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build_repeat_families.c
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#include <stdio.h>
#include <stdlib.h>
#include <time.h>
#include <math.h>
#include "cmd_line_opts.h"
#include "build_repeat_families.h"
/* build_repeat_families.c -- build list of repeat families */
// RMH: From Version.c created by the Makefile
extern const char *Version;
int MAXLENGTH; /* Length of sequence. It's a misnomer, primarily for backwards compatability. */
#define PADLENGTH 11000 /* should be >= L+MAXOFFSET */
int l; /* Length of l-mers to look at. Odd or even is OK */
#define smalll 6
#define SEEDMISMATCHES 0 /* allow this many mismatches from seed */
#define HASH_SIZE 16000057 /* prime */
#define SMALLHASH_SIZE 5003 /* prime */
char* SEQUENCE_FILE; /* Where to get sequence data from. */
char* OUTPUT_FILE; /* Where to put output. */
char* LMER_TABLE_FILE; /* Where the lmer table is stored. */
int MINTHRESH; /* at end, remove l-mers with freq < MINTHRESH */
int TANDEMDIST; /* l-mers must be this far apart to avoid tandem repeats */
int VERBOSE; /* How chatty? Real chatty? Really really chatty? Super extra really chatty? */
int L; /* How far to extend. max total length of master is 2*L+l (L >>> l) */
int MAXOFFSET; /* max offset (5) */
int MAXN; /* max #occ of lmer (10000) */
int MAXR; /* max #families (100000) */
int MATCH; /* match score (1) */
int MISMATCH; /* mismatch score (-1) */
int GAP; /* gap (indel) score (-5) */
int CAPPENALTY; /* cap on penalty for exiting alignment (-20) */
int MINIMPROVEMENT; /* amount totalbestscore must improve for each extra letter (3) */
int WHEN_TO_STOP; /* stop if no improvement after extending this far (500) */
#define REMOVE_DEGENERATES 0
#define EXTRAMASK 1 /* default is 1 */
float MAXENTROPY; /* ignore freq l-mers with entropy greater than this (-0.70) */
int GOODLENGTH; /* minimum length of a good subfamily (50) */
int default_l(int);
/*
* -------- Internal global variables --------
*/
int length; /* length of genome sequence */
char *sequence; /* [2*MAXLENGTH+3*PADLENGTH]; */
char *removed; /* [2*MAXLENGTH+3*PADLENGTH]; */
char *master;
char **masters; /* MAXR * (2*L+l) but allocate dynamically */
int *masters_allocated;
int *masterstart;
int *masterend;
int *pos;
char *rev; // RMH: Flag indicating if N is a forward/reverse strand lmer
int *upperBoundI; // RMH: Index into boundaries for lmer upper sequence bound
int N;
int ***score; /* 2 * MAXN * (2*MAXOFFSET+1) */
int **score_of_besty; /* MAXN * (2*MAXOFFSET+1) */
int **maskscore; /* 2 * (2*MAXOFFSET+1) */
/* Reduce memory use by freeing once no longer needed */
int totalbestscore; /* alignment score for this y or w */
int besttotalbestscore; /* best alignment score for any y or w seen so far */
int *bestbestscore; /* best alignment score for this n for any y or w seen so far */
int *savebestscore;
int besty, bestw, nrepeatocc, nactiverepeatocc, bestnrepeatocc, bestnactiverepeatocc, R;
int bestrepeaty, bestsequencey, bestrepeatw, bestsequencew, repeat2sequence;
int maxrepeaty, minrepeatw;
int **distmat;
int prevbestfreq, prevbesthash;
int *boundaries; // RMH: Fasta sequence boundaries. This contains
// a non-zero ( zero-based ) position for the
// start of each sequence. The first sequence
// position is assumed to be 0 and therefore is
// not stored in this array. ( NOTE: This is the
// pre "PADLENGTH" padded position.
#define IUPAC(c) c == 'R' || c=='r' || c=='Y' || c=='y' || c=='M' || c=='m' || c=='K' || c=='k' || c=='W' || c=='w' || c=='S' || c=='s' || c=='B' || c=='b' || c=='D' || c=='d' || c=='H' || c=='h' || c=='V' || c=='v'
void usage()
{
fprintf(stderr, "RepeatScout Version %s\n\nUsage: \n"
"RepeatScout -sequence <seq> -output <out> -freq <freq> -l <l> [opts]\n"
" -L # size of region to extend left or right (10000) \n"
" -match # reward for a match (+1) \n"
" -mismatch # penalty for a mismatch (-1) \n"
" -gap # penalty for a gap (-5)\n"
" -maxgap # maximum number of gaps allowed (5) \n"
" -maxoccurrences # cap on the number of sequences to align (10,000) \n"
" -maxrepeats # stop work after reporting this number of repeats (10000)\n"
" -cappenalty # cap on penalty for exiting alignment of a sequence (-20)\n"
" -tandemdist # of bases that must intervene between two l-mers for both to be counted (500)\n"
" -minthresh # stop if fewer than this number of l-mers are found in the seeding phase (3)\n"
" -minimprovement # amount that a the alignment needs to improve each step to be considered progress (3)\n"
" -stopafter # stop the alignment after this number of no-progress columns (100)\n"
" -goodlength # minimum required length for a sequence to be reported (50)\n"
" -maxentropy # entropy (complexity) threshold for an l-mer to be considered (-.7)\n"
" -v[v[v[v]]] How verbose do you want it to be? -vvvv is super-verbose.\n",
Version );
exit(1);
}
int main(int argc, char* argv[])
{
time_t start, finish;
double duration;
int x;
struct llist **headptr;
struct llist *besttmp;
FILE *fp;
start = time(0);
if( 0 == 1 *
co_get_string(argc, argv, "-sequence", &SEQUENCE_FILE) *
co_get_string(argc, argv, "-output", &OUTPUT_FILE) *
co_get_string(argc, argv, "-freq", &LMER_TABLE_FILE)
) {
usage();
exit(1);
}
fp = fopen(SEQUENCE_FILE, "ro");
if( NULL == fp ) {
fprintf(stderr, "Could not open sequence file %s\n", SEQUENCE_FILE);
exit(1);
}
fseek(fp, 0, SEEK_END);
MAXLENGTH = ftell(fp);
fclose(fp);
co_get_int(argc, argv, "-l", &l) || (l = default_l(MAXLENGTH));
sequence = (char *) malloc( (2 * MAXLENGTH + 3 * PADLENGTH) * sizeof(char) );
if( NULL == sequence ) {
fprintf(stderr, "Could not allocate space for sequence\n");
exit(1);
}
removed = (char *) malloc( (2 * MAXLENGTH + 3 * PADLENGTH) * sizeof(char) );
if( NULL == removed ) {
fprintf(stderr, "Could not allocate space for masking array\n");
exit(1);
}
co_get_int(argc, argv, "-L", &L) || (L=10000);
co_get_int(argc, argv, "-match", &MATCH) || (MATCH=1);
co_get_int(argc, argv, "-mismatch", &MISMATCH) || (MISMATCH=-1);
co_get_int(argc, argv, "-gap", &GAP) || (GAP=-5);
co_get_int(argc, argv, "-maxgap", &MAXOFFSET) || (MAXOFFSET=5);
co_get_int(argc, argv, "-maxoccurrences", &MAXN) || (MAXN = 10000);
co_get_int(argc, argv, "-maxrepeats", &MAXR) || (MAXR = 100000);
co_get_int(argc, argv, "-cappenalty", &CAPPENALTY) || (CAPPENALTY=-20);
co_get_int(argc, argv, "-minimprovement", &MINIMPROVEMENT) || (MINIMPROVEMENT=3);
co_get_int(argc, argv, "-stopafter", &WHEN_TO_STOP) || (WHEN_TO_STOP=100);
co_get_float(argc, argv, "-maxentropy", &MAXENTROPY) || (MAXENTROPY=-0.7);
co_get_int(argc, argv, "-goodlength", &GOODLENGTH) || (GOODLENGTH=50);
co_get_int(argc, argv, "-tandemdist", &TANDEMDIST) || (TANDEMDIST=500);
co_get_int(argc, argv, "-minthresh", &MINTHRESH) || (MINTHRESH=3);
VERBOSE = co_get_bool(argc, argv, "-v", &x) ? 1 :
co_get_bool(argc, argv, "-vv", &x) ? 2 :
co_get_bool(argc, argv, "-vvv", &x) ? 3 :
co_get_bool(argc, argv, "-vvvv", &x) ? 20: 0;
master = (char *)malloc( (2*L+l+1) * sizeof(char));
master[2*L+l] = (char)NULL;
if( NULL == master ) {
fprintf(stderr, "Could not allocate space for master array\n");
exit(1);
}
masters_allocated = (int *)malloc( MAXR * sizeof(int) );
if( NULL == masters_allocated ) {
fprintf(stderr, "Could not allocated space for the master's allocation table\n");
exit(1);
}
masterstart = (int *)malloc( MAXR * sizeof(int) );
if( NULL == masterstart ) {
fprintf(stderr, "Could not allocated space for the master start positions\n");
exit(1);
}
masterend = (int *)malloc( MAXR * sizeof(int) );
if( NULL == masterend) {
fprintf(stderr, "Could not allocated space for the master stop positions\n");
exit(1);
}
// RMH: Initialize the rev array
rev = (char *)malloc( MAXN * sizeof(char) );
if( NULL == rev ) {
fprintf(stderr, "Could not allocated space for the reversed array\n");
exit(1);
}
// RMH: Initialize the upperBoundI array
upperBoundI = (int *)malloc( MAXN * sizeof(int) );
if( NULL == upperBoundI ) {
fprintf(stderr, "Could not allocated space for the upperBoundI array\n");
exit(1);
}
pos = (int *)malloc( MAXN * sizeof(int) );
if( NULL == pos ) {
fprintf(stderr, "Could not allocated space for the position array\n");
exit(1);
}
bestbestscore = (int *)malloc( MAXN * sizeof(int) );
savebestscore = (int *)malloc( MAXN * sizeof(int) );
if( NULL == bestbestscore || NULL == savebestscore ) {
fprintf(stderr, "Could not allocated space for internal arrays\n");
exit(1);
}
/* print parameters */
if(VERBOSE) print_parameters();
/* build sequence */
length = build_sequence(sequence,SEQUENCE_FILE);
// RMH: This is no longer needed. We use one copy of
// the sequence now. Saves space and makes further
// modifications easier.
//add_rc(sequence); if(VERBOSE) fprintf(stderr,"Done building sequence\n");
for(x=0; x<length; x++) removed[x] = 0;
/* allocate space */
allocate_space();
/* build headptr */
if((headptr = (struct llist **) malloc(HASH_SIZE*sizeof(*headptr))) == NULL)
{
fprintf(stderr,"Out of memory\n"); exit(1);
}
if(VERBOSE) fprintf(stderr,"Done allocating headptr\n");
build_headptr(headptr);
if(VERBOSE) fprintf(stderr,"Done building headptr\n");
if( (fp = fopen(OUTPUT_FILE, "w")) == NULL)
{
fprintf(stderr,"Could not open input file %s\n", OUTPUT_FILE); exit(1);
}
R = 0;
prevbestfreq = 1000000000;
prevbesthash = 0;
while(1)
{
besttmp = find_besttmp(headptr);
if((besttmp == NULL) || (besttmp->freq < MINTHRESH)) /* 2nd cond added 6/9/04 */
{
if(VERBOSE) printf("Stopped at R=%d since no more frequent l-mers\n",R);
if(VERBOSE) fprintf(stderr,"Stopped at R=%d since no more frequent l-mers\n",R);
break;
}
/* build master */
for(x=0; x<l; x++) master[L+x] = sequence[(besttmp->lastocc)+x];
build_pos(besttmp); /* computes N */
// RMH: Added because I was seeing some strange cases.
if ( N < MINTHRESH )
{
printf("Warning: N ( %d ) is less than MINTHRESH ( %d ) yet "
"besttmp->freq = %d....hmmm\nlmer = ",
N, MINTHRESH, besttmp->freq );
for(x=0; x<l; x++)
printf("%c", num_to_char( sequence[(besttmp->lastocc)+x] ) );
printf("\nh = %d\n", prevbesthash );
besttmp->freq = N;
continue;
}
if(masters_allocated[R] == 0)
{
if((masters[R] = (char *) malloc((2*L+l)*sizeof(*masters[R]))) == NULL)
{ fprintf(stderr,"Out of memory\n"); exit(1); }
masters_allocated[R] = 1;
}
extend_right();
extend_left();
if(masterend[R]-masterstart[R]+1 >= GOODLENGTH)
{
if(VERBOSE)
{
printf("R=%d: Master lmer hit is ",R);
for(x=0; x<l; x++) printf("%c",num_to_char(master[L+x]));
printf("\n");
fprintf(stderr,"R=%d: Master lmer hit is ",R);
for(x=0; x<l; x++) fprintf(stderr,"%c",num_to_char(master[L+x]));
fprintf(stderr,"\n");
}
if((SEEDMISMATCHES == 0) && (N != MAXN) && (N != besttmp->freq))
{
if(VERBOSE) fprintf(stderr,"WARNING N=%d but goodfreq=%d\n",N,besttmp->freq); /* exit(1); */
if(VERBOSE) printf("WARNING N=%d but goodfreq=%d\n",N,besttmp->freq); /* exit(1); */
}
fprintf(fp,">R=%d\n",R);
for(x=masterstart[R]; x<=masterend[R]; x++)
{
fprintf(fp,"%c",num_to_char(master[x]));
if((x-masterstart[R])%80 == 79) fprintf(fp,"\n");
}
if((x-masterstart[R])%80 > 0) fprintf(fp,"\n");
if(VERBOSE)
{
printf("R=%d: N is %d\n",R,N);
fprintf(stderr,"R=%d: N is %d\n",R,N);
printf("AFTER EXTENDING LEFT, FAMILY %d IS:\n",R);
printf("%d letters total:\n",masterend[R]-masterstart[R]+1);
for(x=masterstart[R]; x<=masterend[R]; x++)
{
printf("%c",num_to_char(master[x]));
if((x-masterstart[R])%80 == 79) printf("\n");
}
if((x-masterstart[R])%80 > 0) printf("\n");
fprintf(stderr,"AFTER EXTENDING LEFT, FAMILY %d IS:\n",R);
fprintf(stderr,"%d letters total:\n",masterend[R]-masterstart[R]+1);
for(x=masterstart[R]; x<=masterend[R]; x++)
{
fprintf(stderr,"%c",num_to_char(master[x]));
if((x-masterstart[R])%80 == 79) fprintf(stderr,"\n");
}
if((x-masterstart[R])%80 > 0) fprintf(stderr,"\n");
}
finish = time(0);
duration = difftime(finish,start);
if(VERBOSE) printf("Time1 to this point is %.1f sec = %.1f min = %.1f hr\n",duration, duration/60.0, duration/3600.0);
if(VERBOSE) fprintf(stderr,"Time1 to this point is %.1f sec = %.1f min = %.1f hr\n",duration, duration/60.0, duration/3600.0);
R++;
if(R == MAXR) break;
mask_headptr(headptr); /* removed[x]=1 means l-mer x was removed */
finish = time(0);
duration = difftime(finish,start);
if(VERBOSE) printf("Time2 to this point is %.1f sec = %.1f min = %.1f hr\n\n",duration, duration/60.0, duration/3600.0);
if(VERBOSE) fprintf(stderr,"Time2 to this point is %.1f sec = %.1f min = %.1f hr\n\n",duration, duration/60.0, duration/3600.0);
}
else
{
R++;
if(R == MAXR) break;
mask_headptr(headptr);
R--;
}
}
finish = time(0);
duration = difftime(finish,start);
if(VERBOSE) printf("Program duration is %.1f sec = %.1f min = %.1f hr\n",duration, duration/60.0, duration/3600.0);
fprintf(stderr,"Program duration is %.1f sec = %.1f min = %.1f hr\n",duration, duration/60.0, duration/3600.0);
return 0;
}
/* ************************************************************** */
void build_headptr(struct llist **headptr)
{
FILE *fp;
char string[l];
int thisfreq, thisocc, x, h, n;
struct llist *tmp;
if( (fp = fopen(LMER_TABLE_FILE, "r")) == NULL)
{
fprintf(stderr,"Could not open input file %s\n", LMER_TABLE_FILE); exit(1);
}
/* set each head pointer *headptr to NULL */
for(h=0; h<HASH_SIZE; h++)
headptr[h] = NULL;
n = 0;
while(1)
{
fscanf(fp,"%s",string);
fscanf(fp,"%d",&thisfreq);
fscanf(fp,"%d",&thisocc);
/* printf("Processing string %s thisfreq %d\n",string,thisfreq); */
if(string[0] < 10) break; /* end of file */
for(x=0; x<l; x++) string[x] = char_to_num(string[x]); /* must translate */
h = hash_function(string);
if(h<0) continue;
tmp = headptr[h];
while(tmp != NULL)
{
if(lmermatcheither(sequence+(tmp->lastocc),string) == 1) /* forward or rc match */
{
/* already in there. Means we have reached end of file: all done */
break;
}
tmp = tmp->next;
}
/* add new guys */
if(tmp != NULL) break; /* all done */
if(compute_entropy(sequence+thisocc) > MAXENTROPY) continue; /* skip */
if((tmp = (struct llist *) malloc(sizeof(*tmp))) == NULL)
{
fprintf(stderr,"Out of memory\n"); exit(1);
}
n++;
tmp->freq = thisfreq;
tmp->lastocc = thisocc;
tmp->next = headptr[h]; /* either NULL, or some other l-mer with hash h */
tmp->pos = NULL;
headptr[h] = tmp;
}
fclose(fp);
trim_headptr(headptr);
build_all_pos(headptr);
}
void trim_headptr(struct llist **headptr)
{
int h;
struct llist *tmp, *prevtmp, *nexttmp;
/* remove l-mers with freq < MINTHRESH */
for(h=0; h<HASH_SIZE; h++)
{
prevtmp = NULL;
tmp = headptr[h];
while(tmp != NULL)
{
if(tmp->freq >= MINTHRESH)
{ /* don't remove tmp */
// RMH: Let build_all_pos rebuild this ( based on seq boundaries )
tmp->freq = 0;
prevtmp = tmp;
tmp = tmp->next;
continue;
}
/* remove tmp */
nexttmp = tmp->next;
free(tmp);
tmp = nexttmp;
if(prevtmp == NULL) /* first guy in linked list */
headptr[h] = tmp;
else
prevtmp->next = tmp;
}
}
}
void build_all_pos(struct llist **headptr)
{
int x, h, pos1, pos2;
// RMH: Added for rev/fwd strand mods
struct posllist *postmp2;
struct llist *tmp;
struct posllist *postmp, *prevpostmp, *nextpostmp;
int currBoundary = 0;
if(VERBOSE) fprintf(stderr,"Starting build_all_pos 1\n");
for(x=l-1; x<length-l+1; x++)
{
// RMH: Make sure we are not on a sequence boundary.
// NOTE: I have decided to adjust the frequency
// also at this stage. This should take care
// of build_lmer_table including elements
// which cross sequence boundaries. I don't
// like adjusting it here but until build_lmer_table
// is revamped or we switch to elmer....
//
if ( boundaries[currBoundary] > 0 )
{
if ( x == boundaries[currBoundary] + PADLENGTH )
{
currBoundary++;
}
if ( x+l > boundaries[currBoundary] + PADLENGTH )
{
if(VERBOSE) printf("Skipping lmer @ %d due to sequence boundary\n", (x+l) );
continue;
}
}
/* look for this l-mer in headptr */
// RMH: This may be a good place for an optimisation.
// We could use the bit table trick to disqualify
// lmers that can't be in the hash table. Thus
// reducing the hash table lookup cost.
h = hash_function(sequence+x);
if(h<0) continue;
tmp = headptr[h];
while(tmp != NULL)
{
// RMH: Changed this to "either" now that we are not loading
// into memory the reverse complemented sequence.
if( ((SEEDMISMATCHES==0) && (lmermatcheither(sequence+(tmp->lastocc),sequence+x))) /* seq incl rc */ ||
((SEEDMISMATCHES>0) && (mismatches(sequence+(tmp->lastocc),sequence+x)<=SEEDMISMATCHES)))
{
/* a hit. Add position x to tmp->pos */
if((postmp = (struct posllist *) malloc(sizeof(*postmp))) == NULL)
{
fprintf(stderr,"Out of memory\n"); exit(1);
}
postmp->this = x;
postmp->next = tmp->pos;
tmp->pos = postmp;
tmp->freq++;
}
tmp = tmp->next;
}
}
if(VERBOSE) fprintf(stderr,"Starting build_all_pos 2\n");
/* extra code to remove position pairs within TANDEMDIST */
// RMH: NOTE - Tandem repeat removal creates assymetry in the
// algorithm. When two lmers are within TANDEMDIST
// apart the first one is removed and the last one
// kept. Obviously this is dependent on the strand
// you feed the program. Setting tandemdist to 0
// will restore symmetry for testing purposes.
for(h=0; h<HASH_SIZE; h++)
{
tmp = headptr[h];
while(tmp != NULL)
{
/* mark within-TANDEMDIST guys as negative */
postmp = tmp->pos;
while((postmp != NULL) && (postmp->next != NULL))
{
pos1 = postmp->this;
// RMH: Fwd/Rev strand mods
// Tandem distance needs to be measured from the last
// occurance of a same-stranded lmer.
postmp2 = postmp;
while ( ( postmp2 = postmp2->next ) != NULL )
{
pos2 = postmp2->this;
if ( pos1-pos2 >= TANDEMDIST )
break;
if ( lmermatch(sequence+pos1,sequence+pos2) )
{
postmp->this = -pos1;
break;
}
}
postmp = postmp->next;
}
/* remove guys marked as negative */
postmp = tmp->pos;
prevpostmp = NULL;
while(postmp != NULL)
{
if(postmp->this >= 0)
{ /* don't remove postmp */
prevpostmp = postmp;
postmp = postmp->next;
continue;
}
/* remove postmp */
nextpostmp = postmp->next;
// RMH: Reduce frequency as we remove them?
// TODO: Consider if this is what we want.
tmp->freq--;
removed[-postmp->this] = 1;
//
free(postmp);
postmp = nextpostmp;
if(prevpostmp == NULL) /* first guy in linked list */
tmp->pos = postmp;
else
prevpostmp->next = postmp;
}
tmp = tmp->next;
}
}
return;
if(VERBOSE) fprintf(stderr,"Done with build_all_pos\n");
}
struct llist *find_besttmp(struct llist **headptr)
{
int h;
struct llist *tmp, *besttmp;
int bestfreq;
/* first, try to match prevbestfreq */
for(h=prevbesthash; h<HASH_SIZE; h++)
{
tmp = headptr[h];
while(tmp != NULL)
{
if(tmp->freq == prevbestfreq)
{
prevbesthash = h;
return tmp;
}
tmp = tmp->next;
}
}
/* otherwise, just find best */
besttmp = NULL;
bestfreq = 0;
for(h=0; h<HASH_SIZE; h++)
{
tmp = headptr[h];
while(tmp != NULL)
{
if(tmp->freq > bestfreq)
{
besttmp = tmp;
bestfreq = tmp->freq;
prevbesthash = h;
}
tmp = tmp->next;
}
}
prevbestfreq = bestfreq;
return besttmp;
}
void allocate_space()
{
int r, x, n;
/* char **masters; MAXR * (2*L+l) but allocate dynamically */
if((masters = (char **) malloc(MAXR*sizeof(*masters))) == NULL)
{ fprintf(stderr,"Out of memory\n"); exit(1); }
for(r=0; r<MAXR; r++) masters_allocated[r] = 0;
if((distmat = (int **) malloc((l+1)*sizeof(*distmat))) == NULL)
{ fprintf(stderr,"Out of memory\n"); exit(1); }
for(x=0; x<=l; x++)
{
if((distmat[x] = (int *) malloc((l+1)*sizeof(*distmat[x]))) == NULL)
{ fprintf(stderr,"Out of memory\n"); exit(1); }
}
/* int ***score; 2 * MAXN * (2*MAXOFFSET+1) */
if((score = (int ***) malloc(2*sizeof(*score))) == NULL)
{ fprintf(stderr,"Out of memory\n"); exit(1); }
for(x=0; x<2; x++)
{
if((score[x] = (int **) malloc(MAXN*sizeof(*score[x]))) == NULL)
{ fprintf(stderr,"Out of memory\n"); exit(1); }
for(n=0; n<MAXN; n++)
{
if((score[x][n] = (int *) malloc((2*MAXOFFSET+1)*sizeof(*score[x][n]))) == NULL)
{ fprintf(stderr,"Out of memory\n"); exit(1); }
}
}
/* int **score_of_besty; MAXN * (2*MAXOFFSET+1) */
if((score_of_besty = (int **) malloc(MAXN*sizeof(*score_of_besty))) == NULL)
{ fprintf(stderr,"Out of memory\n"); exit(1); }
for(n=0; n<MAXN; n++)
{
if((score_of_besty[n] = (int *) malloc((2*MAXOFFSET+1)*sizeof(*score_of_besty[n]))) == NULL)
{ fprintf(stderr,"Out of memory\n"); exit(1); }
}
/* int **maskscore; 2 * (2*MAXOFFSET+1) */
if((maskscore = (int **) malloc(2*sizeof(*maskscore))) == NULL)
{ fprintf(stderr,"Out of memory\n"); exit(1); }
for(x=0; x<2; x++)
{
if((maskscore[x] = (int *) malloc((2*MAXOFFSET+1)*sizeof(*maskscore[x]))) == NULL)
{ fprintf(stderr,"Out of memory\n"); exit(1); }
}
}
void print_parameters()
{
printf("Parameters:\n");
printf("SEQUENCE_FILE %s\n",SEQUENCE_FILE);
printf("LMER_TABLE_FILE %s\n",LMER_TABLE_FILE);
printf("MAXLENGTH %d\n",MAXLENGTH);
printf("PADLENGTH %d\n",PADLENGTH);
printf("l %d\n",l);
printf("SEEDMISMATCHES %d\n",SEEDMISMATCHES);
printf("HASH_SIZE %d\n",HASH_SIZE);
printf("L %d\n",L);
printf("MAXOFFSET %d\n",MAXOFFSET);
printf("MAXN %d\n",MAXN);
printf("MAXR %d\n",MAXR);
printf("MATCH %d MISMATCH %d GAP %d\n",MATCH,MISMATCH,GAP);
printf("MINTHRESH %d\n",MINTHRESH);
printf("CAPPENALTY %d MINIMPROVEMENT %d\n",CAPPENALTY,MINIMPROVEMENT);
printf("WHEN_TO_STOP %d\n",WHEN_TO_STOP);
printf("REMOVE_DEGENERATES %d\n",REMOVE_DEGENERATES);
printf("TANDEMDIST %d\n",TANDEMDIST);
printf("EXTRAMASK %d\n",EXTRAMASK);
printf("MAXENTROPY %f\n",MAXENTROPY);
}
int build_sequence(char *sequence, char *filename)
{
int i, j, seq;
char c;
FILE *fp;
int boundariesSize = 100;
// RMH: Initialize the boundaries array
boundaries = (int *)malloc( boundariesSize * sizeof(int) );
if( NULL == boundaries ) {
fprintf(stderr, "Could not allocated space for the boundaries array\n");
exit(1);
}
if( (fp = fopen(filename, "r")) == NULL)
{
fprintf(stderr,"Could not open input file %s\n", filename); exit(1);
}
for(i=0; i<PADLENGTH; i++) sequence[i] = 99;
i = 0;
seq = 0;
while( !feof(fp) && (i<MAXLENGTH) )
{ /* process one line of file */
c = getc(fp);
if(c == EOF) continue;
if(c == '\n') continue;
if(c == '>')
{
for(j=0; (getc(fp) != '\n') && !feof(fp); j++)
;
// RMH: Store boundary info
if ( seq > 0 )
{
if ( seq > boundariesSize )
{
boundariesSize += 100;
boundaries = realloc( boundaries, boundariesSize * sizeof(int) );
if( NULL == boundaries ) {
fprintf(stderr, "Could not allocated more space for the "
"boundaries array\n");
exit(1);
}
}
//printf("Adding sequence boundary[%d] = %d, %d\n",
// ( seq-1 ), i, i+PADLENGTH );
boundaries[seq-1] = i;
}
seq++;
}
else
{
if(c > 64)
{
sequence[i+PADLENGTH] = char_to_num(c);
i++;
}
for(j=0; ((c = getc(fp)) != '\n') && !feof(fp) && (i<MAXLENGTH); j++)
{
if(c > 64)
{
sequence[i+PADLENGTH] = char_to_num(c);
i++;
}
}
}
}
if ( seq == 0 )
seq = 1;
if ( seq+1 >= boundariesSize )
{
boundariesSize += 100;
boundaries = realloc( boundaries, boundariesSize * sizeof(int) );
if( NULL == boundaries ) {
fprintf(stderr, "Could not allocated more space for the "
"boundaries array\n");
exit(1);
}
}
boundaries[seq-1] = i + 1;
//printf("Adding sequence boundary[%d] = %d, %d\n", seq-1, (i + 1), (i+1)+PADLENGTH );
boundaries[seq] = 0;
fclose(fp);
return (i+PADLENGTH); /* length of genome */
}
void add_rc(char *sequence)
{
int x;
for(x=0; x<PADLENGTH; x++)
sequence[length+x] = 99;
for(x=0; x<length; x++)
{
if(sequence[length-1-x] == 99)
sequence[length+PADLENGTH+x] = 99;
else
sequence[length+PADLENGTH+x] = 3 - sequence[length-1-x];
}
length = 2*length + PADLENGTH;
}
void build_pos(struct llist *besttmp)
{
struct posllist *postmp;
int x = 0;
postmp = besttmp->pos;
N = 0;
while(postmp != NULL)
{
if(removed[postmp->this] == 0)
{
pos[N] = postmp->this;
// RMH: Fwd/Rev Mods
// NOTE: This could be more efficiently calculated in build_all_pos
if ( lmermatch(sequence+besttmp->lastocc,sequence+postmp->this) )
rev[N] = 0;
else
rev[N] = 1;
// RMH: Find boundaries for lmer
upperBoundI[N] = -1;
x = 0;
while ( boundaries[x] != 0 )
{
if ( boundaries[x] + PADLENGTH > pos[N] )
{
upperBoundI[N] = x;
break;
}
x++;
}
N++;
if(N == MAXN) break;
}
postmp = postmp->next;
}
return;
}
void extend_right()
{
int y, n, bestscore, tempscore, offset; /* bestscore is alignment score for single n */
char a, besta;
int newtotalbestscore, newtotalbestscore_a; /* for best a and that a, resp. */
besta = 0;
/* initialize score[(L+l-1)%2][][] */
//
// Initialize running score by initializing the score for
// the last base in lmer. This is simply the seed score with
// -MAXOFFSET to +MAXOFFSET gaps.
//
y = L+l-1;
for(n=0; n<N; n++)
{
for(offset=-MAXOFFSET; offset<=MAXOFFSET; offset++)
{
score[y%2][n][offset+MAXOFFSET] = l * MATCH;
if(offset < 0) score[y%2][n][offset+MAXOFFSET] += -offset * GAP;
if(offset > 0) score[y%2][n][offset+MAXOFFSET] += offset * GAP;
}
bestbestscore[n] = l * MATCH;
}
/* extend right */
besty = L+l-1;
for(n=0; n<N; n++)
{
for(offset=-MAXOFFSET; offset<=MAXOFFSET; offset++)
score_of_besty[n][offset+MAXOFFSET] = score[y%2][n][offset+MAXOFFSET];
}
besttotalbestscore = 0;
compute_totalbestscore_right(y); /* should be N*l*MATCH */
if(VERBOSE >= 4) print_totalbestscore_right(y);
for(y=L+l; y<2*L+l; y++) /* determine master[y] and score[y%2][][] */
{
newtotalbestscore = 0;
for(a=0; a<4; a++)
{
newtotalbestscore_a = 0;
for(n=0; n<N; n++)
{
bestscore = bestbestscore[n] + CAPPENALTY;
if(bestscore < 0) bestscore = 0;
for(offset=-MAXOFFSET; offset<=MAXOFFSET; offset++)
{
tempscore = compute_score_right(y,n,offset,a);
if(tempscore > bestscore)
bestscore = tempscore;
}
newtotalbestscore_a += bestscore;
}
if(newtotalbestscore_a > newtotalbestscore)
{
newtotalbestscore = newtotalbestscore_a;
besta = a;
}
}
master[y] = besta;
for(n=0; n<N; n++)
{
for(offset=-MAXOFFSET; offset<=MAXOFFSET; offset++)
score[y%2][n][offset+MAXOFFSET] = compute_score_right(y,n,offset,besta);
}
compute_totalbestscore_right(y);
if(VERBOSE >= 4) print_totalbestscore_right(y);
if(y - besty >= WHEN_TO_STOP) break;
}
if(y == 2*L+l)
{
if(VERBOSE) printf("OOPS, extended right all the way to %d\n",y);
if(VERBOSE) fprintf(stderr,"OOPS, extended right all the way to %d\n",y);
/* exit(1); */
}
y = besty;
totalbestscore = besttotalbestscore;
nrepeatocc = bestnrepeatocc;
nactiverepeatocc = bestnactiverepeatocc;
if(VERBOSE >= 2) printf("AFTER EXTENDING RIGHT, FAMILY %d IS:\n",R);
if(VERBOSE >= 2) print_totalbestscore_right(y);
}
void extend_left()
{
int w, n, bestscore, tempscore, offset;
char a, besta;
int newtotalbestscore, newtotalbestscore_a;
besta = 0;
/* initialize score[L%2][][] */
w = L;
for(n=0; n<N; n++)
{
bestscore = savebestscore[n] + CAPPENALTY;
for(offset=-MAXOFFSET; offset<=MAXOFFSET; offset++)
{
if(score_of_besty[n][offset+MAXOFFSET] > bestscore)
bestscore = score_of_besty[n][offset+MAXOFFSET];
}
for(offset=-MAXOFFSET; offset<=MAXOFFSET; offset++)
{
score[w%2][n][offset+MAXOFFSET] = bestscore;
if(offset < 0) score[w%2][n][offset+MAXOFFSET] += -offset * GAP;
if(offset > 0) score[w%2][n][offset+MAXOFFSET] += offset * GAP;
}
bestbestscore[n] = bestscore;
}
/* extend left */
bestw = L;
compute_totalbestscore_left(w);
// RMH:
if(VERBOSE >= 4) print_totalbestscore_left(w);
for(w=L-1; w>=0; w--) /* determine master[w] and score[w%2][][] */
{
newtotalbestscore = 0;
for(a=0; a<4; a++)
{
newtotalbestscore_a = 0;
for(n=0; n<N; n++)
{
bestscore = bestbestscore[n] + CAPPENALTY;
if(bestscore < 0) bestscore = 0;
for(offset=-MAXOFFSET; offset<=MAXOFFSET; offset++)
{
tempscore = compute_score_left(w,n,offset,a);
if(tempscore > bestscore)
bestscore = tempscore;
}
newtotalbestscore_a += bestscore;
}
if(newtotalbestscore_a > newtotalbestscore)
{
newtotalbestscore = newtotalbestscore_a;
besta = a;
}
}
master[w] = besta;
for(n=0; n<N; n++)
{
for(offset=-MAXOFFSET; offset<=MAXOFFSET; offset++)
score[w%2][n][offset+MAXOFFSET] = compute_score_left(w,n,offset,besta);
}
compute_totalbestscore_left(w);
if(VERBOSE >= 4) print_totalbestscore_left(w);