variant_manip.h

/* 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.
*/

#ifndef VARIANT_MANIP_H
#define VARIANT_MANIP_H

#include <cstdlib>
#include <cstdint>
#include <cstring>
#include <cmath>
#include <cfloat>
#include <vector>
#include <map>
#include <queue>
#include <list>
#include <string>
#include <iostream>
#include <algorithm>
#include "htslib/faidx.h"
#include "htslib/kstring.h"
#include "htslib/vcf.h"
#include "hts_utils.h"

//int BitCount(unsigned int u)
//{
//     unsigned int uCount;
//
//#ifndef countbit32
//#define countbit32(x) (y = u - ((u >> 1) & 033333333333) - ((u >> 2) & 011111111111); ((y + (y >> 3)) & 030707070707) % 63);
//
//#endif

#define VT_REF      0   //dlen==0 && diff==0
#define VT_SNP      1   //min(rlen,alen)==1 && diff==1
#define VT_MNP      2   //min(rlen,alen)==diff
#define VT_INDEL    4   //diff!=0 && (rlen==1 || alen==1)
#define VT_CLUMPED  8   //all others

/**
 * Allele.
 *
 * Allele can be described to be a SNP or INDEL or etc. with respect to the reference
 * type - give the variant type
 * len  - difference in length between the ref and alt with positive inferring an insertion and negative inferring a deletion
 * tlen - assuming variant is VNTR, tlen is the tract length of the repeated motif of the VNTR
 */
class Allele
{
    public:

    int32_t type;
    int32_t diff;  //number of difference bases when bases are compared
    int32_t alen;  //length(alt)
    int32_t dlen;  //length(alt)-length(ref)
    int32_t tlen;  //tract length with respect to reference
    int32_t mlen;  //min shared length
    int32_t ts;    //no of transitions
    int32_t tv;    //no of tranversions (mlen-ts)
    int32_t ins;   //no of insertions

    Allele(int32_t type, int32_t diff, int32_t alen, int32_t dlen, int32_t tlen, int32_t mlen, int32_t ts, int32_t ins)
    {
        this->type = type;
        this->diff = diff;
        this->alen = alen;
        this->dlen = dlen;
        this->tlen = tlen;
        this->mlen = mlen;
        this->ts = ts;
        this->tv = mlen-ts;
        this->ins = ins;
    }

    Allele()
    {
        clear();
    };

    ~Allele() {};

    void clear()
    {
        type = VT_REF;
        diff = 0;
        alen = 0;
        dlen = 0;
        tlen = 0;
        mlen = 0;
        ts = 0;
        tv = 0;
        ins = 0;
    }

    void print()
    {
        std::cerr << "\ttype: " << type << "\n";
        std::cerr << "\tdiff: " << diff << "\n";
        std::cerr << "\talen: " << alen << "\n";
        std::cerr << "\tdlen: " << dlen << "\n";
        std::cerr << "\ttlen: " << tlen << "\n";
    };
};

/**
 * Variant.
 * Describes the variant in question.
 */
class Variant
{
    public:

    int32_t type;    //aggegrated type from the alleles
    int32_t rlen;    //reference length
    kstring_t motif; //motif
    int32_t mlen;    //motif length
    int32_t tlen;    //reference tract length
    std::vector<Allele> alleles;

    Variant()
    {
        type = VT_REF;
        motif = {0,0,0};
        mlen = 0;
        tlen = 0;
        alleles.clear();
    }

    ~Variant()
    {
        if (motif.m)
        {
            free(motif.s);
        }
    }

    /**
     * Prints variant information.
     */
    void print();

    /**
     * Converts VTYPE to string.
     */
    std::string vtype2string(int32_t VTYPE);

    void clear()
    {
        type = 0;
        motif.l = 0;
        mlen = 0;
        tlen = 0;
        alleles.clear();
    }
};

/**
 * Methods for manipulating variants
 */
class VariantManip
{
    public:
    faidx_t *fai;
    bool reference_present;

    /**
     * Constructor.
     *
     * @ref_fasta_file reference sequence FASTA file.
     */
    VariantManip(std::string ref_fasta_file);

    /**
     * Constructor.
     */
    VariantManip();

    /**
     * Detects near by STRs.
     */
    bool detect_str(bcf_hdr_t *h, bcf1_t *v, Variant& variant);

    /**
     * Detects near by STRs.
     */
    bool detect_str(const char* chrom, uint32_t pos1, Variant& variant);

    /**
     * Converts VTYPE to string.
     */
    std::string vtype2string(int32_t VTYPE);

    /**
     * Converts VTYPE to string.
     */
    void vtype2string(int32_t vtype, kstring_t *s);

    /**
     * Classifies variants.
     */
    int32_t classify_variant(bcf_hdr_t *h, bcf1_t *v, Variant& variant, bool in_situ_left_trimming = true);

    /**
     * Classifies variants.
     */
    int32_t classify_variant(bcf_hdr_t *h, bcf1_t *v);

    /**
     * Classifies variants.
     */
    int32_t classify_variant(const char* chrom, uint32_t pos1, char** allele, int32_t n_allele, Variant& variant, bool in_situ_left_trimming = true);

    /**
     * Classifies variants.
     */
    int32_t classify_variant(const char* chrom, uint32_t pos1, char** allele, int32_t n_allele);

    /**
     * Left trims a variant with unnecesary nucleotides.
     */
    void left_trim(std::vector<std::string>& alleles, uint32_t& pos1, uint32_t& left_trimmed) ;

    /**
     * Left aligns a variant.
     */
    void left_align(std::vector<std::string>& alleles, uint32_t& pos1, const char* chrom, uint32_t& leftAligned, uint32_t& right_trimmed);

    /**
     * Generates a probing haplotype with flanks around the variant of interest.
     */
    void generate_probes(const char* chrom,
                        int32_t pos1, uint32_t probeDiff,
                        std::vector<std::string>& alleles, //store alleles
                        std::vector<std::string>& probes, //store probes
                        uint32_t min_flank_length,
                        int32_t& preambleLength); //store preamble length

    private:

    /**
     * Recursive helper method for generateProbes.
     */
    void generate_probes(const char* chrom,
                        int32_t pos1,
                        uint32_t flankLength,
                        uint32_t& currentDiff,
                        uint32_t& length,
                        uint32_t gald,
                        std::vector<uint32_t>& diff,
                        std::vector<std::string>& alleles,
                        std::vector<std::string>& probes);

};

#endif