decompose_blocksub.cpp

/* 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 "decompose_blocksub.h"
#include "needle.h"

namespace
{

struct Triple
{
    int pos_ref;
    int pos_alt;
    int len_ref;
    int len_alt;

    Triple() : pos_ref(0), pos_alt(0), len_ref(0), len_alt(0)
    {}

    Triple(int pos_ref, int pos_alt, int len_ref, int len_alt) : pos_ref(pos_ref), pos_alt(pos_alt), len_ref(len_ref), len_alt(len_alt)
    {}
};

class Igor : Program
{
    public:

    ///////////
    //options//
    ///////////
    bool aggressive_mode;
    bool keep_mnv;
    bool output_phased_genotypes;
    int max_mnv_dist;
    std::string input_vcf_file;
    std::string output_vcf_file;
    std::vector<GenomeInterval> intervals;
    std::string ref_fasta_file;

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

    kstring_t s;
    kstring_t new_alleles;
    kstring_t old_alleles;
    kstring_t ref_mnv, alt_mnv;

    /////////
    //stats//
    /////////
    uint32_t no_additional_snps;
    uint32_t no_biallelic_blocksub;
    uint32_t new_no_variants;
    uint32_t no_variants;

    /////////
    //tools//
    /////////
    VariantManip *vm;

    Igor(int argc, char **argv)
    {
        version = "0.5";

        //////////////////////////
        //options initialization//
        //////////////////////////
        try
        {
            std::string desc = "decomposes biallelic block substitutions into its constituent SNPs.";

            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, "", "file", cmd);
            TCLAP::ValueArg<std::string> arg_output_vcf_file("o", "o", "output VCF file [-]", false, "-", "str", cmd);
            TCLAP::ValueArg<int>  arg_max_mnv_dist("d", "d", "MNVs max distance (when -m option is used) [2]", false, 2, "int", cmd);
            TCLAP::SwitchArg arg_aggressive("a", "a", "enable aggressive/alignment mode [false]", cmd, false);
            TCLAP::SwitchArg arg_mnv("m", "m", "keep MNVs (multi-nucleotide variants) [false]", cmd, false);
            TCLAP::SwitchArg arg_output_phased_genotypes("p", "p", "Output phased genotypes and PS tags for decomposed variants [false]", cmd, false);
            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();
            aggressive_mode = arg_aggressive.getValue();
            keep_mnv = arg_mnv.getValue();
            max_mnv_dist = arg_max_mnv_dist.getValue();
            output_phased_genotypes = arg_output_phased_genotypes.getValue();
            parse_intervals(intervals, arg_interval_list.getValue(), arg_intervals.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, 1000);
        odw->link_hdr(odr->hdr);
        bcf_hdr_append(odw->hdr, "##INFO=<ID=OLD_CLUMPED,Number=1,Type=String,Description=\"Original chr:pos:ref:alt encoding\">\n");

        if (output_phased_genotypes)
        {
            bcf_hdr_append(odw->hdr, "##FORMAT=<ID=PS,Number=1,Type=Integer,Description=\"ID for set of phased genotypes\">\n");
        }

        odw->write_hdr();

        s = {0,0,0};
        old_alleles = {0,0,0};
        new_alleles = {0,0,0};
        ref_mnv = {0,0,0};
        alt_mnv = {0,0,0};

        ////////////////////////
        //stats initialization//
        ////////////////////////
        no_additional_snps = 0;
        no_biallelic_blocksub = 0;
        new_no_variants = 0;
        no_variants = 0;

        ////////////////////////
        //tools initialization//
        ////////////////////////
    }

    void print_decomposed_var(bcf1_t *v, int pos, char* ref, char *alt, BCFOrderedWriter *odw) {
        bcf1_t *nv = odw->get_bcf1_from_pool();
        bcf_copy(nv, v);
        bcf_unpack(nv, BCF_UN_ALL);

        bcf_set_pos1(nv, pos);
        new_alleles.l=0;
        kputs(ref, &new_alleles);
        kputc(',', &new_alleles);
        kputs(alt, &new_alleles);

        bcf_update_alleles_str(odw->hdr, nv, new_alleles.s);
        bcf_update_info_string(odw->hdr, nv, "OLD_CLUMPED", old_alleles.s);
        odw->write(nv);
    }

    void decompose_blocksub()
    {
        v = odw->get_bcf1_from_pool();
        Variant variant;

        while (odr->read(v))
        {
            bcf_unpack(v, BCF_UN_ALL);

            int32_t n_allele = bcf_get_n_allele(v);
            char** allele = bcf_get_allele(v);

            size_t ref_len = strlen(allele[0]);
            size_t alt_len = n_allele==1 ? 0 : strlen(allele[1]);
            if (aggressive_mode && (ref_len!=alt_len) && (ref_len!=1) && (alt_len>1))
            {
                // Use alignment for decomposition of substitutions where REF
                // and ALT have different lengths and the variant is not an
                // insertion or deletion.

                // Perform alignment of REF[1:] and ALT[1:]
                NeedlemanWunsch nw(true);
                nw.align(allele[0] + 1, allele[1] + 1);
                nw.trace_path();
                // Force-align first characters
                if (allele[0][0] == allele[1][0])
                    nw.trace.insert(nw.trace.begin(), NeedlemanWunsch::CIGAR_M);
                else
                    nw.trace.insert(nw.trace.begin(), NeedlemanWunsch::CIGAR_X);
                nw.read--;
                nw.ref--;

                // Break apart alignment
                std::vector<Triple> chunks;
                bool hasError = false;
                int pos_ref = 0, pos_alt = 0, k = 0;
                Triple nextChunk(pos_ref, pos_alt, 0, 0);
                while (pos_ref <= nw.len_ref || pos_alt <= nw.len_read)
                {
                    switch ((int32_t)nw.trace.at(k++))
                    {
                        case NeedlemanWunsch::CIGAR_M:
                            if (hasError)
                                chunks.push_back(nextChunk);
                            nextChunk = Triple(pos_ref++, pos_alt++, 1, 1);
                            hasError = false;
                            break;
                        case NeedlemanWunsch::CIGAR_X:
                            if (hasError)
                                chunks.push_back(nextChunk);
                            nextChunk = Triple(pos_ref++, pos_alt++, 1, 1);
                            hasError = true;
                            break;
                        case NeedlemanWunsch::CIGAR_D:
                            nextChunk.len_ref++;
                            pos_ref++;
                            hasError = true;
                            break;
                        case NeedlemanWunsch::CIGAR_I:
                            nextChunk.len_alt++;
                            pos_alt++;
                            hasError = true;
                            break;
                    }
                }
                if (hasError)
                    chunks.push_back(nextChunk);

                // Build new BCF records.
                int32_t rid = bcf_get_rid(v);
                int32_t pos1 = bcf_get_pos1(v);
                char** allele = bcf_get_allele(v);

                char* ref = strdup(allele[0]);
                char* alt = strdup(allele[1]);

                old_alleles.l = 0;
                bcf_variant2string(odw->hdr, v, &old_alleles);

                for (size_t i=0; i<chunks.size(); ++i)
                {
                    bcf1_t *nv = odw->get_bcf1_from_pool();
                    bcf_copy(nv, v);
                    bcf_unpack(nv, BCF_UN_ALL);
                    bcf_set_pos1(nv, pos1+chunks[i].pos_ref);
                    std::vector<int32_t> start_pos_of_phased_block;
                    int32_t no_samples = bcf_get_n_sample(v);
                        
                    new_alleles.l=0;
                    for (int j=chunks[i].pos_ref; j<chunks[i].pos_ref+chunks[i].len_ref; ++j)
                        kputc(ref[j], &new_alleles);
                    kputc(',', &new_alleles);
                    for (int j=chunks[i].pos_alt; j<chunks[i].pos_alt+chunks[i].len_alt; ++j)
                        kputc(alt[j], &new_alleles);

                    bcf_update_alleles_str(odw->hdr, nv, new_alleles.s);
                    bcf_update_info_string(odw->hdr, nv, "OLD_CLUMPED", old_alleles.s);

                    if (output_phased_genotypes)
                    {
                        // Update genotypes with '|' to represent phased blocks, and add PS tag with pos of first
                        // decomposed variant as block ID.
                        start_pos_of_phased_block.resize(no_samples, pos1 + chunks[0].pos_ref);
                        bcf_update_format_int32(odw->hdr, nv, "PS", &start_pos_of_phased_block[0], no_samples);

                        int* gts = NULL; 
                        int n_gts = 0;
                        int ploidy = bcf_get_genotypes(odw->hdr, nv, &gts, &n_gts);

                        for (int32_t igt=0; igt < n_gts; ++igt)
                        {
                            gts[igt] = bcf_gt_phased(bcf_gt_allele(gts[igt]));
                        }

                        bcf_update_genotypes(odw->hdr, nv, gts, n_gts);
                        free(gts);
                    }
                    
                    odw->write(nv);
                    kputc('\0', &new_alleles);

                    ++new_no_variants;
                    ++no_additional_snps;
                }

                free(ref);
                free(alt);

                ++no_biallelic_blocksub;
            }
            else if (n_allele==2 && (ref_len!=1) && (ref_len==strlen(allele[1])))
            {
                int32_t rid = bcf_get_rid(v);
                int32_t pos1 = bcf_get_pos1(v);
                std::vector<int32_t> start_pos_of_phased_block;
                int32_t no_samples = bcf_get_n_sample(v);
                
                char** allele = bcf_get_allele(v);
                char* ref = strdup(allele[0]);
                char* alt = strdup(allele[1]);
                int prev_snv_pos = -1;
                int mnv_start_pos = -1;

                old_alleles.l = 0;
                bcf_variant2string(odw->hdr, v, &old_alleles);
                for (size_t i=0; i<ref_len; ++i)
                {
                    if (ref[i]!=alt[i])
                    {
                        if(keep_mnv) {
                            if(prev_snv_pos == -1 || i - prev_snv_pos <= max_mnv_dist) {
                                prev_snv_pos = i;
                                // Remember the pos of first SNP in the MNV
                                if(mnv_start_pos == -1) {
                                    mnv_start_pos = i;
                                }
                                kputc(ref[i], &ref_mnv);
                                kputc(alt[i], &alt_mnv);
                                //std::clog << "PREV_MNV_POS: " << prev_snv_pos << "\n";
                            }
                            //std::clog << "I: " << i << ", PREV_SNV_POS: " << prev_snv_pos << ", MNV_START_POS: " << mnv_start_pos << "\n";
                        } else {
                            start_pos_of_phased_block.resize(no_samples, pos1 + i);
                        
                            bcf1_t *nv = odw->get_bcf1_from_pool();
                            bcf_copy(nv, v);
                            bcf_unpack(nv, BCF_UN_ALL);

                            bcf_set_pos1(nv, pos1+i);
                            new_alleles.l=0;
                            kputc(ref[i], &new_alleles);
                            kputc(',', &new_alleles);
                            kputc(alt[i], &new_alleles);

                            bcf_update_alleles_str(odw->hdr, nv, new_alleles.s);
                            bcf_update_info_string(odw->hdr, nv, "OLD_CLUMPED", old_alleles.s);

                            if (output_phased_genotypes)
                            {
                                // Update genotypes with '|' to represent phased blocks, and add PS tag with pos of first
                                // decomposed variant as block ID.
                                bcf_update_format_int32(odw->hdr, nv, "PS", &start_pos_of_phased_block[0], no_samples);

                                int* gts = NULL; 
                                int n_gts = 0;
                                int ploidy = bcf_get_genotypes(odw->hdr, nv, &gts, &n_gts);

                                for (int32_t igt=0; igt < n_gts; ++igt)
                                {
                                    gts[igt] = bcf_gt_phased(bcf_gt_allele(gts[igt]));
                                }

                                bcf_update_genotypes(odw->hdr, nv, gts, n_gts);
                                free(gts);
                            }

                            odw->write(nv);
                        }
                        
                        
                        // FIXME: we should move these somewhere else
                        ++new_no_variants;
                        ++no_additional_snps;
                    } else if(keep_mnv) {
                        if(prev_snv_pos != -1 && i - prev_snv_pos < max_mnv_dist) {
                            kputc(ref[i], &ref_mnv);
                            kputc(alt[i], &alt_mnv);
                        // We have a record to print!
                        } else if(prev_snv_pos != -1) {
                            // Remove last nucleotides that are similare between alt and ref
                            ref_mnv.s[prev_snv_pos - mnv_start_pos + 1] = '\0';
                            alt_mnv.s[prev_snv_pos - mnv_start_pos + 1] = '\0';

                            // Print MNV record
                            print_decomposed_var(v, pos1 + mnv_start_pos, ref_mnv.s, alt_mnv.s, odw);

                            // Reset MNV variables
                            prev_snv_pos = -1;
                            mnv_start_pos = -1;
                            ref_mnv.l=0;
                            alt_mnv.l=0;
                        }
                    }
                }
                
                if(keep_mnv && prev_snv_pos != -1) {
                    // Remove last nucleotides that are similare between alt and ref
                    ref_mnv.s[prev_snv_pos - mnv_start_pos + 1] = '\0';
                    alt_mnv.s[prev_snv_pos - mnv_start_pos + 1] = '\0';
                    // print MNV record !
                    print_decomposed_var(v, pos1 + mnv_start_pos, ref_mnv.s, alt_mnv.s, odw);
                }

                // Reset MNV variables
                ref_mnv.l=0;
                alt_mnv.l=0;

                free(ref);
                free(alt);

                ++no_biallelic_blocksub;
            }
            else
            {
                odw->write(v);
                v = odw->get_bcf1_from_pool();
                ++new_no_variants;
            }

            ++no_variants;
        }

        odw->close();
        odr->close();
    };

    void print_options()
    {
        std::clog << "decompose_blocksub 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";
        print_int_op("         [i] intervals               ", intervals);
        print_boo_op("         [a] align/aggressive mode   ", aggressive_mode);
        print_boo_op("         [m] keep MNVs (Multi-Nucleotide Variants)   ", keep_mnv);
        print_boo_op("         [d] MNVs max distance (when -m option is used)   ", max_mnv_dist);
        print_boo_op("         [p] output phased genotypes ", output_phased_genotypes);
        std::clog << "\n";
    }

    void print_stats()
    {
        std::clog << "\n";
        std::clog << "stats: no. variants                       : " << no_variants << "\n";
        std::clog << "       no. biallelic block substitutions  : " << no_biallelic_blocksub << "\n";
        std::clog << "\n";
        std::clog << "       no. additional SNPs                : " << no_additional_snps << "\n";
        std::clog << "       no. variants after decomposition   : " << new_no_variants << "\n";
        std::clog << "\n";
    };

    ~Igor() {};

    private:
};

}

void decompose_blocksub(int argc, char ** argv)
{
    Igor igor(argc, argv);
    igor.print_options();
    igor.initialize();
    igor.decompose_blocksub();
    igor.print_stats();
};