AP_seq_dna.cxx

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#include "AP_seq_dna.hxx"

#include <arb_mem.h>
#include <AP_pro_a_nucs.hxx>
#include <AP_filter.hxx>
#include <ARB_Tree.hxx>


inline bool hasGap(char c) { return c & AP_GAP; }
inline bool isGap(char c)  { return c == AP_GAP; }

inline bool notHasGap(char c) { return !hasGap(c); }
inline bool notIsGap(char c)  { return !isGap(c); }

// -------------------------------
//      AP_sequence_parsimony

char *AP_sequence_parsimony::table;

AP_sequence_parsimony::AP_sequence_parsimony(const AliView *aliview) :
    AP_combinableSeq(aliview),
    seq_pars(NULp)
{}

AP_sequence_parsimony::~AP_sequence_parsimony() {
    free(seq_pars);
}

AP_combinableSeq *AP_sequence_parsimony::dup() const {
    return new AP_sequence_parsimony(get_aliview());
}

int AP_sequence_parsimony::cmp_combined(const AP_combinableSeq *other) const {
    const AP_sequence_parsimony *sother = DOWNCAST(const AP_sequence_parsimony*, other);

    const unsigned char *s1 = get_usequence();
    const unsigned char *s2 = sother->get_usequence();

    size_t len = get_sequence_length();

    for (size_t i = 0; i<len; ++i) {
        int comp = int(s1[i]) - int(s2[i]);
        if (comp) return comp;
    }

    return 0;
}

void AP_sequence_parsimony::build_table() {
    table = (char *)AP_create_dna_to_ap_bases();
}



/* --------------------------------------------------------------------------------
 * combine(const AP_sequence *lefts, const AP_sequence *rights)
 * set(char *isequence)
 *
 * for wagner & fitch parsimony algorithm
 *
 * Note: is_set_flag is used by AP_tree_nlen::parsimony_rek()
 *       see ../../PARSIMONY/AP_tree_nlen.cxx@parsimony_rek
*/

// #define SHOW_SEQ

void AP_sequence_parsimony::set(const char *isequence) {
    size_t sequence_len = get_filter()->get_filtered_length();
    ARB_alloc_aligned(seq_pars, sequence_len+1);
    memset(seq_pars, AP_DOT, (size_t)sequence_len+1); // init with dots

    const uchar *simplify = get_filter()->get_simplify_table();
    if (!table) this->build_table();

    const AP_filter *filt = get_filter();
    if (filt->does_bootstrap()) {
        size_t iseqlen = strlen(isequence);

        for (size_t i = 0; i<sequence_len; ++i) {
            size_t pos = filt->bootstrapped_seqpos(i); // random indices (but same for all species)

            ap_assert(pos<iseqlen);
            if (pos >= iseqlen) continue;

            unsigned char c = (unsigned char)isequence[pos];

#if defined(SHOW_SEQ)
            fputc(simplify[c], stdout);
#endif // SHOW_SEQ

            seq_pars[i] = table[simplify[c]];
        }
    }
    else {
        const size_t* base_pos = filt->get_filterpos_2_seqpos();

        for (size_t i = 0; i < sequence_len; ++i) {
            size_t pos = base_pos[i];
            unsigned char c = (unsigned char)isequence[pos];
            seq_pars[i] = table[simplify[c]];

#if defined(SHOW_SEQ)
                fputc(simplify[c], stdout);
#endif // SHOW_SEQ
        }
    }

#if defined(SHOW_SEQ)
    fputc('\n', stdout);
#endif // SHOW_SEQ

    mark_sequence_set(true);
}

void AP_sequence_parsimony::unset() {
    freenull(seq_pars);
    mark_sequence_set(false);
}

template <class COUNT, class SITE>
static long do_combine(size_t sequence_len,
                       const char * __restrict p1,
                       const char * __restrict p2,
                       char * __restrict p,
                       COUNT count,
                       SITE site)
{
    for (size_t idx = 0; idx<sequence_len; ++idx) { // LOOP_VECTORIZED=4 (ok, do_combine is used 4 times)
        char c1 = p1[idx];
        char c2 = p2[idx];

        char c = c1 & c2;
        p[idx] = (c==0)?c1|c2:c;

        count.add(idx, c);
        site.add(idx, c);
    }

    return count.sum;
}

template <class COUNT>
static long do_countMutations(size_t sequence_len,
                              const char * __restrict p1,
                              const char * __restrict p2,
                              COUNT count)
{
    for (size_t idx = 0; idx<sequence_len; ++idx) { // LOOP_VECTORIZED=2 (ok, do_countMutations is used 2 times)
        char c1 = p1[idx];
        char c2 = p2[idx];

        char c = c1 & c2;

        count.add(idx, c);
    }

    return count.sum;
}

struct count_unweighted {
    long sum;
    count_unweighted():sum(0){}
    void add(size_t, char c) {
        sum += !c;
    }
};

struct count_weighted {
    long            sum;
    const GB_UINT4 *weights;

    count_weighted(const GB_UINT4 *w) : sum(0), weights(w) {}
    void add(size_t idx, char c) {
        sum += !c * weights[idx];
    }
};

struct count_nothing {
    void add(size_t, char) {}
};

struct count_mutpsite {
    char *sites;
    count_mutpsite(char *s) : sites(s) {}
    void add(size_t idx, char c) {
        // below code is equal to "if (!c) ++sites[idx]", the difference
        // is that no branch is required and sites[idx] is always
        // written, allowing vectorization.
        //
        // For unknown reasons gcc 4.8.1, 4.9.2 and 5.1.0
        // refuses to vectorize 'c==0?1:0' or '!c'

        sites[idx] += ((c | -c) >> 7 & 1) ^ 1;
    }
};

#define NEVER_COMBINE_ASYNC

#if defined(Cxx11)
# if !defined(NEVER_COMBINE_ASYNC)
#  define ASYNC_COMBINE
# endif
#endif

#if defined(ASYNC_COMBINE)
# include <future>
#endif

class CombinableSeq : virtual Noncopyable {
    // input (read-only):
    size_t sequence_len;
    const char *s1;
    const char *s2;

    const GB_UINT4 *weights; // NULp -> unweighted

    // output:
    char *out;               // should not be shared!
    char *mutation_per_site; // NULp -> do not count (Warning: shared memory -> do not modify unguarded!)

    Mutations calculate() const;

#if defined(ASYNC_COMBINE)
    std::future<Mutations> f;
    void allow_async_calc(bool allow_async) {
        ap_assert(!f.valid());
        if (allow_async) {
            f = std::async( [this]() { return calculate(); } );
            ap_assert(f.valid());
        }
    }
    Mutations calc_result() {
        Mutations result;
        if (f.valid()) {
            try {
                result = f.get();
            }
            catch (std::system_error& serr) {
                fprintf(stderr, "catched system_error %i: %s\n", serr.code().value(), serr.what());
                result = -1;
            }
        }
        else {
            result = calculate();
        }
        return result;
    }
#else
# if defined(NEVER_COMBINE_ASYNC)
    void allow_async_calc(bool IF_ASSERTION_USED(allow_async)) {
        ap_assert(!allow_async); // asynchronous calculation completely disabled atm
    }
# else // !NEVER_COMBINE_ASYNC
    void allow_async_calc(bool) {}
# endif
    Mutations calc_result() { return calculate(); }
#endif

public:
    CombinableSeq(size_t seq_len, const char *seq1, const char *seq2, char *result, char *mutation_per_site_, const GB_UINT4 *weights_, bool allow_async) :
        sequence_len(seq_len),
        s1(seq1),
        s2(seq2),
        weights(weights_),
        out(result),
        mutation_per_site(mutation_per_site_)
    {
        // cannot calculate asynchronously if mutation_per_site is specified!
        // (mutation_per_site is shared between all instances of CombinableSeq and gets modified by calculate())
        allow_async_calc(allow_async && !mutation_per_site);
    }

    Mutations get_result() {
        return calc_result();
    }
};

Mutations CombinableSeq::calculate() const {
    Mutations mutations;
    if (!out) {
        ap_assert(!mutation_per_site);
        if (!weights) {
            mutations = do_countMutations(sequence_len, s1, s2, count_unweighted());
        }
        else {
            mutations = do_countMutations(sequence_len, s1, s2, count_weighted(weights));
        }
    }
    else if (!weights) {
        if (mutation_per_site) {
            mutations = do_combine(sequence_len, s1, s2, out,
                                   count_unweighted(),
                                   count_mutpsite(mutation_per_site));
        }
        else {
            mutations = do_combine(sequence_len, s1, s2, out,
                                   count_unweighted(),
                                   count_nothing());
        }
    }
    else {
        UNCOVERED(); // by unittests!
        if (mutation_per_site) {
            mutations = do_combine(sequence_len, s1, s2, out,
                                   count_weighted(weights),
                                   count_mutpsite(mutation_per_site));
        }
        else {
            mutations = do_combine(sequence_len, s1, s2, out,
                                   count_weighted(weights),
                                   count_nothing());
        }
    }

    return mutations;
}

Mutations AP_sequence_parsimony::combine_seq(const AP_combinableSeq *lefts, const AP_combinableSeq *rights, char *mutation_per_site) {
    const AP_sequence_parsimony *left  = DOWNCAST(const AP_sequence_parsimony*, lefts);
    const AP_sequence_parsimony *right = DOWNCAST(const AP_sequence_parsimony*, rights);

    size_t sequence_len = get_sequence_length();
    if (!seq_pars) {
        ARB_alloc_aligned(seq_pars, sequence_len + 1);
    }

    const GB_UINT4 *weights = get_weights()->is_unweighted() ? NULp : get_weights()->get_weights();
    CombinableSeq   cs(sequence_len, left->get_sequence(), right->get_sequence(), seq_pars, mutation_per_site, weights, false);
    long            result  = cs.get_result();

    inc_combine_count();
    mark_sequence_set(true);

    ap_assert(result >= 0);
    return result;
}

Mutations AP_sequence_parsimony::mutations_if_combined_with(const AP_combinableSeq *other) {
    size_t          sequence_len = get_sequence_length();
    const GB_UINT4 *weights      = get_weights()->is_unweighted() ? NULp : get_weights()->get_weights();

    const AP_sequence_parsimony *pother = DOWNCAST(const AP_sequence_parsimony*, other);

    CombinableSeq cs(sequence_len, get_sequence(), pother->get_sequence(), NULp, NULp, weights, false);
    long          result = cs.get_result();

    inc_combine_count();
    ap_assert(result >= 0);
    return result;
}

void AP_sequence_parsimony::partial_match(const AP_combinableSeq *part_, long *overlapPtr, long *penaltyPtr) const {
    // matches the partial sequences 'part_' against 'this'
    // '*penaltyPtr' is set to the number of mismatches (possibly weighted)
    // '*overlapPtr' is set to the number of base positions both sequences overlap
    //          example:
    //          fullseq      'XXX---XXX'        'XXX---XXX'
    //          partialseq   '-XX---XX-'        '---XXX---'
    //          overlap       7                  3
    //
    // algorithm is similar to AP_sequence_parsimony::combine()
    // Note: changes done here should also be be applied to AP_seq_protein.cxx@partial_match_impl

    const AP_sequence_parsimony *part = (const AP_sequence_parsimony *)part_;

    const char *pf = get_sequence();
    const char *pp = part->get_sequence();

    const AP_weights *weights = get_weights();

    long min_end; // minimum of both last non-gap positions
    for (min_end = get_sequence_length()-1; min_end >= 0; --min_end) {
        char both = pf[min_end]|pp[min_end];
        if (notHasGap(both)) { // last non-gap found
            if (notHasGap(pf[min_end])) { // occurred in full sequence
                for (; min_end >= 0; --min_end) { // search same in partial sequence
                    if (notHasGap(pp[min_end])) break;
                }
            }
            else {
                ap_assert(notHasGap(pp[min_end])); // occurred in partial sequence
                for (; min_end >= 0; --min_end) { // search same in full sequence
                    if (notHasGap(pf[min_end])) break;
                }
            }
            break;
        }
    }

    long penalty = 0;
    long overlap = 0;

    if (min_end >= 0) {
        long max_start; // maximum of both first non-gap positions
        for (max_start = 0; max_start <= min_end; ++max_start) {
            char both = pf[max_start]|pp[max_start];
            if (notHasGap(both)) { // first non-gap found
                if (notHasGap(pf[max_start])) { // occurred in full sequence
                    for (; max_start <= min_end; ++max_start) { // search same in partial
                        if (notHasGap(pp[max_start])) break;
                    }
                }
                else {
                    ap_assert(notHasGap(pp[max_start])); // occurred in partial sequence
                    for (; max_start <= min_end; ++max_start) { // search same in full
                        if (notHasGap(pf[max_start])) break;
                    }
                }
                break;
            }
        }

        if (max_start <= min_end) { // if sequences overlap
            for (long idx = max_start; idx <= min_end; ++idx) {
                if ((pf[idx]&pp[idx]) == 0) { // bases are distinct (aka mismatch)
                    penalty += weights->weight(idx);
                }
            }
            overlap = min_end-max_start+1;
        }
    }

    *overlapPtr = overlap;
    *penaltyPtr = penalty;
}

AP_FLOAT AP_sequence_parsimony::count_weighted_bases() const {
    static char *hits = NULp;
    if (!hits) {
        ARB_alloc(hits, 256);
        memset(hits, 1, 256); // count ambiguous characters half

        hits[AP_A] = 2; // count real characters full
        hits[AP_C] = 2;
        hits[AP_G] = 2;
        hits[AP_T] = 2;

        hits[AP_GAP] = 0; // don't count gaps
        hits[AP_DOT] = 0; // don't count dots (and other stuff)
    }

    const AP_weights *weights = get_weights();
    const  char      *p       = get_sequence();

    long   sum          = 0;
    size_t sequence_len = get_sequence_length();

    for (size_t i = 0; i<sequence_len; ++i) {
        sum += hits[safeCharIndex(p[i])] * weights->weight(i);
    }

    AP_FLOAT wcount = sum * 0.5;
    return wcount;
}

uint32_t AP_sequence_parsimony::checksum() const {
    const char *seq = get_sequence();
    return GB_checksum(seq, sizeof(*seq)*get_sequence_length(), 0, NULp);
}