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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/>.
*/
#include "aligner_cache.h"
#include "aligner_seed.h"
#include "search_globals.h"
#include "gfm.h"
using namespace std;
/**
* Construct a constraint with no edits of any kind allowed.
*/
Constraint Constraint::exact() {
Constraint c;
c.edits = c.mms = c.ins = c.dels = c.penalty = 0;
return c;
}
/**
* Construct a constraint where the only constraint is a total
* penalty constraint.
*/
Constraint Constraint::penaltyBased(int pen) {
Constraint c;
c.penalty = pen;
return c;
}
/**
* Construct a constraint where the only constraint is a total
* penalty constraint related to the length of the read.
*/
Constraint Constraint::penaltyFuncBased(const SimpleFunc& f) {
Constraint c;
c.penFunc = f;
return c;
}
/**
* Construct a constraint where the only constraint is a total
* penalty constraint.
*/
Constraint Constraint::mmBased(int mms) {
Constraint c;
c.mms = mms;
c.edits = c.dels = c.ins = 0;
return c;
}
/**
* Construct a constraint where the only constraint is a total
* penalty constraint.
*/
Constraint Constraint::editBased(int edits) {
Constraint c;
c.edits = edits;
c.dels = c.ins = c.mms = 0;
return c;
}
//
// Some static methods for constructing some standard SeedPolicies
//
/**
* 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
Seed::instantiate(
const Read& read,
const BTDnaString& seq, // seed read sequence
const BTString& qual, // seed quality sequence
const Scoring& pens,
int depth,
int seedoffidx,
int seedtypeidx,
bool fw,
InstantiatedSeed& is) const
{
assert(overall != NULL);
int seedlen = len;
if((int)read.length() < seedlen) {
// Shrink seed length to fit read if necessary
seedlen = (int)read.length();
}
assert_gt(seedlen, 0);
is.steps.resize(seedlen);
is.zones.resize(seedlen);
// Fill in 'steps' and 'zones'
//
// The 'steps' list indicates which read character should be
// incorporated at each step of the search process. Often we will
// simply proceed from one end to the other, in which case the
// 'steps' list is ascending or descending. In some cases (e.g.
// the 2mm case), we might want to switch directions at least once
// during the search, in which case 'steps' will jump in the
// middle. When an element of the 'steps' list is negative, this
// indicates that the next
//
// The 'zones' list indicates which zone constraint is active at
// each step. Each element of the 'zones' list is a pair; the
// first pair element indicates the applicable zone when
// considering either mismatch or delete (ref gap) events, while
// the second pair element indicates the applicable zone when
// considering insertion (read gap) events. When either pair
// element is a negative number, that indicates that we are about
// to leave the zone for good, at which point we may need to
// evaluate whether we have reached the zone's budget.
//
switch(type) {
case SEED_TYPE_EXACT: {
for(int k = 0; k < seedlen; k++) {
is.steps[k] = -(seedlen - k);
// Zone 0 all the way
is.zones[k].first = is.zones[k].second = 0;
}
break;
}
case SEED_TYPE_LEFT_TO_RIGHT: {
for(int k = 0; k < seedlen; k++) {
is.steps[k] = k+1;
// Zone 0 from 0 up to ceil(len/2), then 1
is.zones[k].first = is.zones[k].second = ((k < (seedlen+1)/2) ? 0 : 1);
}
// Zone 1 ends at the RHS
is.zones[seedlen-1].first = is.zones[seedlen-1].second = -1;
break;
}
case SEED_TYPE_RIGHT_TO_LEFT: {
for(int k = 0; k < seedlen; k++) {
is.steps[k] = -(seedlen - k);
// Zone 0 from 0 up to floor(len/2), then 1
is.zones[k].first = ((k < seedlen/2) ? 0 : 1);
// Inserts: Zone 0 from 0 up to ceil(len/2)-1, then 1
is.zones[k].second = ((k < (seedlen+1)/2+1) ? 0 : 1);
}
is.zones[seedlen-1].first = is.zones[seedlen-1].second = -1;
break;
}
case SEED_TYPE_INSIDE_OUT: {
// Zone 0 from ceil(N/4) up to N-floor(N/4)
int step = 0;
for(int k = (seedlen+3)/4; k < seedlen - (seedlen/4); k++) {
is.zones[step].first = is.zones[step].second = 0;
is.steps[step++] = k+1;
}
// Zone 1 from N-floor(N/4) up
for(int k = seedlen - (seedlen/4); k < seedlen; k++) {
is.zones[step].first = is.zones[step].second = 1;
is.steps[step++] = k+1;
}
// No Zone 1 if seedlen is short (like 2)
//assert_eq(1, is.zones[step-1].first);
is.zones[step-1].first = is.zones[step-1].second = -1;
// Zone 2 from ((seedlen+3)/4)-1 down to 0
for(int k = ((seedlen+3)/4)-1; k >= 0; k--) {
is.zones[step].first = is.zones[step].second = 2;
is.steps[step++] = -(k+1);
}
assert_eq(2, is.zones[step-1].first);
is.zones[step-1].first = is.zones[step-1].second = -2;
assert_eq(seedlen, step);
break;
}
default:
throw 1;
}
// Instantiate constraints
for(int i = 0; i < 3; i++) {
is.cons[i] = zones[i];
is.cons[i].instantiate(read.length());
}
is.overall = *overall;
is.overall.instantiate(read.length());
// Take a sweep through the seed sequence. Consider where the Ns
// occur and how zones are laid out. Calculate the maximum number
// of positions we can jump over initially (e.g. with the ftab) and
// perhaps set this function's return value to false, indicating
// that the arrangements of Ns prevents the seed from aligning.
bool streak = true;
is.maxjump = 0;
bool ret = true;
bool ltr = (is.steps[0] > 0); // true -> left-to-right
for(size_t i = 0; i < is.steps.size(); i++) {
assert_neq(0, is.steps[i]);
int off = is.steps[i];
off = abs(off)-1;
Constraint& cons = is.cons[abs(is.zones[i].first)];
int c = seq[off]; assert_range(0, 4, c);
int q = qual[off];
if(ltr != (is.steps[i] > 0) || // changed direction
is.zones[i].first != 0 || // changed zone
is.zones[i].second != 0) // changed zone
{
streak = false;
}
if(c == 4) {
// Induced mismatch
if(cons.canN(q, pens)) {
cons.chargeN(q, pens);
} else {
// Seed disqualified due to arrangement of Ns
return false;
}
}
if(streak) is.maxjump++;
}
is.seedoff = depth;
is.seedoffidx = seedoffidx;
is.fw = fw;
is.s = *this;
return ret;
}
/**
* Return a set consisting of 1 seed encapsulating an exact matching
* strategy.
*/
void
Seed::zeroMmSeeds(int ln, EList<Seed>& pols, Constraint& oall) {
oall.init();
// Seed policy 1: left-to-right search
pols.expand();
pols.back().len = ln;
pols.back().type = SEED_TYPE_EXACT;
pols.back().zones[0] = Constraint::exact();
pols.back().zones[1] = Constraint::exact();
pols.back().zones[2] = Constraint::exact(); // not used
pols.back().overall = &oall;
}
/**
* Return a set of 2 seeds encapsulating a half-and-half 1mm strategy.
*/
void
Seed::oneMmSeeds(int ln, EList<Seed>& pols, Constraint& oall) {
oall.init();
// Seed policy 1: left-to-right search
pols.expand();
pols.back().len = ln;
pols.back().type = SEED_TYPE_LEFT_TO_RIGHT;
pols.back().zones[0] = Constraint::exact();
pols.back().zones[1] = Constraint::mmBased(1);
pols.back().zones[2] = Constraint::exact(); // not used
pols.back().overall = &oall;
// Seed policy 2: right-to-left search
pols.expand();
pols.back().len = ln;
pols.back().type = SEED_TYPE_RIGHT_TO_LEFT;
pols.back().zones[0] = Constraint::exact();
pols.back().zones[1] = Constraint::mmBased(1);
pols.back().zones[1].mmsCeil = 0;
pols.back().zones[2] = Constraint::exact(); // not used
pols.back().overall = &oall;
}
/**
* Return a set of 3 seeds encapsulating search roots for:
*
* 1. Starting from the left-hand side and searching toward the
* right-hand side allowing 2 mismatches in the right half.
* 2. Starting from the right-hand side and searching toward the
* left-hand side allowing 2 mismatches in the left half.
* 3. Starting (effectively) from the center and searching out toward
* both the left and right-hand sides, allowing one mismatch on
* either side.
*
* This is not exhaustive. There are 2 mismatch cases mised; if you
* imagine the seed as divided into four successive quarters A, B, C
* and D, the cases we miss are when mismatches occur in A and C or B
* and D.
*/
void
Seed::twoMmSeeds(int ln, EList<Seed>& pols, Constraint& oall) {
oall.init();
// Seed policy 1: left-to-right search
pols.expand();
pols.back().len = ln;
pols.back().type = SEED_TYPE_LEFT_TO_RIGHT;
pols.back().zones[0] = Constraint::exact();
pols.back().zones[1] = Constraint::mmBased(2);
pols.back().zones[2] = Constraint::exact(); // not used
pols.back().overall = &oall;
// Seed policy 2: right-to-left search
pols.expand();
pols.back().len = ln;
pols.back().type = SEED_TYPE_RIGHT_TO_LEFT;
pols.back().zones[0] = Constraint::exact();
pols.back().zones[1] = Constraint::mmBased(2);
pols.back().zones[1].mmsCeil = 1; // Must have used at least 1 mismatch
pols.back().zones[2] = Constraint::exact(); // not used
pols.back().overall = &oall;
// Seed policy 3: inside-out search
pols.expand();
pols.back().len = ln;
pols.back().type = SEED_TYPE_INSIDE_OUT;
pols.back().zones[0] = Constraint::exact();
pols.back().zones[1] = Constraint::mmBased(1);
pols.back().zones[1].mmsCeil = 0; // Must have used at least 1 mismatch
pols.back().zones[2] = Constraint::mmBased(1);
pols.back().zones[2].mmsCeil = 0; // Must have used at least 1 mismatch
pols.back().overall = &oall;
}
/**
* Types of actions that can be taken by the SeedAligner.
*/
enum {
SA_ACTION_TYPE_RESET = 1,
SA_ACTION_TYPE_SEARCH_SEED, // 2
SA_ACTION_TYPE_FTAB, // 3
SA_ACTION_TYPE_FCHR, // 4
SA_ACTION_TYPE_MATCH, // 5
SA_ACTION_TYPE_EDIT // 6
};
#define MIN(x, y) ((x < y) ? x : y)
#ifdef ALIGNER_SEED_MAIN
#include <getopt.h>
#include <string>
/**
* Parse an int out of optarg and enforce that it be at least 'lower';
* if it is less than 'lower', than output the given error message and
* exit with an error and a usage message.
*/
static int parseInt(const char *errmsg, const char *arg) {
long l;
char *endPtr = NULL;
l = strtol(arg, &endPtr, 10);
if (endPtr != NULL) {
return (int32_t)l;
}
cerr << errmsg << endl;
throw 1;
return -1;
}
enum {
ARG_NOFW = 256,
ARG_NORC,
ARG_MM,
ARG_SHMEM,
ARG_TESTS,
ARG_RANDOM_TESTS,
ARG_SEED
};
static const char *short_opts = "vCt";
static struct option long_opts[] = {
{(char*)"verbose", no_argument, 0, 'v'},
{(char*)"color", no_argument, 0, 'C'},
{(char*)"timing", no_argument, 0, 't'},
{(char*)"nofw", no_argument, 0, ARG_NOFW},
{(char*)"norc", no_argument, 0, ARG_NORC},
{(char*)"mm", no_argument, 0, ARG_MM},
{(char*)"shmem", no_argument, 0, ARG_SHMEM},
{(char*)"tests", no_argument, 0, ARG_TESTS},
{(char*)"random", required_argument, 0, ARG_RANDOM_TESTS},
{(char*)"seed", required_argument, 0, ARG_SEED},
};
static void printUsage(ostream& os) {
os << "Usage: ac [options]* <index> <patterns>" << endl;
os << "Options:" << endl;
os << " --mm memory-mapped mode" << endl;
os << " --shmem shared memory mode" << endl;
os << " --nofw don't align forward-oriented read" << endl;
os << " --norc don't align reverse-complemented read" << endl;
os << " -t/--timing show timing information" << endl;
os << " -C/--color colorspace mode" << endl;
os << " -v/--verbose talkative mode" << endl;
}
bool gNorc = false;
bool gNofw = false;
bool gColor = false;
int gVerbose = 0;
int gGapBarrier = 1;
bool gColorExEnds = true;
int gSnpPhred = 30;
bool gReportOverhangs = true;
extern void aligner_seed_tests();
extern void aligner_random_seed_tests(
int num_tests,
uint32_t qslo,
uint32_t qshi,
bool color,
uint32_t seed);
/**
* A way of feeding simply tests to the seed alignment infrastructure.
*/
int main(int argc, char **argv) {
bool useMm = false;
bool useShmem = false;
bool mmSweep = false;
bool noRefNames = false;
bool sanity = false;
bool timing = false;
int option_index = 0;
int seed = 777;
int next_option;
do {
next_option = getopt_long(
argc, argv, short_opts, long_opts, &option_index);
switch (next_option) {
case 'v': gVerbose = true; break;
case 'C': gColor = true; break;
case 't': timing = true; break;
case ARG_NOFW: gNofw = true; break;
case ARG_NORC: gNorc = true; break;
case ARG_MM: useMm = true; break;
case ARG_SHMEM: useShmem = true; break;
case ARG_SEED: seed = parseInt("", optarg); break;
case ARG_TESTS: {
aligner_seed_tests();
aligner_random_seed_tests(
100, // num references
100, // queries per reference lo
400, // queries per reference hi
false, // true -> generate colorspace reference/reads
18); // pseudo-random seed
return 0;
}
case ARG_RANDOM_TESTS: {
seed = parseInt("", optarg);
aligner_random_seed_tests(
100, // num references
100, // queries per reference lo
400, // queries per reference hi
false, // true -> generate colorspace reference/reads
seed); // pseudo-random seed
return 0;
}
case -1: break;
default: {
cerr << "Unknown option: " << (char)next_option << endl;
printUsage(cerr);
exit(1);
}
}
} while(next_option != -1);
char *reffn;
if(optind >= argc) {
cerr << "No reference; quitting..." << endl;
return 1;
}
reffn = argv[optind++];
if(optind >= argc) {
cerr << "No reads; quitting..." << endl;
return 1;
}
string gfmBase(reffn);
BitPairReference ref(
gfmBase, // base path
gColor, // whether we expect it to be colorspace
sanity, // whether to sanity-check reference as it's loaded
NULL, // fasta files to sanity check reference against
NULL, // another way of specifying original sequences
false, // true -> infiles (2 args ago) contains raw seqs
useMm, // use memory mapping to load index?
useShmem, // use shared memory (not memory mapping)
mmSweep, // touch all the pages after memory-mapping the index
gVerbose, // verbose
gVerbose); // verbose but just for startup messages
Timer *t = new Timer(cerr, "Time loading fw index: ", timing);
GFM gfmFw(
gfmBase,
0, // don't need entireReverse for fw index
true, // index is for the forward direction
-1, // offrate (irrelevant)
useMm, // whether to use memory-mapped files
useShmem, // whether to use shared memory
mmSweep, // sweep memory-mapped files
!noRefNames, // load names?
false, // load SA sample?
true, // load ftab?
true, // load rstarts?
NULL, // reference map, or NULL if none is needed
gVerbose, // whether to be talkative
gVerbose, // talkative during initialization
false, // handle memory exceptions, don't pass them up
sanity);
delete t;
t = new Timer(cerr, "Time loading bw index: ", timing);
GFM gfmBw(
gfmBase + ".rev",
1, // need entireReverse
false, // index is for the backward direction
-1, // offrate (irrelevant)
useMm, // whether to use memory-mapped files
useShmem, // whether to use shared memory
mmSweep, // sweep memory-mapped files
!noRefNames, // load names?
false, // load SA sample?
true, // load ftab?
false, // load rstarts?
NULL, // reference map, or NULL if none is needed
gVerbose, // whether to be talkative
gVerbose, // talkative during initialization
false, // handle memory exceptions, don't pass them up
sanity);
delete t;
for(int i = optind; i < argc; i++) {
}
}
#endif
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