normalize.cpp

/* 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;
    bool print;

    ///////
    //i/o//
    ///////
    BCFOrderedReader *odr;
    BCFOrderedWriter *odw;
    bcf1_t *v;

    /////////
    //stats//
    /////////
    uint32_t no_variants;

    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";

            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::SwitchArg arg_quiet("q", "q", "do not print options and summary []", 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());
            print = !arg_quiet.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=1,Type=String,Description=\"Original chr:pos:ref:alt encoding\">\n");
        odw->write_hdr();
        
        ////////////////////////
        //stats initialization//
        ////////////////////////
        no_variants = 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()
    {
        uint32_t left_extended = 0;
        uint32_t left_trimmed = 0;
        uint32_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;

        while (odr->read(v))
        {
            bcf_unpack(v, BCF_UN_INFO);
            
            if (!vm->is_normalized(v))
            {
                const char* chrom = odr->get_seqname(v);
                uint32_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;
                            }
                        }
                    }
                }
            }

            ++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";
        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 << "\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;
};