read_aligner.hh

/*
This file is part of khmer, https://github.com/dib-lab/khmer/, and is
Copyright (C) 2013-2015, Michigan State University.
Copyright (C) 2015, The Regents of the University of California.

Redistribution and use in source and binary forms, with or without
modification, are permitted provided that the following conditions are
met:

    * Redistributions of source code must retain the above copyright
      notice, this list of conditions and the following disclaimer.

    * Redistributions in binary form must reproduce the above
      copyright notice, this list of conditions and the following
      disclaimer in the documentation and/or other materials provided
      with the distribution.

    * Neither the name of the Michigan State University nor the names
      of its contributors may be used to endorse or promote products
      derived from this software without specific prior written
      permission.

THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS
"AS IS" AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT
LIMITED TO, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR
A PARTICULAR PURPOSE ARE DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT
HOLDER OR CONTRIBUTORS BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL,
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LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES; LOSS OF USE,
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(INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE
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LICENSE (END)

Contact: khmer-project@idyll.org
*/
#ifndef READ_ALIGNER_HH
#define READ_ALIGNER_HH

#include <math.h>
#include <stddef.h>
#include <algorithm>
#include <limits>
#include <memory>
#include <queue>
#include <set>
#include <string>
#include <vector>

#include "khmer.hh"
#include "hashgraph.hh"
#include "kmer_hash.hh"

#define READ_ALIGNER_DEBUG 0

namespace khmer
{

enum State { MATCH, INSERT_READ, INSERT_GRAPH,
             MATCH_UNTRUSTED, INSERT_READ_UNTRUSTED, INSERT_GRAPH_UNTRUSTED
           };

// Constants for state transitions
enum Transition { MM, MIr, MIg, MMu, MIru, MIgu,
                  IrM, IrIr, IrMu, IrIru,
                  IgM, IgIg, IgMu, IgIgu,
                  MuM, MuIr, MuIg, MuMu, MuIru, MuIgu,
                  IruM, IruIr, IruMu, IruIru,
                  IguM, IguIg, IguMu, IguIgu,
                  disallowed
                };

/*
Ig_t-Ig_t       0.2294619
Ig_t-Ig_u       0.0021453
Ig_t-M_t        0.7611255
Ig_t-M_u        0.0072673
Ig_u-Ig_t       0.0431328
Ig_u-Ig_u       0.1821200
Ig_u-M_t        0.1384551
Ig_u-M_u        0.6362921
Ir_t-Ir_t       0.4647955
Ir_t-Ir_u       0.0096792
Ir_t-M_t        0.5196194
Ir_t-M_u        0.0059060
Ir_u-Ir_t       0.0036995
Ir_u-Ir_u       0.5885548
Ir_u-M_t        0.1434529
Ir_u-M_u        0.2642928
M_t-Ig_t        0.0000334
M_t-Ig_u        0.0000003
M_t-Ir_t        0.0000735
M_t-Ir_u        0.0000017
M_t-M_t 0.9848843
M_t-M_u 0.0150068
M_u-Ig_t        0.0001836
M_u-Ig_u        0.0004173
M_u-Ir_t        0.0000262
M_u-Ir_u        0.0033370
M_u-M_t 0.0799009
M_u-M_u 0.9161349

*/
// log probabilities for state transitions
static double trans_default[] = { log2(0.9848843), log2(0.0000735), log2(0.0000334), log2(0.0150068), log2(0.0000017), log2(0.0000003),  // M_t
                                  log2(0.5196194), log2(0.4647955), log2(0.0059060), log2(0.0096792),                        // Ir_t
                                  log2(0.7611255), log2(0.2294619), log2(0.0072673), log2(0.0021453),                        // Ig_t
                                  log2(0.0799009), log2(0.0000262), log2(0.0001836), log2(0.9161349), log2(0.0033370), log2(0.0004173),  // M_u
                                  log2(0.1434529), log2(0.0036995), log2(0.2642928), log2(0.5885548),                        // Ir_u
                                  log2(0.1384551), log2(0.0431328), log2(0.6362921), log2(0.1821200),                        // Ig_u
                                };
/*{ log2(.80), log2(.045), log2(.045), log2(.06), log2(.025), log2(.025),
                                  log2(.875), log2(.045), log2(.055), log2(.025),
                                  log2(.875), log2(.045), log2(.055), log2(.025),
			    log2(.80), log2(.045), log2(.045), log2(.06), log2(.025), log2(.025),
                                  log2(.875), log2(.045), log2(.055), log2(.025),
                                  log2(.875), log2(.045), log2(.055), log2(.025),
};*/

enum Nucl {A, C, G, T};
static const char nucl_lookup[4] = {'A', 'C', 'G', 'T'};
static const double background_prob = 0;//log2(.99);

struct AlignmentNode {
    AlignmentNode* prev;
    Nucl base;
    size_t seq_idx;
    State state;
    Transition trans;
    HashIntoType fwd_hash;
    HashIntoType rc_hash;

    double score;
    double f_score;
    double h_score;
    bool trusted;
    BoundedCounterType cov;

    size_t num_indels;

    size_t length;

    AlignmentNode(AlignmentNode* _prev, Nucl _emission, size_t _seq_idx,
                  State _state, Transition _trans, HashIntoType _fwd_hash,
                  HashIntoType _rc_hash, size_t _length)
        :prev(_prev), base(_emission), seq_idx(_seq_idx),
         state(_state), trans(_trans), fwd_hash(_fwd_hash),
         rc_hash(_rc_hash), score(0), f_score(0), h_score(0), trusted(false),
         cov(0), num_indels(0), length(_length) {}

    bool operator== (const AlignmentNode& rhs) const
    {
        return (seq_idx == rhs.seq_idx) && (state == rhs.state) &&
               uniqify_rc(fwd_hash, rc_hash) == uniqify_rc(rhs.fwd_hash, rhs.rc_hash)
               && trans == rhs.trans;
    }

    bool operator< (const AlignmentNode& rhs) const
    {
        return f_score < rhs.f_score;
    }
};

class AlignmentNodeCompare
{
public:
    bool operator()(AlignmentNode* o1, AlignmentNode* o2)
    {
        if (o1->f_score < o2->f_score) {
            return true;
        } else {
            return false;
        }
    }
};

typedef std::priority_queue<AlignmentNode*,
        std::vector<AlignmentNode*>,
        AlignmentNodeCompare> NodeHeap;

struct ScoringMatrix {
    const double trusted_match;
    const double trusted_mismatch;
    const double untrusted_match;
    const double untrusted_mismatch;

    const double* tsc;

    ScoringMatrix(double trusted_match, double trusted_mismatch,
                  double untrusted_match, double untrusted_mismatch,
                  double* trans)
        : trusted_match(trusted_match), trusted_mismatch(trusted_mismatch),
          untrusted_match(untrusted_match),
          untrusted_mismatch(untrusted_mismatch), tsc(trans) {}
};


struct Alignment {
    std::string graph_alignment;
    std::string read_alignment;
    std::string trusted;
    std::vector<BoundedCounterType> covs;
    double score;
    bool truncated;
};


class ReadAligner
{
private:

    Alignment* ExtractAlignment(AlignmentNode*,
                                bool forward, const std::string&);

    void Enumerate(NodeHeap&, std::vector<AlignmentNode*>& all_nodes,
                   AlignmentNode*, bool, const std::string&);
    Alignment* Subalign(AlignmentNode*, size_t, bool, const std::string&);

#if READ_ALIGNER_DEBUG
    void WriteNode(AlignmentNode* curr);
#endif

    // These variables are required to use the _revhash and hash macros
    // might as well just compute them once
    const HashIntoType bitmask;
    const size_t rc_left_shift;

    khmer::Countgraph* m_ch;
    ScoringMatrix m_sm;

    size_t m_trusted_cutoff;
    double m_bits_theta;

    HashIntoType comp_bitmask(WordLength k)
    {
        HashIntoType ret = 0;
        for (size_t i = 0; i < k; i++) {
            ret = (ret << 2) | 3;
        }
        return ret;
    }
public:
    Alignment* Align(const std::string&);
    Alignment* AlignForward(const std::string&);

    ReadAligner(khmer::Countgraph* ch,
                BoundedCounterType trusted_cutoff, double bits_theta)
        : bitmask(comp_bitmask(ch->ksize())),
          rc_left_shift(ch->ksize() * 2 - 2),
          m_ch(ch), m_sm(
              log2(.955), log2(.04), log2(.004),
              log2(.001), trans_default),
          m_trusted_cutoff(trusted_cutoff),
          m_bits_theta(bits_theta)
    {
#if READ_ALIGNER_DEBUG
        std::cerr << "Trusted cutoff: " << m_trusted_cutoff
                  << " bits theta: " << bits_theta
                  << " trusted match: " << m_sm.trusted_match
                  << " untrusted match: " << m_sm.untrusted_match
                  << " trusted mismatch: " << m_sm.trusted_mismatch
                  << " untrusted mismatch: " << m_sm.untrusted_mismatch
                  << std::endl;
#endif
    }

    ReadAligner(khmer::Countgraph* ch,
                BoundedCounterType trusted_cutoff, double bits_theta,
                double* scoring_matrix, double* transitions)
        : bitmask(comp_bitmask(ch->ksize())),
          rc_left_shift(ch->ksize() * 2 - 2),
          m_ch(ch), m_sm(scoring_matrix[0], scoring_matrix[1],
                         scoring_matrix[2], scoring_matrix[3],
                         transitions),
          m_trusted_cutoff(trusted_cutoff),
          m_bits_theta(bits_theta) {};

    ScoringMatrix getScoringMatrix();

};
}
#endif // READ_ALIGNER_HH