] Variant contains N bases, skipping annotation: %s\n", __FILE__, __LINE__, __FUNCTION__, var.c_str());
odw->write(v);
v = odw->get_bcf1_from_pool();
continue;
}
if (debug)
{
bcf_print_liten(h,v);
}
if (vtype==VT_VNTR)
{
VNTR& vntr = variant.vntr;
int32_t beg1 = bcf_get_pos1(v);
int32_t end1 = bcf_get_end1(v);
va->annotate(variant, FINAL);
//assumes MOTIF is present
bcf_update_info_int32(h, v, MLEN.c_str(), &vntr.mlen, 1);
bcf_update_info_int32(h, v, END.c_str(), &variant.end1, 1);
bcf_update_info_string(h, v, RU.c_str(), vntr.ru.c_str());
bcf_update_info_string(h, v, BASIS.c_str(), vntr.basis.c_str());
bcf_update_info_int32(h, v, BLEN.c_str(), &vntr.blen, 1);
int32_t repeat_tract[2] = {beg1, end1};
bcf_update_info_int32(h, v, REPEAT_TRACT.c_str(), &repeat_tract, 2);
bcf_update_info_int32(h, v, COMP.c_str(), &vntr.comp[0], 4);
bcf_update_info_float(h, v, ENTROPY.c_str(), &vntr.entropy, 1);
bcf_update_info_float(h, v, ENTROPY2.c_str(), &vntr.entropy2, 1);
bcf_update_info_int32(h, v, RL.c_str(), &vntr.rl, 1);
int32_t ru_count[2] = {vntr.no_perfect_ru, vntr.no_ru};
bcf_update_info_int32(h, v, RU_COUNTS.c_str(), &ru_count, 2);
bcf_update_info_float(h, v, SCORE.c_str(), &vntr.score, 1);
bcf_update_info_int32(h, v, TRF_SCORE.c_str(), &vntr.trf_score, 1);
update_flankseq(h, v, variant.chrom.c_str(),
variant.beg1-10, variant.beg1-1,
variant.end1+1, variant.end1+10);
++no_vntrs_annotated;
}
odw->write(v);
v = odw->get_bcf1_from_pool();
}
odw->close();
odr->close();
};
private:
};
}
void annotate_vntrs(int argc, char ** argv)
{
Igor igor(argc, argv);
igor.print_options();
igor.initialize();
igor.annotate_vntrs();
igor.print_stats();
};
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