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/*
* Copyright 2011, Ben Langmead <langmea@cs.jhu.edu>
*
* This file is part of Bowtie 2.
*
* Bowtie 2 is free software: you can redistribute it and/or modify
* it under the terms of the GNU General Public License as published by
* the Free Software Foundation, either version 3 of the License, or
* (at your option) any later version.
*
* Bowtie 2 is distributed in the hope that it will be useful,
* but WITHOUT ANY WARRANTY; without even the implied warranty of
* MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the
* GNU General Public License for more details.
*
* You should have received a copy of the GNU General Public License
* along with Bowtie 2. If not, see <http://www.gnu.org/licenses/>.
*/
#ifndef ALIGNER_SEED_H_
#define ALIGNER_SEED_H_
#include <iostream>
#include <utility>
#include <limits>
#include <vector>
#include "qual.h"
#include "ds.h"
#include "sstring.h"
#include "alphabet.h"
#include "edit.h"
#include "read.h"
// Threading is necessary to synchronize the classes that dump
// intermediate alignment results to files. Otherwise, all data herein
// is constant and shared, or per-thread.
#include "threading.h"
#include "aligner_result.h"
#include "aligner_cache.h"
#include "scoring.h"
#include "mem_ids.h"
#include "simple_func.h"
#include "btypes.h"
/**
* A constraint to apply to an alignment zone, or to an overall
* alignment.
*
* The constraint can put both caps and ceilings on the number and
* types of edits allowed.
*/
struct Constraint {
Constraint() { init(); }
/**
* Initialize Constraint to be fully permissive.
*/
void init() {
edits = mms = ins = dels = penalty = editsCeil = mmsCeil =
insCeil = delsCeil = penaltyCeil = MAX_I;
penFunc.reset();
instantiated = false;
}
/**
* Return true iff penalities and constraints prevent us from
* adding any edits.
*/
bool mustMatch() const {
assert(instantiated);
return (mms == 0 && edits == 0) ||
penalty == 0 ||
(mms == 0 && dels == 0 && ins == 0);
}
/**
* Return true iff a mismatch of the given quality is permitted.
*/
bool canMismatch(int q, const Scoring& cm) const {
assert(instantiated);
return (mms > 0 || edits > 0) &&
penalty >= cm.mm(q);
}
/**
* Return true iff a mismatch of the given quality is permitted.
*/
bool canN(int q, const Scoring& cm) const {
assert(instantiated);
return (mms > 0 || edits > 0) &&
penalty >= cm.n(q);
}
/**
* Return true iff a mismatch of *any* quality (even qual=1) is
* permitted.
*/
bool canMismatch() const {
assert(instantiated);
return (mms > 0 || edits > 0) && penalty > 0;
}
/**
* Return true iff a mismatch of *any* quality (even qual=1) is
* permitted.
*/
bool canN() const {
assert(instantiated);
return (mms > 0 || edits > 0);
}
/**
* Return true iff a deletion of the given extension (0=open, 1=1st
* extension, etc) is permitted.
*/
bool canDelete(int ex, const Scoring& cm) const {
assert(instantiated);
return (dels > 0 && edits > 0) &&
penalty >= cm.del(ex);
}
/**
* Return true iff a deletion of any extension is permitted.
*/
bool canDelete() const {
assert(instantiated);
return (dels > 0 || edits > 0) &&
penalty > 0;
}
/**
* Return true iff an insertion of the given extension (0=open,
* 1=1st extension, etc) is permitted.
*/
bool canInsert(int ex, const Scoring& cm) const {
assert(instantiated);
return (ins > 0 || edits > 0) &&
penalty >= cm.ins(ex);
}
/**
* Return true iff an insertion of any extension is permitted.
*/
bool canInsert() const {
assert(instantiated);
return (ins > 0 || edits > 0) &&
penalty > 0;
}
/**
* Return true iff a gap of any extension is permitted
*/
bool canGap() const {
assert(instantiated);
return ((ins > 0 || dels > 0) || edits > 0) && penalty > 0;
}
/**
* Charge a mismatch of the given quality.
*/
void chargeMismatch(int q, const Scoring& cm) {
assert(instantiated);
if(mms == 0) { assert_gt(edits, 0); edits--; }
else mms--;
penalty -= cm.mm(q);
assert_geq(mms, 0);
assert_geq(edits, 0);
assert_geq(penalty, 0);
}
/**
* Charge an N mismatch of the given quality.
*/
void chargeN(int q, const Scoring& cm) {
assert(instantiated);
if(mms == 0) { assert_gt(edits, 0); edits--; }
else mms--;
penalty -= cm.n(q);
assert_geq(mms, 0);
assert_geq(edits, 0);
assert_geq(penalty, 0);
}
/**
* Charge a deletion of the given extension.
*/
void chargeDelete(int ex, const Scoring& cm) {
assert(instantiated);
dels--;
edits--;
penalty -= cm.del(ex);
assert_geq(dels, 0);
assert_geq(edits, 0);
assert_geq(penalty, 0);
}
/**
* Charge an insertion of the given extension.
*/
void chargeInsert(int ex, const Scoring& cm) {
assert(instantiated);
ins--;
edits--;
penalty -= cm.ins(ex);
assert_geq(ins, 0);
assert_geq(edits, 0);
assert_geq(penalty, 0);
}
/**
* Once the constrained area is completely explored, call this
* function to check whether there were *at least* as many
* dissimilarities as required by the constraint. Bounds like this
* are helpful to resolve instances where two search roots would
* otherwise overlap in what alignments they can find.
*/
bool acceptable() const {
assert(instantiated);
return edits <= editsCeil &&
mms <= mmsCeil &&
ins <= insCeil &&
dels <= delsCeil &&
penalty <= penaltyCeil;
}
/**
* Instantiate a constraint w/r/t the read length and the constant
* and linear coefficients for the penalty function.
*/
static int instantiate(size_t rdlen, const SimpleFunc& func) {
return func.f<int>((double)rdlen);
}
/**
* Instantiate this constraint w/r/t the read length.
*/
void instantiate(size_t rdlen) {
assert(!instantiated);
if(penFunc.initialized()) {
penalty = Constraint::instantiate(rdlen, penFunc);
}
instantiated = true;
}
int edits; // # edits permitted
int mms; // # mismatches permitted
int ins; // # insertions permitted
int dels; // # deletions permitted
int penalty; // penalty total permitted
int editsCeil; // <= this many edits can be left at the end
int mmsCeil; // <= this many mismatches can be left at the end
int insCeil; // <= this many inserts can be left at the end
int delsCeil; // <= this many deletions can be left at the end
int penaltyCeil;// <= this much leftover penalty can be left at the end
SimpleFunc penFunc;// penalty function; function of read len
bool instantiated; // whether constraint is instantiated w/r/t read len
//
// Some static methods for constructing some standard Constraints
//
/**
* Construct a constraint with no edits of any kind allowed.
*/
static Constraint exact();
/**
* Construct a constraint where the only constraint is a total
* penalty constraint.
*/
static Constraint penaltyBased(int pen);
/**
* Construct a constraint where the only constraint is a total
* penalty constraint related to the length of the read.
*/
static Constraint penaltyFuncBased(const SimpleFunc& func);
/**
* Construct a constraint where the only constraint is a total
* penalty constraint.
*/
static Constraint mmBased(int mms);
/**
* Construct a constraint where the only constraint is a total
* penalty constraint.
*/
static Constraint editBased(int edits);
};
/**
* We divide seed search strategies into three categories:
*
* 1. A left-to-right search where the left half of the read is
* constrained to match exactly and the right half is subject to
* some looser constraint (e.g. 1mm or 2mm)
* 2. Same as 1, but going right to left with the exact matching half
* on the right.
* 3. Inside-out search where the center half of the read is
* constrained to match exactly, and the extreme quarters of the
* read are subject to a looser constraint.
*/
enum {
SEED_TYPE_EXACT = 1,
SEED_TYPE_LEFT_TO_RIGHT,
SEED_TYPE_RIGHT_TO_LEFT,
SEED_TYPE_INSIDE_OUT
};
struct InstantiatedSeed;
/**
* Policy dictating how to size and arrange seeds along the length of
* the read, and what constraints to force on the zones of the seed.
* We assume that seeds are plopped down at regular intervals from the
* 5' to 3' ends, with the first seed flush to the 5' end.
*
* If the read is shorter than a single seed, one seed is used and it
* is shrunk to accommodate the read.
*/
struct Seed {
int len; // length of a seed
int type; // dictates anchor portion, direction of search
Constraint *overall; // for the overall alignment
Seed() { init(0, 0, NULL); }
/**
* Construct and initialize this seed with given length and type.
*/
Seed(int ln, int ty, Constraint* oc) {
init(ln, ty, oc);
}
/**
* Initialize this seed with given length and type.
*/
void init(int ln, int ty, Constraint* oc) {
len = ln;
type = ty;
overall = oc;
}
// If the seed is split into halves, we just use zones[0] and
// zones[1]; 0 is the near half and 1 is the far half. If the seed
// is split into thirds (i.e. inside-out) then 0 is the center, 1
// is the far portion on the left, and 2 is the far portion on the
// right.
Constraint zones[3];
/**
* Once the constrained seed is completely explored, call this
* function to check whether there were *at least* as many
* dissimilarities as required by all constraints. Bounds like this
* are helpful to resolve instances where two search roots would
* otherwise overlap in what alignments they can find.
*/
bool acceptable() {
assert(overall != NULL);
return zones[0].acceptable() &&
zones[1].acceptable() &&
zones[2].acceptable() &&
overall->acceptable();
}
/**
* Given a read, depth and orientation, extract a seed data structure
* from the read and fill in the steps & zones arrays. The Seed
* contains the sequence and quality values.
*/
bool instantiate(
const Read& read,
const BTDnaString& seq, // already-extracted seed sequence
const BTString& qual, // already-extracted seed quality sequence
const Scoring& pens,
int depth,
int seedoffidx,
int seedtypeidx,
bool fw,
InstantiatedSeed& si) const;
/**
* Return a list of Seed objects encapsulating
*/
static void mmSeeds(
int mms,
int ln,
EList<Seed>& pols,
Constraint& oall)
{
if(mms == 0) {
zeroMmSeeds(ln, pols, oall);
} else if(mms == 1) {
oneMmSeeds(ln, pols, oall);
} else if(mms == 2) {
twoMmSeeds(ln, pols, oall);
} else throw 1;
}
static void zeroMmSeeds(int ln, EList<Seed>&, Constraint&);
static void oneMmSeeds (int ln, EList<Seed>&, Constraint&);
static void twoMmSeeds (int ln, EList<Seed>&, Constraint&);
};
/**
* An instantiated seed is a seed (perhaps modified to fit the read)
* plus all data needed to conduct a search of the seed.
*/
struct InstantiatedSeed {
InstantiatedSeed() : steps(AL_CAT), zones(AL_CAT) { }
// Steps map. There are as many steps as there are positions in
// the seed. The map is a helpful abstraction because we sometimes
// visit seed positions in an irregular order (e.g. inside-out
// search).
EList<int> steps;
// Zones map. For each step, records what constraint to charge an
// edit to. The first entry in each pair gives the constraint for
// non-insert edits and the second entry in each pair gives the
// constraint for insert edits. If the value stored is negative,
// this indicates that the zone is "closed out" after this
// position, so zone acceptility should be checked.
EList<pair<int, int> > zones;
// Nucleotide sequence covering the seed, extracted from read
BTDnaString *seq;
// Quality sequence covering the seed, extracted from read
BTString *qual;
// Initial constraints governing zones 0, 1, 2. We precalculate
// the effect of Ns on these.
Constraint cons[3];
// Overall constraint, tailored to the read length.
Constraint overall;
// Maximum number of positions that the aligner may advance before
// its first step. This lets the aligner know whether it can use
// the ftab or not.
int maxjump;
// Offset of seed from 5' end of read
int seedoff;
// Id for seed offset; ids are such that the smallest index is the
// closest to the 5' end and consecutive ids are adjacent (i.e.
// there are no intervening offsets with seeds)
int seedoffidx;
// Type of seed (left-to-right, etc)
int seedtypeidx;
// Seed comes from forward-oriented read?
bool fw;
// Filtered out due to the pattern of Ns present. If true, this
// seed should be ignored by searchAllSeeds().
bool nfiltered;
// Seed this was instantiated from
Seed s;
#ifndef NDEBUG
/**
* Check that InstantiatedSeed is internally consistent.
*/
bool repOk() const {
return true;
}
#endif
};
/**
* Simple struct for holding a end-to-end alignments for the read with at most
* 2 edits.
*/
struct EEHit {
EEHit() { reset(); }
void reset() {
top = bot = 0;
fw = false;
e1.reset();
e2.reset();
score = MIN_I64;
}
void init(
TIndexOffU top_,
TIndexOffU bot_,
const Edit* e1_,
const Edit* e2_,
bool fw_,
int64_t score_)
{
top = top_; bot = bot_;
if(e1_ != NULL) {
e1 = *e1_;
} else {
e1.reset();
}
if(e2_ != NULL) {
e2 = *e2_;
} else {
e2.reset();
}
fw = fw_;
score = score_;
}
/**
* Return number of mismatches in the alignment.
*/
int mms() const {
if (e2.inited()) return 2;
else if(e1.inited()) return 1;
else return 0;
}
/**
* Return the number of Ns involved in the alignment.
*/
int ns() const {
int ns = 0;
if(e1.inited() && e1.hasN()) {
ns++;
if(e2.inited() && e2.hasN()) {
ns++;
}
}
return ns;
}
/**
* Return the number of Ns involved in the alignment.
*/
int refns() const {
int ns = 0;
if(e1.inited() && e1.chr == 'N') {
ns++;
if(e2.inited() && e2.chr == 'N') {
ns++;
}
}
return ns;
}
/**
* Return true iff there is no hit.
*/
bool empty() const {
return bot <= top;
}
/**
* Higher score = higher priority.
*/
bool operator<(const EEHit& o) const {
return score > o.score;
}
/**
* Return the size of the alignments SA range.s
*/
TIndexOffU size() const { return bot - top; }
#ifndef NDEBUG
/**
* Check that hit is sane w/r/t read.
*/
bool repOk(const Read& rd) const {
assert_gt(bot, top);
if(e1.inited()) {
assert_lt(e1.pos, rd.length());
if(e2.inited()) {
assert_lt(e2.pos, rd.length());
}
}
return true;
}
#endif
TIndexOffU top;
TIndexOffU bot;
Edit e1;
Edit e2;
bool fw;
int64_t score;
};
/**
* Data structure for holding all of the seed hits associated with a read. All
* the seed hits for a given read are encapsulated in a single QVal object. A
* QVal refers to a range of values in the qlist, where each qlist value is a
* BW range and a slot to hold the hit's suffix array offset. QVals are kept
* in two lists (hitsFw_ and hitsRc_), one for seeds on the forward read strand,
* one for seeds on the reverse read strand. The list is indexed by read
* offset index (e.g. 0=closest-to-5', 1=second-closest, etc).
*
* An assumption behind this data structure is that all the seeds are found
* first, then downstream analyses try to extend them. In between finding the
* seed hits and extending them, the sort() member function is called, which
* ranks QVals according to the order they should be extended. Right now the
* policy is that QVals with fewer elements (hits) should be tried first.
*/
class SeedResults {
public:
SeedResults() :
seqFw_(AL_CAT),
seqRc_(AL_CAT),
qualFw_(AL_CAT),
qualRc_(AL_CAT),
hitsFw_(AL_CAT),
hitsRc_(AL_CAT),
isFw_(AL_CAT),
isRc_(AL_CAT),
sortedFw_(AL_CAT),
sortedRc_(AL_CAT),
offIdx2off_(AL_CAT),
rankOffs_(AL_CAT),
rankFws_(AL_CAT),
mm1Hit_(AL_CAT)
{
clear();
}
/**
* Set the current read.
*/
void nextRead(const Read& read) {
read_ = &read;
}
/**
* Set the appropriate element of either hitsFw_ or hitsRc_ to the given
* QVal. A QVal encapsulates all the BW ranges for reference substrings
* that are within some distance of the seed string.
*/
void add(
const QVal& qv, // range of ranges in cache
const AlignmentCache& ac, // cache
uint32_t seedIdx, // seed index (from 5' end)
bool seedFw) // whether seed is from forward read
{
assert(qv.repOk(ac));
assert(repOk(&ac));
assert_lt(seedIdx, hitsFw_.size());
assert_gt(numOffs_, 0); // if this fails, probably failed to call reset
if(qv.empty()) return;
if(seedFw) {
assert(!hitsFw_[seedIdx].valid());
hitsFw_[seedIdx] = qv;
numEltsFw_ += qv.numElts();
numRangesFw_ += qv.numRanges();
if(qv.numRanges() > 0) nonzFw_++;
} else {
assert(!hitsRc_[seedIdx].valid());
hitsRc_[seedIdx] = qv;
numEltsRc_ += qv.numElts();
numRangesRc_ += qv.numRanges();
if(qv.numRanges() > 0) nonzRc_++;
}
numElts_ += qv.numElts();
numRanges_ += qv.numRanges();
if(qv.numRanges() > 0) {
nonzTot_++;
if(qv.numRanges() == 1 && qv.numElts() == 1) {
uniTot_++;
uniTotS_[seedFw ? 0 : 1]++;
} else {
repTot_++;
repTotS_[seedFw ? 0 : 1]++;
}
}
assert(repOk(&ac));
}
/**
* Clear buffered seed hits and state. Set the number of seed
* offsets and the read.
*/
void reset(
const Read& read,
const EList<uint32_t>& offIdx2off,
size_t numOffs)
{
assert_gt(numOffs, 0);
clearSeeds();
numOffs_ = numOffs;
seqFw_.resize(numOffs_);
seqRc_.resize(numOffs_);
qualFw_.resize(numOffs_);
qualRc_.resize(numOffs_);
hitsFw_.resize(numOffs_);
hitsRc_.resize(numOffs_);
isFw_.resize(numOffs_);
isRc_.resize(numOffs_);
sortedFw_.resize(numOffs_);
sortedRc_.resize(numOffs_);
offIdx2off_ = offIdx2off;
for(size_t i = 0; i < numOffs_; i++) {
sortedFw_[i] = sortedRc_[i] = false;
hitsFw_[i].reset();
hitsRc_[i].reset();
isFw_[i].clear();
isRc_[i].clear();
}
read_ = &read;
sorted_ = false;
}
/**
* Clear seed-hit state.
*/
void clearSeeds() {
sortedFw_.clear();
sortedRc_.clear();
rankOffs_.clear();
rankFws_.clear();
offIdx2off_.clear();
hitsFw_.clear();
hitsRc_.clear();
isFw_.clear();
isRc_.clear();
seqFw_.clear();
seqRc_.clear();
nonzTot_ = 0;
uniTot_ = uniTotS_[0] = uniTotS_[1] = 0;
repTot_ = repTotS_[0] = repTotS_[1] = 0;
nonzFw_ = 0;
nonzRc_ = 0;
numOffs_ = 0;
numRanges_ = 0;
numElts_ = 0;
numRangesFw_ = 0;
numEltsFw_ = 0;
numRangesRc_ = 0;
numEltsRc_ = 0;
}
/**
* Clear seed-hit state and end-to-end alignment state.
*/
void clear() {
clearSeeds();
read_ = NULL;
exactFwHit_.reset();
exactRcHit_.reset();
mm1Hit_.clear();
mm1Sorted_ = false;
mm1Elt_ = 0;
assert(empty());
}
/**
* Extract key summaries from this SeedResults and put into 'ssum'.
*/
void toSeedAlSumm(SeedAlSumm& ssum) const {
// Number of positions with at least 1 range
ssum.nonzTot = nonzTot_;
ssum.nonzFw = nonzFw_;
ssum.nonzRc = nonzRc_;
// Number of ranges
ssum.nrangeTot = numRanges_;
ssum.nrangeFw = numRangesFw_;
ssum.nrangeRc = numRangesRc_;
// Number of elements
ssum.neltTot = numElts_;
ssum.neltFw = numEltsFw_;
ssum.neltRc = numEltsRc_;
// Other summaries
ssum.maxNonzRangeFw = ssum.minNonzRangeFw = 0;
ssum.maxNonzRangeRc = ssum.minNonzRangeRc = 0;
ssum.maxNonzEltFw = ssum.minNonzEltFw = 0;
ssum.maxNonzEltRc = ssum.minNonzEltRc = 0;
for(size_t i = 0; i < numOffs_; i++) {
if(hitsFw_[i].valid()) {
if(ssum.minNonzEltFw == 0 || hitsFw_[i].numElts() < ssum.minNonzEltFw) {
ssum.minNonzEltFw = hitsFw_[i].numElts();
}
if(ssum.maxNonzEltFw == 0 || hitsFw_[i].numElts() > ssum.maxNonzEltFw) {
ssum.maxNonzEltFw = hitsFw_[i].numElts();
}
if(ssum.minNonzRangeFw == 0 || hitsFw_[i].numRanges() < ssum.minNonzRangeFw) {
ssum.minNonzRangeFw = hitsFw_[i].numRanges();
}
if(ssum.maxNonzRangeFw == 0 || hitsFw_[i].numRanges() > ssum.maxNonzRangeFw) {
ssum.maxNonzRangeFw = hitsFw_[i].numRanges();
}
}
if(hitsRc_[i].valid()) {
if(ssum.minNonzEltRc == 0 || hitsRc_[i].numElts() < ssum.minNonzEltRc) {
ssum.minNonzEltRc = hitsRc_[i].numElts();
}
if(ssum.maxNonzEltRc == 0 || hitsRc_[i].numElts() > ssum.maxNonzEltRc) {
ssum.maxNonzEltRc = hitsRc_[i].numElts();
}
if(ssum.minNonzRangeRc == 0 || hitsRc_[i].numRanges() < ssum.minNonzRangeRc) {
ssum.minNonzRangeRc = hitsRc_[i].numRanges();
}
if(ssum.maxNonzRangeRc == 0 || hitsRc_[i].numRanges() > ssum.maxNonzRangeRc) {
ssum.maxNonzRangeRc = hitsRc_[i].numRanges();
}
}
}
}
/**
* Return average number of hits per seed.
*/
uint64_t averageHitsPerSeed() const {
if (nonzTot_ == 0)
return std::numeric_limits<uint64_t>::max();
else
return numElts_ / nonzTot_;
}
/**
* Return fraction of seeds that align uniquely.
*/
size_t numUniqueSeeds() const {
return uniTot_;
}
/**
* Return fraction of seeds that aligned uniquely on the given strand.
*/
size_t numUniqueSeedsStrand(bool fw) const {
return uniTotS_[fw ? 0 : 1];
}
/**
* Return fraction of seeds that align repetitively on the given strand.
*/
size_t numRepeatSeeds() const {
return repTot_;
}
/**
* Return fraction of seeds that align repetitively.
*/
size_t numRepeatSeedsStrand(bool fw) const {
return repTotS_[fw ? 0 : 1];
}
/**
* Return median of all the non-zero per-seed # hits
*/
float medianHitsPerSeed() const {
EList<size_t>& median = const_cast<EList<size_t>&>(tmpMedian_);
median.clear();
for(size_t i = 0; i < numOffs_; i++) {
if(hitsFw_[i].valid() && hitsFw_[i].numElts() > 0) {
median.push_back(hitsFw_[i].numElts());
}
if(hitsRc_[i].valid() && hitsRc_[i].numElts() > 0) {
median.push_back(hitsRc_[i].numElts());
}
}
if(tmpMedian_.empty()) {
return 0.0f;
}
median.sort();
float med1 = (float)median[tmpMedian_.size() >> 1];
float med2 = med1;
if((median.size() & 1) == 0) {
med2 = (float)median[(tmpMedian_.size() >> 1) - 1];
}
return med1 + med2 * 0.5f;
}
/**
* Return a number that's meant to quantify how hopeful we are that this
* set of seed hits will lead to good alignments.
*/
double uniquenessFactor() const {
double result = 0.0;
for(size_t i = 0; i < numOffs_; i++) {
if(hitsFw_[i].valid()) {
size_t nelt = hitsFw_[i].numElts();
result += (1.0 / (double)(nelt * nelt));
}
if(hitsRc_[i].valid()) {
size_t nelt = hitsRc_[i].numElts();
result += (1.0 / (double)(nelt * nelt));
}
}
return result;
}
/**
* Return the number of ranges being held.
*/
size_t numRanges() const { return numRanges_; }
/**
* Return the number of elements being held.
*/
size_t numElts() const { return numElts_; }
/**
* Return the number of ranges being held for seeds on the forward
* read strand.
*/
size_t numRangesFw() const { return numRangesFw_; }
/**
* Return the number of elements being held for seeds on the
* forward read strand.
*/
size_t numEltsFw() const { return numEltsFw_; }
/**
* Return the number of ranges being held for seeds on the
* reverse-complement read strand.
*/
size_t numRangesRc() const { return numRangesRc_; }
/**
* Return the number of elements being held for seeds on the
* reverse-complement read strand.
*/
size_t numEltsRc() const { return numEltsRc_; }
/**
* Given an offset index, return the offset that has that index.
*/
size_t idx2off(size_t off) const {
return offIdx2off_[off];
}
/**
* Return true iff there are 0 hits being held.
*/
bool empty() const { return numRanges() == 0; }
/**
* Get the QVal representing all the reference hits for the given
* orientation and seed offset index.
*/
const QVal& hitsAtOffIdx(bool fw, size_t seedoffidx) const {
assert_lt(seedoffidx, numOffs_);
assert(repOk(NULL));
return fw ? hitsFw_[seedoffidx] : hitsRc_[seedoffidx];
}
/**
* Get the Instantiated seeds for the given orientation and offset.
*/
EList<InstantiatedSeed>& instantiatedSeeds(bool fw, size_t seedoffidx) {
assert_lt(seedoffidx, numOffs_);
assert(repOk(NULL));
return fw ? isFw_[seedoffidx] : isRc_[seedoffidx];
}
/**
* Return the number of different seed offsets possible.
*/
size_t numOffs() const { return numOffs_; }
/**
* Return the read from which seeds were extracted, aligned.
*/
const Read& read() const { return *read_; }
#ifndef NDEBUG
/**
* Check that this SeedResults is internally consistent.
*/
bool repOk(
const AlignmentCache* ac,
bool requireInited = false) const
{
if(requireInited) {
assert(read_ != NULL);
}
if(numOffs_ > 0) {
assert_eq(numOffs_, hitsFw_.size());
assert_eq(numOffs_, hitsRc_.size());
assert_leq(numRanges_, numElts_);
assert_leq(nonzTot_, numRanges_);
size_t nonzs = 0;
for(int fw = 0; fw <= 1; fw++) {
const EList<QVal>& rrs = (fw ? hitsFw_ : hitsRc_);
for(size_t i = 0; i < numOffs_; i++) {
if(rrs[i].valid()) {
if(rrs[i].numRanges() > 0) nonzs++;
if(ac != NULL) {
assert(rrs[i].repOk(*ac));
}
}
}
}
assert_eq(nonzs, nonzTot_);
assert(!sorted_ || nonzTot_ == rankFws_.size());
assert(!sorted_ || nonzTot_ == rankOffs_.size());
}
return true;
}
#endif
/**
* Populate rankOffs_ and rankFws_ with the list of QVals that need to be
* examined for this SeedResults, in order. The order is ascending by
* number of elements, so QVals with fewer elements (i.e. seed sequences
* that are more unique) will be tried first and QVals with more elements
* (i.e. seed sequences
*/
void rankSeedHits(RandomSource& rnd, bool all) {
if(all) {
for(uint32_t i = 1; i < numOffs_; i++) {
for(int fwi = 0; fwi <= 1; fwi++) {
bool fw = fwi == 0;
EList<QVal>& rrs = (fw ? hitsFw_ : hitsRc_);
if(rrs[i].valid() && rrs[i].numElts() > 0) {
rankOffs_.push_back(i);
rankFws_.push_back(fw);
}
}
}
if(hitsFw_[0].valid() && hitsFw_[0].numElts() > 0) {
rankOffs_.push_back(0);
rankFws_.push_back(true);
}
if(hitsRc_[0].valid() && hitsRc_[0].numElts() > 0) {
rankOffs_.push_back(0);
rankFws_.push_back(false);
}
} else {
while(rankOffs_.size() < nonzTot_) {
TIndexOffU minsz = MAX_U32;
uint32_t minidx = 0;
bool minfw = true;
// Rank seed-hit positions in ascending order by number of elements
// in all BW ranges
bool rb = rnd.nextBool();
assert(rb == 0 || rb == 1);
for(int fwi = 0; fwi <= 1; fwi++) {
bool fw = (fwi == (rb ? 1 : 0));
EList<QVal>& rrs = (fw ? hitsFw_ : hitsRc_);
EList<bool>& sorted = (fw ? sortedFw_ : sortedRc_);
uint32_t i = (rnd.nextU32() % (uint32_t)numOffs_);
for(uint32_t ii = 0; ii < numOffs_; ii++) {
if(rrs[i].valid() && // valid QVal
rrs[i].numElts() > 0 && // non-empty
!sorted[i] && // not already sorted
rrs[i].numElts() < minsz) // least elts so far?
{
minsz = rrs[i].numElts();
minidx = i;
minfw = (fw == 1);
}
if((++i) == numOffs_) {
i = 0;
}
}
}
assert_neq(MAX_U32, minsz);
if(minfw) {
sortedFw_[minidx] = true;
} else {
sortedRc_[minidx] = true;
}
rankOffs_.push_back(minidx);
rankFws_.push_back(minfw);
}
}
assert_eq(rankOffs_.size(), rankFws_.size());
sorted_ = true;
}
/**
* Return the number of orientation/offsets into the read that have
* at least one seed hit.
*/
size_t nonzeroOffsets() const {
assert(!sorted_ || nonzTot_ == rankFws_.size());
assert(!sorted_ || nonzTot_ == rankOffs_.size());
return nonzTot_;
}
/**
* Return true iff all seeds hit for forward read.
*/
bool allFwSeedsHit() const {
return nonzFw_ == numOffs();
}
/**
* Return true iff all seeds hit for revcomp read.
*/
bool allRcSeedsHit() const {
return nonzRc_ == numOffs();
}
/**
* Return the minimum number of edits that an end-to-end alignment of the
* fw read could have. Uses knowledge of how many seeds have exact hits
* and how the seeds overlap.
*/
size_t fewestEditsEE(bool fw, int seedlen, int per) const {
assert_gt(seedlen, 0);
assert_gt(per, 0);
size_t nonz = fw ? nonzFw_ : nonzRc_;
if(nonz < numOffs()) {
int maxdepth = (seedlen + per - 1) / per;
int missing = (int)(numOffs() - nonz);
return (missing + maxdepth - 1) / maxdepth;
} else {
// Exact hit is possible (not guaranteed)
return 0;
}
}
/**
* Return the number of offsets into the forward read that have at
* least one seed hit.
*/
size_t nonzeroOffsetsFw() const {
return nonzFw_;
}
/**
* Return the number of offsets into the reverse-complement read
* that have at least one seed hit.
*/
size_t nonzeroOffsetsRc() const {
return nonzRc_;
}
/**
* Return a QVal of seed hits of the given rank 'r'. 'offidx' gets the id
* of the offset from 5' from which it was extracted (0 for the 5-most
* offset, 1 for the next closes to 5', etc). 'off' gets the offset from
* the 5' end. 'fw' gets true iff the seed was extracted from the forward
* read.
*/
const QVal& hitsByRank(
size_t r, // in
uint32_t& offidx, // out
uint32_t& off, // out
bool& fw, // out
uint32_t& seedlen) // out
{
assert(sorted_);
assert_lt(r, nonzTot_);
if(rankFws_[r]) {
fw = true;
offidx = rankOffs_[r];
assert_lt(offidx, offIdx2off_.size());
off = offIdx2off_[offidx];
seedlen = (uint32_t)seqFw_[rankOffs_[r]].length();
return hitsFw_[rankOffs_[r]];
} else {
fw = false;
offidx = rankOffs_[r];
assert_lt(offidx, offIdx2off_.size());
off = offIdx2off_[offidx];
seedlen = (uint32_t)seqRc_[rankOffs_[r]].length();
return hitsRc_[rankOffs_[r]];
}
}
/**
* Return an EList of seed hits of the given rank.
*/
const BTDnaString& seqByRank(size_t r) {
assert(sorted_);
assert_lt(r, nonzTot_);
return rankFws_[r] ? seqFw_[rankOffs_[r]] : seqRc_[rankOffs_[r]];
}
/**
* Return an EList of seed hits of the given rank.
*/
const BTString& qualByRank(size_t r) {
assert(sorted_);
assert_lt(r, nonzTot_);
return rankFws_[r] ? qualFw_[rankOffs_[r]] : qualRc_[rankOffs_[r]];
}
/**
* Return the list of extracted seed sequences for seeds on either
* the forward or reverse strand.
*/
EList<BTDnaString>& seqs(bool fw) { return fw ? seqFw_ : seqRc_; }
/**
* Return the list of extracted quality sequences for seeds on
* either the forward or reverse strand.
*/
EList<BTString>& quals(bool fw) { return fw ? qualFw_ : qualRc_; }
/**
* Return exact end-to-end alignment of fw read.
*/
EEHit exactFwEEHit() const { return exactFwHit_; }
/**
* Return exact end-to-end alignment of rc read.
*/
EEHit exactRcEEHit() const { return exactRcHit_; }
/**
* Return const ref to list of 1-mismatch end-to-end alignments.
*/
const EList<EEHit>& mm1EEHits() const { return mm1Hit_; }
/**
* Sort the end-to-end 1-mismatch alignments, prioritizing by score (higher
* score = higher priority).
*/
void sort1mmEe(RandomSource& rnd) {
assert(!mm1Sorted_);
mm1Hit_.sort();
size_t streak = 0;
for(size_t i = 1; i < mm1Hit_.size(); i++) {
if(mm1Hit_[i].score == mm1Hit_[i-1].score) {
if(streak == 0) { streak = 1; }
streak++;
} else {
if(streak > 1) {
assert_geq(i, streak);
mm1Hit_.shufflePortion(i-streak, streak, rnd);
}
streak = 0;
}
}
if(streak > 1) {
mm1Hit_.shufflePortion(mm1Hit_.size() - streak, streak, rnd);
}
mm1Sorted_ = true;
}
/**
* Add an end-to-end 1-mismatch alignment.
*/
void add1mmEe(
TIndexOffU top,
TIndexOffU bot,
const Edit* e1,
const Edit* e2,
bool fw,
int64_t score)
{
mm1Hit_.expand();
mm1Hit_.back().init(top, bot, e1, e2, fw, score);
mm1Elt_ += (bot - top);
}
/**
* Add an end-to-end exact alignment.
*/
void addExactEeFw(
TIndexOffU top,
TIndexOffU bot,
const Edit* e1,
const Edit* e2,
bool fw,
int64_t score)
{
exactFwHit_.init(top, bot, e1, e2, fw, score);
}
/**
* Add an end-to-end exact alignment.
*/
void addExactEeRc(
TIndexOffU top,
TIndexOffU bot,
const Edit* e1,
const Edit* e2,
bool fw,
int64_t score)
{
exactRcHit_.init(top, bot, e1, e2, fw, score);
}
/**
* Clear out the end-to-end exact alignments.
*/
void clearExactE2eHits() {
exactFwHit_.reset();
exactRcHit_.reset();
}
/**
* Clear out the end-to-end 1-mismatch alignments.
*/
void clear1mmE2eHits() {
mm1Hit_.clear(); // 1-mismatch end-to-end hits
mm1Elt_ = 0; // number of 1-mismatch hit rows
mm1Sorted_ = false; // true iff we've sorted the mm1Hit_ list
}
/**
* Return the number of distinct exact and 1-mismatch end-to-end hits
* found.
*/
size_t numE2eHits() const {
return exactFwHit_.size() + exactRcHit_.size() + mm1Elt_;
}
/**
* Return the number of distinct exact end-to-end hits found.
*/
size_t numExactE2eHits() const {
return exactFwHit_.size() + exactRcHit_.size();
}
/**
* Return the number of distinct 1-mismatch end-to-end hits found.
*/
size_t num1mmE2eHits() const {
return mm1Elt_;
}
/**
* Return the length of the read that yielded the seed hits.
*/
size_t readLength() const {
assert(read_ != NULL);
return read_->length();
}
protected:
// As seed hits and edits are added they're sorted into these
// containers
EList<BTDnaString> seqFw_; // seqs for seeds from forward read
EList<BTDnaString> seqRc_; // seqs for seeds from revcomp read
EList<BTString> qualFw_; // quals for seeds from forward read
EList<BTString> qualRc_; // quals for seeds from revcomp read
EList<QVal> hitsFw_; // hits for forward read
EList<QVal> hitsRc_; // hits for revcomp read
EList<EList<InstantiatedSeed> > isFw_; // hits for forward read
EList<EList<InstantiatedSeed> > isRc_; // hits for revcomp read
EList<bool> sortedFw_; // true iff fw QVal was sorted/ranked
EList<bool> sortedRc_; // true iff rc QVal was sorted/ranked
size_t nonzTot_; // # offsets with non-zero size
size_t uniTot_; // # offsets unique hit
size_t uniTotS_[2]; // # offsets unique hit on each strand
size_t repTot_; // # offsets repetitive hit
size_t repTotS_[2]; // # offsets repetitive hit on each strand
size_t nonzFw_; // # offsets into fw read with non-0 size
size_t nonzRc_; // # offsets into rc read with non-0 size
size_t numRanges_; // # ranges added
size_t numElts_; // # elements added
size_t numRangesFw_; // # ranges added for fw seeds
size_t numEltsFw_; // # elements added for fw seeds
size_t numRangesRc_; // # ranges added for rc seeds
size_t numEltsRc_; // # elements added for rc seeds
EList<uint32_t> offIdx2off_;// map from offset indexes to offsets from 5' end
// When the sort routine is called, the seed hits collected so far
// are sorted into another set of containers that allow easy access
// to hits from the lowest-ranked offset (the one with the fewest
// BW elements) to the greatest-ranked offset. Offsets with 0 hits
// are ignored.
EList<uint32_t> rankOffs_; // sorted offests of seeds to try
EList<bool> rankFws_; // sorted orientations assoc. with rankOffs_
bool sorted_; // true if sort() called since last reset
// These fields set once per read
size_t numOffs_; // # different seed offsets possible
const Read* read_; // read from which seeds were extracted
EEHit exactFwHit_; // end-to-end exact hit for fw read
EEHit exactRcHit_; // end-to-end exact hit for rc read
EList<EEHit> mm1Hit_; // 1-mismatch end-to-end hits
size_t mm1Elt_; // number of 1-mismatch hit rows
bool mm1Sorted_; // true iff we've sorted the mm1Hit_ list
EList<size_t> tmpMedian_; // temporary storage for calculating median
};
// Forward decl
class Ebwt;
struct SideLocus;
/**
* Encapsulates a sumamry of what the searchAllSeeds aligner did.
*/
struct SeedSearchMetrics {
SeedSearchMetrics() : mutex_m() {
reset();
}
/**
* Merge this metrics object with the given object, i.e., sum each
* category. This is the only safe way to update a
* SeedSearchMetrics object shread by multiple threads.
*/
void merge(const SeedSearchMetrics& m, bool getLock = false) {
seedsearch += m.seedsearch;
nrange += m.nrange;
nelt += m.nelt;
possearch += m.possearch;
intrahit += m.intrahit;
interhit += m.interhit;
filteredseed += m.filteredseed;
ooms += m.ooms;
bwops += m.bwops;
bweds += m.bweds;
bestmin0 += m.bestmin0;
bestmin1 += m.bestmin1;
bestmin2 += m.bestmin2;
}
/**
* Set all counters to 0.
*/
void reset() {
seedsearch =
nrange =
nelt =
possearch =
intrahit =
interhit =
filteredseed =
ooms =
bwops =
bweds =
bestmin0 =
bestmin1 =
bestmin2 = 0;
}
uint64_t seedsearch; // # times we executed strategy in InstantiatedSeed
uint64_t nrange; // # ranges found
uint64_t nelt; // # range elements found
uint64_t possearch; // # offsets where aligner executed >= 1 strategy
uint64_t intrahit; // # offsets where current-read cache gave answer
uint64_t interhit; // # offsets where across-read cache gave answer
uint64_t filteredseed; // # seed instantiations skipped due to Ns
uint64_t ooms; // out-of-memory errors
uint64_t bwops; // Burrows-Wheeler operations
uint64_t bweds; // Burrows-Wheeler edits
uint64_t bestmin0; // # times the best min # edits was 0
uint64_t bestmin1; // # times the best min # edits was 1
uint64_t bestmin2; // # times the best min # edits was 2
MUTEX_T mutex_m;
};
/**
* Wrap the search cache with all the relevant objects
*/
class SeedSearchCache {
public:
SeedSearchCache(
const BTDnaString& _seq, // sequence of current seed
const BTString& _qual // quality string for current seed
)
: qv()
, seq(_seq)
, qual(_qual)
, cachedEls()
, cachep(NULL)
{
cachedEls.reserve(16); // do not expect I will need more
}
/**
* This function is called whenever we start to align a new read or
* read substring.
*
* See AlignmentCacheIface::beginAlign for details
*/
int beginAlign(AlignmentCacheIface& cache)
{
int ret = cache.beginAlign(seq, qual, qv);
if (ret>=0) {
cachep = &cache;
}
return ret;
}
/**
* Add an alignment to the running list of alignments being
* compiled for the current read in the local cache.
*/
bool addAllCached(bool getLock = true)
{
if (!aligning()) return false;
const size_t nEls = cachedEls.size();
bool success = true;
for(size_t i=0; i<nEls; i++) {
AddEl &el = cachedEls[i];
success &= cachep->addOnTheFly(el.sak, el.topf, el.botf, el.topb, el.botb, getLock);
}
cachedEls.clear();
return success;
}
/**
* Called when is finished aligning a read (and so is finished
* adding associated reference strings). Returns a copy of the
* final QVal object and resets the alignment state of the
* current-read cache.
*
* Also, if the alignment is cacheable, it commits it to the next
* cache up in the cache hierarchy.
*/
void finishAlign(bool getLock = true)
{
assert(cachep!=NULL);
qv = cachep->finishAlign(getLock);
cachep = NULL;
}
/**
* Add an alignment to the running list of alignments being
* compiled for the current read in the local memory buffer.
*/
void addOnTheFly(
const BTDnaString& rfseq, // reference sequence close to read seq
TIndexOffU topf, // top in BWT index
TIndexOffU botf, // bot in BWT index
TIndexOffU topb, // top in BWT' index
TIndexOffU botb) // bot in BWT' index
{
cachedEls.emplace_back(rfseq, topf, botf, topb, botb);
}
/**
* Return true iff we're in the middle of aligning a sequence.
*/
bool aligning() const { return ((cachep!=NULL) && (cachep->aligning())); }
bool qvValid() const { return qv.valid();}
const QVal& getQv() const {return qv;}
const BTDnaString& getSeq() const {return seq;}
const BTString& getQual() const {return qual;}
protected:
class AddEl {
public:
AddEl(
const BTDnaString& rfseq, // reference sequence close to read seq
TIndexOffU _topf, // top in BWT index
TIndexOffU _botf, // bot in BWT index
TIndexOffU _topb, // top in BWT' index
TIndexOffU _botb // bot in BWT' index
) :
ASSERT_ONLY(tmp(), )
sak(rfseq ASSERT_ONLY(, tmp)),
topf(_topf), botf(_botf), topb(_topb), botb(_botb)
{}
ASSERT_ONLY(BTDnaString tmp;)
SAKey sak;
TIndexOffU topf; // top in BWT index
TIndexOffU botf; // bot in BWT index
TIndexOffU topb; // top in BWT' index
TIndexOffU botb; // bot in BWT' index
};
QVal qv;
const BTDnaString& seq; // sequence of current seed
const BTString& qual; // quality string for current seed
std::vector<AddEl> cachedEls; // tmp storage of values that will go in the cache
AlignmentCacheIface* cachep; // local alignment cache for seed alignment, set at beginAliginings
};
/**
* Wrap the search cache with all the relevant objects
*/
class SeedSearchMultiCache {
public:
SeedSearchMultiCache(
)
: cacheVec()
{}
void emplace_back(
const BTDnaString& seq, // sequence of current seed
const BTString& qual, // quality string for current seed
int seedoffidx, // seed index
bool fw // is it fw?
)
{
cacheVec.emplace_back(seq, qual, seedoffidx, fw);
}
// Same semantics as std::vector
void reserve(size_t new_cap) { cacheVec.reserve(new_cap); }
size_t size() const {return cacheVec.size(); }
void clear() { cacheVec.clear(); }
void pop_back() { cacheVec.pop_back(); }
// Access one of the search caches
const SeedSearchCache& operator[](size_t idx) const { return cacheVec[idx].srcache; }
SeedSearchCache& operator[](size_t idx) { return cacheVec[idx].srcache; }
int getSeedOffIdx(size_t idx) const { return cacheVec[idx].seedoffidx; }
bool getFw(size_t idx) const { return cacheVec[idx].fw; }
protected:
class CacheEl {
public:
CacheEl(
const BTDnaString& _seq, // sequence of current seed
const BTString& _qual, // quality string for current seed
int _seedoffidx, // seed index
bool _fw // is it fw?
)
: srcache(_seq, _qual)
, seedoffidx(_seedoffidx)
, fw(_fw) {}
SeedSearchCache srcache; // search wrapper
int seedoffidx; // seed index
bool fw; // is it fw?
};
std::vector<CacheEl> cacheVec;
};
/**
* Given an index and a seeding scheme, searches for seed hits.
*/
class SeedAligner {
public:
/**
* Initialize with index.
*/
SeedAligner() : edits_(AL_CAT), offIdx2off_(AL_CAT) { }
/**
* Given a read and a few coordinates that describe a substring of the
* read (or its reverse complement), fill in 'seq' and 'qual' objects
* with the seed sequence and qualities.
*/
void instantiateSeq(
const Read& read, // input read
BTDnaString& seq, // output sequence
BTString& qual, // output qualities
int len, // seed length
int depth, // seed's 0-based offset from 5' end
bool fw) const; // seed's orientation
/**
* Iterate through the seeds that cover the read and initiate a
* search for each seed.
*/
std::pair<int, int> instantiateSeeds(
const EList<Seed>& seeds, // search seeds
size_t off, // offset into read to start extracting
int per, // interval between seeds
const Read& read, // read to align
const Scoring& pens, // scoring scheme
bool nofw, // don't align forward read
bool norc, // don't align revcomp read
AlignmentCacheIface& cache, // holds some seed hits from previous reads
SeedResults& sr, // holds all the seed hits
SeedSearchMetrics& met, // metrics
std::pair<int, int>& instFw,
std::pair<int, int>& instRc);
/**
* Iterate through the seeds that cover the read and initiate a
* search for each seed.
*/
void searchAllSeeds(
const EList<Seed>& seeds, // search seeds
const Ebwt* ebwtFw, // BWT index
const Ebwt* ebwtBw, // BWT' index
const Read& read, // read to align
const Scoring& pens, // scoring scheme
size_t ncut_f, // min seed quality for BWT
AlignmentCacheIface& cache, // local seed alignment cache
SeedResults& hits, // holds all the seed hits
SeedSearchMetrics& met, // metrics
PerReadMetrics& prm); // per-read metrics
/**
* Sanity-check a partial alignment produced during oneMmSearch.
*/
bool sanityPartial(
const Ebwt* ebwtFw, // BWT index
const Ebwt* ebwtBw, // BWT' index
const BTDnaString& seq,
size_t dep,
size_t len,
bool do1mm,
TIndexOffU topfw,
TIndexOffU botfw,
TIndexOffU topbw,
TIndexOffU botbw);
/**
* Do an exact-matching sweet to establish a lower bound on number of edits
* and to find exact alignments.
*/
size_t exactSweep(
const Ebwt& ebwt, // BWT index
const Read& read, // read to align
const Scoring& sc, // scoring scheme
bool nofw, // don't align forward read
bool norc, // don't align revcomp read
size_t mineMax, // don't care about edit bounds > this
size_t& mineFw, // minimum # edits for forward read
size_t& mineRc, // minimum # edits for revcomp read
bool repex, // report 0mm hits?
SeedResults& hits, // holds all the seed hits (and exact hit)
SeedSearchMetrics& met); // metrics
/**
* Search for end-to-end alignments with up to 1 mismatch.
*/
bool oneMmSearch(
const Ebwt* ebwtFw, // BWT index
const Ebwt* ebwtBw, // BWT' index
const Read& read, // read to align
const Scoring& sc, // scoring
int64_t minsc, // minimum score
bool nofw, // don't align forward read
bool norc, // don't align revcomp read
bool local, // 1mm hits must be legal local alignments
bool repex, // report 0mm hits?
bool rep1mm, // report 1mm hits?
SeedResults& hits, // holds all the seed hits (and exact hit)
SeedSearchMetrics& met); // metrics
protected:
class SeedAlignerSearchParams;
/**
* Report a seed hit found by searchSeedBi(), but first try to extend it out in
* either direction as far as possible without hitting any edits. This will
* allow us to prioritize the seed hits better later on. Call reportHit() when
* we're done, which actually adds the hit to the cache. Returns result from
* calling reportHit().
*/
void extendAndReportHit(
SeedSearchCache &cache, // local seed alignment cache
size_t off, // offset of seed currently being searched
bool fw, // orientation of seed currently being searched
TIndexOffU topf, // top in BWT
TIndexOffU botf, // bot in BWT
TIndexOffU topb, // top in BWT'
TIndexOffU botb, // bot in BWT'
uint16_t len, // length of hit
DoublyLinkedList<Edit> *prevEdit); // previous edit
/**
* Report a seed hit found by searchSeedBi() by adding it to the cache.
*/
void reportHit(
SeedSearchCache &cache, // local seed alignment cache
TIndexOffU topf, // top in BWT
TIndexOffU botf, // bot in BWT
TIndexOffU topb, // top in BWT'
TIndexOffU botb, // bot in BWT'
uint16_t len, // length of hit
DoublyLinkedList<Edit> *prevEdit); // previous edit
void reportHit(
SeedSearchCache &cache, // local seed alignment cache
const BwtTopBot &bwt, // The 4 BWT idxs
uint16_t len, // length of hit
DoublyLinkedList<Edit> *prevEdit) // previous edit
{ reportHit(cache, bwt.topf, bwt.botf, bwt.topb, bwt.botb, len, prevEdit); }
/**
* Main, recursive implementation of the seed search.
* Given a vector of instantiated seeds, search
*/
void searchSeedBi(const size_t nparams, SeedAlignerSearchParams paramVec[]);
// helper function
bool startSearchSeedBi(SeedAlignerSearchParams &p);
/**
* Get tloc and bloc ready for the next step.
*/
void nextLocsBi(
const InstantiatedSeed& seed, // current instantiated seed
SideLocus& tloc, // top locus
SideLocus& bloc, // bot locus
TIndexOffU topf, // top in BWT
TIndexOffU botf, // bot in BWT
TIndexOffU topb, // top in BWT'
TIndexOffU botb, // bot in BWT'
int step); // step to get ready for
void nextLocsBi(
const InstantiatedSeed& seed, // current instantiated seed
SideLocus& tloc, // top locus
SideLocus& bloc, // bot locus
const BwtTopBot &bwt, // The 4 BWT idxs
int step) // step to get ready for
{ nextLocsBi(seed, tloc, bloc, bwt.topf, bwt.botf, bwt.topb, bwt.botb, step); }
void prefetchNextLocsBi(
const InstantiatedSeed& seed, // current instantiated seed
TIndexOffU topf, // top in BWT
TIndexOffU botf, // bot in BWT
TIndexOffU topb, // top in BWT'
TIndexOffU botb, // bot in BWT'
int step); // step to get ready for
void prefetchNextLocsBi(
const InstantiatedSeed& seed, // current instantiated seed
const BwtTopBot &bwt, // The 4 BWT idxs
int step) // step to get ready for
{ prefetchNextLocsBi(seed, bwt.topf, bwt.botf, bwt.topb, bwt.botb, step); }
// Following are set in searchAllSeeds then used by searchSeed()
// and other protected members.
const Ebwt* ebwtFw_; // forward index (BWT)
const Ebwt* ebwtBw_; // backward/mirror index (BWT')
const Scoring* sc_; // scoring scheme
const Read* read_; // read whose seeds are currently being aligned
size_t ncut_f_; // min seed quality for BWT
EList<Edit> edits_; // temporary place to sort edits
EList<uint32_t> offIdx2off_;// offset idx to read offset map, set up instantiateSeeds()
uint64_t bwops_; // Burrows-Wheeler operations
uint64_t bwedits_; // Burrows-Wheeler edits
BTDnaString tmprfdnastr_; // used in reportHit
ASSERT_ONLY(ESet<BTDnaString> hits_); // Ref hits so far for seed being aligned
BTDnaString tmpdnastr_;
};
#define INIT_LOCS(top, bot, tloc, bloc, e) { \
if(bot - top == 1) { \
tloc.initFromRow(top, (e).eh(), (e).ebwt()); \
bloc.invalidate(); \
} else { \
SideLocus::initFromTopBot(top, bot, (e).eh(), (e).ebwt(), tloc, bloc); \
assert(bloc.valid()); \
} \
}
#define SANITY_CHECK_4TUP(t, b, tp, bp) { \
ASSERT_ONLY(TIndexOffU tot = (b[0]-t[0])+(b[1]-t[1])+(b[2]-t[2])+(b[3]-t[3])); \
ASSERT_ONLY(TIndexOffU totp = (bp[0]-tp[0])+(bp[1]-tp[1])+(bp[2]-tp[2])+(bp[3]-tp[3])); \
assert_eq(tot, totp); \
}
#endif /*ALIGNER_SEED_H_*/
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