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static char rcsid[] = "$Id: stage2.c 202031 2016-12-29 16:20:14Z twu $";
#ifdef HAVE_CONFIG_H
#include <config.h>
#endif
#include "stage2.h"
#include <stdio.h>
#include <stdlib.h>
#include <string.h>
#include <math.h>
#include "assert.h"
#include "mem.h"
#include "comp.h"
#include "pair.h"
#include "pairdef.h"
#include "listdef.h"
#include "intlist.h"
#include "intlistdef.h"
#include "diag.h"
#include "genome_sites.h"
#include "complement.h"
#include "maxent_hr.h"
/* Tests whether genomicseg == query in convert_to_nucleotides, and
whether oligoindex_hr gives same results as oligoindex */
/* #define EXTRACT_GENOMICSEG 1 */
/* #define USE_DIAGPOOL 1 -- Defined in diagpool.h */
/* #define SQUARE 1 */
#define SUFF_PCTCOVERAGE_OLIGOINDEX 0.90
/* #define SUFF_PCTCOVERAGE_STAGE2 0.10 */
#define SUFF_NCOVERED 200
#define SUFF_MAXNCONSECUTIVE 20
#define MAX_NACTIVE 100 /* 100 previously considered too low, but may
be okay in conjunction with
diagonalization */
#define MAX_GRAND_LOOKBACK 200
/* Penalty for genomic distances */
#define INTRON_PENALTY_UNKNOWN 8
#define INTRON_PENALTY_INCONSISTENT 16
/* Needs to be high to avoid short exons, but needs to be low to identify short exons. */
/* On an example by Nathan Weeks, needed to set this value to be 1 or
0 to find a short exon. Setting to 0 gives too many short exons.
Also found querydist_credit to be a bad idea. */
#define NINTRON_PENALTY_MISMATCH 1
/* #define USE_QUERYDIST_CREDIT 1 */
#define NON_CANONICAL_PENALTY_ENDS 4
#define NON_CANONICAL_PENALTY_MIDDLE 4
#define MISS_BEHIND 16
#define GREEDY_ADVANCE 6
#define FINAL_SCORE_TOLERANCE 8
#define ENOUGH_CONSECUTIVE 32
#define INFINITE 1000000
/* EQUAL_DISTANCE used to be 3 for PMAP and 6 for GMAP, but that
allowed indels in repetitive regions. Now have separate
variables. */
#ifdef PMAP
#define EQUAL_DISTANCE_FOR_CONSECUTIVE 0
#define EQUAL_DISTANCE_NOT_SPLICING 3
#else
#define EQUAL_DISTANCE_FOR_CONSECUTIVE 0
#define EQUAL_DISTANCE_NOT_SPLICING 9
#endif
#define INTRON_DEFN 9 /* Cannot exceed 9 */
#define NEAR_END_LENGTH 20 /* Determines whether to ignore EXON_DEFN at ends */
#define EXON_DEFN 30
#define MAX_SKIPPED 3
#define SCORE_FOR_RESTRICT 10
/* #define SUFFICIENT_ROOTNLINKS 10 */ /* Setting this too low can slow down program considerably */
#ifdef PMAP
#define SAMPLE_INTERVAL 1
#define NT_PER_MATCH 3
#define CONSEC_POINTS_PER_MATCH 3 /* Possible increase to reward consecutiveness */
#define NONCODON_INDEL_PENALTY 15
#else
#define SAMPLE_INTERVAL 2 /* For cases where adjacentp == false.
Means that we can find islands of
9-mers */
#define NT_PER_MATCH 1
#define NT_PER_CODON 3
#define CONSEC_POINTS_PER_MATCH 1 /* Possible increase to reward consecutiveness */
#define CONSEC_POINTS_PER_CODON 3 /* Possible increase to reward consecutiveness */
#endif
#define SHIFT_EXTRA 15
#define ONE 1
#define TEN_THOUSAND 8192 /* Power of 2 */
#define HUNDRED_THOUSAND 100000.0
#define ONE_MILLION 1000000.0
static bool splicingp;
static bool use_canonical_middle_p;
static bool use_canonical_ends_p;
static int suboptimal_score_end;
static int suboptimal_score_start;
static Mode_T mode;
static bool snps_p;
static int sufflookback;
static int nsufflookback;
static int maxintronlen;
void
Stage2_setup (bool splicingp_in, bool cross_species_p,
int suboptimal_score_start_in, int suboptimal_score_end_in,
int sufflookback_in, int nsufflookback_in, int maxintronlen_in,
Mode_T mode_in, bool snps_p_in) {
splicingp = splicingp_in;
if (splicingp == true) {
use_canonical_ends_p = true;
} else {
use_canonical_ends_p = false;
}
if (cross_species_p == true) {
use_canonical_middle_p = true;
} else {
use_canonical_middle_p = false;
}
suboptimal_score_start = suboptimal_score_start_in;
suboptimal_score_end = suboptimal_score_end_in;
sufflookback = sufflookback_in;
nsufflookback = nsufflookback_in;
maxintronlen = maxintronlen_in;
mode = mode_in;
snps_p = snps_p_in;
return;
}
/* General */
#ifdef DEBUG
#define debug(x) x
#else
#define debug(x)
#endif
/* Final results of stage 2 */
#ifdef DEBUG0
#define debug0(x) x
#else
#define debug0(x)
#endif
/* Print all links */
#ifdef DEBUG1
#define debug1(x) x
#else
#define debug1(x)
#endif
/* For generating a graph */
#ifdef DEBUG3
#define debug3(x) x
#else
#define debug3(x)
#endif
/* Converting to nucleotides */
#ifdef DEBUG5
#define debug5(x) x
#else
#define debug5(x)
#endif
/* revise_active */
#ifdef DEBUG6
#define debug6(x) x
#else
#define debug6(x)
#endif
/* Shifted canonical */
#ifdef DEBUG7
#define debug7(x) x
#else
#define debug7(x)
#endif
/* find_canonical_dinucleotides */
#ifdef DEBUG8
#define debug8(x) x
#else
#define debug8(x)
#endif
/* Dynamic programming */
/* Can also define debug9(x) as: if (querypos == XX) {x;} */
#ifdef DEBUG9
#define debug9(x) x
#else
#define debug9(x)
#endif
/* binary search */
#ifdef DEBUG10
#define debug10(x) x
#else
#define debug10(x)
#endif
/* Multiple alignments */
#ifdef DEBUG11
#define debug11(x) x
#else
#define debug11(x)
#endif
/* Grand winner */
#ifdef DEBUG12
#define debug12(x) x
#else
#define debug12(x)
#endif
struct Stage2_alloc_T {
int max_querylength_alloc;
bool *coveredp;
Chrpos_T **mappings;
int *npositions;
unsigned int *minactive;
unsigned int *maxactive;
int *firstactive;
int *nactive;
};
void
Stage2_alloc_free (Stage2_alloc_T *old) {
FREE((*old)->firstactive);
FREE((*old)->nactive);
FREE((*old)->maxactive);
FREE((*old)->minactive);
FREE((*old)->npositions);
FREE((*old)->mappings);
FREE((*old)->coveredp);
FREE(*old);
return;
}
Stage2_alloc_T
Stage2_alloc_new (int max_querylength_alloc) {
Stage2_alloc_T new = (Stage2_alloc_T) MALLOC(sizeof(*new));
new->max_querylength_alloc = max_querylength_alloc;
new->coveredp = (bool *) MALLOC(max_querylength_alloc * sizeof(bool));
new->mappings = (Chrpos_T **) MALLOC(max_querylength_alloc * sizeof(Chrpos_T *));
new->npositions = (int *) MALLOC(max_querylength_alloc * sizeof(int));
new->minactive = (unsigned int *) MALLOC(max_querylength_alloc * sizeof(unsigned int));
new->maxactive = (unsigned int *) MALLOC(max_querylength_alloc * sizeof(unsigned int));
new->firstactive = (int *) MALLOC(max_querylength_alloc * sizeof(int));
new->nactive = (int *) MALLOC(max_querylength_alloc * sizeof(int));
return new;
}
#define T Stage2_T
struct T {
List_T middle;
List_T all_starts;
List_T all_ends;
};
void
Stage2_free (T *old) {
/* List_free(&(*old)->middle); -- Not necessary because of pairpool */
List_free(&(*old)->all_starts);
List_free(&(*old)->all_ends);
FREE(*old);
return;
}
static T
Stage2_new (List_T middle, List_T all_starts, List_T all_ends) {
T new = (T) MALLOC(sizeof(*new));
#ifdef DEBUG0
List_T p;
#endif
new->middle = middle;
new->all_starts = all_starts;
new->all_ends = all_ends;
#ifdef DEBUG0
printf("Starts:\n");
for (p = all_starts; p != NULL; p = List_next(p)) {
Pair_dump_list(List_head(p),true);
}
printf("Ends:\n");
for (p = all_ends; p != NULL; p = List_next(p)) {
Pair_dump_list(List_head(p),true);
}
#endif
return new;
}
List_T
Stage2_middle (T this) {
return this->middle;
}
List_T
Stage2_all_starts (T this) {
return this->all_starts;
}
List_T
Stage2_all_ends (T this) {
return this->all_ends;
}
/************************************************************************/
typedef struct Link_T *Link_T;
struct Link_T {
int fwd_consecutive;
int fwd_rootposition;
/*int fwd_rootnlinks;*/ /* Number of links in last branch */
/* int fwd_score; */ /* Kept as a separate structure */
int fwd_pos;
int fwd_hit;
int fwd_tracei; /* Corresponds to a distinct set of branches */
#ifdef DEBUG9
int fwd_intronnfwd;
int fwd_intronnrev;
int fwd_intronnunk;
#endif
#ifdef SEPARATE_FWD_REV
/* No longer checking separate fwd/rev directions */
int rev_consecutive;
int rev_rootposition;
/*int rev_rootnlinks;*/ /* Number of links in last branch */
int rev_score;
int rev_pos;
int rev_hit;
#ifdef DEBUG9
int rev_tracei; /* Corresponds to a distinct set of branches */
int rev_intronnfwd;
int rev_intronnrev;
int rev_intronnunk;
#endif /* rev */
#endif
};
/* lengths2 is has length1 entries. Note that lengths2 may have
negative entries */
static struct Link_T **
Linkmatrix_1d_new (int length1, int *lengths2, int totallength) {
struct Link_T **links;
int i;
/* Outer dimension can be MALLOC, but inner one must be CALLOC */
links = (struct Link_T **) MALLOC(length1 * sizeof(struct Link_T *));
links[0] = (struct Link_T *) CALLOC(totallength,sizeof(struct Link_T));
for (i = 1; i < length1; i++) {
if (lengths2[i-1] < 0) {
links[i] = links[i-1];
} else {
links[i] = &(links[i-1][lengths2[i-1]]);
}
}
return links;
}
static void
Linkmatrix_1d_free (struct Link_T ***links) {
FREE((*links)[0]);
FREE(*links);
return;
}
static struct Link_T **
Linkmatrix_2d_new (int length1, int *lengths2) {
struct Link_T **links;
int i;
links = (struct Link_T **) CALLOC(length1,sizeof(struct Link_T *));
for (i = 0; i < length1; i++) {
if (lengths2[i] <= 0) {
links[i] = (struct Link_T *) NULL;
} else {
links[i] = (struct Link_T *) CALLOC(lengths2[i],sizeof(struct Link_T));
}
}
return links;
}
static void
Linkmatrix_2d_free (struct Link_T ***links, int length1) {
int i;
for (i = 0; i < length1; i++) {
if ((*links)[i]) {
FREE((*links)[i]);
}
}
FREE(*links);
return;
}
#ifdef DEBUG1
#ifdef SEPARATE_FWD_REV
static void
Linkmatrix_print_both (struct Link_T **links, Chrpos_T **mappings, int length1,
int *npositions, char *queryseq_ptr, int indexsize) {
int i, j;
char *oligo;
oligo = (char *) MALLOCA((indexsize+1) * sizeof(char));
for (i = 0; i <= length1-indexsize; i++) {
strncpy(oligo,&(queryseq_ptr[i]),indexsize);
printf("Querypos %d (%s, %d positions):",i,oligo,npositions[i]);
for (j = 0; j < npositions[i]; j++) {
printf(" %d.%u:%d(%d,%d)[%u]-%d(%d,%d)[%u]",
j,mappings[i][j],links[i][j].fwd_score,
links[i][j].fwd_pos,links[i][j].fwd_hit,links[i][j].fwd_tracei,
links[i][j].rev_score,
links[i][j].rev_pos,links[i][j].rev_hit,links[i][j].rev_tracei);
}
printf("\n");
}
printf("\n");
FREEA(oligo);
return;
}
#else
/* For PMAP, indexsize is in aa */
static void
print_fwd (struct Link_T **links, int **fwd_scores,
Chrpos_T **mappings, int length1,
int *npositions, char *queryseq_ptr, int indexsize) {
int i, j, lastpos;
char *oligo;
oligo = (char *) MALLOCA((indexsize+1) * sizeof(char));
lastpos = length1 - indexsize;
for (i = 0; i <= lastpos; i++) {
strncpy(oligo,&(queryseq_ptr[i]),indexsize);
printf("Querypos %d (%s, %d positions):",i,oligo,npositions[i]);
for (j = 0; j < npositions[i]; j++) {
printf(" %d.%u:%d(%d,%d)[%u]",
j,mappings[i][j],fwd_scores[i][j],
links[i][j].fwd_pos,links[i][j].fwd_hit,links[i][j].fwd_tracei);
}
printf("\n");
}
printf("\n");
FREEA(oligo);
return;
}
#endif
#endif
static void
mappings_dump_R (Chrpos_T **mappings, int *npositions, int length1,
int **active, int *firstactive, int indexsize, char *varname) {
int querypos;
int lastpos, hit;
bool printp = false;
lastpos = length1 - indexsize;
printf("%s <- matrix(c(\n",varname);
for (querypos = 0; querypos < lastpos; querypos++) {
if (firstactive) {
if (mappings[querypos] != NULL) {
hit = firstactive[querypos];
while (hit != -1) {
/* Last elt is for score */
if (printp == false) {
printp = true;
} else {
printf(",\n");
}
printf("%d,%d,%d,%d",querypos,mappings[querypos][hit],
hit,active[querypos][hit]);
hit = active[querypos][hit];
}
}
} else {
for (hit = 0; hit < npositions[querypos]; hit++) {
if (printp == false) {
printp = true;
} else {
printf(",\n");
}
printf("%d,%d,%d",querypos,mappings[querypos][hit],hit);
}
}
}
printf("),ncol=2,byrow=T)\n");
return;
}
#if 0
static void
best_path_dump_R (struct Link_T **links, Chrpos_T **mappings,
int querypos, int hit, bool fwdp, char *varname) {
Chrpos_T position;
int prev_querypos, prevhit, save_querypos, savehit;
bool printp = false;
save_querypos = querypos;
savehit = hit;
printf("%s <- matrix(c(\n",varname);
prev_querypos = querypos+1;
while (querypos >= 0) {
position = mappings[querypos][hit];
if (printp == false) {
printp = true;
} else {
printf(",\n");
}
printf("%d,%d",querypos,position);
prev_querypos = querypos;
prevhit = hit;
if (fwdp) {
querypos = links[prev_querypos][prevhit].fwd_pos;
hit = links[prev_querypos][prevhit].fwd_hit;
#ifdef SEPARATE_FWD_REV
} else {
querypos = links[prev_querypos][prevhit].rev_pos;
hit = links[prev_querypos][prevhit].rev_hit;
#endif
}
}
printf("),ncol=2,byrow=T)\n");
querypos = save_querypos;
hit = savehit;
printp = false;
printf("%s <- matrix(c(\n","scores");
prev_querypos = querypos+1;
while (querypos >= 0) {
position = mappings[querypos][hit];
if (printp == false) {
printp = true;
} else {
printf(",\n");
}
if (fwdp == true) {
printf("%d,%d",querypos,links[querypos][hit].fwd_score);
#ifdef SEPARATE_FWD_REV
} else {
printf("%d,%d",querypos,links[querypos][hit].rev_score);
#endif
}
prev_querypos = querypos;
prevhit = hit;
if (fwdp) {
querypos = links[prev_querypos][prevhit].fwd_pos;
hit = links[prev_querypos][prevhit].fwd_hit;
#ifdef SEPARATE_FWD_REV
} else {
querypos = links[prev_querypos][prevhit].rev_pos;
hit = links[prev_querypos][prevhit].rev_hit;
#endif
}
}
printf("),ncol=2,byrow=T)\n");
return;
}
#endif
static void
active_bounds_dump_R (Chrpos_T *minactive, Chrpos_T *maxactive,
int querylength) {
int querypos;
bool printp = false;
printf("querypos <- 0:%d\n",querylength-1);
printf("%s <- c(\n","minactive");
for (querypos = 0; querypos < querylength; querypos++) {
if (printp == false) {
printp = true;
} else {
printf(",\n");
}
printf("%d",minactive[querypos]);
}
printf(")\n");
printp = false;
printf("%s <- c(\n","maxactive");
for (querypos = 0; querypos < querylength; querypos++) {
if (printp == false) {
printp = true;
} else {
printf(",\n");
}
printf("%d",maxactive[querypos]);
}
printf(")\n");
return;
}
#ifdef PMAP
#define QUERYDIST_PENALTY_FACTOR 2
#else
#define QUERYDIST_PENALTY_FACTOR 8
#endif
/************************************************************************
* Procedures for finding canonical introns quickly
************************************************************************/
#ifdef DEBUG8
static void
print_last_dinucl (int *last_dinucl, int genomiclength) {
int pos;
for (pos = 0; pos < genomiclength - 3 + SHIFT_EXTRA; pos++) {
printf("%d %d\n",pos,last_dinucl[pos]);
}
printf("\n");
return;
}
#endif
#if 0
/* Need this procedure because we are skipping some oligomers */
static bool
find_shifted_canonical (Chrpos_T leftpos, Chrpos_T rightpos, int querydistance,
Chrpos_T (*genome_left_position)(Chrpos_T, Chrpos_T, Univcoord_T, Univcoord_T, bool),
Chrpos_T (*genome_right_position)(Chrpos_T, Chrpos_T, Univcoord_T, Univcoord_T, bool),
Univcoord_T chroffset, Univcoord_T chrhigh, bool plusp, bool skip_repetitive_p) {
Chrpos_T leftdi, rightdi;
Chrpos_T last_leftpos, last_rightpos;
int shift, leftmiss, rightmiss;
Chrpos_T left_chrbound, right_chrbound;
/* leftpos = prevposition + querydistance + indexsize_nt - 1; */
/* rightpos = position; */
debug7(printf("Looking for shifted canonical at leftpos %u to rightpos %u, chroffset %u, chrhigh %u\n",
leftpos,rightpos,chroffset,chrhigh));
#if 0
/* previously checked against genomiclength */
if (leftpos > genomiclength || rightpos > genomiclength) {
return false;
}
#else
/* Checking just before call to genome_right_position */
#endif
if (leftpos >= rightpos) {
debug7(printf("leftpos %u >= rightpos %u, so returning false\n",leftpos,rightpos));
return false;
}
if (leftpos < 103) {
left_chrbound = 3; /* Previously 0, but then can find splice site at beginning of segment */
} else {
left_chrbound = leftpos - 100;
}
if (rightpos < 103) {
right_chrbound = 3; /* Previously 0, but then can find splice site at beginning of segment */
} else {
right_chrbound = rightpos - 100;
}
#if 0
if (skip_repetitive_p == false) {
last_leftpos = (*genome_left_position)(leftpos,left_chrbound,chroffset,chrhigh,plusp);
last_rightpos = (*genome_right_position)(rightpos,right_chrbound,chroffset,chrhigh,plusp);
debug7(printf("last_leftpos %u, last_rightpos %u\n",last_leftpos,last_rightpos));
debug7(printf("skip_repetitive_p == false, so returning %u == %u && %u == %u\n",
leftpos,last_leftpos,rightpos,last_rightpos));
return (leftpos == last_leftpos && rightpos == last_rightpos);
}
#endif
/* Allow canonical to be to right of match */
leftpos += SHIFT_EXTRA;
if (leftpos > chrhigh - 3) {
leftpos = chrhigh - 3;
}
rightpos += SHIFT_EXTRA;
if (rightpos > chrhigh - 3) {
rightpos = chrhigh - 3;
}
debug7(printf("after shift, leftpos = %u, rightpos = %u\n",leftpos,rightpos));
shift = 0;
while (shift <= querydistance + SHIFT_EXTRA + SHIFT_EXTRA) {
#if 0
if (leftpos < 0) {
return false;
} else if (rightpos < 0) {
/* Shouldn't need to check if leftpos >= 0 and rightpos >= leftpos, in the other two conditions) */
return false;
} else if (rightpos >= chrlength) {
return false;
}
#endif
if (leftpos < 3) {
return false;
} else if (leftpos > rightpos) {
return false;
}
last_leftpos = (*genome_left_position)(leftpos,left_chrbound,chroffset,chrhigh,plusp);
debug7(printf("last_leftpos %u\n",last_leftpos));
assert(last_leftpos != 0U);
if ((leftdi = last_leftpos) == -1) {
debug7(printf("\n"));
return false;
} else {
leftmiss = (int) (leftpos - leftdi);
}
last_rightpos = (*genome_right_position)(rightpos,right_chrbound,chroffset,chrhigh,plusp);
debug7(printf("last_rightpos %u\n",last_rightpos));
assert(last_rightpos != 0U);
if ((rightdi = last_rightpos) == -1) {
debug7(printf("\n"));
return false;
} else {
rightmiss = (int) (rightpos - rightdi);
}
debug7(printf("shift %d/left %d (miss %d)/right %d (miss %d)\n",shift,leftpos,leftmiss,rightpos,rightmiss));
if (leftmiss == rightmiss) { /* was leftmiss == 0 && rightmiss == 0, which doesn't allow for a shift */
debug7(printf(" => Success at %u..%u (fwd) or %u..%u (rev)\n\n",
leftpos-leftmiss+/*onebasedp*/1U,rightpos-rightmiss+/*onebasedp*/1U,
chrhigh-chroffset-(leftpos-leftmiss),chrhigh-chroffset-(rightpos-rightmiss)));
return true;
} else if (leftmiss >= rightmiss) {
shift += leftmiss;
leftpos -= leftmiss;
rightpos -= leftmiss;
} else {
shift += rightmiss;
leftpos -= rightmiss;
rightpos -= rightmiss;
}
}
debug7(printf("\n"));
return false;
}
#endif
#if 0
/* General case for ranges in score_querypos */
while (prevhit != -1 && (prevposition = mappings[prev_querypos][prevhit]) + indexsize_nt <= position) {
/* printf("fwd: prevposition %u, prevhit %d\n",prevposition,prevhit); */
prevlink = &(links[prev_querypos][prevhit]);
gendistance = position - prevposition - indexsize_nt;
/* diffdistance = abs(gendistance - querydistance); */
if (gendistance > querydistance) {
diffdistance = gendistance - querydistance;
} else {
diffdistance = querydistance - gendistance;
}
if (diffdistance < maxintronlen) {
if (diffdistance <= EQUAL_DISTANCE_NOT_SPLICING) {
debug9(canonicalsgn = 9);
fwd_score = prevlink->fwd_score + CONSEC_POINTS_PER_MATCH;
#ifdef PMAP
if (diffdistance % 3 != 0) {
fwd_score -= NONCODON_INDEL_PENALTY;
}
#endif
} else if (near_end_p == false && prevlink->fwd_consecutive < EXON_DEFN) {
debug9(canonicalsgn = 0);
if (splicingp == true) {
fwd_score = prevlink->fwd_score - (diffdistance/TEN_THOUSAND + 1) - querydist_penalty - NINTRON_PENALTY_MISMATCH;
} else {
fwd_score = prevlink->fwd_score - (diffdistance/ONE + 1) - querydist_penalty - NINTRON_PENALTY_MISMATCH;
}
} else if (splicingp == false) {
debug9(canonicalsgn = 0);
fwd_score = prevlink->fwd_score - (diffdistance/ONE + 1) - querydist_penalty;
} else if (use_shifted_canonical_p == true) {
leftpos = prevposition + querydistance - 1;
/* printf("leftpos %d, last_leftpos %d, rightpos %d\n",leftpos,last_leftpos,rightpos); */
if (leftpos == last_leftpos) {
canonicalp = last_canonicalp;
} else {
debug7(printf("Calling find_shift_canonical fwd\n"));
canonicalp = find_shifted_canonical(leftpos,rightpos,querydistance-indexsize_nt,
/* &lastGT,&lastAG, */
Genome_prev_donor_position,Genome_prev_acceptor_position,
chroffset,chrhigh,plusp,skip_repetitive_p);
/* And need to check for shift_canonical_rev */
last_leftpos = leftpos;
last_canonicalp = canonicalp;
}
if (canonicalp == true) {
debug9(canonicalsgn = +1);
fwd_score = prevlink->fwd_score - (diffdistance/TEN_THOUSAND + 1) - querydist_penalty;
} else {
debug9(canonicalsgn = 0);
fwd_score = prevlink->fwd_score - (diffdistance/TEN_THOUSAND + 1) - querydist_penalty - NINTRON_PENALTY_MISMATCH;
}
} else {
debug9(canonicalsgn = +1);
fwd_score = prevlink->fwd_score - (diffdistance/TEN_THOUSAND + 1) - querydist_penalty;
}
debug9(printf("\tD. Fwd mismatch qpos %d,%d at %ux%d (score = %d -> %d, consec = %d (from #%d), intr = %d-%d-%d, gendist %u, querydist %d, canonicalsgn %d)",
prev_querypos,prevhit,prevposition,active[prev_querypos][prevhit],
prevlink->fwd_score,fwd_score,prevlink->fwd_consecutive,prevlink->fwd_tracei,
best_fwd_intronnfwd,best_fwd_intronnrev,best_fwd_intronnunk,
gendistance,querydistance,canonicalsgn));
/* Allow ties, which should favor shorter intron */
if (fwd_score >= best_fwd_score) {
if (diffdistance <= EQUAL_DISTANCE_FOR_CONSECUTIVE) {
best_fwd_consecutive = prevlink->fwd_consecutive + (querydistance + indexsize_nt);
/* best_fwd_rootnlinks = prevlink->fwd_rootnlinks + 1; */
} else {
best_fwd_consecutive = 0;
/* best_fwd_rootnlinks = 1; */
}
best_fwd_score = fwd_score;
best_fwd_prevpos = prev_querypos;
best_fwd_prevhit = prevhit;
#ifdef DEBUG9
best_fwd_tracei = ++*fwd_tracei;
best_fwd_intronnfwd = prevlink->fwd_intronnfwd;
best_fwd_intronnrev = prevlink->fwd_intronnrev;
best_fwd_intronnunk = prevlink->fwd_intronnunk;
switch (canonicalsgn) {
case 1: best_fwd_intronnfwd++; break;
case 0: best_fwd_intronnunk++; break;
}
#endif
debug9(printf(" => Best fwd at %d (consec = %d)\n",fwd_score,best_fwd_consecutive));
} else {
debug9(printf(" => Loses to %d\n",best_fwd_score));
}
}
prevhit = active[prev_querypos][prevhit];
}
#endif
#if 0
/* SIMD version */
_positions = _mm_set1_epi32(position - indexsize_nt);
_querydistance = _mm_set1_epi32(querydistance);
_splicing_querydist_penalty = _mm_set1_epi32(querydist_penalty+1+NINTRON_PENALTY_MISMATCH);
_max_scores = _mm_set1_epi32(-1000);
prevhit = low_hit;
while (prevhit + 4 < high_hit) {
/* printf("fwd: prevposition %u, prevhit %d\n",prevposition,prevhit); */
_prevpositions = _mm_loadu_epi32(&(mappings[prev_querypos][prevhit]));
_gendistance = _mm_sub_epi32(_positions,_prevpositions);
if (_mm_cmpgt_epi32(_gendistance,_zeroes) == 0) {
break;
} else {
_diffdistance = _mm_abs_epi32(_mm_sub_epi32(_gendistance,_querydistance));
_prev_scores = _mm_loadu_epi32(&(fwd_scores[prev_querypos][prevhit]));
_scores_close = _mm_add_epi32(_prev_scores,_mm_set1_epi32(CONSEC_POINTS_PER_MATCH));
/* Right shift of 13 bits gives division by 8192 */
_scores_splice = _mm_add_epi32(_prev_scores,_mm_sub_epi32(_mm_srli_epi32(_diffdistance,13),_splicing_querydist_penalty));
_scores = _mm_blendv_ps(_scores_close,_scores_splice,_mm_cmpgt_epi32(_diffdistance,_mm_set1_epi32(EQUAL_DISTANCE_NOT_SPLICING)));
_mm_storeu_epi32(_scores);
_max_scores = _mm_max_epi32(_max_scores,_scores);
prevhit += 4;
}
}
/* Take care of serial cases */
/* Compute overall max and return. Caller can find prev_querypos with
largest max and store in fwd_pos[curr_querypos][currhit] and max in
fwd_max[curr_querypos][currhit]. During traceback, recompute at
prev_querypos and find prevhit that gives the max. */
if (diffdistance < maxintronlen) {
if (diffdistance <= EQUAL_DISTANCE_NOT_SPLICING) {
debug9(canonicalsgn = 9);
fwd_score = prevlink->fwd_score + CONSEC_POINTS_PER_MATCH;
#ifdef PMAP
if (diffdistance % 3 != 0) {
fwd_score -= NONCODON_INDEL_PENALTY;
}
#endif
} else if (near_end_p == false && prevlink->fwd_consecutive < EXON_DEFN) {
debug9(canonicalsgn = 0);
if (splicingp == true) {
fwd_score = prevlink->fwd_score - (diffdistance/TEN_THOUSAND + 1) - querydist_penalty - NINTRON_PENALTY_MISMATCH;
} else {
fwd_score = prevlink->fwd_score - (diffdistance/ONE + 1) - querydist_penalty - NINTRON_PENALTY_MISMATCH;
}
} else if (splicingp == false) {
debug9(canonicalsgn = 0);
fwd_score = prevlink->fwd_score - (diffdistance/ONE + 1) - querydist_penalty;
} else if (use_shifted_canonical_p == true) {
leftpos = prevposition + querydistance - 1;
/* printf("leftpos %d, last_leftpos %d, rightpos %d\n",leftpos,last_leftpos,rightpos); */
if (leftpos == last_leftpos) {
canonicalp = last_canonicalp;
} else {
debug7(printf("Calling find_shift_canonical fwd\n"));
canonicalp = find_shifted_canonical(leftpos,rightpos,querydistance-indexsize_nt,
/* &lastGT,&lastAG, */
Genome_prev_donor_position,Genome_prev_acceptor_position,
chroffset,chrhigh,plusp,skip_repetitive_p);
/* And need to check for shift_canonical_rev */
last_leftpos = leftpos;
last_canonicalp = canonicalp;
}
if (canonicalp == true) {
debug9(canonicalsgn = +1);
fwd_score = prevlink->fwd_score - (diffdistance/TEN_THOUSAND + 1) - querydist_penalty;
} else {
debug9(canonicalsgn = 0);
fwd_score = prevlink->fwd_score - (diffdistance/TEN_THOUSAND + 1) - querydist_penalty - NINTRON_PENALTY_MISMATCH;
}
} else {
debug9(canonicalsgn = +1);
fwd_score = prevlink->fwd_score - (diffdistance/TEN_THOUSAND + 1) - querydist_penalty;
}
debug9(printf("\tD. Fwd mismatch qpos %d,%d at %ux%d (score = %d -> %d, consec = %d, intr = %d-%d-%d, gendist %u, querydist %d, canonicalsgn %d)",
prev_querypos,prevhit,prevposition,active[prev_querypos][prevhit],
prevlink->fwd_score,fwd_score,prevlink->fwd_consecutive,
best_fwd_intronnfwd,best_fwd_intronnrev,best_fwd_intronnunk,
gendistance,querydistance,canonicalsgn));
/* Allow ties, which should favor shorter intron */
if (fwd_score >= best_fwd_score) {
if (diffdistance <= EQUAL_DISTANCE_FOR_CONSECUTIVE) {
best_fwd_consecutive = prevlink->fwd_consecutive + (querydistance + indexsize_nt);
/* best_fwd_rootnlinks = prevlink->fwd_rootnlinks + 1; */
} else {
best_fwd_consecutive = 0;
/* best_fwd_rootnlinks = 1; */
}
best_fwd_score = fwd_score;
best_fwd_prevpos = prev_querypos;
best_fwd_prevhit = prevhit;
#ifdef DEBUG9
best_fwd_tracei = ++*fwd_tracei;
best_fwd_intronnfwd = prevlink->fwd_intronnfwd;
best_fwd_intronnrev = prevlink->fwd_intronnrev;
best_fwd_intronnunk = prevlink->fwd_intronnunk;
switch (canonicalsgn) {
case 1: best_fwd_intronnfwd++; break;
case 0: best_fwd_intronnunk++; break;
}
#endif
debug9(printf(" => Best fwd at %d (consec = %d)\n",fwd_score,best_fwd_consecutive));
} else {
debug9(printf(" => Loses to %d\n",best_fwd_score));
}
}
prevhit = active[prev_querypos][prevhit];
}
#endif
static void
score_querypos_lookback_one (int *fwd_tracei, Link_T currlink, int curr_querypos, int currhit,
int querystart, int queryend, unsigned int position,
struct Link_T **links, int **fwd_scores, Chrpos_T **mappings,
int **active, int *firstactive,
Univcoord_T chroffset, Univcoord_T chrhigh, bool plusp,
int indexsize, Intlist_T processed,
bool anchoredp, bool localp, bool splicingp,
bool use_canonical_p, int non_canonical_penalty) {
Link_T prevlink;
struct Link_T *prev_links;
Chrpos_T *prev_mappings;
int *prev_active;
int best_fwd_consecutive = indexsize*NT_PER_MATCH;
int best_fwd_rootposition = position;
/* int best_fwd_rootnlinks = 1; */
int best_fwd_score = 0, fwd_score;
int best_fwd_prevpos = -1, best_fwd_prevhit = -1;
int best_fwd_tracei, last_tracei;
#ifdef DEBUG9
int best_fwd_intronnfwd = 0, best_fwd_intronnrev = 0, best_fwd_intronnunk = 0;
int canonicalsgn = 0;
#endif
bool donep;
int prev_querypos, prevhit;
Chrpos_T prevposition;
int gendistance;
Univcoord_T prevpos, currpos;
int querydistance, diffdistance, lookback, nlookback, nseen, indexsize_nt, indexsize_query;
/* int querydist_penalty; */
int querydist_credit;
int enough_consecutive;
/* bool near_end_p; */
bool canonicalp;
#ifdef PMAP
indexsize_nt = indexsize*3; /* Use when evaluating across genomic positions */
#else
indexsize_nt = indexsize;
#endif
indexsize_query = indexsize; /* Use when evaluating across query positions */
enough_consecutive = 32;
/* Parameters for section D, assuming adjacent is false */
/* adjacentp = false; */
nlookback = nsufflookback;
lookback = sufflookback;
/* A. Evaluate adjacent position (at last one processed) */
if (processed != NULL) {
prev_querypos = Intlist_head(processed);
prev_links = links[prev_querypos];
prev_mappings = mappings[prev_querypos];
prev_active = active[prev_querypos];
#ifdef PMAP
querydistance = (curr_querypos - prev_querypos)*3;
#else
querydistance = curr_querypos - prev_querypos;
#endif
prevhit = firstactive[prev_querypos];
prevposition = position; /* Prevents prevposition + querydistance == position */
while (prevhit != -1 && (prevposition = /*mappings[prev_querypos]*/prev_mappings[prevhit]) + querydistance < position) {
prevhit = /*active[prev_querypos]*/prev_active[prevhit];
}
if (prevposition + querydistance == position) {
prevlink = &(/*links[prev_querypos]*/prev_links[prevhit]);
best_fwd_consecutive = prevlink->fwd_consecutive + querydistance;
best_fwd_rootposition = prevlink->fwd_rootposition;
/* best_fwd_rootnlinks = prevlink->fwd_rootnlinks + 1; */
best_fwd_score = fwd_scores[prev_querypos][prevhit] + CONSEC_POINTS_PER_MATCH*querydistance;
best_fwd_prevpos = prev_querypos;
best_fwd_prevhit = prevhit;
best_fwd_tracei = prevlink->fwd_tracei;
#ifdef DEBUG9
best_fwd_intronnfwd = prevlink->fwd_intronnfwd;
best_fwd_intronnrev = prevlink->fwd_intronnrev;
best_fwd_intronnunk = prevlink->fwd_intronnunk;
#endif
/* adjacentp = true; */
/* Parameters for section D when adjacent is true, so we don't look so far back */
nlookback = 1;
lookback = sufflookback/2;
debug9(printf("\tA. Adjacent qpos %d,%d at %ux%d (scores = %d -> %d, consec = %d (from #%d), intr = %d-%d-%d)\n",
prev_querypos,prevhit,prevposition,active[prev_querypos][prevhit],fwd_scores[prev_querypos][prevhit],
best_fwd_score,best_fwd_consecutive,best_fwd_tracei,
best_fwd_intronnfwd,best_fwd_intronnrev,best_fwd_intronnunk));
}
}
/* Check work list */
if (anchoredp && curr_querypos - indexsize_query <= querystart) {
/* Allow close prevpositions that overlap with anchor */
/* Can give rise to false positives, and increases amount of dynamic programming work */
} else if (0 && anchoredp && curr_querypos == queryend) {
/* Test first position */
} else {
while (processed != NULL && (prev_querypos = Intlist_head(processed)) > curr_querypos - indexsize_query) {
debug9(printf("Skipping prev_querypos %d, because too close\n",prev_querypos));
processed = Intlist_next(processed);
}
}
/* D. Evaluate for mismatches (all other previous querypos) */
donep = false;
nseen = 0;
last_tracei = -1;
for ( ; processed != NULL && best_fwd_consecutive < enough_consecutive && donep == false;
processed = Intlist_next(processed), nseen++) {
prev_querypos = Intlist_head(processed);
#ifdef PMAP
querydistance = (curr_querypos - prev_querypos)*3;
#else
querydistance = curr_querypos - prev_querypos;
#endif
if (nseen > nlookback && querydistance - indexsize_nt > lookback) {
donep = true;
}
if ((prevhit = firstactive[prev_querypos]) != -1) {
/* querydist_penalty = (querydistance - indexsize_nt)/QUERYDIST_PENALTY_FACTOR; */
/* Actually a querydist_penalty */
querydist_credit = -querydistance/indexsize_nt;
prev_mappings = mappings[prev_querypos];
prev_links = links[prev_querypos];
prev_active = active[prev_querypos];
/* Range 0 */
while (prevhit != -1 && prev_links[prevhit].fwd_tracei == last_tracei) {
debug9(printf("Skipping querypos %d with tracei #%d\n",prev_querypos,prev_links[prevhit].fwd_tracei));
prevhit = /*active[prev_querypos]*/prev_active[prevhit];
}
if (prevhit != -1) {
last_tracei = prev_links[prevhit].fwd_tracei;
}
/* Range 1: From Infinity to maxintronlen */
if (splicingp == true) {
/* This is equivalent to diffdistance >= maxintronlen, where
diffdistance = abs(gendistance - querydistance) and
gendistance = (position - prevposition - indexsize_nt) */
while (prevhit != -1 && (prevposition = /*mappings[prev_querypos]*/prev_mappings[prevhit]) + maxintronlen + querydistance <= position) {
/* Skip */
/* printf("fwd: prevposition %u, prevhit %d\n",prevposition,prevhit); */
prevhit = /*active[prev_querypos]*/prev_active[prevhit];
}
}
/* Range 2: From maxintronlen to (prev_querypos + EQUAL_DISTANCE_NOT_SPLICING) */
/* This is equivalent to +diffdistance > EQUAL_DISTANCE_NOT_SPLICING */
while (prevhit != -1 && (prevposition = /*mappings[prev_querypos]*/prev_mappings[prevhit]) + EQUAL_DISTANCE_NOT_SPLICING + querydistance < position) {
/* printf("fwd: prevposition %u, prevhit %d\n",prevposition,prevhit); */
prevlink = &(/*links[prev_querypos]*/prev_links[prevhit]);
gendistance = position - prevposition;
assert(gendistance > querydistance); /* True because gendistance > EQUAL_DISTANCE_NOT_SPLICING + querydistance */
diffdistance = gendistance - querydistance; /* No need for abs() */
fwd_score = fwd_scores[prev_querypos][prevhit] + querydist_credit /*- querydist_penalty*/;
if (splicingp == true) {
fwd_score -= (diffdistance/TEN_THOUSAND + 1);
} else {
fwd_score -= (diffdistance/ONE + 1);
}
if (use_canonical_p == true) {
/* prevpos is lower genomic coordinate than currpos */
/* need to subtract from position and prevposition to compensate for greedy matches */
/* need to add to position and prevposition to compensate for missed matches */
if (plusp == true) {
prevpos = chroffset + prevposition + indexsize_nt;
currpos = chroffset + position - querydistance + indexsize_nt;
assert(prevpos < currpos);
if (prevpos < GREEDY_ADVANCE || currpos < GREEDY_ADVANCE) {
canonicalp = false;
} else if (Genome_sense_canonicalp(/*donor_rightbound*/prevpos + MISS_BEHIND,
/*donor_leftbound*/prevpos - GREEDY_ADVANCE,
/*acceptor_rightbound*/currpos + MISS_BEHIND,
/*acceptor_leftbound*/currpos - GREEDY_ADVANCE,
chroffset) == true) {
debug9(printf("lookback plus: sense canonical\n"));
canonicalp = true;
} else if (Genome_antisense_canonicalp(/*donor_rightbound*/currpos + MISS_BEHIND,
/*donor_leftbound*/currpos - GREEDY_ADVANCE,
/*acceptor_rightbound*/prevpos + MISS_BEHIND,
/*acceptor_leftbound*/prevpos - GREEDY_ADVANCE,
chroffset) == true) {
debug9(printf("lookback plus: antisense canonical\n"));
canonicalp = true;
} else {
debug9(printf("lookback plus: not canonical\n"));
canonicalp = false;
}
} else {
prevpos = chrhigh + 1 - prevposition - indexsize_nt;
currpos = chrhigh + 1 - position + querydistance - indexsize_nt;
assert(currpos < prevpos);
if (currpos < MISS_BEHIND || prevpos < MISS_BEHIND) {
canonicalp = false;
} else if (Genome_sense_canonicalp(/*donor_rightbound*/currpos + GREEDY_ADVANCE,
/*donor_leftbound*/currpos - MISS_BEHIND,
/*acceptor_rightbound*/prevpos + GREEDY_ADVANCE,
/*acceptor_leftbound*/prevpos - MISS_BEHIND,
chroffset) == true) {
debug9(printf("lookback minus: sense canonical\n"));
canonicalp = true;
} else if (Genome_antisense_canonicalp(/*donor_rightbound*/prevpos + GREEDY_ADVANCE,
/*donor_leftbound*/prevpos - MISS_BEHIND,
/*acceptor_rightbound*/currpos + GREEDY_ADVANCE,
/*acceptor_leftbound*/currpos - MISS_BEHIND,
chroffset) == true) {
debug9(printf("lookback minus: antisense canonical\n"));
canonicalp = true;
} else {
debug9(printf("lookback minus: not canonical\n"));
canonicalp = false;
}
}
if (canonicalp == true) {
debug9(canonicalsgn = +1);
} else {
debug9(canonicalsgn = 0);
fwd_score -= non_canonical_penalty;
}
}
debug9(printf("\tD2. Fwd mismatch qpos %d,%d at %ux%d (score = %d -> %d, consec = %d (from #%d), intr = %d-%d-%d, gendist %u, querydist %d, canonicalsgn %d)",
prev_querypos,prevhit,prevposition,active[prev_querypos][prevhit],
fwd_scores[prev_querypos][prevhit],fwd_score,prevlink->fwd_consecutive,prevlink->fwd_tracei,
best_fwd_intronnfwd,best_fwd_intronnrev,best_fwd_intronnunk,
gendistance-indexsize_nt,querydistance-indexsize_nt,canonicalsgn));
/* Disallow ties, which should favor adjacent */
if (fwd_score > best_fwd_score) {
if (diffdistance <= EQUAL_DISTANCE_FOR_CONSECUTIVE) {
best_fwd_consecutive = prevlink->fwd_consecutive + querydistance;
/* best_fwd_rootnlinks = prevlink->fwd_rootnlinks + 1; */
} else {
best_fwd_consecutive = 0;
/* best_fwd_rootnlinks = 1; */
}
best_fwd_rootposition = prevlink->fwd_rootposition;
best_fwd_score = fwd_score;
best_fwd_prevpos = prev_querypos;
best_fwd_prevhit = prevhit;
best_fwd_tracei = ++*fwd_tracei;
#ifdef DEBUG9
best_fwd_intronnfwd = prevlink->fwd_intronnfwd;
best_fwd_intronnrev = prevlink->fwd_intronnrev;
best_fwd_intronnunk = prevlink->fwd_intronnunk;
switch (canonicalsgn) {
case 1: best_fwd_intronnfwd++; break;
case 0: best_fwd_intronnunk++; break;
}
#endif
debug9(printf(" => Best fwd at %d (consec = %d)\n",fwd_score,best_fwd_consecutive));
} else {
debug9(printf(" => Loses to %d\n",best_fwd_score));
}
prevhit = /*active[prev_querypos]*/prev_active[prevhit];
}
/* Scoring appears to be the same as for range 4, which is rarely called, so including in range 4 */
/* Range 3: From (querypos + EQUAL_DISTANCE_NOT_SPLICING) to (querypos - EQUAL_DISTANCE_NOT_SPLICING) */
/* This is equivalent to -diffdistance > EQUAL_DISTANCE_NOT_SPLICING && prevposition + indexsize_nt <= position */
/* Range 4: From (prev_querypos - EQUAL_DISTANCE_NOT_SPLICING) to indexsize_nt */
while (prevhit != -1 && (prevposition = /*mappings[prev_querypos]*/prev_mappings[prevhit]) + indexsize_nt <= position) {
/* printf("fwd: prevposition %u, prevhit %d\n",prevposition,prevhit); */
prevlink = &(/*links[prev_querypos]*/prev_links[prevhit]);
gendistance = position - prevposition;
/* was abs(gendistance - querydistance) */
diffdistance = gendistance > querydistance ? (gendistance - querydistance) : (querydistance - gendistance);
#ifdef BAD_GMAX
fwd_score = prevlink->fwd_score + querydist_credit - (diffdistance/ONE + 1) /*- querydist_penalty*/;
#else
/* diffdistance <= EQUAL_DISTANCE_NOT_SPLICING */
/* This is how version 2013-08-14 did it */
fwd_score = fwd_scores[prev_querypos][prevhit] + CONSEC_POINTS_PER_MATCH;
#endif
#if 0
/* Used in range 4 but not in range 3 */
if (/*near_end_p == false &&*/ prevlink->fwd_consecutive < EXON_DEFN) {
fwd_score -= NINTRON_PENALTY_MISMATCH;
}
#endif
debug9(printf("\tD4. Fwd mismatch qpos %d,%d at %ux%d (score = %d -> %d, consec = %d (from #%d), intr = %d-%d-%d, gendist %u, querydist %d, canonicalsgn %d)",
prev_querypos,prevhit,prevposition,active[prev_querypos][prevhit],
fwd_scores[prev_querypos][prevhit],fwd_score,prevlink->fwd_consecutive,prevlink->fwd_tracei,
best_fwd_intronnfwd,best_fwd_intronnrev,best_fwd_intronnunk,
gendistance-indexsize_nt,querydistance-indexsize_nt,canonicalsgn));
/* Disallow ties, which should favor adjacent */
if (fwd_score > best_fwd_score) {
if (diffdistance <= EQUAL_DISTANCE_FOR_CONSECUTIVE) {
best_fwd_consecutive = prevlink->fwd_consecutive + querydistance;
/* best_fwd_rootnlinks = prevlink->fwd_rootnlinks + 1; */
} else {
best_fwd_consecutive = 0;
/* best_fwd_rootnlinks = 1; */
}
best_fwd_rootposition = prevlink->fwd_rootposition;
best_fwd_score = fwd_score;
best_fwd_prevpos = prev_querypos;
best_fwd_prevhit = prevhit;
/* best_fwd_tracei = ++*fwd_tracei; */
best_fwd_tracei = prevlink->fwd_tracei; /* Keep previous trace, as in range 3 */
#ifdef DEBUG9
best_fwd_intronnfwd = prevlink->fwd_intronnfwd;
best_fwd_intronnrev = prevlink->fwd_intronnrev;
best_fwd_intronnunk = prevlink->fwd_intronnunk;
switch (canonicalsgn) {
case 1: best_fwd_intronnfwd++; break;
case 0: best_fwd_intronnunk++; break;
}
#endif
debug9(printf(" => Best fwd at %d (consec = %d)\n",fwd_score,best_fwd_consecutive));
} else {
debug9(printf(" => Loses to %d\n",best_fwd_score));
}
prevhit = /*active[prev_querypos]*/prev_active[prevhit];
}
}
}
/* Best_score needs to beat something positive to prevent a
small local extension from beating a good canonical intron.
If querypos is too small, don't insert an intron. */
/* linksconsecutive already assigned above */
currlink->fwd_consecutive = best_fwd_consecutive;
currlink->fwd_rootposition = best_fwd_rootposition;
/* currlink->fwd_rootnlinks = best_fwd_rootnlinks; */
currlink->fwd_pos = best_fwd_prevpos;
currlink->fwd_hit = best_fwd_prevhit;
if (currlink->fwd_pos >= 0) {
currlink->fwd_tracei = best_fwd_tracei;
fwd_scores[curr_querypos][currhit] = best_fwd_score;
} else if (anchoredp == true) {
currlink->fwd_tracei = -1;
fwd_scores[curr_querypos][currhit] = -100000;
} else if (localp == true) {
currlink->fwd_tracei = ++*fwd_tracei;
fwd_scores[curr_querypos][currhit] = indexsize_nt;
} else {
currlink->fwd_tracei = ++*fwd_tracei;
fwd_scores[curr_querypos][currhit] = best_fwd_score;
}
#ifdef DEBUG9
currlink->fwd_intronnfwd = best_fwd_intronnfwd;
currlink->fwd_intronnrev = best_fwd_intronnrev;
currlink->fwd_intronnunk = best_fwd_intronnunk;
#endif
debug9(printf("\tChose %d,%d with score %d (fwd) => trace #%d\n",
currlink->fwd_pos,currlink->fwd_hit,fwd_scores[curr_querypos][currhit],currlink->fwd_tracei));
debug3(printf("%d %d %d %d 1\n",querypos,hit,best_prevpos,best_prevhit));
return;
}
static void
score_querypos_lookback_mult (int *fwd_tracei, int low_hit, int high_hit, int curr_querypos,
int querystart, int queryend, unsigned int *positions,
struct Link_T **links, int **fwd_scores,
Chrpos_T **mappings, int **active, int *firstactive,
Univcoord_T chroffset, Univcoord_T chrhigh, bool plusp,
int indexsize, Intlist_T processed,
bool anchoredp, bool localp, bool splicingp,
bool use_canonical_p, int non_canonical_penalty) {
Link_T prevlink, currlink;
Intlist_T last_item, p;
int nhits = high_hit - low_hit, nprocessed, hiti;
struct Link_T *prev_links, *adj_links;
Chrpos_T *prev_mappings, *adj_mappings;
int *prev_active, *adj_active;
int best_fwd_consecutive;
int best_fwd_rootposition;
int best_fwd_score, fwd_score;
int best_fwd_prevpos, best_fwd_prevhit;
int best_fwd_tracei, last_tracei;
#ifdef DEBUG9
int best_fwd_intronnfwd, best_fwd_intronnrev, best_fwd_intronnunk;
int canonicalsgn = 0;
#endif
int adj_querypos, adj_querydistance, prev_querypos, prevhit, adj_frontier, *frontier;
Chrpos_T prevposition, position;
int gendistance;
Univcoord_T prevpos, currpos;
int querydistance, diffdistance, indexsize_nt, indexsize_query;
int max_nseen, max_adjacent_nseen, max_nonadjacent_nseen, nseen;
int querydist_credit;
int enough_consecutive = 32;
bool canonicalp;
#ifdef PMAP
indexsize_nt = indexsize*3; /* Use when evaluating across genomic positions */
#else
indexsize_nt = indexsize;
#endif
indexsize_query = indexsize; /* Use when evaluating across query positions */
/* Determine work load */
/* printf("Work load (lookback): %s\n",Intlist_to_string(processed)); */
last_item = processed;
if (anchoredp && curr_querypos - indexsize_query <= querystart) {
/* Allow close prevpositions that overlap with anchor */
/* Can give rise to false positives, and increases amount of dynamic programming work */
/* debug9(printf("No skipping because close to anchor\n")); */
} else if (0 && anchoredp && curr_querypos == queryend) {
/* Test first position */
} else {
while (processed != NULL && (/*prev_querypos =*/ Intlist_head(processed)) > curr_querypos - indexsize_query) {
debug9(printf("Skipping prev_querypos %d, because too close\n",Intlist_head(processed)));
processed = Intlist_next(processed);
}
}
if (last_item == NULL) {
for (hiti = 0; hiti < nhits; hiti++) {
currlink = &(links[curr_querypos][hiti + low_hit]);
currlink->fwd_consecutive = /*best_fwd_consecutive =*/ indexsize*NT_PER_MATCH;
currlink->fwd_rootposition = /*best_fwd_rootposition =*/ positions[hiti];
currlink->fwd_pos = /*best_fwd_prevpos =*/ -1;
currlink->fwd_hit = /*best_fwd_prevhit =*/ -1;
if (anchoredp == true) {
currlink->fwd_tracei = -1;
fwd_scores[curr_querypos][hiti + low_hit] = -100000;
} else if (localp == true) {
currlink->fwd_tracei = ++*fwd_tracei;
fwd_scores[curr_querypos][hiti + low_hit] = indexsize_nt;
} else {
fwd_scores[curr_querypos][hiti + low_hit] = /*best_fwd_score =*/ 0;
}
}
} else if (processed == NULL) {
debug9(printf("processed is NULL\n"));
/* A. Evaluate adjacent position (at last one processed, if available). Don't evaluate for mismatches (D). */
adj_querypos = Intlist_head(last_item);
adj_links = links[adj_querypos];
adj_mappings = mappings[adj_querypos];
adj_active = active[adj_querypos];
#ifdef PMAP
adj_querydistance = (curr_querypos - adj_querypos)*3;
#else
adj_querydistance = curr_querypos - adj_querypos;
#endif
/* Process prevhit and hiti in parallel. Values are asscending along prevhit chain and from 0 to nhits-1. */
prevhit = firstactive[adj_querypos];
hiti = 0;
while (prevhit != -1 && hiti < nhits) {
if ((prevposition = /*mappings[adj_querypos]*/adj_mappings[prevhit]) + adj_querydistance < (position = positions[hiti])) {
prevhit = /*active[adj_querypos]*/adj_active[prevhit];
} else if (prevposition + adj_querydistance > position) {
currlink = &(links[curr_querypos][hiti + low_hit]);
currlink->fwd_consecutive = /*best_fwd_consecutive =*/ indexsize*NT_PER_MATCH;
currlink->fwd_rootposition = /*best_fwd_rootposition =*/ positions[hiti];
currlink->fwd_pos = /*best_fwd_prevpos =*/ -1;
currlink->fwd_hit = /*best_fwd_prevhit =*/ -1;
if (anchoredp == true) {
currlink->fwd_tracei = -1;
fwd_scores[curr_querypos][hiti + low_hit] = -100000;
} else if (localp == true) {
currlink->fwd_tracei = ++*fwd_tracei;
fwd_scores[curr_querypos][hiti + low_hit] = indexsize_nt;
} else {
fwd_scores[curr_querypos][hiti + low_hit] = /*best_fwd_score =*/ 0;
}
hiti++;
} else {
/* Adjacent position found for hiti */
currlink = &(links[curr_querypos][hiti + low_hit]);
prevlink = &(/*links[adj_querypos]*/adj_links[prevhit]);
currlink->fwd_consecutive = /*best_fwd_consecutive =*/ prevlink->fwd_consecutive + adj_querydistance;
currlink->fwd_rootposition = /*best_fwd_rootposition =*/ prevlink->fwd_rootposition;
currlink->fwd_pos = /*best_fwd_prevpos =*/ adj_querypos;
currlink->fwd_hit = /*best_fwd_prevhit =*/ prevhit;
fwd_scores[curr_querypos][hiti + low_hit] = /*best_fwd_score =*/ fwd_scores[adj_querypos][prevhit] + CONSEC_POINTS_PER_MATCH*adj_querydistance;
#ifdef DEBUG9
printf("\tA. For hit %d, adjacent qpos %d,%d at %ux%d (scores = %d -> %d, consec = %d (from #%d), intr = %d-%d-%d)\n",
hiti,adj_querypos,prevhit,prevposition,active[adj_querypos][prevhit],fwd_scores[adj_querypos][prevhit],
fwd_scores[curr_querypos][hiti + low_hit],currlink->fwd_consecutive,/*best_fwd_tracei*/prevlink->fwd_tracei,
/*best_fwd_intronnfwd*/prevlink->fwd_intronnfwd,
/*best_fwd_intronnrev*/prevlink->fwd_intronnrev,
/*best_fwd_intronnunk*/prevlink->fwd_intronnunk);
#endif
prevhit = /*active[adj_querypos]*/adj_active[prevhit];
hiti++;
}
}
while (hiti < nhits) {
currlink = &(links[curr_querypos][hiti + low_hit]);
currlink->fwd_consecutive = /*best_fwd_consecutive =*/ indexsize*NT_PER_MATCH;
currlink->fwd_rootposition = /*best_fwd_rootposition =*/ positions[hiti];
currlink->fwd_pos = /*best_fwd_prevpos =*/ -1;
currlink->fwd_hit = /*best_fwd_prevhit =*/ -1;
if (anchoredp == true) {
currlink->fwd_tracei = -1;
fwd_scores[curr_querypos][hiti + low_hit] = -100000;
} else if (localp == true) {
currlink->fwd_tracei = ++*fwd_tracei;
fwd_scores[curr_querypos][hiti + low_hit] = indexsize_nt;
} else {
fwd_scores[curr_querypos][hiti + low_hit] = /*best_fwd_score =*/ 0;
}
hiti++;
}
} else {
adj_querypos = Intlist_head(last_item);
adj_links = links[adj_querypos];
adj_mappings = mappings[adj_querypos];
adj_active = active[adj_querypos];
#ifdef PMAP
adj_querydistance = (curr_querypos - adj_querypos)*3;
#else
adj_querydistance = curr_querypos - adj_querypos;
#endif
adj_frontier = firstactive[adj_querypos];
nprocessed = Intlist_length(processed);
frontier = (int *) MALLOCA(nprocessed * sizeof(int));
nseen = 0;
for (p = processed; p != NULL; p = Intlist_next(p)) {
prev_querypos = Intlist_head(p);
querydistance = curr_querypos - prev_querypos;
if (nseen <= /*nlookback*/1 || querydistance - indexsize_nt <= /*lookback*/sufflookback/2) {
max_adjacent_nseen = nseen;
}
if (nseen <= /*nlookback*/nsufflookback || querydistance - indexsize_nt <= /*lookback*/sufflookback) {
max_nonadjacent_nseen = nseen;
}
frontier[nseen++] = firstactive[prev_querypos];
}
for (hiti = 0; hiti < nhits; hiti++) {
position = positions[hiti];
/* A. Evaluate adjacent position (at last one processed) */
prevhit = adj_frontier; /* Get information from last hiti */
prevposition = position; /* Prevents prevposition + adj_querydistance == position */
while (prevhit != -1 && (prevposition = /*mappings[adj_querypos]*/adj_mappings[prevhit]) + adj_querydistance < position) {
prevhit = /*active[adj_querypos]*/adj_active[prevhit];
}
adj_frontier = prevhit; /* Save information for next hiti */
if (prevposition + adj_querydistance == position) {
/* Adjacent found */
prevlink = &(/*links[adj_querypos]*/adj_links[prevhit]);
best_fwd_consecutive = prevlink->fwd_consecutive + adj_querydistance;
best_fwd_rootposition = prevlink->fwd_rootposition;
best_fwd_prevpos = adj_querypos;
best_fwd_prevhit = prevhit;
best_fwd_score = fwd_scores[adj_querypos][prevhit] + CONSEC_POINTS_PER_MATCH*adj_querydistance;
max_nseen = max_adjacent_nseen; /* Look not so far back */
best_fwd_tracei = prevlink->fwd_tracei;
#ifdef DEBUG9
best_fwd_intronnfwd = prevlink->fwd_intronnfwd;
best_fwd_intronnrev = prevlink->fwd_intronnrev;
best_fwd_intronnunk = prevlink->fwd_intronnunk;
#endif
debug9(printf("\tA. For hit %d, adjacent qpos %d,%d at %ux%d (scores = %d -> %d, consec = %d (from #%d), intr = %d-%d-%d)\n",
hiti,adj_querypos,prevhit,prevposition,active[adj_querypos][prevhit],fwd_scores[adj_querypos][prevhit],
best_fwd_score,best_fwd_consecutive,/*best_fwd_tracei*/prevlink->fwd_tracei,
best_fwd_intronnfwd,best_fwd_intronnrev,best_fwd_intronnunk));
} else {
/* Adjacent not found */
best_fwd_consecutive = indexsize*NT_PER_MATCH;
best_fwd_rootposition = position;
best_fwd_prevpos = -1;
best_fwd_prevhit = -1;
best_fwd_score = 0;
max_nseen = max_nonadjacent_nseen; /* Look farther back */
best_fwd_tracei = -1;
#ifdef DEBUG9
best_fwd_intronnfwd = 0;
best_fwd_intronnrev = 0;
best_fwd_intronnunk = 0;
#endif
}
/* D. Evaluate for mismatches (all other previous querypos) */
nseen = 0;
last_tracei = -1;
for (p = processed; p != NULL && best_fwd_consecutive < enough_consecutive && nseen <= max_nseen;
p = Intlist_next(p), nseen++) {
/* Making this check helps with efficiency */
if ((prevhit = frontier[nseen]) != -1) { /* Retrieve starting point from last hiti */
prev_querypos = Intlist_head(p);
#ifdef PMAP
querydistance = (curr_querypos - prev_querypos)*3;
#else
querydistance = curr_querypos - prev_querypos;
#endif
/* Actually a querydist_penalty */
querydist_credit = -querydistance/indexsize_nt;
prev_mappings = mappings[prev_querypos];
prev_links = links[prev_querypos];
prev_active = active[prev_querypos];
/* Range 0 */
while (prevhit != -1 && prev_links[prevhit].fwd_tracei == last_tracei) {
debug9(printf("Skipping querypos %d with tracei #%d\n",prev_querypos,prev_links[prevhit].fwd_tracei));
prevhit = /*active[prev_querypos]*/prev_active[prevhit];
}
if (prevhit != -1) {
last_tracei = prev_links[prevhit].fwd_tracei;
}
/* Range 1: From Infinity to maxintronlen. To be skipped.
This is equivalent to diffdistance >= maxintronlen, where
diffdistance = abs(gendistance - querydistance) and
gendistance = (position - prevposition - indexsize_nt) */
while (prevhit != -1 && (/*prevposition =*/ /*mappings[prev_querypos]*/prev_mappings[prevhit]) + maxintronlen + querydistance <= position) {
/* Accept within range 1 (ignore) */
prevhit = /*active[prev_querypos]*/prev_active[prevhit];
}
frontier[nseen] = prevhit; /* Store as starting point for next hiti */
/* Range 2: From maxintronlen to (prev_querypos + EQUAL_DISTANCE_NOT_SPLICING) */
/* This is equivalent to +diffdistance > EQUAL_DISTANCE_NOT_SPLICING */
while (prevhit != -1 && (prevposition = /*mappings[prev_querypos]*/prev_mappings[prevhit]) + EQUAL_DISTANCE_NOT_SPLICING + querydistance < position) {
prevlink = &(/*links[prev_querypos]*/prev_links[prevhit]);
gendistance = position - prevposition;
assert(gendistance > querydistance); /* True because gendistance > EQUAL_DISTANCE_NOT_SPLICING + querydistance */
diffdistance = gendistance - querydistance; /* No need for abs() */
fwd_score = fwd_scores[prev_querypos][prevhit] + querydist_credit /*- querydist_penalty*/;
if (splicingp == true) {
fwd_score -= (diffdistance/TEN_THOUSAND + 1);
} else {
fwd_score -= (diffdistance/ONE + 1);
}
if (use_canonical_p == true) {
/* prevpos is lower genomic coordinate than currpos */
/* need to subtract from position and prevposition to compensate for greedy matches */
/* need to add to position and prevposition to compensate for missed matches */
if (plusp == true) {
prevpos = chroffset + prevposition + indexsize_nt;
currpos = chroffset + position - querydistance + indexsize_nt;
if (prevpos < GREEDY_ADVANCE || currpos < GREEDY_ADVANCE) {
canonicalp = false;
} else if (Genome_sense_canonicalp(/*donor_rightbound*/prevpos + MISS_BEHIND,
/*donor_leftbound*/prevpos - GREEDY_ADVANCE,
/*acceptor_rightbound*/currpos + MISS_BEHIND,
/*acceptor_leftbound*/currpos - GREEDY_ADVANCE,
chroffset) == true) {
debug9(printf("lookback plus: sense canonical\n"));
canonicalp = true;
} else if (Genome_antisense_canonicalp(/*donor_rightbound*/currpos + MISS_BEHIND,
/*donor_leftbound*/currpos - GREEDY_ADVANCE,
/*acceptor_rightbound*/prevpos + MISS_BEHIND,
/*acceptor_leftbound*/prevpos - GREEDY_ADVANCE,
chroffset) == true) {
debug9(printf("lookback plus: antisense canonical\n"));
canonicalp = true;
} else {
debug9(printf("lookback plus: not canonical\n"));
canonicalp = false;
}
} else {
prevpos = chrhigh + 1 - prevposition - indexsize_nt;
currpos = chrhigh + 1 - position + querydistance - indexsize_nt;
if (currpos < MISS_BEHIND || prevpos < MISS_BEHIND) {
canonicalp = false;
} else if (Genome_sense_canonicalp(/*donor_rightbound*/currpos + GREEDY_ADVANCE,
/*donor_leftbound*/currpos - MISS_BEHIND,
/*acceptor_rightbound*/prevpos + GREEDY_ADVANCE,
/*acceptor_leftbound*/prevpos - MISS_BEHIND,
chroffset) == true) {
debug9(printf("lookback minus: sense canonical\n"));
canonicalp = true;
} else if (Genome_antisense_canonicalp(/*donor_rightbound*/prevpos + GREEDY_ADVANCE,
/*donor_leftbound*/prevpos - MISS_BEHIND,
/*acceptor_rightbound*/currpos + GREEDY_ADVANCE,
/*acceptor_leftbound*/currpos - MISS_BEHIND,
chroffset) == true) {
debug9(printf("lookback minus: antisense canonical\n"));
canonicalp = true;
} else {
debug9(printf("lookback minus: not canonical\n"));
canonicalp = false;
}
}
if (canonicalp == true) {
debug9(canonicalsgn = +1);
} else {
debug9(canonicalsgn = 0);
fwd_score -= non_canonical_penalty;
}
}
debug9(printf("\tD2, hit %d. Fwd mismatch qpos %d,%d at %ux%d (score = %d -> %d, consec = %d (from #%d), intr = %d-%d-%d, gendist %u, querydist %d, canonicalsgn %d)",
hiti,prev_querypos,prevhit,prevposition,active[prev_querypos][prevhit],
fwd_scores[prev_querypos][prevhit],fwd_score,prevlink->fwd_consecutive,prevlink->fwd_tracei,
best_fwd_intronnfwd,best_fwd_intronnrev,best_fwd_intronnunk,
gendistance-indexsize_nt,querydistance-indexsize_nt,canonicalsgn));
/* Disallow ties, which should favor adjacent */
if (fwd_score > best_fwd_score) {
if (diffdistance <= EQUAL_DISTANCE_FOR_CONSECUTIVE) {
best_fwd_consecutive = prevlink->fwd_consecutive + querydistance;
} else {
best_fwd_consecutive = 0;
}
best_fwd_rootposition = prevlink->fwd_rootposition;
best_fwd_score = fwd_score;
best_fwd_prevpos = prev_querypos;
best_fwd_prevhit = prevhit;
best_fwd_tracei = ++*fwd_tracei;
#ifdef DEBUG9
best_fwd_intronnfwd = prevlink->fwd_intronnfwd;
best_fwd_intronnrev = prevlink->fwd_intronnrev;
best_fwd_intronnunk = prevlink->fwd_intronnunk;
switch (canonicalsgn) {
case 1: best_fwd_intronnfwd++; break;
case 0: best_fwd_intronnunk++; break;
}
#endif
debug9(printf(" => Best fwd at %d (consec = %d)\n",fwd_score,best_fwd_consecutive));
} else {
debug9(printf(" => Loses to %d\n",best_fwd_score));
}
prevhit = /*active[prev_querypos]*/prev_active[prevhit];
}
/* Scoring appears to be the same as for range 4, which is rarely called, so including in range 4 */
/* Range 3: From (querypos + EQUAL_DISTANCE_NOT_SPLICING) to (querypos - EQUAL_DISTANCE_NOT_SPLICING) */
/* This is equivalent to -diffdistance > EQUAL_DISTANCE_NOT_SPLICING && prevposition + indexsize_nt <= position */
/* Range 4: From (prev_querypos - EQUAL_DISTANCE_NOT_SPLICING) to indexsize_nt */
while (prevhit != -1 && (prevposition = /*mappings[prev_querypos]*/prev_mappings[prevhit]) + indexsize_nt <= position) {
prevlink = &(/*links[prev_querypos]*/prev_links[prevhit]);
gendistance = position - prevposition;
/* was abs(gendistance - querydistance) */
diffdistance = gendistance > querydistance ? (gendistance - querydistance) : (querydistance - gendistance);
#ifdef BAD_GMAX
fwd_score = prevlink->fwd_score + querydist_credit - (diffdistance/ONE + 1) /*- querydist_penalty*/;
#else
/* diffdistance <= EQUAL_DISTANCE_NOT_SPLICING */
/* This is how version 2013-08-14 did it */
fwd_score = fwd_scores[prev_querypos][prevhit] + CONSEC_POINTS_PER_MATCH;
#endif
debug9(printf("\tD4, hit %d. Fwd mismatch qpos %d,%d at %ux%d (score = %d -> %d, consec = %d (from #%d), intr = %d-%d-%d, gendist %u, querydist %d, canonicalsgn %d)",
hiti,prev_querypos,prevhit,prevposition,active[prev_querypos][prevhit],
fwd_scores[prev_querypos][prevhit],fwd_score,prevlink->fwd_consecutive,prevlink->fwd_tracei,
best_fwd_intronnfwd,best_fwd_intronnrev,best_fwd_intronnunk,
gendistance-indexsize_nt,querydistance-indexsize_nt,canonicalsgn));
/* Disallow ties, which should favor adjacent */
if (fwd_score > best_fwd_score) {
if (diffdistance <= EQUAL_DISTANCE_FOR_CONSECUTIVE) {
best_fwd_consecutive = prevlink->fwd_consecutive + querydistance;
} else {
best_fwd_consecutive = 0;
}
best_fwd_rootposition = prevlink->fwd_rootposition;
best_fwd_score = fwd_score;
best_fwd_prevpos = prev_querypos;
best_fwd_prevhit = prevhit;
/* best_fwd_tracei = ++*fwd_tracei; */
best_fwd_tracei = prevlink->fwd_tracei; /* Keep previous trace, as in range 3 */
#ifdef DEBUG9
best_fwd_intronnfwd = prevlink->fwd_intronnfwd;
best_fwd_intronnrev = prevlink->fwd_intronnrev;
best_fwd_intronnunk = prevlink->fwd_intronnunk;
switch (canonicalsgn) {
case 1: best_fwd_intronnfwd++; break;
case 0: best_fwd_intronnunk++; break;
}
#endif
debug9(printf(" => Best fwd at %d (consec = %d)\n",fwd_score,best_fwd_consecutive));
} else {
debug9(printf(" => Loses to %d\n",best_fwd_score));
}
prevhit = /*active[prev_querypos]*/prev_active[prevhit];
}
}
}
/* Best_score needs to beat something positive to prevent a
small local extension from beating a good canonical intron.
If querypos is too small, don't insert an intron. */
/* linksconsecutive already assigned above */
currlink = &(links[curr_querypos][hiti + low_hit]);
currlink->fwd_consecutive = best_fwd_consecutive;
currlink->fwd_rootposition = best_fwd_rootposition;
currlink->fwd_pos = best_fwd_prevpos;
currlink->fwd_hit = best_fwd_prevhit;
if (currlink->fwd_pos >= 0) {
currlink->fwd_tracei = best_fwd_tracei;
fwd_scores[curr_querypos][hiti + low_hit] = best_fwd_score;
} else if (anchoredp == true) {
currlink->fwd_tracei = -1;
fwd_scores[curr_querypos][hiti + low_hit] = -100000;
} else if (localp == true) {
currlink->fwd_tracei = ++*fwd_tracei;
fwd_scores[curr_querypos][hiti + low_hit] = indexsize_nt;
} else {
currlink->fwd_tracei = ++*fwd_tracei;
fwd_scores[curr_querypos][hiti + low_hit] = best_fwd_score;
}
#ifdef DEBUG9
currlink->fwd_intronnfwd = best_fwd_intronnfwd;
currlink->fwd_intronnrev = best_fwd_intronnrev;
currlink->fwd_intronnunk = best_fwd_intronnunk;
#endif
debug9(printf("\tChose %d,%d with score %d (fwd) => trace #%d\n",
currlink->fwd_pos,currlink->fwd_hit,fwd_scores[curr_querypos][hiti + low_hit],currlink->fwd_tracei));
debug3(printf("%d %d %d %d 1\n",querypos,hit,best_prevpos,best_prevhit));
}
FREEA(frontier);
}
return;
}
static void
score_querypos_lookforward_one (int *fwd_tracei, Link_T currlink, int curr_querypos, int currhit,
int querystart, int queryend, unsigned int position,
struct Link_T **links, int **fwd_scores,
Chrpos_T **mappings, int **active, int *firstactive,
Univcoord_T chroffset, Univcoord_T chrhigh, bool plusp,
int indexsize, Intlist_T processed,
bool anchoredp, bool localp, bool splicingp,
bool use_canonical_p, int non_canonical_penalty) {
Link_T prevlink;
struct Link_T *prev_links;
Chrpos_T *prev_mappings;
int *prev_active;
int best_fwd_consecutive = indexsize*NT_PER_MATCH;
int best_fwd_rootposition = position;
int best_fwd_score = 0, fwd_score;
int best_fwd_prevpos = -1, best_fwd_prevhit = -1;
int best_fwd_tracei, last_tracei;
#ifdef DEBUG9
int best_fwd_intronnfwd = 0, best_fwd_intronnrev = 0, best_fwd_intronnunk = 0;
int canonicalsgn = 0;
#endif
bool donep;
int prev_querypos, prevhit;
Chrpos_T prevposition;
int gendistance;
Univcoord_T prevpos, currpos;
int querydistance, diffdistance, lookback, nlookback, nseen, indexsize_nt, indexsize_query;
/* int querydist_penalty; */
int querydist_credit;
int enough_consecutive;
/* bool near_end_p; */
bool canonicalp;
#ifdef PMAP
indexsize_nt = indexsize*3;
#else
indexsize_nt = indexsize;
#endif
indexsize_query = indexsize; /* Use when evaluating across query positions */
enough_consecutive = 32;
/* Parameters for section D, assuming adjacent is false */
/* adjacentp = false; */
nlookback = nsufflookback;
lookback = sufflookback;
/* A. Evaluate adjacent position (at last one processed) */
if (processed != NULL) {
prev_querypos = Intlist_head(processed);
prev_mappings = mappings[prev_querypos];
prev_links = links[prev_querypos];
prev_active = active[prev_querypos];
#ifdef PMAP
querydistance = (prev_querypos - curr_querypos)*3;
#else
querydistance = prev_querypos - curr_querypos;
#endif
prevhit = firstactive[prev_querypos];
prevposition = position; /* Prevents prevposition == position + querydistance */
while (prevhit != -1 && (prevposition = /*mappings[prev_querypos]*/prev_mappings[prevhit]) > position + querydistance) {
prevhit = /*active[prev_querypos]*/prev_active[prevhit];
}
if (prevposition == position + querydistance) {
prevlink = &(/*links[prev_querypos]*/prev_links[prevhit]);
best_fwd_consecutive = prevlink->fwd_consecutive + querydistance;
/* best_fwd_rootnlinks = prevlink->fwd_rootnlinks + 1; */
best_fwd_rootposition = prevlink->fwd_rootposition;
best_fwd_score = fwd_scores[prev_querypos][prevhit] + CONSEC_POINTS_PER_MATCH*querydistance;
best_fwd_prevpos = prev_querypos;
best_fwd_prevhit = prevhit;
best_fwd_tracei = prevlink->fwd_tracei;
#ifdef DEBUG9
best_fwd_intronnfwd = prevlink->fwd_intronnfwd;
best_fwd_intronnrev = prevlink->fwd_intronnrev;
best_fwd_intronnunk = prevlink->fwd_intronnunk;
#endif
/* adjacentp = true; */
/* Parameters for section D when adjacent is true */
nlookback = 1;
lookback = sufflookback/2;
debug9(printf("\tA. Adjacent qpos %d,%d at %ux%d (scores = %d -> %d, consec = %d (from #%d), intr = %d-%d-%d)\n",
prev_querypos,prevhit,prevposition,active[prev_querypos][prevhit],fwd_scores[prev_querypos][prevhit],
best_fwd_score,best_fwd_consecutive,best_fwd_tracei,
best_fwd_intronnfwd,best_fwd_intronnrev,best_fwd_intronnunk));
}
}
/* Check work list */
if (anchoredp && curr_querypos + indexsize_query >= queryend) {
/* Allow close prevpositions that overlap with anchor */
/* Can give rise to false positives, and increases amount of dynamic programming work */
debug9(printf("No skipping because close to anchor\n"));
} else if (0 && anchoredp && curr_querypos == querystart) {
/* Test end position */
} else {
while (processed != NULL && (prev_querypos = Intlist_head(processed)) < curr_querypos + indexsize_query) {
debug9(printf("Skipping prev_querypos %d, because too close\n",prev_querypos));
processed = Intlist_next(processed);
}
}
/* D. Evaluate for mismatches (all other previous querypos) */
donep = false;
nseen = 0;
last_tracei = -1;
for ( ; processed != NULL && best_fwd_consecutive < enough_consecutive && donep == false;
processed = Intlist_next(processed), nseen++) {
prev_querypos = Intlist_head(processed);
#ifdef PMAP
querydistance = (prev_querypos - curr_querypos)*3;
#else
querydistance = prev_querypos - curr_querypos;
#endif
if (nseen > nlookback && querydistance - indexsize_nt > lookback) {
donep = true;
}
if ((prevhit = firstactive[prev_querypos]) != -1) {
/* querydist_penalty = (querydistance - indexsize_nt)/QUERYDIST_PENALTY_FACTOR; */
/* Actually a querydist_penalty */
querydist_credit = -querydistance/indexsize_nt;
prev_mappings = mappings[prev_querypos];
prev_links = links[prev_querypos];
prev_active = active[prev_querypos];
/* Range 0 */
while (prevhit != -1 && prev_links[prevhit].fwd_tracei == last_tracei) {
debug9(printf("Skipping querypos %d with tracei #%d\n",prev_querypos,prev_links[prevhit].fwd_tracei));
prevhit = /*active[prev_querypos]*/prev_active[prevhit];
}
if (prevhit != -1) {
last_tracei = prev_links[prevhit].fwd_tracei;
}
/* Range 1: From Infinity to maxintronlen */
if (splicingp == true) {
/* This is equivalent to diffdistance >= maxintronlen, where
diffdistance = abs(gendistance - querydistance) and
gendistance = (position - prevposition - indexsize_nt) */
while (prevhit != -1 && (prevposition = /*mappings[prev_querypos]*/prev_mappings[prevhit]) >= position + maxintronlen + querydistance) {
/* Skip */
/* printf("fwd: prevposition %u, prevhit %d\n",prevposition,prevhit); */
prevhit = /*active[prev_querypos]*/prev_active[prevhit];
}
}
/* Range 2: From maxintronlen to (prev_querypos + EQUAL_DISTANCE_NOT_SPLICING) */
/* This is equivalent to +diffdistance > EQUAL_DISTANCE_NOT_SPLICING */
while (prevhit != -1 && (prevposition = /*mappings[prev_querypos]*/prev_mappings[prevhit]) > position + EQUAL_DISTANCE_NOT_SPLICING + querydistance) {
/* printf("fwd: prevposition %u, prevhit %d\n",prevposition,prevhit); */
prevlink = &(/*links[prev_querypos]*/prev_links[prevhit]);
gendistance = prevposition - position;
assert(gendistance > querydistance); /* True because gendistance > EQUAL_DISTANCE_NOT_SPLICING + querydistance */
diffdistance = gendistance - querydistance; /* No need for abs() */
fwd_score = fwd_scores[prev_querypos][prevhit] + querydist_credit /*- querydist_penalty*/;
if (splicingp == true) {
fwd_score -= (diffdistance/TEN_THOUSAND + 1);
} else {
fwd_score -= (diffdistance/ONE + 1);
}
if (use_canonical_p == true) {
/* prevpos is higher genomic coordinate than currpos */
/* need to add to position and prevposition to compensate for greedy matches */
/* need to subtract from position and prevposition to compensate for missed matches */
if (plusp == true) {
prevpos = chroffset + prevposition;
currpos = chroffset + position + querydistance;
if (currpos < MISS_BEHIND || prevpos < MISS_BEHIND) {
canonicalp = false;
} else if (Genome_sense_canonicalp(/*donor_rightbound*/currpos + GREEDY_ADVANCE,
/*donor_leftbound*/currpos - MISS_BEHIND,
/*acceptor_rightbound*/prevpos + GREEDY_ADVANCE,
/*acceptor_leftbound*/prevpos - MISS_BEHIND,
chroffset) == true) {
debug9(printf("lookforward plus: sense canonical\n"));
canonicalp = true;
} else if (Genome_antisense_canonicalp(/*donor_rightbound*/prevpos + GREEDY_ADVANCE,
/*donor_leftbound*/prevpos - MISS_BEHIND,
/*acceptor_rightbound*/currpos + GREEDY_ADVANCE,
/*acceptor_leftbound*/currpos - MISS_BEHIND,
chroffset) == true) {
debug9(printf("lookforward plus: antisense canonical\n"));
canonicalp = true;
} else {
debug9(printf("lookforward plus: not canonical\n"));
canonicalp = false;
}
} else {
prevpos = chrhigh + 1 - prevposition;
currpos = chrhigh + 1 - position - querydistance;
if (prevpos < GREEDY_ADVANCE || currpos < GREEDY_ADVANCE) {
canonicalp = false;
} else if (Genome_sense_canonicalp(/*donor_rightbound*/prevpos + MISS_BEHIND,
/*donor_leftbound*/prevpos - GREEDY_ADVANCE,
/*acceptor_rightbound*/currpos + MISS_BEHIND,
/*acceptor_leftbound*/currpos - GREEDY_ADVANCE,
chroffset) == true) {
debug9(printf("lookforward minus: sense canonical\n"));
canonicalp = true;
} else if (Genome_antisense_canonicalp(/*donor_rightbound*/currpos + MISS_BEHIND,
/*donor_leftbound*/currpos - GREEDY_ADVANCE,
/*acceptor_rightbound*/prevpos + MISS_BEHIND,
/*acceptor_leftbound*/prevpos - GREEDY_ADVANCE,
chroffset) == true) {
debug9(printf("lookforward minus: antisense canonical\n"));
canonicalp = true;
} else {
debug9(printf("lookforward minus: not canonical\n"));
canonicalp = false;
}
}
if (canonicalp == true) {
debug9(canonicalsgn = +1);
} else {
debug9(canonicalsgn = 0);
fwd_score -= non_canonical_penalty;
}
}
debug9(printf("\tD2. Fwd mismatch qpos %d,%d at %ux%d (score = %d -> %d, consec = %d (from #%d), intr = %d-%d-%d, gendist %u, querydist %d, canonicalsgn %d)",
prev_querypos,prevhit,prevposition,active[prev_querypos][prevhit],
fwd_scores[prev_querypos][prevhit],fwd_score,prevlink->fwd_consecutive,prevlink->fwd_tracei,
best_fwd_intronnfwd,best_fwd_intronnrev,best_fwd_intronnunk,
gendistance-indexsize_nt,querydistance-indexsize_nt,canonicalsgn));
/* Disallow ties, which should favor adjacent */
if (fwd_score > best_fwd_score) {
if (diffdistance <= EQUAL_DISTANCE_FOR_CONSECUTIVE) {
best_fwd_consecutive = prevlink->fwd_consecutive + querydistance;
/* best_fwd_rootnlinks = prevlink->fwd_rootnlinks + 1; */
} else {
best_fwd_consecutive = 0;
/* best_fwd_rootnlinks = 1; */
}
best_fwd_rootposition = prevlink->fwd_rootposition;
best_fwd_score = fwd_score;
best_fwd_prevpos = prev_querypos;
best_fwd_prevhit = prevhit;
best_fwd_tracei = ++*fwd_tracei;
#ifdef DEBUG9
best_fwd_intronnfwd = prevlink->fwd_intronnfwd;
best_fwd_intronnrev = prevlink->fwd_intronnrev;
best_fwd_intronnunk = prevlink->fwd_intronnunk;
switch (canonicalsgn) {
case 1: best_fwd_intronnfwd++; break;
case 0: best_fwd_intronnunk++; break;
}
#endif
debug9(printf(" => Best fwd at %d (consec = %d)\n",fwd_score,best_fwd_consecutive));
} else {
debug9(printf(" => Loses to %d\n",best_fwd_score));
}
prevhit = /*active[prev_querypos]*/prev_active[prevhit];
}
/* Scoring appears to be the same as for range 4, which is rarely called, so including in range 4 */
/* Range 3: From (querypos + EQUAL_DISTANCE_NOT_SPLICING) to (querypos - EQUAL_DISTANCE_NOT_SPLICING) */
/* This is equivalent to -diffdistance > EQUAL_DISTANCE_NOT_SPLICING && prevposition + indexsize_nt <= position */
/* Range 4: From (prev_querypos - EQUAL_DISTANCE_NOT_SPLICING) to indexsize_nt */
while (prevhit != -1 && (prevposition = /*mappings[prev_querypos]*/prev_mappings[prevhit]) >= position + indexsize_nt) {
/* printf("fwd: prevposition %u, prevhit %d\n",prevposition,prevhit); */
prevlink = &(/*links[prev_querypos]*/prev_links[prevhit]);
gendistance = prevposition - position;
/* was abs(gendistance - querydistance) */
diffdistance = gendistance > querydistance ? (gendistance - querydistance) : (querydistance - gendistance);
#ifdef BAD_GMAX
fwd_score = prevlink->fwd_score + querydist_credit - (diffdistance/ONE + 1) /*- querydist_penalty*/;
#else
/* diffdistance <= EQUAL_DISTANCE_NOT_SPLICING */
/* This is how version 2013-08-14 did it */
fwd_score = fwd_scores[prev_querypos][prevhit] + CONSEC_POINTS_PER_MATCH;
#endif
#if 0
if (/*near_end_p == false &&*/ prevlink->fwd_consecutive < EXON_DEFN) {
fwd_score -= NINTRON_PENALTY_MISMATCH;
}
#endif
debug9(printf("\tD4. Fwd mismatch qpos %d,%d at %ux%d (score = %d -> %d, consec = %d (from #%d), intr = %d-%d-%d, gendist %u, querydist %d, canonicalsgn %d)",
prev_querypos,prevhit,prevposition,active[prev_querypos][prevhit],
fwd_scores[prev_querypos][prevhit],fwd_score,prevlink->fwd_consecutive,prevlink->fwd_tracei,
best_fwd_intronnfwd,best_fwd_intronnrev,best_fwd_intronnunk,
gendistance-indexsize_nt,querydistance-indexsize_nt,canonicalsgn));
/* Disallow ties, which should favor adjacent */
if (fwd_score > best_fwd_score) {
if (diffdistance <= EQUAL_DISTANCE_FOR_CONSECUTIVE) {
best_fwd_consecutive = prevlink->fwd_consecutive + querydistance;
/* best_fwd_rootnlinks = prevlink->fwd_rootnlinks + 1; */
} else {
best_fwd_consecutive = 0;
/* best_fwd_rootnlinks = 1; */
}
best_fwd_rootposition = prevlink->fwd_rootposition;
best_fwd_score = fwd_score;
best_fwd_prevpos = prev_querypos;
best_fwd_prevhit = prevhit;
/* best_fwd_tracei = ++*fwd_tracei; */
best_fwd_tracei = prevlink->fwd_tracei; /* Keep previous trace, as in range 3 */
#ifdef DEBUG9
best_fwd_intronnfwd = prevlink->fwd_intronnfwd;
best_fwd_intronnrev = prevlink->fwd_intronnrev;
best_fwd_intronnunk = prevlink->fwd_intronnunk;
switch (canonicalsgn) {
case 1: best_fwd_intronnfwd++; break;
case 0: best_fwd_intronnunk++; break;
}
#endif
debug9(printf(" => Best fwd at %d (consec = %d)\n",fwd_score,best_fwd_consecutive));
} else {
debug9(printf(" => Loses to %d\n",best_fwd_score));
}
prevhit = /*active[prev_querypos]*/prev_active[prevhit];
}
}
}
/* Best_score needs to beat something positive to prevent a
small local extension from beating a good canonical intron.
If querypos is too small, don't insert an intron. */
/* linksconsecutive already assigned above */
currlink->fwd_consecutive = best_fwd_consecutive;
currlink->fwd_rootposition = best_fwd_rootposition;
/* currlink->fwd_rootnlinks = best_fwd_rootnlinks; */
currlink->fwd_pos = best_fwd_prevpos;
currlink->fwd_hit = best_fwd_prevhit;
if (currlink->fwd_pos >= 0) {
currlink->fwd_tracei = best_fwd_tracei;
fwd_scores[curr_querypos][currhit] = best_fwd_score;
} else if (anchoredp == true) {
currlink->fwd_tracei = -1;
fwd_scores[curr_querypos][currhit] = -100000;
} else if (localp == true) {
currlink->fwd_tracei = ++*fwd_tracei;
fwd_scores[curr_querypos][currhit] = indexsize_nt;
} else {
currlink->fwd_tracei = ++*fwd_tracei;
fwd_scores[curr_querypos][currhit] = best_fwd_score;
}
#ifdef DEBUG9
currlink->fwd_intronnfwd = best_fwd_intronnfwd;
currlink->fwd_intronnrev = best_fwd_intronnrev;
currlink->fwd_intronnunk = best_fwd_intronnunk;
#endif
debug9(printf("\tChose %d,%d with score %d (fwd) => trace #%d\n",
currlink->fwd_pos,currlink->fwd_hit,fwd_scores[curr_querypos][currhit],currlink->fwd_tracei));
debug3(printf("%d %d %d %d 1\n",querypos,hit,best_prevpos,best_prevhit));
return;
}
static void
score_querypos_lookforward_mult (int *fwd_tracei, int low_hit, int high_hit, int curr_querypos,
int querystart, int queryend, unsigned int *positions,
struct Link_T **links, int **fwd_scores,
Chrpos_T **mappings, int **active, int *firstactive,
Univcoord_T chroffset, Univcoord_T chrhigh, bool plusp,
int indexsize, Intlist_T processed,
bool anchoredp, bool localp, bool splicingp,
bool use_canonical_p, int non_canonical_penalty) {
Link_T prevlink, currlink;
Intlist_T last_item, p;
int nhits = high_hit - low_hit, nprocessed, hiti;
struct Link_T *prev_links, *adj_links;
Chrpos_T *prev_mappings, *adj_mappings;
int *prev_active, *adj_active;
int best_fwd_consecutive;
int best_fwd_rootposition;
int best_fwd_score, fwd_score;
int best_fwd_prevpos, best_fwd_prevhit;
int best_fwd_tracei, last_tracei;
#ifdef DEBUG9
int best_fwd_intronnfwd, best_fwd_intronnrev, best_fwd_intronnunk;
int canonicalsgn = 0;
#endif
int adj_querypos, adj_querydistance, prev_querypos, prevhit, adj_frontier, *frontier;
Chrpos_T prevposition, position;
int gendistance;
Univcoord_T prevpos, currpos;
int querydistance, diffdistance, indexsize_nt, indexsize_query;
int max_nseen, max_adjacent_nseen, max_nonadjacent_nseen, nseen;
int querydist_credit;
int enough_consecutive = 32;
bool canonicalp;
#ifdef PMAP
indexsize_nt = indexsize*3;
#else
indexsize_nt = indexsize;
#endif
indexsize_query = indexsize; /* Use when evaluating across query positions */
/* Determine work load */
/* printf("Work load (lookforward): %s\n",Intlist_to_string(processed)); */
last_item = processed;
if (anchoredp && curr_querypos + indexsize_query >= queryend) {
/* Allow close prevpositions that overlap with anchor */
/* Can give rise to false positives, and increases amount of dynamic programming work */
/* debug9(printf("No skipping because close to anchor\n")); */
} else if (0 && anchoredp && curr_querypos == querystart) {
/* Test end position */
} else {
while (processed != NULL && (prev_querypos = Intlist_head(processed)) < curr_querypos + indexsize_query) {
debug9(printf("Skipping prev_querypos %d, because too close\n",prev_querypos));
processed = Intlist_next(processed);
}
}
if (last_item == NULL) {
for (hiti = nhits - 1; hiti >= 0; hiti--) {
currlink = &(links[curr_querypos][hiti + low_hit]);
currlink->fwd_consecutive = /*best_fwd_consecutive =*/ indexsize*NT_PER_MATCH;
currlink->fwd_rootposition = /*best_fwd_rootposition =*/ positions[hiti];
currlink->fwd_pos = /*best_fwd_prevpos =*/ -1;
currlink->fwd_hit = /*best_fwd_prevhit =*/ -1;
if (anchoredp == true) {
currlink->fwd_tracei = -1;
fwd_scores[curr_querypos][hiti + low_hit] = -100000;
} else if (localp == true) {
currlink->fwd_tracei = ++*fwd_tracei;
fwd_scores[curr_querypos][hiti + low_hit] = indexsize_nt;
} else {
fwd_scores[curr_querypos][hiti + low_hit] = /*best_fwd_score =*/ 0;
}
}
} else if (processed == NULL) {
/* A. Evaluate adjacent position (at last one processed, if available). Don't evaluate for mismatches (D). */
adj_querypos = Intlist_head(last_item);
adj_links = links[adj_querypos];
adj_mappings = mappings[adj_querypos];
adj_active = active[adj_querypos];
#ifdef PMAP
adj_querydistance = (adj_querypos - curr_querypos)*3;
#else
adj_querydistance = adj_querypos - curr_querypos;
#endif
/* Process prevhit and hiti in parallel. Values are descending along prevhit chain and from nhits-1 to 0. */
prevhit = firstactive[adj_querypos];
hiti = nhits - 1;
while (prevhit != -1 && hiti >= 0) {
if ((prevposition = /*mappings[adj_querypos]*/adj_mappings[prevhit]) > (position = positions[hiti]) + adj_querydistance) {
prevhit = /*active[adj_querypos]*/adj_active[prevhit];
} else if (prevposition < position + adj_querydistance) {
/* Adjacent position not found for hiti */
currlink = &(links[curr_querypos][hiti + low_hit]);
currlink->fwd_consecutive = /*best_fwd_consecutive =*/ indexsize*NT_PER_MATCH;
currlink->fwd_rootposition = /*best_fwd_rootposition =*/ positions[hiti];
currlink->fwd_pos = /*best_fwd_prevpos =*/ -1;
currlink->fwd_hit = /*best_fwd_prevhit =*/ -1;
if (anchoredp == true) {
currlink->fwd_tracei = -1;
fwd_scores[curr_querypos][hiti + low_hit] = -100000;
} else if (localp == true) {
currlink->fwd_tracei = ++*fwd_tracei;
fwd_scores[curr_querypos][hiti + low_hit] = indexsize_nt;
} else {
fwd_scores[curr_querypos][hiti + low_hit] = /*best_fwd_score =*/ 0;
}
hiti--;
} else {
/* Adjacent position found for hiti */
currlink = &(links[curr_querypos][hiti + low_hit]);
prevlink = &(/*links[adj_querypos]*/adj_links[prevhit]);
currlink->fwd_consecutive = /*best_fwd_consecutive =*/ prevlink->fwd_consecutive + adj_querydistance;
currlink->fwd_rootposition = /*best_fwd_rootposition =*/ prevlink->fwd_rootposition;
currlink->fwd_pos = /*best_fwd_prevpos =*/ adj_querypos;
currlink->fwd_hit = /*best_fwd_prevhit =*/ prevhit;
fwd_scores[curr_querypos][hiti + low_hit] = /*best_fwd_score =*/ fwd_scores[adj_querypos][prevhit] + CONSEC_POINTS_PER_MATCH*adj_querydistance;
#ifdef DEBUG9
printf("\tA. For hit %d, adjacent qpos %d,%d at %ux%d (scores = %d -> %d, consec = %d (from #%d), intr = %d-%d-%d)\n",
hiti,adj_querypos,prevhit,prevposition,active[adj_querypos][prevhit],fwd_scores[adj_querypos][prevhit],
fwd_scores[curr_querypos][hiti + low_hit],currlink->fwd_consecutive,/*best_fwd_tracei*/prevlink->fwd_tracei,
/*best_fwd_intronnfwd*/prevlink->fwd_intronnfwd,
/*best_fwd_intronnrev*/prevlink->fwd_intronnrev,
/*best_fwd_intronnunk*/prevlink->fwd_intronnunk);
#endif
prevhit = /*active[adj_querypos]*/adj_active[prevhit];
hiti--;
}
}
while (hiti >= 0) {
/* Adjacent position not found for hiti */
currlink = &(links[curr_querypos][hiti + low_hit]);
currlink->fwd_consecutive = /*best_fwd_consecutive =*/ indexsize*NT_PER_MATCH;
currlink->fwd_rootposition = /*best_fwd_rootposition =*/ positions[hiti];
currlink->fwd_pos = /*best_fwd_prevpos =*/ -1;
currlink->fwd_hit = /*best_fwd_prevhit =*/ -1;
if (anchoredp == true) {
currlink->fwd_tracei = -1;
fwd_scores[curr_querypos][hiti + low_hit] = -100000;
} else if (localp == true) {
currlink->fwd_tracei = ++*fwd_tracei;
fwd_scores[curr_querypos][hiti + low_hit] = indexsize_nt;
} else {
fwd_scores[curr_querypos][hiti + low_hit] = /*best_fwd_score =*/ 0;
}
hiti--;
}
} else {
adj_querypos = Intlist_head(last_item);
adj_links = links[adj_querypos];
adj_mappings = mappings[adj_querypos];
adj_active = active[adj_querypos];
#ifdef PMAP
adj_querydistance = (adj_querypos - curr_querypos)*3;
#else
adj_querydistance = adj_querypos - curr_querypos;
#endif
adj_frontier = firstactive[adj_querypos];
nprocessed = Intlist_length(processed);
frontier = (int *) MALLOCA(nprocessed * sizeof(int));
nseen = 0;
for (p = processed; p != NULL; p = Intlist_next(p)) {
prev_querypos = Intlist_head(p);
querydistance = prev_querypos - curr_querypos;
if (nseen <= /*nlookback*/1 || querydistance - indexsize_nt <= /*lookback*/sufflookback/2) {
max_adjacent_nseen = nseen;
}
if (nseen <= /*nlookback*/nsufflookback || querydistance - indexsize_nt <= /*lookback*/sufflookback) {
max_nonadjacent_nseen = nseen;
}
frontier[nseen++] = firstactive[prev_querypos];
}
for (hiti = nhits - 1; hiti >= 0; hiti--) {
position = positions[hiti];
/* A. Evaluate adjacent position (at last one processed) */
prevhit = adj_frontier; /* Get information from last hiti */
prevposition = position; /* Prevents prevposition == position + adj_querydistance */
while (prevhit != -1 && (prevposition = /*mappings[adj_querypos]*/adj_mappings[prevhit]) > position + adj_querydistance) {
prevhit = /*active[adj_querypos]*/adj_active[prevhit];
}
adj_frontier = prevhit; /* Save information for next hiti */
if (prevposition == position + adj_querydistance) {
/* Adjacent found */
prevlink = &(/*links[adj_querypos]*/adj_links[prevhit]);
best_fwd_consecutive = prevlink->fwd_consecutive + adj_querydistance;
best_fwd_rootposition = prevlink->fwd_rootposition;
best_fwd_prevpos = adj_querypos;
best_fwd_prevhit = prevhit;
best_fwd_score = fwd_scores[adj_querypos][prevhit] + CONSEC_POINTS_PER_MATCH*adj_querydistance;
max_nseen = max_adjacent_nseen; /* Look not so far back */
best_fwd_tracei = prevlink->fwd_tracei;
#ifdef DEBUG9
best_fwd_intronnfwd = prevlink->fwd_intronnfwd;
best_fwd_intronnrev = prevlink->fwd_intronnrev;
best_fwd_intronnunk = prevlink->fwd_intronnunk;
#endif
debug9(printf("\tA. For hit %d, adjacent qpos %d,%d at %ux%d (scores = %d -> %d, consec = %d (from #%d), intr = %d-%d-%d)\n",
hiti,adj_querypos,prevhit,prevposition,active[adj_querypos][prevhit],fwd_scores[adj_querypos][prevhit],
best_fwd_score,best_fwd_consecutive,/*best_fwd_tracei*/prevlink->fwd_tracei,
best_fwd_intronnfwd,best_fwd_intronnrev,best_fwd_intronnunk));
} else {
/* Adjacent not found */
best_fwd_consecutive = indexsize*NT_PER_MATCH;
best_fwd_rootposition = position;
best_fwd_prevpos = -1;
best_fwd_prevhit = -1;
best_fwd_score = 0;
max_nseen = max_nonadjacent_nseen; /* Look farther back */
best_fwd_tracei = -1;
#ifdef DEBUG9
best_fwd_intronnfwd = 0;
best_fwd_intronnrev = 0;
best_fwd_intronnunk = 0;
#endif
}
/* D. Evaluate for mismatches (all other previous querypos) */
nseen = 0;
last_tracei = -1;
for (p = processed; p != NULL && best_fwd_consecutive < enough_consecutive && nseen <= max_nseen;
p = Intlist_next(p), nseen++) {
/* Making this check helps with efficiency */
if ((prevhit = frontier[nseen]) != -1) { /* Retrieve starting point from last hiti */
prev_querypos = Intlist_head(p);
#ifdef PMAP
querydistance = (prev_querypos - curr_querypos)*3;
#else
querydistance = prev_querypos - curr_querypos;
#endif
/* Actually a querydist_penalty */
querydist_credit = -querydistance/indexsize_nt;
prev_mappings = mappings[prev_querypos];
prev_links = links[prev_querypos];
prev_active = active[prev_querypos];
/* Range 0 */
while (prevhit != -1 && prev_links[prevhit].fwd_tracei == last_tracei) {
debug9(printf("Skipping querypos %d with tracei #%d\n",prev_querypos,prev_links[prevhit].fwd_tracei));
prevhit = /*active[prev_querypos]*/prev_active[prevhit];
}
if (prevhit != -1) {
last_tracei = prev_links[prevhit].fwd_tracei;
}
/* Range 1: From Infinity to maxintronlen. To be skipped.
This is equivalent to diffdistance >= maxintronlen, where
diffdistance = abs(gendistance - querydistance) and
gendistance = (position - prevposition - indexsize_nt) */
while (prevhit != -1 && (/*prevposition =*/ /*mappings[prev_querypos]*/prev_mappings[prevhit]) >= position + maxintronlen + querydistance) {
/* Accept within range 1 (ignore) */
prevhit = /*active[prev_querypos]*/prev_active[prevhit];
}
frontier[nseen] = prevhit; /* Store as starting point for next hiti */
/* Range 2: From maxintronlen to (prev_querypos + EQUAL_DISTANCE_NOT_SPLICING) */
/* This is equivalent to +diffdistance > EQUAL_DISTANCE_NOT_SPLICING */
while (prevhit != -1 && (prevposition = /*mappings[prev_querypos]*/prev_mappings[prevhit]) > position + EQUAL_DISTANCE_NOT_SPLICING + querydistance) {
prevlink = &(/*links[prev_querypos]*/prev_links[prevhit]);
gendistance = prevposition - position;
assert(gendistance > querydistance); /* True because gendistance > EQUAL_DISTANCE_NOT_SPLICING + querydistance */
diffdistance = gendistance - querydistance; /* No need for abs() */
fwd_score = fwd_scores[prev_querypos][prevhit] + querydist_credit /*- querydist_penalty*/;
if (splicingp == true) {
fwd_score -= (diffdistance/TEN_THOUSAND + 1);
} else {
fwd_score -= (diffdistance/ONE + 1);
}
if (use_canonical_p == true) {
/* prevpos is higher genomic coordinate than currpos */
/* need to add to position and prevposition to compensate for greedy matches */
/* need to subtract from position and prevposition to compensate for missed matches */
if (plusp == true) {
prevpos = chroffset + prevposition;
currpos = chroffset + position + querydistance;
if (currpos < MISS_BEHIND || prevpos < MISS_BEHIND) {
canonicalp = false;
} else if (Genome_sense_canonicalp(/*donor_rightbound*/currpos + GREEDY_ADVANCE,
/*donor_leftbound*/currpos - MISS_BEHIND,
/*acceptor_rightbound*/prevpos + GREEDY_ADVANCE,
/*acceptor_leftbound*/prevpos - MISS_BEHIND,
chroffset) == true) {
debug9(printf("lookforward plus: sense canonical\n"));
canonicalp = true;
} else if (Genome_antisense_canonicalp(/*donor_rightbound*/prevpos + GREEDY_ADVANCE,
/*donor_leftbound*/prevpos - MISS_BEHIND,
/*acceptor_rightbound*/currpos + GREEDY_ADVANCE,
/*acceptor_leftbound*/currpos - MISS_BEHIND,
chroffset) == true) {
debug9(printf("lookforward plus: antisense canonical\n"));
canonicalp = true;
} else {
debug9(printf("lookforward plus: not canonical\n"));
canonicalp = false;
}
} else {
prevpos = chrhigh + 1 - prevposition;
currpos = chrhigh + 1 - position - querydistance;
if (prevpos < GREEDY_ADVANCE || currpos < GREEDY_ADVANCE) {
canonicalp = false;
} else if (Genome_sense_canonicalp(/*donor_rightbound*/prevpos + MISS_BEHIND,
/*donor_leftbound*/prevpos - GREEDY_ADVANCE,
/*acceptor_rightbound*/currpos + MISS_BEHIND,
/*acceptor_leftbound*/currpos - GREEDY_ADVANCE,
chroffset) == true) {
debug9(printf("lookforward minus: sense canonical\n"));
canonicalp = true;
} else if (Genome_antisense_canonicalp(/*donor_rightbound*/currpos + MISS_BEHIND,
/*donor_leftbound*/currpos - GREEDY_ADVANCE,
/*acceptor_rightbound*/prevpos + MISS_BEHIND,
/*acceptor_leftbound*/prevpos - GREEDY_ADVANCE,
chroffset) == true) {
debug9(printf("lookforward minus: antisense canonical\n"));
canonicalp = true;
} else {
debug9(printf("lookforward minus: not canonical\n"));
canonicalp = false;
}
}
if (canonicalp == true) {
debug9(canonicalsgn = +1);
} else {
debug9(canonicalsgn = 0);
fwd_score -= non_canonical_penalty;
}
}
debug9(printf("\tD2, hit %d. Fwd mismatch qpos %d,%d at %ux%d (score = %d -> %d, consec = %d (from #%d), intr = %d-%d-%d, gendist %u, querydist %d, canonicalsgn %d)",
hiti,prev_querypos,prevhit,prevposition,active[prev_querypos][prevhit],
fwd_scores[prev_querypos][prevhit],fwd_score,prevlink->fwd_consecutive,prevlink->fwd_tracei,
best_fwd_intronnfwd,best_fwd_intronnrev,best_fwd_intronnunk,
gendistance-indexsize_nt,querydistance-indexsize_nt,canonicalsgn));
/* Disallow ties, which should favor adjacent */
if (fwd_score > best_fwd_score) {
if (diffdistance <= EQUAL_DISTANCE_FOR_CONSECUTIVE) {
best_fwd_consecutive = prevlink->fwd_consecutive + querydistance;
} else {
best_fwd_consecutive = 0;
}
best_fwd_rootposition = prevlink->fwd_rootposition;
best_fwd_score = fwd_score;
best_fwd_prevpos = prev_querypos;
best_fwd_prevhit = prevhit;
best_fwd_tracei = ++*fwd_tracei;
#ifdef DEBUG9
best_fwd_intronnfwd = prevlink->fwd_intronnfwd;
best_fwd_intronnrev = prevlink->fwd_intronnrev;
best_fwd_intronnunk = prevlink->fwd_intronnunk;
switch (canonicalsgn) {
case 1: best_fwd_intronnfwd++; break;
case 0: best_fwd_intronnunk++; break;
}
#endif
debug9(printf(" => Best fwd at %d (consec = %d)\n",fwd_score,best_fwd_consecutive));
} else {
debug9(printf(" => Loses to %d\n",best_fwd_score));
}
prevhit = /*active[prev_querypos]*/prev_active[prevhit];
}
/* Scoring appears to be the same as for range 4, which is rarely called, so including in range 4 */
/* Range 3: From (querypos + EQUAL_DISTANCE_NOT_SPLICING) to (querypos - EQUAL_DISTANCE_NOT_SPLICING) */
/* This is equivalent to -diffdistance > EQUAL_DISTANCE_NOT_SPLICING && prevposition + indexsize_nt <= position */
/* Range 4: From (prev_querypos - EQUAL_DISTANCE_NOT_SPLICING) to indexsize_nt */
while (prevhit != -1 && (prevposition = /*mappings[prev_querypos]*/prev_mappings[prevhit]) >= position + indexsize_nt) {
prevlink = &(/*links[prev_querypos]*/prev_links[prevhit]);
gendistance = prevposition - position;
/* was abs(gendistance - querydistance) */
diffdistance = gendistance > querydistance ? (gendistance - querydistance) : (querydistance - gendistance);
#ifdef BAD_GMAX
fwd_score = fwd_scores[prev_querypos][prevhit] + querydist_credit - (diffdistance/ONE + 1) /*- querydist_penalty*/;
#else
/* diffdistance <= EQUAL_DISTANCE_NOT_SPLICING */
/* This is how version 2013-08-14 did it */
fwd_score = fwd_scores[prev_querypos][prevhit] + CONSEC_POINTS_PER_MATCH;
#endif
debug9(printf("\tD4, hit %d. Fwd mismatch qpos %d,%d at %ux%d (score = %d -> %d, consec = %d (from #%d), intr = %d-%d-%d, gendist %u, querydist %d, canonicalsgn %d)",
hiti,prev_querypos,prevhit,prevposition,active[prev_querypos][prevhit],
fwd_scores[prev_querypos][prevhit],fwd_score,prevlink->fwd_consecutive,prevlink->fwd_tracei,
best_fwd_intronnfwd,best_fwd_intronnrev,best_fwd_intronnunk,
gendistance-indexsize_nt,querydistance-indexsize_nt,canonicalsgn));
/* Disallow ties, which should favor adjacent */
if (fwd_score > best_fwd_score) {
if (diffdistance <= EQUAL_DISTANCE_FOR_CONSECUTIVE) {
best_fwd_consecutive = prevlink->fwd_consecutive + querydistance;
} else {
best_fwd_consecutive = 0;
}
best_fwd_rootposition = prevlink->fwd_rootposition;
best_fwd_score = fwd_score;
best_fwd_prevpos = prev_querypos;
best_fwd_prevhit = prevhit;
/* best_fwd_tracei = ++*fwd_tracei; */
best_fwd_tracei = prevlink->fwd_tracei; /* Keep previous trace, as in range 3 */
#ifdef DEBUG9
best_fwd_intronnfwd = prevlink->fwd_intronnfwd;
best_fwd_intronnrev = prevlink->fwd_intronnrev;
best_fwd_intronnunk = prevlink->fwd_intronnunk;
switch (canonicalsgn) {
case 1: best_fwd_intronnfwd++; break;
case 0: best_fwd_intronnunk++; break;
}
#endif
debug9(printf(" => Best fwd at %d (consec = %d)\n",fwd_score,best_fwd_consecutive));
} else {
debug9(printf(" => Loses to %d\n",best_fwd_score));
}
prevhit = /*active[prev_querypos]*/prev_active[prevhit];
}
}
}
/* Best_score needs to beat something positive to prevent a
small local extension from beating a good canonical intron.
If querypos is too small, don't insert an intron. */
/* linksconsecutive already assigned above */
currlink = &(links[curr_querypos][hiti + low_hit]);
currlink->fwd_consecutive = best_fwd_consecutive;
currlink->fwd_rootposition = best_fwd_rootposition;
currlink->fwd_pos = best_fwd_prevpos;
currlink->fwd_hit = best_fwd_prevhit;
if (currlink->fwd_pos >= 0) {
currlink->fwd_tracei = best_fwd_tracei;
fwd_scores[curr_querypos][hiti + low_hit] = best_fwd_score;
} else if (anchoredp == true) {
currlink->fwd_tracei = -1;
fwd_scores[curr_querypos][hiti + low_hit] = -100000;
} else if (localp == true) {
currlink->fwd_tracei = ++*fwd_tracei;
fwd_scores[curr_querypos][hiti + low_hit] = indexsize_nt;
} else {
currlink->fwd_tracei = ++*fwd_tracei;
fwd_scores[curr_querypos][hiti + low_hit] = best_fwd_score;
}
#ifdef DEBUG9
currlink->fwd_intronnfwd = best_fwd_intronnfwd;
currlink->fwd_intronnrev = best_fwd_intronnrev;
currlink->fwd_intronnunk = best_fwd_intronnunk;
#endif
debug9(printf("\tChose %d,%d with score %d (fwd) => trace #%d\n",
currlink->fwd_pos,currlink->fwd_hit,fwd_scores[curr_querypos][hiti + low_hit],currlink->fwd_tracei));
debug3(printf("%d %d %d %d 1\n",querypos,hit,best_prevpos,best_prevhit));
}
FREEA(frontier);
}
return;
}
static void
revise_active_lookback (int **active, int *firstactive, int *nactive,
int low_hit, int high_hit, int **fwd_scores, int querypos) {
int best_score, threshold, score;
int hit, *ptr;
debug6(printf("Revising querypos %d from low_hit %d to high_hit %d. Scores:\n",querypos,low_hit,high_hit));
if ((hit = low_hit) >= high_hit) {
debug6(printf("1. Initializing firstactive for querypos %d to be -1\n",querypos));
firstactive[querypos] = -1;
nactive[querypos] = 0;
} else {
debug6(printf("At hit %d, fwd_score is %d",hit,fwd_scores[querypos][hit]));
best_score = fwd_scores[querypos][hit];
#ifdef SEPARATE_FWD_REV
debug6(printf(" and rev_score is %d",rev_scores[querypos][hit]));
if ((score = rev_scores[querypos][hit]) > best_score) {
best_score = score;
}
#endif
debug6(printf("\n"));
for (hit++; hit < high_hit; hit++) {
debug6(printf("At hit %d, fwd_score is %d",hit,fwd_scores[querypos][hit]));
if ((score = fwd_scores[querypos][hit]) > best_score) {
best_score = score;
}
#ifdef SEPARATE_FWD_REV
debug6(printf(" and rev_score is %d",rev_scores[querypos][hit]));
if ((score = rev_scores[querypos][hit]) > best_score) {
best_score = score;
}
#endif
debug6(printf("\n"));
}
threshold = best_score - SCORE_FOR_RESTRICT;
if (threshold < 0) {
threshold = 0;
}
nactive[querypos] = 0;
firstactive[querypos] = -1;
ptr = &(firstactive[querypos]);
hit = low_hit;
while (hit < high_hit) {
while (hit < high_hit && fwd_scores[querypos][hit] <= threshold
#ifdef SEPARATE_FWD_REV
&& rev_scores[querypos][hit] <= threshold
#endif
) {
hit++;
}
*ptr = hit;
if (hit < high_hit) {
nactive[querypos] += 1;
ptr = &(active[querypos][hit]);
hit++;
}
}
*ptr = -1;
}
debug6(
printf("Valid hits (%d) at querypos %d (firstactive %d):",nactive[querypos],querypos,firstactive[querypos]);
hit = firstactive[querypos];
while (hit != -1) {
printf(" %d",hit);
hit = active[querypos][hit];
}
printf("\n");
);
return;
}
static void
revise_active_lookforward (int **active, int *firstactive, int *nactive,
int low_hit, int high_hit, int **fwd_scores, int querypos) {
int best_score, threshold, score;
int hit, *ptr;
debug6(printf("Revising querypos %d from high_hit %d to low_hit %d. Scores:\n",querypos,high_hit,low_hit));
if ((hit = high_hit - 1) < low_hit) {
debug6(printf("2. Initializing firstactive for querypos %d to be -1\n",querypos));
firstactive[querypos] = -1;
nactive[querypos] = 0;
} else {
debug6(printf("At hit %d, fwd_score is %d",hit,fwd_scores[querypos][hit]));
best_score = fwd_scores[querypos][hit];
#ifdef SEPARATE_FWD_REV
debug6(printf(" and rev_score is %d",rev_scores[querypos][hit]));
if ((score = rev_scores[querypos][hit]) > best_score) {
best_score = score;
}
#endif
debug6(printf("\n"));
for (--hit; hit >= low_hit; --hit) {
debug6(printf("At hit %d, fwd_score is %d",hit,fwd_scores[querypos][hit]));
if ((score = fwd_scores[querypos][hit]) > best_score) {
best_score = score;
}
#ifdef SEPARATE_FWD_REV
debug6(printf(" and rev_score is %d",rev_scores[querypos][hit]));
if ((score = rev_scores[querypos][hit]) > best_score) {
best_score = score;
}
#endif
debug6(printf("\n"));
}
threshold = best_score - SCORE_FOR_RESTRICT;
if (threshold < 0) {
threshold = 0;
}
nactive[querypos] = 0;
firstactive[querypos] = -1;
ptr = &(firstactive[querypos]);
hit = high_hit - 1;
while (hit >= low_hit) {
while (hit >= low_hit && fwd_scores[querypos][hit] <= threshold
#ifdef SEPARATE_FWD_REV
&& rev_scores[querypos][hit] <= threshold
#endif
) {
--hit;
}
*ptr = hit;
if (hit >= low_hit) {
nactive[querypos] += 1;
ptr = &(active[querypos][hit]);
--hit;
}
}
*ptr = -1;
}
debug6(
printf("Valid hits (%d) at querypos %d (firstactive %d):",nactive[querypos],querypos,firstactive[querypos]);
hit = firstactive[querypos];
while (hit != -1) {
printf(" %d",hit);
hit = active[querypos][hit];
}
printf("\n");
);
return;
}
static int **
intmatrix_1d_new (int length1, int *lengths2, int totallength) {
int **matrix;
int i;
matrix = (int **) CALLOC(length1,sizeof(int *));
matrix[0] = (int *) CALLOC(totallength,sizeof(int));
for (i = 1; i < length1; i++) {
if (lengths2[i-1] <= 0) {
matrix[i] = matrix[i-1];
} else {
matrix[i] = &(matrix[i-1][lengths2[i-1]]);
}
}
return matrix;
}
static void
intmatrix_1d_free (int ***matrix) {
FREE((*matrix)[0]);
FREE(*matrix);
return;
}
static int **
intmatrix_2d_new (int length1, int *lengths2) {
int **matrix;
int i;
matrix = (int **) CALLOC(length1,sizeof(int *));
for (i = 0; i < length1; i++) {
if (lengths2[i] <= 0) {
matrix[i] = (int *) NULL;
} else {
matrix[i] = (int *) CALLOC(lengths2[i],sizeof(int));
}
}
return matrix;
}
static void
intmatrix_2d_free (int ***matrix, int length1) {
int i;
for (i = 0; i < length1; i++) {
if ((*matrix)[i]) {
FREE((*matrix)[i]);
}
}
FREE(*matrix);
return;
}
/************************************************************************
* Cells used for ranking hits
************************************************************************/
#if 0
typedef struct Cell_T *Cell_T;
struct Cell_T {
int rootposition;
int querypos;
int hit;
bool fwdp;
int score;
};
/* Replaced by Cellpool_T routines */
static void
Cell_free (Cell_T *old) {
FREE(*old);
return;
}
static Cell_T
Cell_new (int rootposition, int querypos, int hit, bool fwdp, int score) {
Cell_T new = (Cell_T) MALLOC(sizeof(*new));
new->rootposition = rootposition;
new->querypos = querypos;
new->hit = hit;
new->fwdp = fwdp;
new->score = score;
return new;
}
#endif
static int
Cell_rootposition_left_cmp (const void *a, const void *b) {
Cell_T x = * (Cell_T *) a;
Cell_T y = * (Cell_T *) b;
if (x->rootposition < y->rootposition) {
return -1;
} else if (y->rootposition < x->rootposition) {
return +1;
#if 0
} else if (x->tracei < y->tracei) {
return -1;
} else if (y->tracei < x->tracei) {
return +1;
#endif
} else if (x->score > y->score) {
return -1;
} else if (y->score > x->score) {
return +1;
} else if (x->querypos > y->querypos) {
return -1;
} else if (y->querypos > x->querypos) {
return +1;
} else if (x->hit < y->hit) {
return -1;
} else if (y->hit < x->hit) {
return +1;
} else if (x->fwdp == true && y->fwdp == false) {
return -1;
} else if (y->fwdp == true && x->fwdp == false) {
return +1;
} else {
return 0;
}
}
static int
Cell_rootposition_right_cmp (const void *a, const void *b) {
Cell_T x = * (Cell_T *) a;
Cell_T y = * (Cell_T *) b;
if (x->rootposition < y->rootposition) {
return -1;
} else if (y->rootposition < x->rootposition) {
return +1;
#if 0
} else if (x->tracei < y->tracei) {
return -1;
} else if (y->tracei < x->tracei) {
return +1;
#endif
} else if (x->score > y->score) {
return -1;
} else if (y->score > x->score) {
return +1;
} else if (x->querypos > y->querypos) {
return -1;
} else if (y->querypos > x->querypos) {
return +1;
} else if (x->hit > y->hit) {
return -1;
} else if (y->hit > x->hit) {
return +1;
} else if (x->fwdp == true && y->fwdp == false) {
return -1;
} else if (y->fwdp == true && x->fwdp == false) {
return +1;
} else {
return 0;
}
}
static int
Cell_score_cmp (const void *a, const void *b) {
Cell_T x = * (Cell_T *) a;
Cell_T y = * (Cell_T *) b;
if (x->score > y->score) {
return -1;
} else if (y->score > x->score) {
return +1;
} else {
return 0;
}
}
#ifdef USE_THRESHOLD_SCORE
/* Doesn't work well for short dynamic programming at the ends of a read */
static Cell_T *
Linkmatrix_get_cells_fwd (int *nunique, struct Link_T **links, int querystart, int queryend, int *npositions,
int indexsize, int bestscore, bool favor_right_p, Cellpool_T cellpool) {
Cell_T *sorted, *cells;
List_T celllist = NULL;
int querypos, hit;
int rootposition, last_rootposition;
int threshold_score, best_score_for_root;
int ngood, ncells, i, k;
if (bestscore > 2*suboptimal_score_end) {
threshold_score = bestscore - suboptimal_score_end;
} else {
threshold_score = bestscore/2;
}
if (threshold_score <= indexsize) {
threshold_score = indexsize + 1;
}
ncells = 0;
for (querypos = querystart; querypos <= queryend; querypos++) {
ngood = 0;
for (hit = 0; hit < npositions[querypos]; hit++) {
if (links[querypos][hit].fwd_score >= threshold_score) {
ngood++;
}
}
if (ngood > 0 && ngood <= 10) {
for (hit = 0; hit < npositions[querypos]; hit++) {
debug11(printf(" At %d,%d, comparing score %d with threshold_score %d\n",
querypos,hit,links[querypos][hit].fwd_score,threshold_score));
if (links[querypos][hit].fwd_score >= threshold_score) {
rootposition = links[querypos][hit].fwd_rootposition;
/* tracei = links[querypos][hit].fwd_tracei; */
celllist = Cellpool_push(celllist,cellpool,rootposition,querypos,hit,/*fwdp*/true,
links[querypos][hit].fwd_score);
ncells++;
}
}
}
}
if (ncells == 0) {
*nunique = 0;
return (Cell_T *) NULL;
} else {
/* Take best result for each tracei */
/* Using alloca can give a stack overflow */
cells = (Cell_T *) List_to_array(celllist,NULL);
/* List_free(&celllist); -- No need with cellpool */
if (favor_right_p == true) {
qsort(cells,ncells,sizeof(Cell_T),Cell_rootposition_right_cmp);
} else {
qsort(cells,ncells,sizeof(Cell_T),Cell_rootposition_left_cmp);
}
sorted = (Cell_T *) MALLOC(ncells * sizeof(Cell_T)); /* Return value */
k = 0;
last_rootposition = -1;
best_score_for_root = -1;
for (i = 0; i < ncells; i++) {
if (cells[i]->rootposition != last_rootposition) {
debug11(printf("Pushing rootposition %d, trace #%d, score %d, pos %d, hit %d\n",
cells[i]->rootposition,cells[i]->tracei,cells[i]->score,cells[i]->querypos,cells[i]->hit));
sorted[k++] = cells[i];
last_rootposition = cells[i]->rootposition;
best_score_for_root = cells[i]->score;
} else if (cells[i]->querypos == best_score_for_root) {
debug11(printf("Equivalent cell for rootposition %d, trace #%d, score %d, pos %d, hit %d\n",
cells[i]->rootposition,cells[i]->tracei,cells[i]->score,cells[i]->querypos,cells[i]->hit));
sorted[k++] = cells[i];
/* last_rootposition = cells[i]->rootposition;*/
/* best_score_for_root = cells[i]->score; */
} else {
/* Cell_free(&(cells[i])); -- no need with cellpool */
}
}
debug11(printf("\n"));
FREE(cells);
*nunique = k;
qsort(sorted,*nunique,sizeof(Cell_T),Cell_score_cmp);
return sorted;
}
}
#else
static Cell_T *
get_cells_fwd (int *nunique, struct Link_T **links, int **fwd_scores,
int querystart, int queryend, int *npositions,
bool favor_right_p, Cellpool_T cellpool) {
Cell_T *sorted, *cells;
List_T celllist = NULL;
int querypos, hit;
int rootposition, last_rootposition;
int best_score_for_root;
int ncells, i, k;
ncells = 0;
for (querypos = querystart; querypos <= queryend; querypos++) {
for (hit = 0; hit < npositions[querypos]; hit++) {
if (fwd_scores[querypos][hit] > 0) {
rootposition = links[querypos][hit].fwd_rootposition;
/* tracei = links[querypos][hit].fwd_tracei; */
celllist = Cellpool_push(celllist,cellpool,rootposition,querypos,hit,/*fwdp*/true,
fwd_scores[querypos][hit]);
ncells++;
}
}
}
debug12(printf("Have %d cells\n",ncells));
if (ncells == 0) {
*nunique = 0;
return (Cell_T *) NULL;
} else {
/* Take best result for each tracei */
/* Using alloca can give a stack overflow */
cells = (Cell_T *) List_to_array(celllist,NULL);
/* List_free(&celllist); -- No need with cellpool */
if (favor_right_p == true) {
qsort(cells,ncells,sizeof(Cell_T),Cell_rootposition_right_cmp);
} else {
qsort(cells,ncells,sizeof(Cell_T),Cell_rootposition_left_cmp);
}
sorted = (Cell_T *) MALLOC(ncells * sizeof(Cell_T)); /* Return value */
k = 0;
last_rootposition = -1;
best_score_for_root = -1;
for (i = 0; i < ncells; i++) {
if (cells[i]->rootposition != last_rootposition) {
/* Take best cell at this rootposition */
debug11(printf("Pushing rootposition %d, score %d, pos %d, hit %d\n",
cells[i]->rootposition,cells[i]->score,cells[i]->querypos,cells[i]->hit));
sorted[k++] = cells[i];
last_rootposition = cells[i]->rootposition;
best_score_for_root = cells[i]->score;
} else if (cells[i]->score == best_score_for_root) {
/* Take equivalent cell for this rootposition */
debug11(printf("Pushing equivalent end for rootposition %d, score %d, pos %d, hit %d\n",
cells[i]->rootposition,cells[i]->score,cells[i]->querypos,cells[i]->hit));
sorted[k++] = cells[i];
/* last_rootposition = cells[i]->rootposition; */
/* best_score_for_root = cells[i]->score; */
} else {
/* Cell_free(&(cells[i])); -- no need with cellpool */
}
}
debug11(printf("\n"));
FREE(cells);
*nunique = k;
qsort(sorted,*nunique,sizeof(Cell_T),Cell_score_cmp);
return sorted;
}
}
#endif
#if 0
static Cell_T *
Linkmatrix_get_cells_both (int *nunique, struct Link_T **links, int querystart, int queryend, int *npositions,
int indexsize, int bestscore, bool favor_right_p, Cellpool_T cellpool) {
Cell_T *sorted, *cells;
List_T celllist = NULL;
int querypos, hit;
int rootposition, last_rootposition;
int threshold_score, best_score_for_root;
int ngood, ncells, i, k;
if (bestscore > 2*suboptimal_score_end) {
threshold_score = bestscore - suboptimal_score_end;
} else {
threshold_score = bestscore/2;
}
if (threshold_score <= indexsize) {
threshold_score = indexsize + 1;
}
debug11(printf("Entered Linkmatrix_get_cells_both with querystart %d, queryend %d, threshold score %d\n",
querystart,queryend,threshold_score));
ncells = 0;
for (querypos = querystart; querypos <= queryend; querypos++) {
ngood = 0;
for (hit = 0; hit < npositions[querypos]; hit++) {
if (links[querypos][hit].fwd_score >= threshold_score) {
ngood++;
}
#ifdef SEPARATE_FWD_REV
if (links[querypos][hit].rev_score >= threshold_score) {
ngood++;
}
#endif
}
if (ngood > 0 && ngood <= 10) {
for (hit = 0; hit < npositions[querypos]; hit++) {
if (links[querypos][hit].fwd_score >= threshold_score) {
rootposition = links[querypos][hit].fwd_rootposition;
/* tracei = links[querypos][hit].fwd_tracei; */
celllist = Cellpool_push(celllist,cellpool,rootposition,querypos,hit,/*fwdp*/true,
links[querypos][hit].fwd_score);
ncells++;
}
#ifdef SEPARATE_FWD_REV
if (links[querypos][hit].rev_score >= threshold_score) {
rootposition = links[querypos][hit].rev_rootposition;
/* tracei = links[querypos][hit].rev_tracei; */
celllist = Cellpool_push(celllist,cellpool,rootposition,querypos,hit,/*fwdp*/false,
links[querypos][hit].rev_score);
ncells++;
}
#endif
}
}
}
debug12(printf("Have %d cells\n",ncells));
if (ncells == 0) {
*nunique = 0;
return (Cell_T *) NULL;
} else {
/* Take best result for each tracei */
/* Using alloca can give a stack overflow */
cells = (Cell_T *) List_to_array(celllist,NULL);
/* List_free(&celllist); -- no need with cellpool */
if (favor_right_p == true) {
qsort(cells,ncells,sizeof(Cell_T),Cell_rootposition_right_cmp);
} else {
qsort(cells,ncells,sizeof(Cell_T),Cell_rootposition_left_cmp);
}
sorted = (Cell_T *) MALLOC(ncells * sizeof(Cell_T)); /* Return value */
k = 0;
last_rootposition = -1;
best_score_for_root = -1;
for (i = 0; i < ncells; i++) {
if (cells[i]->rootposition != last_rootposition) {
/* Take best cell at this rootposition */
debug11(printf("rootposition %d, score %d, pos %d, hit %d\n",
cells[i]->rootposition,cells[i]->score,cells[i]->querypos,cells[i]->hit));
sorted[k++] = cells[i];
last_rootposition = cells[i]->rootposition;
best_score_for_root = cells[i]->score;
} else if (cells[i]->score == best_score_for_root) {
/* Take equivalent end cell for this rootposition */
debug11(printf("equivalent end for rootposition %d, score %d, pos %d, hit %d\n",
cells[i]->rootposition,cells[i]->score,cells[i]->querypos,cells[i]->hit));
sorted[k++] = cells[i];
/* last_rootposition = cells[i]->rootposition; */
/* best_score_for_root = cells[i]->score; */
} else {
/* Cell_free(&(cells[i])); -- no need with cellpool */
}
}
debug11(printf("\n"));
FREE(cells);
*nunique = k;
qsort(sorted,*nunique,sizeof(Cell_T),Cell_score_cmp);
return sorted;
}
}
#endif
static int
binary_search (int lowi, int highi, Chrpos_T *mappings, Chrpos_T goal) {
int middlei;
debug10(printf("entered binary search with lowi=%d, highi=%d, goal=%u\n",lowi,highi,goal));
if (mappings == NULL) {
return -1;
} else {
while (lowi < highi) {
middlei = lowi + ((highi - lowi) / 2);
debug10(printf(" binary: %d:%u %d:%u %d:%u vs. %u\n",
lowi,mappings[lowi],middlei,mappings[middlei],
highi,mappings[highi],goal));
if (goal < mappings[middlei]) {
highi = middlei;
} else if (goal > mappings[middlei]) {
lowi = middlei + 1;
} else {
debug10(printf("binary search returns %d\n",middlei));
return middlei;
}
}
debug10(printf("binary search returns %d\n",highi));
return highi;
}
}
/* Returns celllist */
/* For PMAP, indexsize is in aa. */
static Cell_T *
align_compute_scores_lookback (int *ncells, struct Link_T **links, int **fwd_scores,
Chrpos_T **mappings, int *npositions, int totalpositions,
bool oned_matrix_p, Chrpos_T *minactive, Chrpos_T *maxactive,
int *firstactive, int *nactive, Cellpool_T cellpool,
int querystart, int queryend, int querylength,
Univcoord_T chroffset, Univcoord_T chrhigh, bool plusp,
int indexsize,
#ifdef DEBUG9
char *queryseq_ptr,
#endif
bool anchoredp, int anchor_querypos, Chrpos_T anchor_position,
bool localp, bool skip_repetitive_p,
bool use_canonical_p, int non_canonical_penalty, bool debug_graphic_p, bool favor_right_p) {
Cell_T *cells;
Link_T currlink, prevlink;
int querypos, indexsize_nt, indexsize_query, hit, nhits, low_hit, high_hit;
int nskipped, min_hits, specific_querypos, specific_low_hit, specific_high_hit, next_querypos;
Intlist_T processed = NULL;
int best_overall_score = 0;
int grand_fwd_score, grand_fwd_querypos, grand_fwd_hit, best_fwd_hit, best_fwd_score;
#ifdef SEPARATE_FWD_REV
int grand_rev_score, grand_rev_querypos, grand_rev_hit, best_rev_hit, best_rev_score;
debug9(int rev_tracei = 0);
#endif
int **active;
Chrpos_T position, prevposition;
int fwd_tracei = 0;
#if 0
int *lastGT, *lastAG;
#ifndef PMAP
int *lastCT, *lastAC;
#endif
#endif
#ifdef DEBUG9
char *oligo;
#endif
#ifdef DEBUG12
Link_T termlink = NULL;
#endif
#ifdef PMAP
indexsize_nt = indexsize*3;
#else
indexsize_nt = indexsize;
#endif
indexsize_query = indexsize; /* Use when evaluating across query positions */
#ifdef DEBUG9
oligo = (char *) CALLOC(indexsize+1,sizeof(char));
#endif
debug0(printf("Lookback: querystart = %d, queryend = %d, indexsize = %d\n",querystart,queryend,indexsize));
assert(oned_matrix_p == true);
if (oned_matrix_p == true) {
active = intmatrix_1d_new(querylength,npositions,totalpositions);
} else {
active = intmatrix_2d_new(querylength,npositions);
}
#if 0
firstactive = (int *) MALLOC(querylength * sizeof(int));
nactive = (int *) MALLOC(querylength * sizeof(int));
#endif
/* Initialize */
for (querypos = 0; querypos < querystart; querypos++) {
debug6(printf("3. Initializing firstactive for querypos %d to be -1\n",querypos));
firstactive[querypos] = -1;
nactive[querypos] = 0;
}
while (querypos <= queryend && npositions[querypos] <= 0) {
debug6(printf("4. Initializing firstactive for querypos %d to be -1\n",querypos));
debug9(printf("Skipping querypos %d which has no positions\n",querypos));
firstactive[querypos] = -1;
nactive[querypos] = 0;
querypos++;
}
if (anchoredp == true) {
/* Guaranteed to find a hit */
hit = binary_search(0,npositions[anchor_querypos],mappings[anchor_querypos],/*goal*/anchor_position);
if (mappings[anchor_querypos] == NULL) {
printf("mappings at anchor_querypos %d is NULL. mappings = %p\n",anchor_querypos,mappings);
abort();
}
currlink = &(links[anchor_querypos][hit]);
#ifndef SEPARATE_FWD_REV
currlink->fwd_pos = currlink->fwd_hit = -1;
currlink->fwd_consecutive = EXON_DEFN;
currlink->fwd_tracei = 0;
fwd_scores[anchor_querypos][hit] = indexsize_nt;
#else
fprintf(stderr,"Not implemented yet\n");
abort();
#endif
debug6(printf("Setting firstactive for anchorpos %d to be %d\n",anchor_querypos,hit));
firstactive[anchor_querypos] = hit;
nactive[anchor_querypos] = 1;
active[anchor_querypos][hit] = -1;
debug6(printf("Pushing anchorpos %d as processed\n",anchor_querypos));
processed = Intlist_push(processed,anchor_querypos);
} else if (querypos <= queryend) {
for (hit = 0; hit < npositions[querypos]; hit++) {
currlink = &(links[querypos][hit]);
#ifndef SEPARATE_FWD_REV
currlink->fwd_pos = currlink->fwd_hit = -1;
currlink->fwd_consecutive = indexsize_nt;
currlink->fwd_tracei = -1;
/* currlink->fwd_rootnlinks = 1; */
fwd_scores[querypos][hit] = indexsize_nt;
#else
currlink->fwd_pos = currlink->fwd_hit = -1;
currlink->fwd_consecutive = indexsize_nt;
currlink->fwd_tracei = -1;
/* currlink->fwd_rootnlinks = 1; */
fwd_scores[querypos][hit] = indexsize_nt;
if (splicingp == true) {
currlink->rev_pos = currlink->rev_hit = -1;
currlink->rev_consecutive = indexsize_nt;
currlink->rev_tracei = -1;
/* currlink->rev_rootnlinks = 1; */
rev_scores[querypos][hit] = indexsize_nt;
}
#endif
}
revise_active_lookback(active,firstactive,nactive,0,npositions[querypos],fwd_scores,querypos);
}
grand_fwd_score = 0;
grand_fwd_querypos = -1;
grand_fwd_hit = -1;
#ifdef SEPARATE_FWD_REV
if (splicingp == true) {
grand_rev_score = 0;
grand_rev_querypos = -1;
grand_rev_hit = -1;
}
#endif
nskipped = 0;
min_hits = 1000000;
specific_querypos = -1;
/* querypos += 1; -- this causes querypos at querystart to be ignored */
while (querypos <= queryend) {
best_fwd_score = 0;
best_fwd_hit = -1;
#ifdef SEPARATE_FWD_REV
best_rev_score = 0;
best_rev_hit = -1;
#endif
debug9(printf("Positions at querypos %d (forward order):",querypos);
for (hit = 0; hit < npositions[querypos]; hit++) {
printf(" %u",mappings[querypos][hit]);
}
printf("\n");
);
hit = 0;
while (hit < npositions[querypos] && mappings[querypos][hit] < minactive[querypos]) {
hit++;
}
low_hit = hit;
while (hit < npositions[querypos] && mappings[querypos][hit] <= maxactive[querypos]) {
hit++;
}
high_hit = hit;
debug9(printf("Querypos %d has hit %d..%d out of %d (minactive = %u, maxactive = %u)\n",
querypos,low_hit,high_hit-1,npositions[querypos],minactive[querypos],maxactive[querypos]));
/* Can't use nactive yet, so use high_hit - low_hit */
if (skip_repetitive_p && high_hit - low_hit >= MAX_NACTIVE && nskipped <= MAX_SKIPPED) { /* Previously turned off */
debug6(printf("Too many active (%d - %d) at querypos %d. Setting firstactive to be -1\n",high_hit,low_hit,querypos));
firstactive[querypos] = -1;
nactive[querypos] = 0;
nskipped++;
debug9(printf(" %d skipped because of %d hits\n",nskipped,high_hit - low_hit + 1));
/* Store most specific querypos in section of skipped */
if (high_hit - low_hit < min_hits) {
min_hits = high_hit - low_hit;
specific_querypos = querypos;
specific_low_hit = low_hit;
specific_high_hit = high_hit;
}
querypos++;
} else {
if (nskipped > MAX_SKIPPED) {
debug9(printf("Too many skipped. Going back to specific querypos %d\n",specific_querypos));
next_querypos = querypos;
querypos = specific_querypos;
low_hit = specific_low_hit;
high_hit = specific_high_hit;
} else {
next_querypos = querypos + 1;
}
if ((nhits = high_hit - low_hit) > 0) {
if (nhits == 1) {
currlink = &(links[querypos][low_hit]);
position = mappings[querypos][low_hit];
debug9(strncpy(oligo,&(queryseq_ptr[querypos]),indexsize));
debug9(printf("Finding link looking back from querypos %d,%d at %ux%d (%s). prev_querypos was %d\n",
querypos,low_hit,position,active[querypos][low_hit],oligo,processed ? Intlist_head(processed) : -1));
score_querypos_lookback_one(&fwd_tracei,currlink,querypos,low_hit,querystart,queryend,position,
links,fwd_scores,mappings,active,firstactive,chroffset,chrhigh,plusp,
indexsize,processed,
anchoredp,localp,splicingp,use_canonical_p,
non_canonical_penalty);
if (fwd_scores[querypos][low_hit] > 0) {
debug9(printf("Single hit at low_hit %d has score %d\n",low_hit,fwd_scores[querypos][low_hit]));
best_fwd_score = fwd_scores[querypos][low_hit];
best_fwd_hit = low_hit;
}
} else {
debug9(strncpy(oligo,&(queryseq_ptr[querypos]),indexsize));
debug9(printf("Finding links looking back from querypos %d,%d..%d at (%u..%u) (%s). prev_querypos was %d\n",
querypos,low_hit,high_hit-1,mappings[querypos][low_hit],mappings[querypos][high_hit-1],
oligo,processed ? Intlist_head(processed) : -1));
score_querypos_lookback_mult(&fwd_tracei,low_hit,high_hit,querypos,querystart,queryend,
/*positions*/&(mappings[querypos][low_hit]),
links,fwd_scores,mappings,active,firstactive,chroffset,chrhigh,plusp,
indexsize,processed,
anchoredp,localp,splicingp,use_canonical_p,
non_canonical_penalty);
debug9(printf("Checking hits from low_hit %d to high_hit %d\n",low_hit,high_hit));
for (hit = low_hit; hit < high_hit; hit++) {
debug9(printf("Hit %d has score %d\n",hit,fwd_scores[querypos][hit]));
if (fwd_scores[querypos][hit] > best_fwd_score) {
best_fwd_score = fwd_scores[querypos][hit];
best_fwd_hit = hit;
}
}
}
if (best_fwd_score > best_overall_score) {
best_overall_score = best_fwd_score;
}
nskipped = 0;
min_hits = 1000000;
specific_querypos = -1;
#ifndef SEPARATE_FWD_REV
debug9(printf("Overall result at querypos %d yields best_fwd_hit %d\n",
querypos,best_fwd_hit));
#else
debug9(printf("Overall result at querypos %d yields best_fwd_hit %d and best_rev_hit %d\n",
querypos,best_fwd_hit,best_rev_hit));
#endif
if (splicingp == true && best_fwd_hit >= 0 && links[querypos][best_fwd_hit].fwd_hit < 0 &&
grand_fwd_querypos >= 0 && querypos >= grand_fwd_querypos + indexsize_query) {
if ((best_fwd_score = fwd_scores[grand_fwd_querypos][grand_fwd_hit] - (querypos - grand_fwd_querypos)) > 0) {
prevposition = mappings[grand_fwd_querypos][grand_fwd_hit];
debug12(printf("Considering prevposition %u to position %u as a grand fwd lookback\n",prevposition,position));
for (hit = low_hit; hit < high_hit; hit++) {
if ((position = mappings[querypos][hit]) > prevposition + maxintronlen) {
debug12(printf(" => Too long\n"));
} else if (position >= prevposition + indexsize_nt) {
currlink = &(links[querypos][hit]);
currlink->fwd_consecutive = indexsize_nt;
currlink->fwd_pos = grand_fwd_querypos;
currlink->fwd_hit = grand_fwd_hit;
currlink->fwd_tracei = ++fwd_tracei;
fwd_scores[querypos][hit] = best_fwd_score;
#ifdef DEBUG9
prevlink = &(links[grand_fwd_querypos][grand_fwd_hit]);
currlink->fwd_intronnfwd = prevlink->fwd_intronnfwd;
currlink->fwd_intronnrev = prevlink->fwd_intronnrev;
currlink->fwd_intronnunk = prevlink->fwd_intronnunk + 1;
#endif
}
}
debug12(printf("At querypos %d, setting all fwd hits to point back to grand_fwd %d,%d with a score of %d\n",
querypos,grand_fwd_querypos,grand_fwd_hit,fwd_scores[grand_fwd_querypos][grand_fwd_hit]));
}
}
/* Use >= to favor longer path in case of ties */
if (best_fwd_hit >= 0 && best_fwd_score >= grand_fwd_score &&
links[querypos][best_fwd_hit].fwd_consecutive > EXON_DEFN) {
grand_fwd_score = best_fwd_score;
grand_fwd_querypos = querypos;
grand_fwd_hit = best_fwd_hit;
debug12(termlink = &(links[querypos][best_fwd_hit]));
debug12(printf("At querypos %d, revising grand fwd to be hit %d with score of %d (pointing back to %d,%d)\n",
querypos,best_fwd_hit,best_fwd_score,termlink->fwd_pos,termlink->fwd_hit));
}
#ifdef SEPARATE_FWD_REV
if (best_rev_score > best_overall_score) {
best_overall_score = best_rev_score;
}
if (splicingp == false || use_canonical_p == false) {
/* rev scores should be the same as the fwd scores */
} else {
if (best_rev_hit >= 0 && links[querypos][best_rev_hit].rev_hit < 0 &&
grand_rev_querypos >= 0 && querypos >= grand_rev_querypos + indexsize_query) {
prevlink = &(links[grand_rev_querypos][grand_rev_hit]);
if ((best_rev_score = prevlink->rev_score - (querypos - grand_rev_querypos)) > 0) {
prevposition = mappings[grand_rev_querypos][grand_rev_hit];
debug12(printf("Considering prevposition %u to position %u as a grand rev lookback\n",prevposition,position));
for (hit = low_hit; hit < high_hit; hit++) {
if ((position = mappings[querypos][hit]) > prevposition + maxintronlen) {
debug12(printf(" => Too long\n"));
} else if (position >= prevposition + indexsize_nt) {
currlink = &(links[querypos][hit]);
currlink->rev_consecutive = indexsize_nt;
/* currlink->rev_rootnlinks = 1; */
currlink->rev_pos = grand_rev_querypos;
currlink->rev_hit = grand_rev_hit;
currlink->rev_score = best_rev_score;
#ifdef DEBUG9
currlink->rev_tracei = ++rev_tracei;
currlink->rev_intronnrev = prevlink->rev_intronnfwd;
currlink->rev_intronnrev = prevlink->rev_intronnrev;
currlink->rev_intronnunk = prevlink->rev_intronnunk + 1;
#endif
}
}
debug12(printf("At querypos %d, setting all rev hits to point back to grand_rev %d,%d with a score of %d\n",
querypos,grand_rev_querypos,grand_rev_hit,prevlink->rev_score));
}
}
/* Use >= to favor longer path in case of ties */
if (best_rev_hit >= 0 && best_rev_score >= grand_rev_score &&
links[querypos][best_rev_hit].rev_consecutive > EXON_DEFN) {
grand_rev_score = best_rev_score;
grand_rev_querypos = querypos;
grand_rev_hit = best_rev_hit;
}
}
#endif
}
revise_active_lookback(active,firstactive,nactive,low_hit,high_hit,fwd_scores,querypos);
/* Need to push querypos, even if firstactive[querypos] == -1 */
/* Want to skip npositions[querypos] == 0, so we can find adjacent despite mismatch or overabundance */
if (npositions[querypos] > 0) {
debug6(printf("Pushing querypos %d onto processed\n",querypos));
processed = Intlist_push(processed,querypos);
}
querypos = next_querypos;
}
}
debug9(printf("End of loop lookback\n"));
Intlist_free(&processed);
/* These are the final active oligomers, after pruning by score */
if (debug_graphic_p == true) {
mappings_dump_R(mappings,npositions,querylength,active,firstactive,indexsize,"active.mers");
}
#if 0
FREE(nactive);
FREE(firstactive);
#endif
if (oned_matrix_p == true) {
intmatrix_1d_free(&active);
} else {
intmatrix_2d_free(&active,querylength);
}
/* Grand winners */
debug12(printf("Finding grand winners, using root position method\n"));
#ifdef SEPARATE_FWD_REV
if (splicingp == false || use_canonical_p == false) {
cells = Linkmatrix_get_cells_fwd(&(*ncells),links,querystart,queryend,npositions,
favor_right_p,cellpool);
} else {
cells = Linkmatrix_get_cells_both(&(*ncells),links,querystart,queryend,npositions,
indexsize,best_overall_score,favor_right_p,cellpool);
}
#else
cells = get_cells_fwd(&(*ncells),links,fwd_scores,querystart,queryend,npositions,
favor_right_p,cellpool);
#endif
debug9(FREE(oligo));
return cells;
}
static char complCode[128] = COMPLEMENT_LC;
/* genomicstart == chroffset + chrpos */
/* arguments were genomicpos, genomicstart, genomiclength */
static char
get_genomic_nt (char *g_alt, Chrpos_T chrpos, Univcoord_T chroffset,
Univcoord_T chrhigh, bool watsonp) {
char c2, c2_alt;
if (watsonp) {
return Genome_get_char_blocks(&(*g_alt),chroffset + chrpos);
} else {
c2 = Genome_get_char_blocks(&c2_alt,chrhigh - chrpos);
*g_alt = complCode[(int) c2_alt];
return complCode[(int) c2];
}
}
static List_T
traceback_one (int querypos, int hit, struct Link_T **links, Chrpos_T **mappings,
char *queryseq_ptr, char *queryuc_ptr,
#ifdef PMAP
Univcoord_T chroffset, Univcoord_T chrhigh, bool watsonp, bool lookbackp,
#endif
#ifdef DEBUG0
int **fwd_scores, int indexsize,
#endif
Pairpool_T pairpool, bool fwdp) {
List_T path = NULL;
Chrpos_T position;
int prev_querypos, prevhit;
char c2;
#ifdef PMAP
char c2_alt;
#endif
#ifdef DEBUG0
char *oligo;
#endif
while (querypos >= 0) {
position = mappings[querypos][hit];
#ifdef PMAP
/* Change querypos positions from protein to nucleotide */
if (lookbackp == true) {
c2 = get_genomic_nt(&c2_alt,position+2,chroffset,chrhigh,watsonp);
path = Pairpool_push(path,pairpool,querypos*3+2,position+2,/*cdna*/c2,MATCH_COMP,c2,c2_alt,
/*dynprogindex*/0);
c2 = get_genomic_nt(&c2_alt,position+1,chroffset,chrhigh,watsonp);
path = Pairpool_push(path,pairpool,querypos*3+1,position+1,/*cdna*/c2,MATCH_COMP,c2,c2_alt,
/*dynprogindex*/0);
c2 = get_genomic_nt(&c2_alt,position,chroffset,chrhigh,watsonp);
path = Pairpool_push(path,pairpool,querypos*3,position,/*cdna*/c2,MATCH_COMP,c2,c2_alt,
/*dynprogindex*/0);
} else {
c2 = get_genomic_nt(&c2_alt,position,chroffset,chrhigh,watsonp);
path = Pairpool_push(path,pairpool,querypos*3,position,/*cdna*/c2,MATCH_COMP,c2,c2_alt,
/*dynprogindex*/0);
c2 = get_genomic_nt(&c2_alt,position+1,chroffset,chrhigh,watsonp);
path = Pairpool_push(path,pairpool,querypos*3+1,position+1,/*cdna*/c2,MATCH_COMP,c2,c2_alt,
/*dynprogindex*/0);
c2 = get_genomic_nt(&c2_alt,position+2,chroffset,chrhigh,watsonp);
path = Pairpool_push(path,pairpool,querypos*3+2,position+2,/*cdna*/c2,MATCH_COMP,c2,c2_alt,
/*dynprogindex*/0);
}
#else
/* genomic nucleotide same as queryseq */
c2 = queryuc_ptr[querypos];
path = Pairpool_push(path,pairpool,querypos,position,queryseq_ptr[querypos],MATCH_COMP,
c2,/*genomealt*/c2,/*dynprogindex*/0);
#endif
#ifdef DEBUG0
debug0(oligo = (char *) CALLOC(indexsize+1,sizeof(char)));
debug0(strncpy(oligo,&(queryseq_ptr[querypos]),indexsize));
if (fwdp == true) {
debug0(printf("Pushing %d,%d (%s) at %u, score = %d, consec = %d",
querypos,hit,oligo,position,
fwd_scores[querypos][hit],links[querypos][hit].fwd_consecutive));
debug9(printf(" (from #%d), intr = %d(+)/%d(-)/%d(?)",
links[querypos][hit].fwd_tracei,links[querypos][hit].fwd_intronnfwd,links[querypos][hit].fwd_intronnrev,
links[querypos][hit].fwd_intronnunk));
debug0(printf("\n"));
#ifdef SEPARATE_FWD_REV
} else {
debug0(printf("Pushing %d,%d (%s) at %u, score = %d, consec = %d",
querypos,hit,oligo,position,
links[querypos][hit].rev_score,links[querypos][hit].rev_consecutive));
debug9(printf(" (from #%d), intr = %d(+)/%d(-)/%d(?)",
links[querypos][hit].rev_tracei,links[querypos][hit].rev_intronnfwd,links[querypos][hit].rev_intronnrev,
links[querypos][hit].rev_intronnunk));
debug0(printf("\n"));
#endif
}
#endif
debug0(FREE(oligo));
/* prevposition = position; */
prev_querypos = querypos;
prevhit = hit;
if (fwdp == true) {
querypos = links[prev_querypos][prevhit].fwd_pos;
hit = links[prev_querypos][prevhit].fwd_hit;
#ifdef SEPARATE_FWD_REV
} else {
querypos = links[prev_querypos][prevhit].rev_pos;
hit = links[prev_querypos][prevhit].rev_hit;
#endif
}
debug3(printf("%d %d %d %d 3\n",prev_querypos,prevhit,querypos,hit));
}
debug0(printf("Done\n\n"));
return path;
}
static List_T
traceback_one_snps (int querypos, int hit, struct Link_T **links, Chrpos_T **mappings,
char *queryseq_ptr,
Univcoord_T chroffset, Univcoord_T chrhigh, bool watsonp,
#ifdef DEBUG0
int **fwd_scores, int indexsize,
#endif
Pairpool_T pairpool, bool fwdp) {
List_T path = NULL;
Chrpos_T position;
int prev_querypos, prevhit;
char c2, c2_alt;
#ifdef DEBUG0
char *oligo;
#endif
while (querypos >= 0) {
position = mappings[querypos][hit];
#ifdef PMAP
/* Change querypos positions from protein to nucleotide */
c2 = get_genomic_nt(&c2_alt,position+2,chroffset,chrhigh,watsonp);
path = Pairpool_push(path,pairpool,querypos*3+2,position+2,/*cdna*/c2,MATCH_COMP,c2,c2_alt,
/*dynprogindex*/0);
c2 = get_genomic_nt(&c2_alt,position+1,chroffset,chrhigh,watsonp);
path = Pairpool_push(path,pairpool,querypos*3+1,position+1,/*cdna*/c2,MATCH_COMP,c2,c2_alt,
/*dynprogindex*/0);
c2 = get_genomic_nt(&c2_alt,position,chroffset,chrhigh,watsonp);
path = Pairpool_push(path,pairpool,querypos*3,position,/*cdna*/c2,MATCH_COMP,c2,c2_alt,
/*dynprogindex*/0);
#else
/* genomic nucleotide or SNP same as queryseq */
c2 = get_genomic_nt(&c2_alt,position,chroffset,chrhigh,watsonp);
path = Pairpool_push(path,pairpool,querypos,position,queryseq_ptr[querypos],MATCH_COMP,c2,c2_alt,
/*dynprogindex*/0);
#endif
#ifdef DEBUG0
debug0(oligo = (char *) CALLOC(indexsize+1,sizeof(char)));
debug0(strncpy(oligo,&(queryseq_ptr[querypos]),indexsize));
if (fwdp == true) {
debug0(printf("Pushing %d,%d (%s) at %u, score = %d, consec = %d",
querypos,hit,oligo,position,
fwd_scores[querypos][hit],links[querypos][hit].fwd_consecutive));
debug9(printf(" (from #%d), intr = %d(+)/%d(-)/%d(?)",
links[querypos][hit].fwd_tracei,links[querypos][hit].fwd_intronnfwd,links[querypos][hit].fwd_intronnrev,
links[querypos][hit].fwd_intronnunk));
debug0(printf("\n"));
#ifdef SEPARATE_FWD_REV
} else {
debug0(printf("Pushing %d,%d (%s) at %u, score = %d, consec = %d",
querypos,hit,oligo,position,
links[querypos][hit].rev_score,links[querypos][hit].rev_consecutive));
debug9(printf(" (from #%d), intr = %d(+)/%d(-)/%d(?)",
links[querypos][hit].rev_tracei,links[querypos][hit].rev_intronnfwd,links[querypos][hit].rev_intronnrev,
links[querypos][hit].rev_intronnunk));
debug0(printf("\n"));
#endif
}
#endif
debug0(FREE(oligo));
/* prevposition = position; */
prev_querypos = querypos;
prevhit = hit;
if (fwdp == true) {
querypos = links[prev_querypos][prevhit].fwd_pos;
hit = links[prev_querypos][prevhit].fwd_hit;
#ifdef SEPARATE_FWD_REV
} else {
querypos = links[prev_querypos][prevhit].rev_pos;
hit = links[prev_querypos][prevhit].rev_hit;
#endif
}
debug3(printf("%d %d %d %d 3\n",prev_querypos,prevhit,querypos,hit));
}
debug0(printf("Done\n\n"));
return path;
}
/* Performs dynamic programming. For PMAP, indexsize is in aa. */
static List_T
align_compute_lookback (Chrpos_T **mappings, int *npositions, int totalpositions,
bool oned_matrix_p, Chrpos_T *minactive, Chrpos_T *maxactive,
int *firstactive, int *nactive, Cellpool_T cellpool,
char *queryseq_ptr, char *queryuc_ptr, int querylength, int querystart, int queryend,
Univcoord_T chroffset, Univcoord_T chrhigh, bool plusp,
int indexsize, Pairpool_T pairpool,
bool anchoredp, int anchor_querypos, Chrpos_T anchor_position,
bool localp, bool skip_repetitive_p, bool use_canonical_p, int non_canonical_penalty,
bool favor_right_p, int max_nalignments, bool debug_graphic_p) {
List_T all_paths = NULL;
struct Link_T **links;
int **fwd_scores;
Cell_T *cells, cell;
int ncells, i;
bool fwdp;
int querypos, hit;
int bestscore;
if (oned_matrix_p == true) {
links = Linkmatrix_1d_new(querylength,npositions,totalpositions);
fwd_scores = intmatrix_1d_new(querylength,npositions,totalpositions);
} else {
links = Linkmatrix_2d_new(querylength,npositions);
fwd_scores = intmatrix_2d_new(querylength,npositions);
}
/* These are all oligomers */
if (debug_graphic_p == true) {
mappings_dump_R(mappings,npositions,querylength,/*active*/NULL,/*firstactive*/NULL,indexsize,"all.mers");
}
cells = align_compute_scores_lookback(&ncells,links,fwd_scores,
mappings,npositions,totalpositions,
oned_matrix_p,minactive,maxactive,firstactive,nactive,cellpool,
querystart,queryend,querylength,
chroffset,chrhigh,plusp,
indexsize,
#ifdef DEBUG9
queryseq_ptr,
#endif
anchoredp,anchor_querypos,anchor_position,localp,
skip_repetitive_p,use_canonical_p,non_canonical_penalty,
debug_graphic_p,favor_right_p);
#ifdef SEPARATE_FWD_REV
debug1(Linkmatrix_print_both(links,mappings,querylength,npositions,queryseq_ptr,indexsize));
#else
debug1(print_fwd(links,fwd_scores,mappings,querylength,npositions,queryseq_ptr,indexsize));
#endif
if (ncells == 0) {
all_paths = (List_T) NULL;
} else {
bestscore = cells[0]->score;
debug11(printf("Looping on %d cells, allowing up to %d alignments, plus any with best score %d\n",
ncells,max_nalignments,bestscore));
if (snps_p == true) {
for (i = 0; i < ncells && (i < max_nalignments || cells[i]->score == bestscore)
&& cells[i]->score > bestscore - FINAL_SCORE_TOLERANCE; i++) {
cell = cells[i];
querypos = cell->querypos;
hit = cell->hit;
fwdp = cell->fwdp;
debug11(printf("Starting subpath %d for rootposition %d with score %d, querypos %d, hit %d, position %u\n",
i,cell->rootposition,cell->score,querypos,hit,mappings[querypos][hit]));
all_paths = List_push(all_paths,(void *) traceback_one_snps(querypos,hit,links,mappings,queryseq_ptr,
chroffset,chrhigh,/*watsonp*/plusp,
#ifdef DEBUG0
fwd_scores,indexsize,
#endif
pairpool,fwdp));
}
} else {
for (i = 0; i < ncells && (i < max_nalignments || cells[i]->score == bestscore)
&& cells[i]->score > bestscore - FINAL_SCORE_TOLERANCE; i++) {
cell = cells[i];
querypos = cell->querypos;
hit = cell->hit;
fwdp = cell->fwdp;
debug11(printf("Starting subpath %d for rootposition %d with score %d, querypos %d, hit %d, position %u\n",
i,cell->rootposition,cell->score,querypos,hit,mappings[querypos][hit]));
#if 0
if (debug_graphic_p == true) {
best_path_dump_R(links,mappings,querypos,hit,fwdp,"best.path");
printf("plot(all.mers,col=\"black\",pch=\".\",xlab=\"Query\",ylab=\"Genomic\")\n");
printf("points(active.mers,col=\"red\",pch=\".\")\n");
printf("points(best.path,col=\"green\",pch=\".\")\n");
printf("lines(querypos,minactive,col=\"blue\")\n");
printf("lines(querypos,maxactive,col=\"blue\")\n");
}
#endif
all_paths = List_push(all_paths,(void *) traceback_one(querypos,hit,links,mappings,queryseq_ptr,queryuc_ptr,
#ifdef PMAP
chroffset,chrhigh,/*watsonp*/plusp,/*lookbackp*/true,
#endif
#ifdef DEBUG0
fwd_scores,indexsize,
#endif
pairpool,fwdp));
}
}
debug11(printf("\n"));
#if 0
/* No need with cellpool */
for (i = 0; i < ncells; i++) {
cell = cells[i];
Cell_free(&cell);
}
#endif
FREE(cells);
}
if (oned_matrix_p == true) {
Linkmatrix_1d_free(&links);
intmatrix_1d_free(&fwd_scores);
} else {
Linkmatrix_2d_free(&links,querylength);
intmatrix_2d_free(&fwd_scores,querylength);
}
#if 0
for (p = all_paths; p != NULL; p = List_next(p)) {
Pair_dump_list(List_head(p),/*zerobasedp*/true);
printf("\n");
}
#endif
return all_paths;
}
/* Returns celllist */
/* For PMAP, indexsize is in aa. */
static Cell_T *
align_compute_scores_lookforward (int *ncells, struct Link_T **links, int **fwd_scores,
Chrpos_T **mappings, int *npositions, int totalpositions,
bool oned_matrix_p, Chrpos_T *minactive, Chrpos_T *maxactive,
int *firstactive, int *nactive, Cellpool_T cellpool,
int querystart, int queryend, int querylength,
Univcoord_T chroffset, Univcoord_T chrhigh, bool plusp,
int indexsize,
#ifdef DEBUG9
char *queryseq_ptr,
#endif
bool anchoredp, int anchor_querypos, Chrpos_T anchor_position,
bool localp, bool skip_repetitive_p,
bool use_canonical_p, int non_canonical_penalty,
bool debug_graphic_p, bool favor_right_p) {
Cell_T *cells;
Link_T currlink, prevlink;
int querypos, indexsize_nt, indexsize_query, hit, nhits, low_hit, high_hit;
int nskipped, min_hits, specific_querypos, specific_low_hit, specific_high_hit, next_querypos;
Intlist_T processed = NULL;
int best_overall_score = 0;
int grand_fwd_score, grand_fwd_querypos, grand_fwd_hit, best_fwd_hit, best_fwd_score;
#ifdef SEPARATE_FWD_REV
int grand_rev_score, grand_rev_querypos, grand_rev_hit, best_rev_hit, best_rev_score;
debug9(int rev_tracei = 0);
#endif
int **active;
Chrpos_T position, prevposition;
int fwd_tracei = 0;
#if 0
int *lastGT, *lastAG;
#ifndef PMAP
int *lastCT, *lastAC;
#endif
#endif
#ifdef DEBUG9
char *oligo;
#endif
#ifdef DEBUG12
Link_T termlink = NULL;
#endif
#ifdef PMAP
indexsize_nt = indexsize*3;
#else
indexsize_nt = indexsize;
#endif
indexsize_query = indexsize; /* Use when evaluating across query positions */
#ifdef DEBUG9
oligo = (char *) CALLOC(indexsize+1,sizeof(char));
#endif
debug0(printf("Lookforward: querystart = %d, queryend = %d, indexsize = %d\n",querystart,queryend,indexsize));
if (oned_matrix_p == true) {
active = intmatrix_1d_new(querylength,npositions,totalpositions);
} else {
active = intmatrix_2d_new(querylength,npositions);
}
#if 0
firstactive = (int *) MALLOC(querylength * sizeof(int));
nactive = (int *) MALLOC(querylength * sizeof(int));
#endif
/* Initialize */
for (querypos = querylength - 1; querypos > queryend; querypos--) {
debug6(printf("5. Initializing firstactive for querypos %d to be -1\n",querypos));
firstactive[querypos] = -1;
nactive[querypos] = 0;
}
while (querypos >= querystart && npositions[querypos] <= 0) {
debug6(printf("6. Initializing firstactive for querypos %d to be -1\n",querypos));
debug9(printf("Skipping querypos %d which has no positions\n",querypos));
firstactive[querypos] = -1;
nactive[querypos] = 0;
querypos--;
}
if (anchoredp == true) {
/* Guaranteed to find a hit */
hit = binary_search(0,npositions[anchor_querypos],mappings[anchor_querypos],/*goal*/anchor_position);
if (mappings[anchor_querypos] == NULL) {
printf("mappings at anchor_querypos %d is NULL. mappings = %p\n",anchor_querypos,mappings);
abort();
}
currlink = &(links[anchor_querypos][hit]);
#ifndef SEPARATE_FWD_REV
currlink->fwd_pos = currlink->fwd_hit = -1;
currlink->fwd_consecutive = EXON_DEFN;
currlink->fwd_tracei = 0;
fwd_scores[anchor_querypos][hit] = indexsize_nt;
#else
fprintf(stderr,"Not implemented yet\n");
abort();
#endif
debug6(printf("Setting firstactive for anchorpos %d to be %d\n",anchor_querypos,hit));
firstactive[anchor_querypos] = hit;
nactive[anchor_querypos] = 1;
active[anchor_querypos][hit] = -1;
debug6(printf("Pushing anchorpos %d as processed\n",anchor_querypos));
processed = Intlist_push(processed,anchor_querypos);
} else if (querypos >= querystart) {
for (hit = npositions[querypos] - 1; hit >= 0; --hit) {
currlink = &(links[querypos][hit]);
#ifndef SEPARATE_FWD_REV
currlink->fwd_pos = currlink->fwd_hit = -1;
currlink->fwd_consecutive = indexsize_nt;
currlink->fwd_tracei = -1;
/* currlink->fwd_rootnlinks = 1; */
fwd_scores[querypos][hit] = indexsize_nt;
#else
currlink->fwd_pos = currlink->fwd_hit = -1;
currlink->fwd_score = indexsize_nt;
currlink->fwd_consecutive = indexsize_nt;
currlink->fwd_tracei = -1;
/* currlink->fwd_rootnlinks = 1; */
if (splicingp == true) {
currlink->rev_pos = currlink->rev_hit = -1;
currlink->rev_consecutive = indexsize_nt;
currlink->rev_tracei = -1;
/* currlink->rev_rootnlinks = 1; */
rev_scores[querypos][hit] = indexsize_nt;
}
#endif
}
revise_active_lookforward(active,firstactive,nactive,0,npositions[querypos],fwd_scores,querypos);
}
grand_fwd_score = 0;
grand_fwd_querypos = -1;
grand_fwd_hit = -1;
#ifdef SEPARATE_FWD_REV
if (splicingp == true) {
grand_rev_score = 0;
grand_rev_querypos = -1;
grand_rev_hit = -1;
}
#endif
nskipped = 0;
min_hits = 1000000;
specific_querypos = -1;
/* querypos -= 1; -- this causes querypos at queryend to be ignored */
while (querypos >= querystart) {
best_fwd_score = 0;
best_fwd_hit = -1;
#ifdef SEPARATE_FWD_REV
best_rev_score = 0;
best_rev_hit = -1;
#endif
debug9(printf("Positions at querypos %d (reverse order):",querypos);
for (hit = npositions[querypos] - 1; hit >= 0; --hit) {
printf(" %u",mappings[querypos][hit]);
}
printf("\n");
);
hit = npositions[querypos] - 1;
while (hit >= 0 && mappings[querypos][hit] > maxactive[querypos]) {
--hit;
}
high_hit = hit + 1;
while (hit >= 0 && mappings[querypos][hit] >= minactive[querypos]) {
--hit;
}
low_hit = hit + 1;
debug9(printf("Querypos %d has hit %d..%d out of %d (minactive = %u, maxactive = %u)\n",
querypos,high_hit-1,low_hit,npositions[querypos],minactive[querypos],maxactive[querypos]));
/* Can't use nactive yet, so use high_hit - low_hit */
if (skip_repetitive_p && high_hit - low_hit >= MAX_NACTIVE && nskipped <= MAX_SKIPPED) { /* Previously turned off */
debug6(printf("Too many active (%d - %d) at querypos %d. Setting firstactive to be -1\n",high_hit,low_hit,querypos));
firstactive[querypos] = -1;
nactive[querypos] = 0;
nskipped++;
debug9(printf(" %d skipped because of %d hits\n",nskipped,high_hit - low_hit + 1));
/* Store most specific querypos in section of skipped */
if (high_hit - low_hit < min_hits) {
min_hits = high_hit - low_hit;
specific_querypos = querypos;
specific_low_hit = low_hit;
specific_high_hit = high_hit;
}
querypos--;
} else {
if (nskipped > MAX_SKIPPED) {
debug9(printf("Too many skipped. Going back to specific querypos %d\n",specific_querypos));
next_querypos = querypos;
querypos = specific_querypos;
low_hit = specific_low_hit;
high_hit = specific_high_hit;
} else {
next_querypos = querypos - 1;
}
if ((nhits = high_hit - low_hit) > 0) {
if (nhits == 1) {
currlink = &(links[querypos][low_hit]);
position = mappings[querypos][low_hit];
debug9(strncpy(oligo,&(queryseq_ptr[querypos]),indexsize));
debug9(printf("Finding link looking forward from querypos %d,%d at %ux%d (%s). prev_querypos was %d\n",
querypos,low_hit,position,active[querypos][low_hit],oligo,processed ? Intlist_head(processed) : -1));
score_querypos_lookforward_one(&fwd_tracei,currlink,querypos,low_hit,querystart,queryend,position,
links,fwd_scores,mappings,active,firstactive,
chroffset,chrhigh,plusp,
indexsize,processed,
anchoredp,localp,splicingp,use_canonical_p,
non_canonical_penalty);
if (fwd_scores[querypos][low_hit] > 0) {
debug9(printf("Single hit at low_hit %d has score %d\n",low_hit,fwd_scores[querypos][low_hit]));
best_fwd_score = fwd_scores[querypos][low_hit];
best_fwd_hit = low_hit;
}
} else {
debug9(strncpy(oligo,&(queryseq_ptr[querypos]),indexsize));
debug9(printf("Finding links looking forward from querypos %d,%d..%d at (%u..%u) (%s). prev_querypos was %d\n",
querypos,high_hit-1,low_hit,mappings[querypos][high_hit-1],mappings[querypos][low_hit],
oligo,processed ? Intlist_head(processed) : -1));
score_querypos_lookforward_mult(&fwd_tracei,low_hit,high_hit,querypos,querystart,queryend,
/*positions*/&(mappings[querypos][low_hit]),
links,fwd_scores,mappings,active,firstactive,chroffset,chrhigh,plusp,
indexsize,processed,
anchoredp,localp,splicingp,use_canonical_p,
non_canonical_penalty);
debug9(printf("Checking hits from high_hit %d to low_hit %d\n",high_hit,low_hit));
for (hit = high_hit - 1; hit >= low_hit; hit--) {
debug9(printf("Hit %d has score %d\n",hit,fwd_scores[querypos][hit]));
if (fwd_scores[querypos][hit] > best_fwd_score) {
best_fwd_score = fwd_scores[querypos][hit];
best_fwd_hit = hit;
}
}
}
if (best_fwd_score > best_overall_score) {
best_overall_score = best_fwd_score;
}
nskipped = 0;
min_hits = 1000000;
specific_querypos = -1;
#ifndef SEPARATE_FWD_REV
debug9(printf("Overall result at querypos %d yields best_fwd_hit %d\n",
querypos,best_fwd_hit));
#else
debug9(printf("Overall result at querypos %d yields best_fwd_hit %d and best_rev_hit %d\n",
querypos,best_fwd_hit,best_rev_hit));
#endif
if (splicingp == true && best_fwd_hit >= 0 && links[querypos][best_fwd_hit].fwd_hit < 0 &&
grand_fwd_querypos <= querylength - indexsize_query && querypos + indexsize_query <= grand_fwd_querypos) {
if ((best_fwd_score = fwd_scores[grand_fwd_querypos][grand_fwd_hit] - (grand_fwd_querypos - querypos)) > 0) {
prevposition = mappings[grand_fwd_querypos][grand_fwd_hit];
debug12(printf("Considering prevposition %u to position %u as a grand fwd lookforward\n",prevposition,position));
for (hit = high_hit - 1; hit >= low_hit; --hit) {
if ((position = mappings[querypos][hit]) + maxintronlen < prevposition) {
debug12(printf(" => Too long\n"));
} else if (position + indexsize_nt <= prevposition) {
currlink = &(links[querypos][hit]);
currlink->fwd_consecutive = indexsize_nt;
currlink->fwd_pos = grand_fwd_querypos;
currlink->fwd_hit = grand_fwd_hit;
currlink->fwd_tracei = ++fwd_tracei;
/* currlink->fwd_rootnlinks = 1; */
fwd_scores[querypos][hit] = best_fwd_score;
#ifdef DEBUG9
currlink->fwd_intronnfwd = prevlink->fwd_intronnfwd;
currlink->fwd_intronnrev = prevlink->fwd_intronnrev;
currlink->fwd_intronnunk = prevlink->fwd_intronnunk + 1;
#endif
}
}
debug12(printf("At querypos %d, setting all fwd hits to point back to grand_fwd %d,%d with a score of %d\n",
querypos,grand_fwd_querypos,grand_fwd_hit,fwd_scores[grand_fwd_querypos][grand_fwd_hit]));
}
}
/* Use >= to favor longer path in case of ties */
if (best_fwd_hit >= 0 && best_fwd_score >= grand_fwd_score &&
links[querypos][best_fwd_hit].fwd_consecutive > EXON_DEFN) {
grand_fwd_score = best_fwd_score;
grand_fwd_querypos = querypos;
grand_fwd_hit = best_fwd_hit;
debug12(termlink = &(links[querypos][best_fwd_hit]));
debug12(printf("At querypos %d, revising grand fwd to be hit %d with score of %d (pointing back to %d,%d)\n",
querypos,best_fwd_hit,best_fwd_score,termlink->fwd_pos,termlink->fwd_hit));
}
#ifdef SEPARATE_FWD_REV
if (best_rev_score > best_overall_score) {
best_overall_score = best_rev_score;
}
if (splicingp == false || use_canonical_p == false) {
/* rev scores should be the same as the fwd scores */
} else {
if (best_rev_hit >= 0 && links[querypos][best_rev_hit].rev_hit < 0 &&
grand_rev_querypos <= querylength - indexsize_query && querypos + indexsize_query <= grand_rev_querypos) {
prevlink = &(links[grand_rev_querypos][grand_rev_hit]);
if ((best_rev_score = prevlink->rev_score - (grand_rev_querypos - querypos)) > 0) {
prevposition = mappings[grand_rev_querypos][grand_rev_hit];
debug12(printf("Considering prevposition %u to position %u as a grand rev lookforward\n",prevposition,position));
for (hit = high_hit - 1; hit >= low_hit; --hit) {
if ((position = mappings[querypos][hit]) + maxintronlen < prevposition) {
debug12(printf(" => Too long\n"));
} else if (position + indexsize_nt <= prevposition) {
currlink = &(links[querypos][hit]);
currlink->rev_consecutive = indexsize_nt;
/* currlink->rev_rootnlinks = 1; */
currlink->rev_pos = grand_rev_querypos;
currlink->rev_hit = grand_rev_hit;
currlink->rev_score = best_rev_score;
#ifdef DEBUG9
currlink->rev_tracei = ++rev_tracei;
currlink->rev_intronnrev = prevlink->rev_intronnfwd;
currlink->rev_intronnrev = prevlink->rev_intronnrev;
currlink->rev_intronnunk = prevlink->rev_intronnunk + 1;
#endif
}
}
debug12(printf("At querypos %d, setting all rev hits to point back to grand_rev %d,%d with a score of %d\n",
querypos,grand_rev_querypos,grand_rev_hit,prevlink->rev_score));
}
}
/* Use >= to favor longer path in case of ties */
if (best_rev_hit >= 0 && best_rev_score >= grand_rev_score &&
links[querypos][best_rev_hit].rev_consecutive > EXON_DEFN) {
grand_rev_score = best_rev_score;
grand_rev_querypos = querypos;
grand_rev_hit = best_rev_hit;
}
}
#endif
}
revise_active_lookforward(active,firstactive,nactive,low_hit,high_hit,fwd_scores,querypos);
/* Need to push querypos, even if firstactive[querypos] == -1 */
/* Want to skip npositions[querypos] == 0, so we can find adjacent despite mismatch or overabundance */
if (npositions[querypos] > 0) {
debug6(printf("Pushing querypos %d onto processed\n",querypos));
processed = Intlist_push(processed,querypos);
}
querypos = next_querypos;
}
}
debug9(printf("End of loop lookforward\n"));
Intlist_free(&processed);
/* These are the final active oligomers, after pruning by score */
if (debug_graphic_p == true) {
mappings_dump_R(mappings,npositions,querylength,active,firstactive,indexsize,"active.mers");
}
#if 0
FREE(nactive);
FREE(firstactive);
#endif
if (oned_matrix_p == true) {
intmatrix_1d_free(&active);
} else {
intmatrix_2d_free(&active,querylength);
}
/* Grand winners */
debug12(printf("Finding grand winners, using root position method\n"));
#ifdef SEPARATE_FWD_REV
if (splicingp == false || use_canonical_p == false) {
cells = Linkmatrix_get_cells_fwd(&(*ncells),links,querystart,queryend,npositions,
favor_right_p,cellpool);
} else {
cells = Linkmatrix_get_cells_both(&(*ncells),links,querystart,queryend,npositions,
indexsize,best_overall_score,favor_right_p,cellpool);
}
#else
cells = get_cells_fwd(&(*ncells),links,fwd_scores,querystart,queryend,npositions,
favor_right_p,cellpool);
#endif
debug9(FREE(oligo));
return cells;
}
/* Performs dynamic programming. For PMAP, indexsize is in aa. */
static List_T
align_compute_lookforward (Chrpos_T **mappings, int *npositions, int totalpositions,
bool oned_matrix_p, Chrpos_T *minactive, Chrpos_T *maxactive,
int *firstactive, int *nactive, Cellpool_T cellpool,
char *queryseq_ptr, char *queryuc_ptr, int querylength, int querystart, int queryend,
Univcoord_T chroffset, Univcoord_T chrhigh, bool plusp,
int indexsize, Pairpool_T pairpool,
bool anchoredp, int anchor_querypos, Chrpos_T anchor_position,
bool localp, bool skip_repetitive_p, bool use_canonical_p, int non_canonical_penalty,
bool favor_right_p, int max_nalignments, bool debug_graphic_p) {
List_T all_paths = NULL;
struct Link_T **links;
int **fwd_scores;
Cell_T *cells, cell;
int ncells, i;
bool fwdp;
int querypos, hit;
int bestscore;
if (oned_matrix_p == true) {
links = Linkmatrix_1d_new(querylength,npositions,totalpositions);
fwd_scores = intmatrix_1d_new(querylength,npositions,totalpositions);
} else {
links = Linkmatrix_2d_new(querylength,npositions);
fwd_scores = intmatrix_2d_new(querylength,npositions);
}
/* These are all oligomers */
if (debug_graphic_p == true) {
mappings_dump_R(mappings,npositions,querylength,/*active*/NULL,/*firstactive*/NULL,indexsize,"all.mers");
}
cells = align_compute_scores_lookforward(&ncells,links,fwd_scores,
mappings,npositions,totalpositions,
oned_matrix_p,minactive,maxactive,firstactive,nactive,cellpool,
querystart,queryend,querylength,
chroffset,chrhigh,plusp,
indexsize,
#ifdef DEBUG9
queryseq_ptr,
#endif
anchoredp,anchor_querypos,anchor_position,localp,
skip_repetitive_p,use_canonical_p,non_canonical_penalty,
debug_graphic_p,favor_right_p);
#ifdef SEPARATE_FWD_REV
debug1(Linkmatrix_print_both(links,mappings,querylength,npositions,queryseq_ptr,indexsize));
#else
debug1(print_fwd(links,fwd_scores,mappings,querylength,npositions,queryseq_ptr,indexsize));
#endif
if (ncells == 0) {
all_paths = (List_T) NULL;
} else {
bestscore = cells[0]->score;
debug11(printf("Looping on %d cells, allowing up to %d alignments, plus any with best score %d\n",
ncells,max_nalignments,bestscore));
for (i = 0; i < ncells && (i < max_nalignments || cells[i]->score == bestscore)
&& cells[i]->score > bestscore - FINAL_SCORE_TOLERANCE; i++) {
cell = cells[i];
querypos = cell->querypos;
hit = cell->hit;
fwdp = cell->fwdp;
debug11(printf("Starting subpath %d at rootposition %d with score %d, querypos %d, hit %d, position %u\n",
i,cell->rootposition,cell->score,querypos,hit,mappings[querypos][hit]));
if (debug_graphic_p == true) {
/* best_path_dump_R(links,mappings,querypos,hit,fwdp,"best.path"); */
printf("plot(all.mers,col=\"black\",pch=\".\",xlab=\"Query\",ylab=\"Genomic\")\n");
printf("points(active.mers,col=\"red\",pch=\".\")\n");
printf("points(best.path,col=\"green\",pch=\".\")\n");
printf("lines(querypos,minactive,col=\"blue\")\n");
printf("lines(querypos,maxactive,col=\"blue\")\n");
}
if (snps_p == true) {
all_paths = List_push(all_paths,(void *) traceback_one_snps(querypos,hit,links,mappings,queryseq_ptr,
chroffset,chrhigh,/*watsonp*/plusp,
#ifdef DEBUG0
fwd_scores,indexsize,
#endif
pairpool,fwdp));
} else {
all_paths = List_push(all_paths,(void *) traceback_one(querypos,hit,links,mappings,queryseq_ptr,queryuc_ptr,
#ifdef PMAP
chroffset,chrhigh,/*watsonp*/plusp,/*lookbackp*/false,
#endif
#ifdef DEBUG0
fwd_scores,indexsize,
#endif
pairpool,fwdp));
}
}
debug11(printf("\n"));
#if 0
/* No need with cellpool */
for (i = 0; i < ncells; i++) {
cell = cells[i];
Cell_free(&cell);
}
#endif
FREE(cells);
}
if (oned_matrix_p == true) {
Linkmatrix_1d_free(&links);
intmatrix_1d_free(&fwd_scores);
} else {
Linkmatrix_2d_free(&links,querylength);
intmatrix_2d_free(&fwd_scores,querylength);
}
#if 0
for (p = all_paths; p != NULL; p = List_next(p)) {
Pair_dump_list(List_head(p),/*zerobasedp*/true);
printf("\n");
}
#endif
return all_paths;
}
#if 0
/* Modified from stage3.c */
static void
get_splicesite_probs (double *left_prob, double *right_prob,
Chrpos_T left_genomepos, Chrpos_T right_genomepos,
Univcoord_T chroffset, Univcoord_T chrhigh, int genestrand, bool watsonp) {
Univcoord_T splicesitepos;
if (watsonp == true) {
splicesitepos = chroffset + left_genomepos;
if (genestrand > 0) {
*left_prob = Maxent_hr_donor_prob(splicesitepos /*?*/+ 1,chroffset);
debug5(printf("1. donor splicesitepos is %u (%u), prob %f\n",
splicesitepos,splicesitepos-chroffset,*left_prob));
} else {
*left_prob = Maxent_hr_antiacceptor_prob(splicesitepos /**/+ 1,chroffset);
debug5(printf("2. antiacceptor splicesitepos is %u (%u), prob %f\n",
splicesitepos,splicesitepos-chroffset,*left_prob));
}
} else {
splicesitepos = chrhigh - left_genomepos + 1;
if (genestrand > 0) {
*left_prob = Maxent_hr_acceptor_prob(splicesitepos /*?*/- 1,chroffset);
debug5(printf("4. acceptor splicesitepos is %u (%u), prob %f\n",
splicesitepos,splicesitepos-chroffset,*left_prob));
} else {
*left_prob = Maxent_hr_antidonor_prob(splicesitepos /**/- 1,chroffset);
debug5(printf("3. antidonor splicesitepos is %u (%u), prob %f\n",
splicesitepos,splicesitepos-chroffset,*left_prob));
}
}
if (watsonp == true) {
splicesitepos = chroffset + right_genomepos + 1;
if (genestrand > 0) {
*right_prob = Maxent_hr_acceptor_prob(splicesitepos /*?*/- 1,chroffset);
debug5(printf("5. acceptor splicesitepos is %u (%u), prob %f\n",
splicesitepos,splicesitepos-chroffset,*right_prob));
} else {
*right_prob = Maxent_hr_antidonor_prob(splicesitepos /**/- 1,chroffset);
debug5(printf("6. antidonor splicesitepos is %u (%u), prob %f\n",
splicesitepos,splicesitepos-chroffset,*right_prob));
}
} else {
splicesitepos = chrhigh - right_genomepos;
if (genestrand > 0) {
*right_prob = Maxent_hr_donor_prob(splicesitepos /*?*/+ 1,chroffset);
debug5(printf("8. donor splicesitepos is %u (%u), prob %f\n",
splicesitepos,splicesitepos-chroffset,*right_prob));
} else {
*right_prob = Maxent_hr_antiacceptor_prob(splicesitepos /**/+ 1,chroffset);
debug5(printf("7. antiacceptor splicesitepos is %u (%u), prob %f\n",
splicesitepos,splicesitepos-chroffset,*right_prob));
}
}
return;
}
#endif
/* queryseq_ptr is NULL for PMAP. querypos here is in nt. */
static List_T
convert_to_nucleotides (List_T path,
#ifndef PMAP
char *queryseq_ptr, char *queryuc_ptr,
#endif
Univcoord_T chroffset, Univcoord_T chrhigh, bool watsonp,
int query_offset, Pairpool_T pairpool, int indexsize_nt,
bool include_gapholders_p) {
List_T pairs = NULL;
Pair_T pair;
int querypos, lastquerypos, queryjump, genomejump, fill, default_fill;
int genomepos, lastgenomepos;
char c, c_alt;
debug5(printf("Beginning convert_to_nucleotides with %d pairs. query_offset = %d, indexsize_nt = %d\n",
List_length(path),query_offset,indexsize_nt));
/* pairptr = path; */
/* path = Pairpool_pop(path,&pair); */
pair = (Pair_T) path->first;
querypos = pair->querypos;
genomepos = pair->genomepos;
#ifdef PMAP
default_fill = indexsize_nt - 3;
#else
default_fill = indexsize_nt - 1;
#endif
lastquerypos = querypos + default_fill;
lastgenomepos = genomepos + default_fill;
while (lastquerypos > querypos) {
debug5(printf("querypos %d vs lastquerypos %d, lastgenomepos %d\n",querypos,lastquerypos,lastgenomepos));
#ifdef PMAP
c = get_genomic_nt(&c_alt,lastgenomepos,chroffset,chrhigh,watsonp);
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,/*cdna*/c,MATCH_COMP,c,c_alt,
/*dynprogindex*/0);
debug5(printf("Pushing %c | %c at %d,%d\n",c,c,lastquerypos,lastgenomepos));
#elif defined(EXTRACT_GENOMICSEG)
if (queryuc_ptr[lastquerypos] == genomicuc_ptr[lastgenomepos]) {
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],MISMATCH_COMP,
genomicseg_ptr[lastgenomepos],/*genomealt*/GENOMEALT_DEFERRED,
/*dynprogindex*/0);
debug5(printf("Pushing %c | %c at %d,%d\n",queryseq_ptr[lastquerypos],queryuc_ptr[lastquerypos],
lastquerypos+query_offset,lastgenomepos));
} else {
abort();
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],MISMATCH_COMP,
genomicseg_ptr[lastgenomepos],/*genomealt*/GENOMEALT_DEFERRED,
/*dynprogindex*/0);
debug5(printf("Pushing %c %c at %d,%d\n",queryseq_ptr[lastquerypos],genomicseg_ptr[lastgenomepos],
lastquerypos+query_offset,lastgenomepos));
}
#else
if (mode == STANDARD) {
c = queryuc_ptr[lastquerypos];
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],MATCH_COMP,c,/*genomealt*/c,
/*dynprogindex*/0);
debug5(printf("Pushing %c | %c at %d,%d\n",queryseq_ptr[lastquerypos],queryuc_ptr[lastquerypos],
lastquerypos+query_offset,lastgenomepos));
} else {
c = get_genomic_nt(&c_alt,lastgenomepos,chroffset,chrhigh,watsonp);
if (queryuc_ptr[lastquerypos] == c) {
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],MATCH_COMP,c,c_alt,/*dynprogindex*/0);
debug5(printf("Pushing %c | %c at %d,%d\n",queryseq_ptr[lastquerypos],c,
lastquerypos+query_offset,lastgenomepos));
} else {
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],AMBIGUOUS_COMP,c,c_alt,/*dynprogindex*/0);
debug5(printf("Pushing %c : %c at %d,%d\n",queryseq_ptr[lastquerypos],c,
lastquerypos+query_offset,lastgenomepos));
}
}
#endif
--lastquerypos;
--lastgenomepos;
}
/* Take care of observed first pair in oligomer */
if (mode == STANDARD) {
pair->querypos += query_offset; /* Revise coordinates */
/*pair->genomepos += genomic_offset;*/ /* Revise coordinates */
#ifdef WASTE
pairs = Pairpool_push_existing(pairs,pairpool,pair);
#else
pairs = List_transfer_one(pairs,&path);
#endif
debug5(printf("Transferring %c : %c at %d,%d (first pair)\n",pair->cdna,c,
pair->querypos+query_offset,pair->genomepos));
} else {
c = get_genomic_nt(&c_alt,pair->genomepos,chroffset,chrhigh,watsonp);
if (pair->cdna == c) {
pair->querypos += query_offset; /* Revise coordinates */
/*pair->genomepos += genomic_offset;*/ /* Revise coordinates */
#ifdef WASTE
pairs = Pairpool_push_existing(pairs,pairpool,pair);
#else
pairs = List_transfer_one(pairs,&path);
#endif
debug5(printf("Transferring %c : %c at %d,%d (first pair)\n",pair->cdna,c,
pair->querypos+query_offset,pair->genomepos));
} else {
path = Pairpool_pop(path,&pair);
pairs = Pairpool_push(pairs,pairpool,pair->querypos+query_offset,pair->genomepos,
pair->cdna,AMBIGUOUS_COMP,c,c_alt,/*dynprogindex*/0);
debug5(printf("Pushing %c : %c at %d,%d (first pair)\n",pair->cdna,c,
pair->querypos+query_offset,pair->genomepos));
}
}
lastquerypos = querypos;
lastgenomepos = genomepos;
while (path != NULL) {
/* pairptr = path; */
/* path = Pairpool_pop(path,&pair); */
pair = (Pair_T) path->first;
querypos = pair->querypos;
genomepos = pair->genomepos;
queryjump = lastquerypos - 1 - querypos;
genomejump = lastgenomepos - 1 - genomepos;
if (queryjump == 0 && genomejump == 0) {
/* Do nothing */
} else {
debug5(printf("At querypos %d, saw queryjump of %d and genomejump of %d\n",querypos,queryjump,genomejump));
if (querypos + default_fill >= lastquerypos || genomepos + default_fill >= lastgenomepos) {
if (lastquerypos - querypos < (int) (lastgenomepos - genomepos)) {
#if 0
/* This can occur with wobble mask */
fprintf(stderr,"Partial fill from querypos %d to %d (genomepos goes from %u to %u)\n",
querypos,lastquerypos,genomepos,lastgenomepos);
abort();
#endif
fill = lastquerypos - querypos - 1;
} else {
#if 0
/* This can occur with wobble mask */
fprintf(stderr,"Partial fill from genomepos %u to %u (querypos goes from %d to %d)\n",
genomepos,lastgenomepos,querypos,lastquerypos);
abort();
#endif
fill = lastgenomepos - genomepos - 1;
}
} else {
fill = default_fill;
}
/* Recompute queryjump and genomejump */
queryjump -= fill;
genomejump -= fill;
debug5(printf(" Revised queryjump of %d and genomejump of %d\n",queryjump,genomejump));
if (include_gapholders_p == true && (genomejump > 0 || queryjump > 0)) {
debug5(printf(" Pushing gapholder\n"));
pairs = Pairpool_push_gapholder(pairs,pairpool,queryjump,genomejump,
/*leftpair*/NULL,/*rightpair*/NULL,/*knownp*/false);
#if 0
/* Need to run on both genestrands, and save both results in pair */
if (queryjump == 0) {
get_splicesite_probs(&left_prob,&right_prob,genomepos+fill,lastgenomepos,
chroffset,chrhigh,/*genestrand*/+1,watsonp);
}
#endif
}
/* Fill rest of oligomer */
lastquerypos = querypos + fill;
lastgenomepos = genomepos + fill;
debug5(printf(" Fill from querypos %d down to %d\n",lastquerypos,querypos));
while (lastquerypos > querypos) {
#ifdef PMAP
c = get_genomic_nt(&c_alt,lastgenomepos,chroffset,chrhigh,watsonp);
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,/*cdna*/c,MATCH_COMP,c,c_alt,
/*dynprogindex*/0);
debug5(printf("Pushing %c | %c at %d,%d\n",c,c,lastquerypos+query_offset,lastgenomepos));
#elif defined(EXTRACT_GENOMICSEG)
if (queryuc_ptr[lastquerypos] == genomicuc_ptr[lastgenomepos]) {
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],MATCH_COMP,
queryuc_ptr[lastquerypos],/*genomealt*/GENOMEALT_DEFERRED,
/*dynprogindex*/0);
debug5(printf("Pushing %c | %c at %d,%d\n",queryseq_ptr[lastquerypos],genomicseg_ptr[lastgenomepos],
lastquerypos+query_offset,lastgenomepos));
} else {
abort();
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],MISMATCH_COMP,
genomicseg_ptr[lastgenomepos],/*genomealt*/GENOMEALT_DEFERRED,
/*dynprogindex*/0);
debug5(printf("Pushing %c %c at %d,%d\n",queryseq_ptr[lastquerypos],genomicseg_ptr[lastgenomepos],
lastquerypos+query_offset,lastgenomepos));
}
#else
if (mode == STANDARD) {
/* assert(queryuc_ptr[lastquerypos] == get_genomic_nt(&c_alt,lastgenomepos,genomicstart,genomiclength,watsonp)); */
c = queryuc_ptr[lastquerypos];
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],MATCH_COMP,c,/*genomealt*/c,
/*dynprogindex*/0);
debug5(printf("Pushing %c | %c at %d,%d\n",queryseq_ptr[lastquerypos],queryuc_ptr[lastquerypos],
lastquerypos+query_offset,lastgenomepos));
} else {
c = get_genomic_nt(&c_alt,lastgenomepos,chroffset,chrhigh,watsonp);
if (queryuc_ptr[lastquerypos] == c) {
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],MATCH_COMP,c,c_alt,/*dynprogindex*/0);
debug5(printf("Pushing %c | %c at %d,%d\n",queryseq_ptr[lastquerypos],c,
lastquerypos+query_offset,lastgenomepos));
} else {
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],AMBIGUOUS_COMP,c,c_alt,/*dynprogindex*/0);
debug5(printf("Pushing %c : %c at %d,%d\n",queryseq_ptr[lastquerypos],c,
lastquerypos+query_offset,lastgenomepos));
}
}
#endif
--lastquerypos;
--lastgenomepos;
}
}
/* Take care of observed match */
if (mode == STANDARD) {
pair->querypos += query_offset; /* Revise coordinates */
/*pair->genomepos += genomic_offset;*/ /* Revise coordinates */
#ifdef WASTE
pairs = Pairpool_push_existing(pairs,pairpool,pair);
#else
pairs = List_transfer_one(pairs,&path);
#endif
debug5(printf("Transferring %c : %c at %d,%d\n",pair->cdna,c,
pair->querypos+query_offset,pair->genomepos));
} else {
c = get_genomic_nt(&c_alt,pair->genomepos,chroffset,chrhigh,watsonp);
if (pair->cdna == c) {
pair->querypos += query_offset; /* Revise coordinates */
/*pair->genomepos += genomic_offset;*/ /* Revise coordinates */
#ifdef WASTE
pairs = Pairpool_push_existing(pairs,pairpool,pair);
#else
pairs = List_transfer_one(pairs,&path);
#endif
debug5(printf("Transferring %c : %c at %d,%d\n",pair->cdna,c,
pair->querypos+query_offset,pair->genomepos));
} else {
path = Pairpool_pop(path,&pair);
pairs = Pairpool_push(pairs,pairpool,pair->querypos+query_offset,pair->genomepos,
pair->cdna,AMBIGUOUS_COMP,c,c_alt,/*dynprogindex*/0);
debug5(printf("Pushing %c : %c at %d,%d (observed)\n",pair->cdna,c,
pair->querypos+query_offset,pair->genomepos));
}
}
lastquerypos = querypos;
lastgenomepos = genomepos;
}
debug5(Pair_dump_list(pairs,true));
/* pairs is in ascending querypos order */
return pairs; /* Used to return List_reverse(pairs) */
}
/* queryseq_ptr is NULL for PMAP. querypos here is in nt. */
static List_T
convert_to_nucleotides_snps (List_T path,
#ifndef PMAP
char *queryseq_ptr, char *queryuc_ptr,
#endif
Univcoord_T chroffset, Univcoord_T chrhigh, bool watsonp,
int query_offset, Pairpool_T pairpool, int indexsize_nt,
bool include_gapholders_p) {
List_T pairs = NULL;
Pair_T pair;
int querypos, genomepos, lastquerypos, lastgenomepos, queryjump, genomejump, fill, default_fill;
char c, c_alt;
debug5(printf("Beginning convert_to_nucleotides_snps with %d pairs\n",List_length(path)));
/* pairptr = path; */
/* path = Pairpool_pop(path,&pair); */
pair = (Pair_T) path->first;
querypos = pair->querypos;
genomepos = pair->genomepos;
#ifdef PMAP
default_fill = indexsize_nt - 3;
#else
default_fill = indexsize_nt - 1;
#endif
lastquerypos = querypos + default_fill;
lastgenomepos = genomepos + default_fill;
while (lastquerypos > querypos) {
debug5(printf("lastquerypos %d, lastgenomepos %d\n",
lastquerypos,lastgenomepos));
#ifdef PMAP
c = get_genomic_nt(&c_alt,lastgenomepos,chroffset,chrhigh,watsonp);
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,/*cdna*/c,MATCH_COMP,c,c_alt,
/*dynprogindex*/0);
debug5(printf("Pushing %c | %c at %d,%d\n",c,c,lastquerypos,lastgenomepos));
#elif defined(EXTRACT_GENOMICSEG)
if (queryuc_ptr[lastquerypos] == genomicuc_ptr[lastgenomepos]) {
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],MISMATCH_COMP,
genomicseg_ptr[lastgenomepos],/*genomealt*/GENOMEALT_DEFERRED,
/*dynprogindex*/0);
debug5(printf("Pushing %c | %c at %d,%d\n",queryseq_ptr[lastquerypos],queryuc_ptr[lastquerypos],
lastquerypos+query_offset,lastgenomepos));
} else {
abort();
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],MISMATCH_COMP,
genomicseg_ptr[lastgenomepos],/*genomealt*/GENOMEALT_DEFERRED,
/*dynprogindex*/0);
debug5(printf("Pushing %c %c at %d,%d\n",queryseq_ptr[lastquerypos],genomicseg_ptr[lastgenomepos],
lastquerypos+query_offset,lastgenomepos));
}
#else
if (mode == STANDARD) {
/* assert(queryuc_ptr[lastquerypos] == get_genomic_nt(&c_alt,lastgenomepos,chroffset,chrhigh,watsonp)); */
c = get_genomic_nt(&c_alt,lastgenomepos,chroffset,chrhigh,watsonp);
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],MATCH_COMP,c,c_alt,
/*dynprogindex*/0);
debug5(printf("Pushing %c | %c at %d,%d\n",queryseq_ptr[lastquerypos],queryuc_ptr[lastquerypos],
lastquerypos+query_offset,lastgenomepos));
} else {
c = get_genomic_nt(&c_alt,lastgenomepos,chroffset,chrhigh,watsonp);
if (queryuc_ptr[lastquerypos] == c) {
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],MATCH_COMP,c,c_alt,/*dynprogindex*/0);
debug5(printf("Pushing %c | %c at %d,%d\n",queryseq_ptr[lastquerypos],c,
lastquerypos+query_offset,lastgenomepos));
} else {
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],AMBIGUOUS_COMP,c,c_alt,/*dynprogindex*/0);
debug5(printf("Pushing %c : %c at %d,%d\n",queryseq_ptr[lastquerypos],c,
lastquerypos+query_offset,lastgenomepos));
}
}
#endif
--lastquerypos;
--lastgenomepos;
}
/* Take care of observed first pair in oligomer */
if (mode == STANDARD) {
pair->querypos += query_offset; /* Revise coordinates */
/*pair->genomepos += genomic_offset;*/ /* Revise coordinates */
#ifdef WASTE
pairs = Pairpool_push_existing(pairs,pairpool,pair);
#else
pairs = List_transfer_one(pairs,&path);
#endif
debug5(printf("Transferring %c : %c at %d,%d\n",pair->cdna,c,
pair->querypos+query_offset,pair->genomepos));
} else {
c = get_genomic_nt(&c_alt,pair->genomepos,chroffset,chrhigh,watsonp);
if (pair->cdna == c) {
pair->querypos += query_offset; /* Revise coordinates */
/*pair->genomepos += genomic_offset;*/ /* Revise coordinates */
#ifdef WASTE
pairs = Pairpool_push_existing(pairs,pairpool,pair);
#else
pairs = List_transfer_one(pairs,&path);
#endif
debug5(printf("Transferring %c : %c at %d,%d\n",pair->cdna,c,
pair->querypos+query_offset,pair->genomepos));
} else {
path = Pairpool_pop(path,&pair);
pairs = Pairpool_push(pairs,pairpool,pair->querypos+query_offset,pair->genomepos,
pair->cdna,AMBIGUOUS_COMP,c,c_alt,/*dynprogindex*/0);
debug5(printf("Pushing %c : %c at %d,%d (first pair)\n",pair->cdna,c,
pair->querypos+query_offset,pair->genomepos));
}
}
lastquerypos = querypos;
lastgenomepos = genomepos;
while (path != NULL) {
/* pairptr = path; */
/* path = Pairpool_pop(path,&pair); */
pair = (Pair_T) path->first;
querypos = pair->querypos;
genomepos = pair->genomepos;
queryjump = lastquerypos - 1 - querypos;
genomejump = lastgenomepos - 1 - genomepos;
if (queryjump == 0 && genomejump == 0) {
/* Do nothing */
} else {
debug5(printf("At querypos %d, saw queryjump of %d and genomejump of %d\n",querypos,queryjump,genomejump));
if (querypos + default_fill >= lastquerypos || genomepos + default_fill >= lastgenomepos) {
if (lastquerypos - querypos < lastgenomepos - genomepos) {
#if 0
/* This can occur with wobble mask */
fprintf(stderr,"Partial fill from querypos %d to %d (genomepos goes from %u to %u)\n",
querypos,lastquerypos,genomepos,lastgenomepos);
abort();
#endif
fill = lastquerypos - querypos - 1;
} else {
#if 0
/* This can occur with wobble mask */
fprintf(stderr,"Partial fill from genomepos %u to %u (querypos goes from %d to %d)\n",
genomepos,lastgenomepos,querypos,lastquerypos);
abort();
#endif
fill = lastgenomepos - genomepos - 1;
}
} else {
fill = default_fill;
}
/* Recompute queryjump and genomejump */
queryjump -= fill;
genomejump -= fill;
debug5(printf(" Revised queryjump of %d and genomejump of %d\n",queryjump,genomejump));
if (include_gapholders_p == true && (genomejump > 0 || queryjump > 0)) {
debug5(printf(" Pushing gapholder\n"));
pairs = Pairpool_push_gapholder(pairs,pairpool,queryjump,genomejump,
/*leftpair*/NULL,/*rightpair*/NULL,/*knownp*/false);
}
/* Fill rest of oligomer */
lastquerypos = querypos + fill;
lastgenomepos = genomepos + fill;
debug5(printf(" Fill from querypos %d down to %d\n",lastquerypos,querypos));
while (lastquerypos > querypos) {
#ifdef PMAP
c = get_genomic_nt(&c_alt,lastgenomepos,chroffset,chrhigh,watsonp);
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,/*cdna*/c,MATCH_COMP,c,c_alt,
/*dynprogindex*/0);
debug5(printf("Pushing %c | %c at %d,%d\n",c,c,lastquerypos+query_offset,lastgenomepos));
#elif defined(EXTRACT_GENOMICSEG)
if (queryuc_ptr[lastquerypos] == genomicuc_ptr[lastgenomepos]) {
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],MATCH_COMP,
queryuc_ptr[lastquerypos],/*genomealt*/GENOMEALT_DEFERRED,
/*dynprogindex*/0);
debug5(printf("Pushing %c | %c at %d,%d\n",queryseq_ptr[lastquerypos],genomicseg_ptr[lastgenomepos],
lastquerypos+query_offset,lastgenomepos));
} else {
abort();
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],MISMATCH_COMP,
genomicseg_ptr[lastgenomepos],/*genomealt*/GENOMEALT_DEFERRED,
/*dynprogindex*/0);
debug5(printf("Pushing %c %c at %d,%d\n",queryseq_ptr[lastquerypos],genomicseg_ptr[lastgenomepos],
lastquerypos+query_offset,lastgenomepos));
}
#else
if (mode == STANDARD) {
c = get_genomic_nt(&c_alt,lastgenomepos,chroffset,chrhigh,watsonp);
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],MATCH_COMP,c,c_alt,
/*dynprogindex*/0);
debug5(printf("Pushing %c | %c at %d,%d\n",queryseq_ptr[lastquerypos],queryuc_ptr[lastquerypos],
lastquerypos+query_offset,lastgenomepos));
} else {
c = get_genomic_nt(&c_alt,lastgenomepos,chroffset,chrhigh,watsonp);
if (queryuc_ptr[lastquerypos] == c) {
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],MATCH_COMP,c,c_alt,/*dynprogindex*/0);
debug5(printf("Pushing %c | %c at %d,%d\n",queryseq_ptr[lastquerypos],c,
lastquerypos+query_offset,lastgenomepos));
} else {
pairs = Pairpool_push(pairs,pairpool,lastquerypos+query_offset,lastgenomepos,
queryseq_ptr[lastquerypos],AMBIGUOUS_COMP,c,c_alt,/*dynprogindex*/0);
debug5(printf("Pushing %c : %c at %d,%d\n",queryseq_ptr[lastquerypos],c,
lastquerypos+query_offset,lastgenomepos));
}
}
#endif
--lastquerypos;
--lastgenomepos;
}
}
/* Take care of observed match */
if (mode == STANDARD) {
pair->querypos += query_offset; /* Revise coordinates */
/*pair->genomepos += genomic_offset;*/ /* Revise coordinates */
#ifdef WASTE
pairs = Pairpool_push_existing(pairs,pairpool,pair);
#else
pairs = List_transfer_one(pairs,&path);
#endif
debug5(printf("Transferring %c : %c at %d,%d\n",pair->cdna,c,
pair->querypos+query_offset,pair->genomepos));
} else {
c = get_genomic_nt(&c_alt,pair->genomepos,chroffset,chrhigh,watsonp);
if (pair->cdna == c) {
pair->querypos += query_offset; /* Revise coordinates */
/*pair->genomepos += genomic_offset;*/ /* Revise coordinates */
#ifdef WASTE
pairs = Pairpool_push_existing(pairs,pairpool,pair);
#else
pairs = List_transfer_one(pairs,&path);
#endif
debug5(printf("Transferring %c : %c at %d,%d\n",pair->cdna,c,
pair->querypos+query_offset,pair->genomepos));
} else {
path = Pairpool_pop(path,&pair);
pairs = Pairpool_push(pairs,pairpool,pair->querypos+query_offset,pair->genomepos,
pair->cdna,AMBIGUOUS_COMP,c,c_alt,/*dynprogindex*/0);
debug5(printf("Pushing %c : %c at %d,%d (observed)\n",pair->cdna,c,
pair->querypos+query_offset,pair->genomepos));
}
}
lastquerypos = querypos;
lastgenomepos = genomepos;
}
debug5(Pair_dump_list(pairs,true));
/* pairs is in ascending querypos order */
return pairs; /* Used to return List_reverse(pairs) */
}
/* Returns ncovered */
int
Stage2_scan (int *stage2_source, char *queryuc_ptr, int querylength,
Chrpos_T chrstart, Chrpos_T chrend,
Univcoord_T chroffset, Univcoord_T chrhigh, bool plusp,
int genestrand, Stage2_alloc_T stage2_alloc, Oligoindex_array_T oligoindices,
Diagpool_T diagpool, bool debug_graphic_p) {
int ncovered;
int source;
/* int indexsize; */
Oligoindex_T oligoindex;
Chrpos_T **mappings;
bool *coveredp, oned_matrix_p;
int *npositions, totalpositions;
double pct_coverage;
int maxnconsecutive;
/* double diag_runtime; */
List_T diagonals;
#ifndef USE_DIAGPOOL
List_p;
Diag_T diag;
#endif
#ifdef EXTRACT_GENOMICSEG
Count_T *counts;
#endif
if (debug_graphic_p == true) {
/* printf("par(mfrow=c(1,2),cex=0.2)\n"); */
printf("par(cex=0.3)\n");
printf("layout(matrix(c(1,2),1,2),widths=c(0.5,0.5),heights=c(1))\n");
}
if (querylength > stage2_alloc->max_querylength_alloc) {
coveredp = (bool *) CALLOC(querylength,sizeof(bool));
mappings = (Chrpos_T **) MALLOC(querylength * sizeof(Chrpos_T *));
npositions = (int *) CALLOC(querylength,sizeof(int));
} else {
coveredp = stage2_alloc->coveredp;
mappings = stage2_alloc->mappings;
npositions = stage2_alloc->npositions;
memset(coveredp,0,querylength * sizeof(bool));
memset(npositions,0,querylength * sizeof(int));
}
totalpositions = 0;
maxnconsecutive = 0;
source = 0;
pct_coverage = 0.0;
Diagpool_reset(diagpool);
diagonals = (List_T) NULL;
while (source < Oligoindex_array_length(oligoindices) && pct_coverage < SUFF_PCTCOVERAGE_OLIGOINDEX) {
oligoindex = Oligoindex_array_elt(oligoindices,source);
/* indexsize = Oligoindex_indexsize(oligoindex); */ /* Different sources can have different indexsizes */
#ifdef PMAP
if (plusp == true) {
Oligoindex_pmap_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend,/*plusp*/true,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/chrstart);
} else {
/* Need to add 1 to mappingend to cover same range as plusp */
Oligoindex_pmap_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend+1,/*plusp*/false,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/(chrhigh-chroffset)-chrend);
}
#else
#ifdef EXTRACT_GENOMICSEG
Oligoindex_tally(oligoindex,genomicuc_ptr,/*genomiclength*/chrend-chrstart,queryuc_ptr,querylength,
/*sequencepos*/0);
counts = Oligoindex_counts_copy(oligoindex);
#endif
if (plusp == true) {
Oligoindex_hr_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend,/*plusp*/true,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/chrstart,genestrand);
} else {
/* Need to add 1 to mappingend to cover same range as plusp */
Oligoindex_hr_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend+1,/*plusp*/false,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/(chrhigh-chroffset)-chrend,genestrand);
}
#ifdef EXTRACT_GENOMICSEG
assert(Oligoindex_counts_equal(oligoindex,counts));
/* Oligoindex_counts_dump(oligoindex,counts); */
FREE(counts);
#endif
#endif
diagonals = Oligoindex_get_mappings(diagonals,coveredp,mappings,npositions,&totalpositions,
&oned_matrix_p,&maxnconsecutive,oligoindices,oligoindex,queryuc_ptr,
/*querystart*/0,/*queryend*/querylength,querylength,
chrstart,chrend,chroffset,chrhigh,plusp,diagpool);
pct_coverage = Diag_update_coverage(coveredp,&ncovered,diagonals,querylength);
debug(printf("Stage2_scan: source = %d, ncovered = %d, pct_coverage = %f\n",source,ncovered,pct_coverage));
source++;
}
*stage2_source = source;
#ifdef USE_DIAGPOOL
/* No need to free diagonals */
#else
for (p = diagonals; p != NULL; p = List_next(p)) {
diag = (Diag_T) List_head(p);
Diag_free(&diag);
}
List_free(&diagonals);
#endif
if (querylength > stage2_alloc->max_querylength_alloc) {
FREE(npositions);
FREE(coveredp);
FREE(mappings); /* Don't need to free contents of mappings */
}
#if 1
for (source = 0; source < Oligoindex_array_length(oligoindices); source++) {
oligoindex = Oligoindex_array_elt(oligoindices,source);
Oligoindex_untally(oligoindex,queryuc_ptr,querylength);
}
#endif
return ncovered;
}
List_T
Stage2_compute (char *queryseq_ptr, char *queryuc_ptr, int querylength, int query_offset,
Chrpos_T chrstart, Chrpos_T chrend,
Univcoord_T chroffset, Univcoord_T chrhigh, bool plusp, int genestrand,
#ifndef GSNAP
Stage2_alloc_T stage2_alloc, double proceed_pctcoverage,
#endif
Oligoindex_array_T oligoindices,
Pairpool_T pairpool, Diagpool_T diagpool, Cellpool_T cellpool,
bool localp, bool skip_repetitive_p,
bool favor_right_p, int max_nalignments, bool debug_graphic_p,
Stopwatch_T stopwatch, bool diag_debug) {
List_T all_stage2results = NULL, all_paths, all_ends, all_starts, end_paths, start_paths, path, pairs, p, q;
List_T middle;
Pair_T firstpair, lastpair;
int diag_querystart, diag_queryend;
int indexsize, indexsize_nt;
Oligoindex_T oligoindex;
Chrpos_T **mappings;
bool *coveredp, oned_matrix_p;
int source;
int *npositions, totalpositions;
Chrpos_T *minactive, *maxactive;
int *firstactive, *nactive;
int maxnconsecutive;
/* double diag_runtime; */
List_T diagonals;
int anchor_querypos, querystart, queryend;
Chrpos_T anchor_position;
#ifdef GSNAP
Univcoord_T mappingstart, mappingend;
Chrpos_T chrpos, mappinglength;
#else
double pct_coverage;
int ncovered;
#endif
#ifndef USE_DIAGPOOL
List_T p;
Diag_T diag;
#endif
#ifdef DEBUG
int nunique;
#endif
#ifdef DEBUG0
int i;
#endif
#ifdef EXTRACT_GENOMICSEG
Count_T *counts;
#endif
debug(printf("Entered Stage2_compute with chrstart %u and chrend %u\n",chrstart,chrend));
Stopwatch_start(stopwatch);
if (debug_graphic_p == true) {
/* printf("par(mfrow=c(1,2),cex=0.2)\n"); */
printf("par(cex=0.3)\n");
printf("layout(matrix(c(1,2),1,2),widths=c(0.5,0.5),heights=c(1))\n");
}
#ifdef GSNAP
coveredp = (bool *) CALLOCA(querylength,sizeof(bool));
mappings = (Chrpos_T **) MALLOCA(querylength * sizeof(Chrpos_T *));
npositions = (int *) CALLOCA(querylength,sizeof(int));
minactive = (unsigned int *) MALLOCA(querylength * sizeof(unsigned int));
maxactive = (unsigned int *) MALLOCA(querylength * sizeof(unsigned int));
firstactive = (int *) MALLOCA(querylength * sizeof(int));
nactive = (int *) MALLOCA(querylength * sizeof(int));
#else
if (querylength > stage2_alloc->max_querylength_alloc) {
coveredp = (bool *) CALLOC(querylength,sizeof(bool));
mappings = (Chrpos_T **) MALLOC(querylength * sizeof(Chrpos_T *));
npositions = (int *) CALLOC(querylength,sizeof(int));
minactive = (unsigned int *) MALLOC(querylength * sizeof(unsigned int));
maxactive = (unsigned int *) MALLOC(querylength * sizeof(unsigned int));
firstactive = (int *) MALLOC(querylength * sizeof(int));
nactive = (int *) MALLOC(querylength * sizeof(int));
} else {
coveredp = stage2_alloc->coveredp;
mappings = stage2_alloc->mappings;
npositions = stage2_alloc->npositions;
minactive = stage2_alloc->minactive;
maxactive = stage2_alloc->maxactive;
firstactive = stage2_alloc->firstactive;
nactive = stage2_alloc->nactive;
memset(coveredp,0,querylength * sizeof(bool));
memset(npositions,0,querylength * sizeof(int));
}
#endif
totalpositions = 0;
maxnconsecutive = 0;
source = 0;
#ifdef USE_DIAGPOOL
Diagpool_reset(diagpool);
#endif
Cellpool_reset(cellpool);
diagonals = (List_T) NULL;
#ifdef GSNAP
mappingstart = chroffset + chrstart;
if (plusp == true) {
mappingend = chroffset + chrend;
chrpos = chrstart;
} else {
mappingend = chroffset + chrend + 1;
chrpos = (chrhigh - chroffset) - chrend;
}
mappinglength = (Chrpos_T) (mappingend - mappingstart);
if (mappinglength > 100000) {
/* 9-mers */
source = 0;
} else if (mappinglength > 10000) {
/* 8-mers */
source = 1;
} else {
/* 7-mers */
source = 2;
}
oligoindex = Oligoindex_array_elt(oligoindices,source);
indexsize = Oligoindex_indexsize(oligoindex); /* Different sources can have different indexsizes */
/* printf("indexsize = %d\n",indexsize); */
Oligoindex_hr_tally(oligoindex,mappingstart,mappingend,plusp,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
chrpos,genestrand);
diagonals = Oligoindex_get_mappings(diagonals,coveredp,mappings,npositions,&totalpositions,
&oned_matrix_p,&maxnconsecutive,oligoindices,oligoindex,queryuc_ptr,
/*querystart*/0,/*queryend*/querylength,querylength,
chrstart,chrend,chroffset,chrhigh,plusp,diagpool);
#else
/* GMAP */
pct_coverage = 0.0;
while (source < Oligoindex_array_length(oligoindices) && pct_coverage < SUFF_PCTCOVERAGE_OLIGOINDEX) {
oligoindex = Oligoindex_array_elt(oligoindices,source);
indexsize = Oligoindex_indexsize(oligoindex); /* Different sources can have different indexsizes */
#ifdef PMAP
if (plusp == true) {
Oligoindex_pmap_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend,/*plusp*/true,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/chrstart);
} else {
Oligoindex_pmap_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend+1,/*plusp*/false,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/(chrhigh-chroffset)-chrend);
}
#else
#if 0
/* Previously used this for user_genomicseg, but now creating genome_blocks on the fly */
Oligoindex_tally(oligoindex,genomicuc_ptr,/*genomiclength*/chrend-chrstart,queryuc_ptr,querylength,
/*sequencepos*/0);
#endif
#ifdef EXTRACT_GENOMICSEG
/* printf("indexsize = %d\n",indexsize); */
/* printf("Query: %.*s\n",querylength,queryuc_ptr); */
/* printf("Genome: %s\n",genomicuc_ptr); */
Oligoindex_tally(oligoindex,genomicuc_ptr,/*genomiclength*/mappingend-mappingstart,
queryuc_ptr,querylength,sequencepos);
counts = Oligoindex_counts_copy(oligoindex);
/* printf("plusp %d\n",plusp); */
/* printf("genomicstart %u, genomicend %u, genomiclength %d\n",genomicstart,genomicend,genomiclength); */
/* printf("mappingstart %u, mappingend %u\n",mappingstart,mappingend); */
#endif
if (plusp == true) {
Oligoindex_hr_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend,/*plusp*/true,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/chrstart,genestrand);
} else {
Oligoindex_hr_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend+1,/*plusp*/false,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/(chrhigh-chroffset)-chrend,genestrand);
}
#ifdef EXTRACT_GENOMICSEG
assert(Oligoindex_counts_equal(oligoindex,counts));
/* Oligoindex_counts_dump(oligoindex,counts); */
FREE(counts);
#endif
#endif
diagonals = Oligoindex_get_mappings(diagonals,coveredp,mappings,npositions,&totalpositions,
&oned_matrix_p,&maxnconsecutive,oligoindices,oligoindex,queryuc_ptr,
/*querystart*/0,/*queryend*/querylength,querylength,
chrstart,chrend,chroffset,chrhigh,plusp,diagpool);
pct_coverage = Diag_update_coverage(coveredp,&ncovered,diagonals,querylength);
debug(printf("Stage2_compute: source = %d, ndiagonals = %d, ncovered = %d, pct_coverage = %f\n",
source,List_length(diagonals),ncovered,pct_coverage));
source++;
}
#endif
/* *stage2_source = source; */
/* *stage2_indexsize = indexsize; */
#ifdef PMAP
indexsize_nt = 3*indexsize;
#else
indexsize_nt = indexsize;
#endif
/* diag_runtime = */ Stopwatch_stop(stopwatch);
Stopwatch_start(stopwatch);
if (diag_debug == true) {
/* Do nothing */
middle = (List_T) NULL;
} else if (totalpositions == 0) {
debug(printf("Quitting because totalpositions is zero\n"));
middle = (List_T) NULL;
#ifndef GSNAP
} else if (querylength > 150 && pct_coverage < proceed_pctcoverage && ncovered < SUFF_NCOVERED) {
/* Filter only on long queries */
debug(printf("Quitting because querylength %d > 150, and pct_coverage is only %f < %f, and ncovered is only %d < %d, maxnconsecutive = %d\n",
querylength,pct_coverage,proceed_pctcoverage,ncovered,SUFF_NCOVERED,maxnconsecutive));
middle = (List_T) NULL;
#endif
} else {
debug(printf("Proceeding because maxnconsecutive is %d and pct_coverage is %f > %f or ncovered = %d > %d\n",
maxnconsecutive,pct_coverage,proceed_pctcoverage,ncovered,SUFF_NCOVERED));
debug(printf("Performing diag on genomiclength %u\n",chrend-chrstart));
Diag_compute_bounds(&diag_querystart,&diag_queryend,minactive,maxactive,diagonals,querylength,
debug_graphic_p,chrstart,chrend,chroffset,chrhigh,plusp);
debug(
nunique = Diag_compute_bounds(&diag_querystart,&diag_queryend,minactive,maxactive,diagonals,querylength,
debug_graphic_p,chrstart,chrend,chroffset,chrhigh,plusp);
fprintf(stderr,"%d diagonals (%d not dominated), maxnconsecutive = %d\n",
List_length(diagonals),nunique,maxnconsecutive);
);
if (debug_graphic_p == true) {
active_bounds_dump_R(minactive,maxactive,querylength);
printf("lines(querypos,minactive,col=\"blue\")\n");
printf("lines(querypos,maxactive,col=\"blue\")\n");
}
all_paths = align_compute_lookback(mappings,npositions,totalpositions,
oned_matrix_p,minactive,maxactive,firstactive,nactive,cellpool,
queryseq_ptr,queryuc_ptr,querylength,
/*querystart*/diag_querystart,/*queryend*/diag_queryend,
chroffset,chrhigh,plusp,
indexsize,pairpool,
/*anchoredp*/false,/*anchor_querypos*/0,/*anchor_position*/0,
localp,skip_repetitive_p,use_canonical_middle_p,NON_CANONICAL_PENALTY_MIDDLE,
favor_right_p,max_nalignments,debug_graphic_p);
for (p = all_paths; p != NULL; p = List_next(p)) {
path = (List_T) p->first;
firstpair = path->first;
pairs = List_reverse(path);
lastpair = pairs->first;
debug5(printf("Converting middle\n"));
if (snps_p == true) {
middle = convert_to_nucleotides_snps(pairs,
#ifndef PMAP
queryseq_ptr,queryuc_ptr,
#endif
chroffset,chrhigh,/*watsonp*/plusp,
query_offset,pairpool,indexsize_nt,
/*include_gapholders_p*/true);
} else {
middle = convert_to_nucleotides(pairs,
#ifndef PMAP
queryseq_ptr,queryuc_ptr,
#endif
chroffset,chrhigh,/*watsonp*/plusp,
query_offset,pairpool,indexsize_nt,
/*include_gapholders_p*/true);
}
#ifdef PMAP
anchor_querypos = lastpair->querypos/3;
anchor_position = lastpair->genomepos - 2;
#else
anchor_querypos = lastpair->querypos;
anchor_position = lastpair->genomepos;
#endif
querystart = anchor_querypos + 1;
queryend = querylength - 1;
debug0(printf("For end, anchor querypos %d, anchor_position %u\n",anchor_querypos,anchor_position));
all_ends = (List_T) NULL;
end_paths = align_compute_lookback(mappings,npositions,totalpositions,
oned_matrix_p,minactive,maxactive,firstactive,nactive,cellpool,
queryseq_ptr,queryuc_ptr,querylength,querystart,queryend,
chroffset,chrhigh,plusp,
indexsize,pairpool,
/*anchoredp*/true,anchor_querypos,anchor_position,
localp,skip_repetitive_p,use_canonical_ends_p,NON_CANONICAL_PENALTY_ENDS,
favor_right_p,max_nalignments,debug_graphic_p);
/* fprintf(stderr,"%d ends\n",List_length(end_paths)); */
if (List_length(end_paths) == 1) {
pairs = (List_T) List_head(end_paths);
path = List_reverse(pairs);
debug5(printf("Converting single end\n"));
if (snps_p == true) {
pairs = convert_to_nucleotides_snps(path,
#ifndef PMAP
queryseq_ptr,queryuc_ptr,
#endif
chroffset,chrhigh,/*watsonp*/plusp,
query_offset,pairpool,indexsize_nt,
/*include_gapholders_p*/false);
} else {
pairs = convert_to_nucleotides(path,
#ifndef PMAP
queryseq_ptr,queryuc_ptr,
#endif
chroffset,chrhigh,/*watsonp*/plusp,
query_offset,pairpool,indexsize_nt,
/*include_gapholders_p*/false);
}
middle = Pairpool_remove_gapholders(middle);
middle = List_reverse(Pairpool_join_end3(List_reverse(middle),pairs,pairpool,/*copy_end_p*/false));
debug0(printf("ATTACHING SINGLE END TO MIDDLE\n"));
debug0(Pair_dump_list(middle,true));
} else {
debug0(i = 0);
for (q = end_paths; q != NULL; q = List_next(q)) {
pairs = (List_T) List_head(q);
path = List_reverse(pairs);
debug5(printf("Converting one end\n"));
if (snps_p == true) {
pairs = convert_to_nucleotides_snps(path,
#ifndef PMAP
queryseq_ptr,queryuc_ptr,
#endif
chroffset,chrhigh,/*watsonp*/plusp,
query_offset,pairpool,indexsize_nt,
/*include_gapholders_p*/false);
} else {
pairs = convert_to_nucleotides(path,
#ifndef PMAP
queryseq_ptr,queryuc_ptr,
#endif
chroffset,chrhigh,/*watsonp*/plusp,
query_offset,pairpool,indexsize_nt,
/*include_gapholders_p*/false);
}
debug0(printf("END %d/%d\n",i++,List_length(end_paths)));
debug0(Pair_dump_list(pairs,true));
all_ends = List_push(all_ends,(void *) pairs);
}
}
List_free(&end_paths);
#ifdef PMAP
anchor_querypos = firstpair->querypos/3;
anchor_position = firstpair->genomepos;
#else
anchor_querypos = firstpair->querypos;
anchor_position = firstpair->genomepos;
#endif
debug0(printf("For start, anchor querypos %d, anchor_position %u\n",anchor_querypos,anchor_position));
querystart = 0;
queryend = anchor_querypos - 1;
all_starts = (List_T) NULL;
start_paths = align_compute_lookforward(mappings,npositions,totalpositions,
oned_matrix_p,minactive,maxactive,firstactive,nactive,cellpool,
queryseq_ptr,queryuc_ptr,querylength,querystart,queryend,
chroffset,chrhigh,plusp,
indexsize,pairpool,
/*anchoredp*/true,anchor_querypos,anchor_position,
localp,skip_repetitive_p,use_canonical_ends_p,NON_CANONICAL_PENALTY_ENDS,
favor_right_p,max_nalignments,debug_graphic_p);
/* fprintf(stderr,"%d starts\n",List_length(start_paths)); */
if (List_length(start_paths) == 1) {
path = (List_T) List_head(start_paths);
debug5(printf("Converting single start\n"));
if (snps_p == true) {
pairs = convert_to_nucleotides_snps(path,
#ifndef PMAP
queryseq_ptr,queryuc_ptr,
#endif
chroffset,chrhigh,/*watsonp*/plusp,
query_offset,pairpool,indexsize_nt,
/*include_gapholders_p*/false);
} else {
pairs = convert_to_nucleotides(path,
#ifndef PMAP
queryseq_ptr,queryuc_ptr,
#endif
chroffset,chrhigh,/*watsonp*/plusp,
query_offset,pairpool,indexsize_nt,
/*include_gapholders_p*/false);
}
path = List_reverse(pairs);
middle = Pairpool_remove_gapholders(middle);
middle = Pairpool_join_end5(middle,path,pairpool,/*copy_end_p*/false);
debug0(printf("ATTACHING SINGLE START TO MIDDLE\n"));
debug0(Pair_dump_list(middle,true));
} else {
debug0(i = 0);
for (q = start_paths; q != NULL; q = List_next(q)) {
path = (List_T) List_head(q);
debug5(printf("Converting one start\n"));
if (snps_p == true) {
pairs = convert_to_nucleotides_snps(path,
#ifndef PMAP
queryseq_ptr,queryuc_ptr,
#endif
chroffset,chrhigh,/*watsonp*/plusp,
query_offset,pairpool,indexsize_nt,
/*include_gapholders_p*/false);
} else {
pairs = convert_to_nucleotides(path,
#ifndef PMAP
queryseq_ptr,queryuc_ptr,
#endif
chroffset,chrhigh,/*watsonp*/plusp,
query_offset,pairpool,indexsize_nt,
/*include_gapholders_p*/false);
}
path = List_reverse(pairs);
debug0(printf("START %d/%d\n",i++,List_length(start_paths)));
debug0(Pair_dump_list(path,true));
all_starts = List_push(all_starts,(void *) path);
}
}
List_free(&start_paths);
all_stage2results = List_push(all_stage2results,(void *) Stage2_new(middle,all_starts,all_ends));
}
List_free(&all_paths);
}
#ifdef GSNAP
FREEA(nactive);
FREEA(firstactive);
FREEA(maxactive);
FREEA(minactive);
FREEA(npositions);
FREEA(coveredp);
FREEA(mappings); /* Don't need to free contents of mappings */
#else
if (querylength > stage2_alloc->max_querylength_alloc) {
FREE(nactive);
FREE(firstactive);
FREE(maxactive);
FREE(minactive);
FREE(npositions);
FREE(coveredp);
FREE(mappings); /* Don't need to free contents of mappings */
}
#endif
#if 1
for (source = 0; source < Oligoindex_array_length(oligoindices); source++) {
oligoindex = Oligoindex_array_elt(oligoindices,source);
Oligoindex_untally(oligoindex,queryuc_ptr,querylength);
}
#endif
Stopwatch_stop(stopwatch);
if (diag_debug == true) {
return diagonals;
} else {
#ifdef USE_DIAGPOOL
/* No need to free diagonals */
#else
for (p = diagonals; p != NULL; p = List_next(p)) {
diag = (Diag_T) List_head(p);
Diag_free(&diag);
}
List_free(&diagonals);
#endif
}
debug0(printf("Done with stage2. Returning %d results\n",List_length(all_stage2results)));
return all_stage2results;
}
/* Since this stage2 is called from stage3 with a small segment of the
query, we can use alloca instead of stage2_alloc */
List_T
Stage2_compute_one (char *queryseq_ptr, char *queryuc_ptr, int querylength, int query_offset,
Chrpos_T chrstart, Chrpos_T chrend,
Univcoord_T chroffset, Univcoord_T chrhigh, bool plusp, int genestrand,
Oligoindex_array_T oligoindices,
Pairpool_T pairpool, Diagpool_T diagpool, Cellpool_T cellpool,
bool localp, bool skip_repetitive_p,
bool favor_right_p, bool debug_graphic_p) {
List_T pairs, all_paths;
List_T middle, path;
int indexsize, indexsize_nt;
Oligoindex_T oligoindex;
Chrpos_T **mappings;
bool *coveredp, oned_matrix_p;
int source;
int *npositions, totalpositions;
Chrpos_T *minactive, *maxactive;
int *firstactive, *nactive;
int ncovered;
double pct_coverage;
int maxnconsecutive;
/* double diag_runtime; */
List_T diagonals;
debug(printf("Entered Stage2_compute_one with chrstart %u and chrend %u\n",chrstart,chrend));
coveredp = (bool *) CALLOCA(querylength,sizeof(bool));
mappings = (Chrpos_T **) MALLOCA(querylength * sizeof(Chrpos_T *));
npositions = (int *) CALLOCA(querylength,sizeof(int));
minactive = (unsigned int *) MALLOCA(querylength * sizeof(unsigned int));
maxactive = (unsigned int *) MALLOCA(querylength * sizeof(unsigned int));
firstactive = (int *) MALLOCA(querylength * sizeof(int));
nactive = (int *) MALLOCA(querylength * sizeof(int));
totalpositions = 0;
maxnconsecutive = 0;
source = 0;
pct_coverage = 0.0;
#ifdef USE_DIAGPOOL
Diagpool_reset(diagpool);
#endif
Cellpool_reset(cellpool);
diagonals = (List_T) NULL;
while (source < Oligoindex_array_length(oligoindices) && pct_coverage < SUFF_PCTCOVERAGE_OLIGOINDEX) {
oligoindex = Oligoindex_array_elt(oligoindices,source);
indexsize = Oligoindex_indexsize(oligoindex); /* Different sources can have different indexsizes */
#ifdef PMAP
if (plusp == true) {
Oligoindex_pmap_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend,/*plusp*/true,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/chrstart);
} else {
Oligoindex_pmap_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend+1,/*plusp*/false,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/(chrhigh-chroffset)-chrend);
}
#else
if (plusp == true) {
Oligoindex_hr_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend,/*plusp*/true,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/chrstart,genestrand);
} else {
Oligoindex_hr_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend+1,/*plusp*/false,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/(chrhigh-chroffset)-chrend,genestrand);
}
#endif
diagonals = Oligoindex_get_mappings(diagonals,coveredp,mappings,npositions,&totalpositions,
&oned_matrix_p,&maxnconsecutive,oligoindices,oligoindex,queryuc_ptr,
/*querystart*/0,/*queryend*/querylength,querylength,
chrstart,chrend,chroffset,chrhigh,plusp,diagpool);
pct_coverage = Diag_update_coverage(coveredp,&ncovered,diagonals,querylength);
debug(printf("Stage2_compute: source = %d, ncovered = %d, pct_coverage = %f\n",source,ncovered,pct_coverage));
source++;
}
/* *stage2_source = source; */
/* *stage2_indexsize = indexsize; */
#ifdef PMAP
indexsize_nt = 3*indexsize;
#else
indexsize_nt = indexsize;
#endif
if (totalpositions == 0) {
debug(printf("Quitting because totalpositions is zero\n"));
middle = (List_T) NULL;
} else {
debug(printf("Proceeding because pct_coverage is %f > %f or ncovered = %d > %d\n",
maxnconsecutive,pct_coverage,ncovered,SUFF_NCOVERED));
debug(printf("Performing diag on genomiclength %u\n",chrend-chrstart));
Diag_max_bounds(minactive,maxactive,querylength,chrstart,chrend,chroffset,chrhigh,plusp);
if ((all_paths = align_compute_lookback(mappings,npositions,totalpositions,
oned_matrix_p,minactive,maxactive,firstactive,nactive,cellpool,
queryseq_ptr,queryuc_ptr,querylength,
/*querystart*/0,/*queryend*/querylength-1,
chroffset,chrhigh,plusp,
indexsize,pairpool,
/*anchoredp*/false,/*anchor_querypos*/0,/*anchor_position*/0,
localp,skip_repetitive_p,use_canonical_middle_p,NON_CANONICAL_PENALTY_MIDDLE,
favor_right_p,/*max_nalignments*/1,debug_graphic_p)) == NULL) {
middle = (List_T) NULL;
} else if ((path = (List_T) List_head(all_paths)) == NULL) {
middle = (List_T) NULL;
} else if (snps_p == true) {
pairs = List_reverse(path);
middle = convert_to_nucleotides_snps(pairs,
#ifndef PMAP
queryseq_ptr,queryuc_ptr,
#endif
chroffset,chrhigh,/*watsonp*/plusp,
query_offset,pairpool,indexsize_nt,
/*include_gapholders_p*/true);
} else {
pairs = List_reverse(path);
middle = convert_to_nucleotides(pairs,
#ifndef PMAP
queryseq_ptr,queryuc_ptr,
#endif
chroffset,chrhigh,/*watsonp*/plusp,
query_offset,pairpool,indexsize_nt,
/*include_gapholders_p*/true);
}
List_free(&all_paths);
}
FREEA(nactive);
FREEA(firstactive);
FREEA(maxactive);
FREEA(minactive);
FREEA(npositions);
FREEA(coveredp);
FREEA(mappings); /* Don't need to free contents of mappings */
#if 1
for (source = 0; source < Oligoindex_array_length(oligoindices); source++) {
oligoindex = Oligoindex_array_elt(oligoindices,source);
Oligoindex_untally(oligoindex,queryuc_ptr,querylength);
}
#endif
#ifdef USE_DIAGPOOL
/* No need to free diagonals */
#else
for (p = diagonals; p != NULL; p = List_next(p)) {
diag = (Diag_T) List_head(p);
Diag_free(&diag);
}
List_free(&diagonals);
#endif
return List_reverse(middle);
}
/* Called by GSNAP for ends of substring alignments */
List_T
Stage2_compute_starts (char *queryseq_ptr, char *queryuc_ptr, int querylength, int query_offset,
Chrpos_T chrstart, Chrpos_T chrend,
Univcoord_T chroffset, Univcoord_T chrhigh, bool plusp, int genestrand,
Oligoindex_array_T oligoindices,
Pairpool_T pairpool, Diagpool_T diagpool, Cellpool_T cellpool,
bool localp,
bool skip_repetitive_p,
bool favor_right_p, int max_nalignments, bool debug_graphic_p) {
List_T all_results;
List_T pairs, all_paths, p;
List_T path;
int indexsize, indexsize_nt;
Oligoindex_T oligoindex;
Chrpos_T **mappings;
bool *coveredp, oned_matrix_p;
int source;
int *npositions, totalpositions;
Chrpos_T *minactive, *maxactive;
int *firstactive, *nactive;
int ncovered;
double pct_coverage;
int maxnconsecutive;
/* double diag_runtime; */
List_T diagonals;
debug(printf("Entered Stage2_compute_starts with chrstart %u and chrend %u\n",chrstart,chrend));
coveredp = (bool *) CALLOCA(querylength,sizeof(bool));
mappings = (Chrpos_T **) MALLOCA(querylength * sizeof(Chrpos_T *));
npositions = (int *) CALLOCA(querylength,sizeof(int));
minactive = (unsigned int *) MALLOCA(querylength * sizeof(unsigned int));
maxactive = (unsigned int *) MALLOCA(querylength * sizeof(unsigned int));
firstactive = (int *) MALLOCA(querylength * sizeof(int));
nactive = (int *) MALLOCA(querylength * sizeof(int));
totalpositions = 0;
maxnconsecutive = 0;
source = 0;
pct_coverage = 0.0;
#ifdef USE_DIAGPOOL
Diagpool_reset(diagpool);
#endif
Cellpool_reset(cellpool);
diagonals = (List_T) NULL;
while (source < Oligoindex_array_length(oligoindices) && pct_coverage < SUFF_PCTCOVERAGE_OLIGOINDEX) {
oligoindex = Oligoindex_array_elt(oligoindices,source);
indexsize = Oligoindex_indexsize(oligoindex); /* Different sources can have different indexsizes */
#ifdef PMAP
if (plusp == true) {
Oligoindex_pmap_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend,/*plusp*/true,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/chrstart);
} else {
Oligoindex_pmap_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend+1,/*plusp*/false,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/(chrhigh-chroffset)-chrend);
}
#else
if (plusp == true) {
Oligoindex_hr_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend,/*plusp*/true,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/chrstart,genestrand);
} else {
Oligoindex_hr_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend+1,/*plusp*/false,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/(chrhigh-chroffset)-chrend,genestrand);
}
#endif
diagonals = Oligoindex_get_mappings(diagonals,coveredp,mappings,npositions,&totalpositions,
&oned_matrix_p,&maxnconsecutive,oligoindices,oligoindex,queryuc_ptr,
/*querystart*/0,/*queryend*/querylength,querylength,
chrstart,chrend,chroffset,chrhigh,plusp,diagpool);
pct_coverage = Diag_update_coverage(coveredp,&ncovered,diagonals,querylength);
debug(printf("Stage2_compute: source = %d, ncovered = %d, pct_coverage = %f\n",source,ncovered,pct_coverage));
source++;
}
/* *stage2_source = source; */
/* *stage2_indexsize = indexsize; */
#ifdef PMAP
indexsize_nt = 3*indexsize;
#else
indexsize_nt = indexsize;
#endif
if (totalpositions == 0) {
debug(printf("Quitting because totalpositions is zero\n"));
all_results = (List_T) NULL;
} else {
debug(printf("Proceeding because maxnconsecutive is %d and pct_coverage is %f or ncovered = %d > %d\n",
maxnconsecutive,pct_coverage,ncovered,SUFF_NCOVERED));
debug(printf("Performing diag on genomiclength %u\n",chrend-chrstart));
Diag_max_bounds(minactive,maxactive,querylength,chrstart,chrend,chroffset,chrhigh,plusp);
if ((all_paths = align_compute_lookforward(mappings,npositions,totalpositions,
oned_matrix_p,minactive,maxactive,firstactive,nactive,cellpool,
queryseq_ptr,queryuc_ptr,querylength,
/*querystart*/0,/*queryend*/querylength-1,
chroffset,chrhigh,plusp,
indexsize,pairpool,
/*anchoredp*/false,/*anchor_querypos*/0,/*anchor_position*/0,
localp,skip_repetitive_p,use_canonical_middle_p,NON_CANONICAL_PENALTY_MIDDLE,
favor_right_p,max_nalignments,debug_graphic_p)) == NULL) {
all_results = (List_T) NULL;
} else if (snps_p == true) {
all_results = (List_T) NULL;
for (p = all_paths; p != NULL; p = List_next(p)) {
path = List_head(p);
pairs = convert_to_nucleotides_snps(path,
#ifndef PMAP
queryseq_ptr,queryuc_ptr,
#endif
chroffset,chrhigh,/*watsonp*/plusp,
query_offset,pairpool,indexsize_nt,
/*include_gapholders_p*/false);
path = List_reverse(pairs);
debug0(printf("START\n"));
debug0(Pair_dump_list(path,true));
all_results = List_push(all_results,(void *) path);
}
} else {
all_results = (List_T) NULL;
for (p = all_paths; p != NULL; p = List_next(p)) {
path = List_head(p);
pairs = convert_to_nucleotides(path,
#ifndef PMAP
queryseq_ptr,queryuc_ptr,
#endif
chroffset,chrhigh,/*watsonp*/plusp,
query_offset,pairpool,indexsize_nt,
/*include_gapholders_p*/false);
path = List_reverse(pairs);
debug0(printf("START\n"));
debug0(Pair_dump_list(path,true));
all_results = List_push(all_results,(void *) path);
}
}
List_free(&all_paths);
}
FREEA(nactive);
FREEA(firstactive);
FREEA(maxactive);
FREEA(minactive);
FREEA(npositions);
FREEA(coveredp);
FREEA(mappings); /* Don't need to free contents of mappings */
#if 1
for (source = 0; source < Oligoindex_array_length(oligoindices); source++) {
oligoindex = Oligoindex_array_elt(oligoindices,source);
Oligoindex_untally(oligoindex,queryuc_ptr,querylength);
}
#endif
#ifdef USE_DIAGPOOL
/* No need to free diagonals */
#else
for (p = diagonals; p != NULL; p = List_next(p)) {
diag = (Diag_T) List_head(p);
Diag_free(&diag);
}
List_free(&diagonals);
#endif
return all_results;
}
/* Called by GSNAP for ends of substring alignments */
List_T
Stage2_compute_ends (char *queryseq_ptr, char *queryuc_ptr, int querylength, int query_offset,
Chrpos_T chrstart, Chrpos_T chrend,
Univcoord_T chroffset, Univcoord_T chrhigh, bool plusp, int genestrand,
Oligoindex_array_T oligoindices,
Pairpool_T pairpool, Diagpool_T diagpool, Cellpool_T cellpool,
bool localp,
bool skip_repetitive_p,
bool favor_right_p, int max_nalignments, bool debug_graphic_p) {
List_T all_results;
List_T pairs, all_paths, p;
List_T path;
int indexsize, indexsize_nt;
Oligoindex_T oligoindex;
Chrpos_T **mappings;
bool *coveredp, oned_matrix_p;
int source;
int *npositions, totalpositions;
Chrpos_T *minactive, *maxactive;
int *firstactive, *nactive;
int ncovered;
double pct_coverage;
int maxnconsecutive;
/* double diag_runtime; */
List_T diagonals;
debug(printf("Entered Stage2_compute_ends with chrstart %u and chrend %u\n",chrstart,chrend));
coveredp = (bool *) CALLOCA(querylength,sizeof(bool));
mappings = (Chrpos_T **) MALLOCA(querylength * sizeof(Chrpos_T *));
npositions = (int *) CALLOCA(querylength,sizeof(int));
minactive = (unsigned int *) MALLOCA(querylength * sizeof(unsigned int));
maxactive = (unsigned int *) MALLOCA(querylength * sizeof(unsigned int));
firstactive = (int *) MALLOCA(querylength * sizeof(int));
nactive = (int *) MALLOCA(querylength * sizeof(int));
totalpositions = 0;
maxnconsecutive = 0;
source = 0;
pct_coverage = 0.0;
#ifdef USE_DIAGPOOL
Diagpool_reset(diagpool);
#endif
Cellpool_reset(cellpool);
diagonals = (List_T) NULL;
while (source < Oligoindex_array_length(oligoindices) && pct_coverage < SUFF_PCTCOVERAGE_OLIGOINDEX) {
oligoindex = Oligoindex_array_elt(oligoindices,source);
indexsize = Oligoindex_indexsize(oligoindex); /* Different sources can have different indexsizes */
#ifdef PMAP
if (plusp == true) {
Oligoindex_pmap_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend,/*plusp*/true,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/chrstart);
} else {
Oligoindex_pmap_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend+1,/*plusp*/false,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/(chrhigh-chroffset)-chrend);
}
#else
if (plusp == true) {
Oligoindex_hr_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend,/*plusp*/true,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/chrstart,genestrand);
} else {
Oligoindex_hr_tally(oligoindex,/*mappingstart*/chroffset+chrstart,
/*mappingend*/chroffset+chrend+1,/*plusp*/false,
queryuc_ptr,/*querystart*/0,/*queryend*/querylength,
/*chrpos*/(chrhigh-chroffset)-chrend,genestrand);
}
#endif
diagonals = Oligoindex_get_mappings(diagonals,coveredp,mappings,npositions,&totalpositions,
&oned_matrix_p,&maxnconsecutive,oligoindices,oligoindex,queryuc_ptr,
/*querystart*/0,/*queryend*/querylength,querylength,
chrstart,chrend,chroffset,chrhigh,plusp,diagpool);
pct_coverage = Diag_update_coverage(coveredp,&ncovered,diagonals,querylength);
debug(printf("Stage2_compute: source = %d, ncovered = %d, pct_coverage = %f\n",source,ncovered,pct_coverage));
source++;
}
/* *stage2_source = source; */
/* *stage2_indexsize = indexsize; */
#ifdef PMAP
indexsize_nt = 3*indexsize;
#else
indexsize_nt = indexsize;
#endif
if (totalpositions <= 0) {
debug(printf("Quitting because totalpositions is zero\n"));
all_results = (List_T) NULL;
} else {
debug(printf("Proceeding because maxnconsecutive is %d and pct_coverage is %f or ncovered = %d > %d\n",
maxnconsecutive,pct_coverage,ncovered,SUFF_NCOVERED));
debug(printf("Performing diag on genomiclength %u\n",chrend-chrstart));
Diag_max_bounds(minactive,maxactive,querylength,chrstart,chrend,chroffset,chrhigh,plusp);
if ((all_paths = align_compute_lookback(mappings,npositions,totalpositions,
oned_matrix_p,minactive,maxactive,firstactive,nactive,cellpool,
queryseq_ptr,queryuc_ptr,querylength,
/*querystart*/0,/*queryend*/querylength-1,
chroffset,chrhigh,plusp,
indexsize,pairpool,
/*anchoredp*/false,/*anchor_querypos*/0,/*anchor_position*/0,
localp,skip_repetitive_p,use_canonical_middle_p,NON_CANONICAL_PENALTY_MIDDLE,
favor_right_p,max_nalignments,debug_graphic_p)) == NULL) {
all_results = (List_T) NULL;
} else if (snps_p == true) {
all_results = (List_T) NULL;
for (p = all_paths; p != NULL; p = List_next(p)) {
pairs = List_head(p);
path = List_reverse(pairs);
pairs = convert_to_nucleotides_snps(path,
#ifndef PMAP
queryseq_ptr,queryuc_ptr,
#endif
chroffset,chrhigh,/*watsonp*/plusp,
query_offset,pairpool,indexsize_nt,
/*include_gapholders_p*/false);
debug0(printf("END\n"));
debug0(Pair_dump_list(pairs,true));
all_results = List_push(all_results,(void *) pairs);
}
} else {
all_results = (List_T) NULL;
for (p = all_paths; p != NULL; p = List_next(p)) {
pairs = List_head(p);
path = List_reverse(pairs);
pairs = convert_to_nucleotides(path,
#ifndef PMAP
queryseq_ptr,queryuc_ptr,
#endif
chroffset,chrhigh,/*watsonp*/plusp,
query_offset,pairpool,indexsize_nt,
/*include_gapholders_p*/false);
debug0(printf("END\n"));
debug0(Pair_dump_list(pairs,true));
all_results = List_push(all_results,(void *) pairs);
}
}
List_free(&all_paths);
}
FREEA(nactive);
FREEA(firstactive);
FREEA(maxactive);
FREEA(minactive);
FREEA(npositions);
FREEA(coveredp);
FREEA(mappings); /* Don't need to free contents of mappings */
#if 1
for (source = 0; source < Oligoindex_array_length(oligoindices); source++) {
oligoindex = Oligoindex_array_elt(oligoindices,source);
Oligoindex_untally(oligoindex,queryuc_ptr,querylength);
}
#endif
#ifdef USE_DIAGPOOL
/* No need to free diagonals */
#else
for (p = diagonals; p != NULL; p = List_next(p)) {
diag = (Diag_T) List_head(p);
Diag_free(&diag);
}
List_free(&diagonals);
#endif
return all_results;
}
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