segment.cpp 24.7 KB
Newer Older
Mikaël Salson's avatar
Mikaël Salson committed
1
/*
2 3 4 5 6 7 8
  This file is part of Vidjil <http://www.vidjil.org>
  Copyright (C) 2011, 2012, 2013, 2014, 2015 by Bonsai bioinformatics 
  at CRIStAL (UMR CNRS 9189, Université Lille) and Inria Lille
  Contributors: 
      Mathieu Giraud <mathieu.giraud@vidjil.org>
      Mikaël Salson <mikael.salson@vidjil.org>
      Marc Duez <marc.duez@vidjil.org>
Mikaël Salson's avatar
Mikaël Salson committed
9 10 11 12 13 14 15 16 17 18 19 20 21 22

  "Vidjil" is free software: you can redistribute it and/or modify
  it under the terms of the GNU General Public License as published by
  the Free Software Foundation, either version 3 of the License, or
  (at your option) any later version.

  "Vidjil" is distributed in the hope that it will be useful,
  but WITHOUT ANY WARRANTY; without even the implied warranty of
  MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
  GNU General Public License for more details.

  You should have received a copy of the GNU General Public License
  along with "Vidjil". If not, see <http://www.gnu.org/licenses/>
*/
Mikaël Salson's avatar
Mikaël Salson committed
23
#include <algorithm>    // std::sort
Mikaël Salson's avatar
Mikaël Salson committed
24 25 26 27
#include <cassert>
#include "segment.h"
#include "tools.h"
#include "affectanalyser.h"
Mikaël Salson's avatar
Mikaël Salson committed
28
#include <sstream>
Marc Duez's avatar
Marc Duez committed
29 30
#include <string>
#include <math.h>
Mikaël Salson's avatar
Mikaël Salson committed
31

Mathieu Giraud's avatar
Mathieu Giraud committed
32
Segmenter::~Segmenter() {}
Mikaël Salson's avatar
Mikaël Salson committed
33

Mathieu Giraud's avatar
Mathieu Giraud committed
34
Sequence Segmenter::getSequence() const {
Mikaël Salson's avatar
Mikaël Salson committed
35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54
  Sequence s ;
  s.label_full = info ;
  s.label = label + " " + (reversed ? "-" : "+");
  s.sequence = revcomp(sequence, reversed);

  return s ;
}

string Segmenter::getJunction(int l) const {
  assert(isSegmented());

  int start = (getLeft() + getRight())/2 - l/2;
  
  if (start < 0 or start + l > (int)sequence.size())  // TODO: +l ou +l-1 ?
    return "" ;

  return getSequence().sequence.substr(start, l);
}

int Segmenter::getLeft() const {
Mathieu Giraud's avatar
Mathieu Giraud committed
55
  return Vend;
Mikaël Salson's avatar
Mikaël Salson committed
56 57 58
}
  
int Segmenter::getRight() const {
Mathieu Giraud's avatar
Mathieu Giraud committed
59
  return Jstart;
Mikaël Salson's avatar
Mikaël Salson committed
60 61 62
}

int Segmenter::getLeftD() const {
Mathieu Giraud's avatar
Mathieu Giraud committed
63
  return Dstart;
Mikaël Salson's avatar
Mikaël Salson committed
64 65 66
}
  
int Segmenter::getRightD() const {
Mathieu Giraud's avatar
Mathieu Giraud committed
67
  return Dend;
Mikaël Salson's avatar
Mikaël Salson committed
68 69 70 71 72 73 74 75 76 77 78 79 80 81
}

bool Segmenter::isReverse() const {
  return reversed;
}

bool Segmenter::isSegmented() const {
  return segmented;
}

bool Segmenter::isDSegmented() const {
  return dSegmented;
}

82 83 84 85
bool KmerSegmenter::isDetected() const {
  return detected;
}

Mikaël Salson's avatar
Mikaël Salson committed
86 87 88 89 90 91 92 93
// Chevauchement

string Segmenter::removeChevauchement()
{
  assert(isSegmented());
  
  string chevauchement = "" ;

Mathieu Giraud's avatar
Mathieu Giraud committed
94
  if (Vend >= Jstart)
Mikaël Salson's avatar
Mikaël Salson committed
95
    {
Mathieu Giraud's avatar
Mathieu Giraud committed
96
      int middle = (Vend + Jstart) / 2 ;
97
      chevauchement = " !ov " + string_of_int (Vend - Jstart + 1);
Mathieu Giraud's avatar
Mathieu Giraud committed
98 99
      Vend = middle ;
      Jstart = middle+1 ;
Mikaël Salson's avatar
Mikaël Salson committed
100 101 102 103 104 105 106 107 108 109 110 111 112 113
    }

  return chevauchement ;
}

// Prettyprint


bool Segmenter::finishSegmentation() 
{
  assert(isSegmented());
  
  string seq = getSequence().sequence;
    
Mathieu Giraud's avatar
Mathieu Giraud committed
114 115 116 117 118
  seg_V = seq.substr(0, Vend+1) ;
  seg_N = seq.substr(Vend+1, Jstart-Vend-1) ;  // Twice computed for FineSegmenter, but only once in KmerSegmenter !
  seg_J = seq.substr(Jstart) ;
  Dstart=0;
  Dend=0;
Mikaël Salson's avatar
Mikaël Salson committed
119 120 121 122 123 124 125 126 127 128 129 130 131

  info = "VJ \t" + string_of_int(FIRST_POS) + " " + info + " " + string_of_int(seq.size() - 1 + FIRST_POS) ;
  info += "\t" + code ;

  info = (reversed ? "- " : "+ ") + info ;

  return true ;
}

bool Segmenter::finishSegmentationD() 
{
  string seq = getSequence().sequence;

Mathieu Giraud's avatar
Mathieu Giraud committed
132 133
  seg_V = seq.substr(0, Vend+1) ; // From pos. 0 to Vend
  seg_J = seq.substr(Jstart) ;
Mikaël Salson's avatar
Mikaël Salson committed
134
  
Mathieu Giraud's avatar
Mathieu Giraud committed
135
  seg_D  = seq.substr(Dstart, Dend-Dstart+1) ; // From Dstart to Dend
Mikaël Salson's avatar
Mikaël Salson committed
136
  
Mathieu Giraud's avatar
Mathieu Giraud committed
137 138 139 140
  info = "VDJ \t0 " + string_of_int(Vend) +
		" " + string_of_int(Dstart) + 
		" " + string_of_int(Dend) +
		" " + string_of_int(Jstart) +
Mikaël Salson's avatar
Mikaël Salson committed
141 142 143 144 145 146 147 148 149
		" " + string_of_int(seq.size()-1+FIRST_POS) ;
		
  info += "\t" + code ;
  
  info = (reversed ? "- " : "+ ") + info ;

  return true ;
}

150 151 152 153 154 155 156 157 158 159 160 161
string Segmenter::getInfoLine() const
{
  string s = ">" ;

  s += label + " " ;
  s += (segmented ? "" : "! ") + info ;
  s += " " + info_extra ;
  s += " " + segmented_germline->code ;
  s += " " + string(segmented_mesg[because]) ;
  return s ;
}

Mikaël Salson's avatar
Mikaël Salson committed
162 163
ostream &operator<<(ostream &out, const Segmenter &s)
{
164
  out << s.getInfoLine() << endl;
Mikaël Salson's avatar
Mikaël Salson committed
165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182

  if (s.segmented)
    {
      out << s.seg_V << endl ;
      out << s.seg_N << endl ;
      out << s.seg_J << endl ;
    }
  else
    {
      out << s.sequence << endl ;
    }

  return out ;
}


// KmerSegmenter (Cheap)

183 184 185
KmerSegmenter::KmerSegmenter() { kaa = 0 ; }

KmerSegmenter::KmerSegmenter(Sequence seq, Germline *germline)
Mikaël Salson's avatar
Mikaël Salson committed
186 187 188 189
{
  label = seq.label ;
  sequence = seq.sequence ;
  info = "" ;
190
  info_extra = "seed";
Mikaël Salson's avatar
Mikaël Salson committed
191
  segmented = false;
192
  segmented_germline = germline ;
193
  reversed = false;
Mathieu Giraud's avatar
Mathieu Giraud committed
194
  Dend=0;
195 196 197
  because = 0 ; // Cause of unsegmentation
  score = 0 ;

198
  int s = (size_t)germline->index->getS() ;
Mikaël Salson's avatar
Mikaël Salson committed
199
  int length = sequence.length() ;
Mikaël Salson's avatar
Mikaël Salson committed
200

201
  if (length < s) 
Mikaël Salson's avatar
Mikaël Salson committed
202
    {
Mathieu Giraud's avatar
Mathieu Giraud committed
203 204
      because = UNSEG_TOO_SHORT;
      kaa = NULL;
205
      return ;
Mikaël Salson's avatar
Mikaël Salson committed
206 207
    }
 
208
  kaa = new KmerAffectAnalyser(*(germline->index), sequence);
Mikaël Salson's avatar
Mikaël Salson committed
209 210
  
  // Check strand consistency among the affectations.
Mikaël Salson's avatar
Mikaël Salson committed
211 212 213 214 215 216 217 218 219
  int strand;
  int nb_strand[2] = {0,0};     // In cell 0 we'll put the number of negative
                                // strand, while in cell 1 we'll put the
                                // positives
  for (int i = 0; i < kaa->count(); i++) { 
    KmerAffect it = kaa->getAffectation(i);
    if (! it.isAmbiguous() && ! it.isUnknown()) {
      strand = affect_strand(it.affect);
      nb_strand[(strand + 1) / 2] ++; // (strand+1) / 2 → 0 if strand == -1; 1 if strand == 1
Mikaël Salson's avatar
Mikaël Salson committed
220 221 222
    }
  }

223 224 225
  KmerAffect before, after;

  // Test on which strand we are, select the before and after KmerAffects
Mikaël Salson's avatar
Mikaël Salson committed
226
  if (nb_strand[0] == 0 && nb_strand[1] == 0) {
227
    because = UNSEG_TOO_FEW_ZERO ;
228
    return ;
Mikaël Salson's avatar
Mikaël Salson committed
229 230
  } else if (nb_strand[0] > RATIO_STRAND * nb_strand[1]) {
    strand = -1;
231 232
    before = KmerAffect(germline->affect_3, -1); 
    after = KmerAffect(germline->affect_5, -1);
Mikaël Salson's avatar
Mikaël Salson committed
233 234
  } else if (nb_strand[1] > RATIO_STRAND * nb_strand[0]) {
    strand = 1;
235 236
    before = KmerAffect(germline->affect_5, 1); 
    after = KmerAffect(germline->affect_3, 1);    
Mikaël Salson's avatar
Mikaël Salson committed
237 238 239
  } else {
    // Ambiguous information: we have positive and negative strands
    // and there is not enough difference to put them aparat.
240 241
    because = UNSEG_STRAND_NOT_CONSISTENT ;
    return ;
Mikaël Salson's avatar
Mikaël Salson committed
242 243
  }

244
  detected = false ;
245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260
  computeSegmentation(strand, before, after);

  if (! because)
    {
      // Now we check the delta between Vend and right
   
      if (Jstart - Vend < germline->delta_min)
	{
	  because = UNSEG_BAD_DELTA_MIN ;
	}

      if (Jstart - Vend > germline->delta_max)
	{
	  because = UNSEG_BAD_DELTA_MAX ;
	}
    } 
Mathieu Giraud's avatar
Mathieu Giraud committed
261

262
  if (!because)
Mathieu Giraud's avatar
Mathieu Giraud committed
263 264
    {
      // Yes, it is segmented
265
      segmented = true;
Mathieu Giraud's avatar
Mathieu Giraud committed
266 267 268 269
      reversed = (strand == -1); 
      because = reversed ? SEG_MINUS : SEG_PLUS ;

      info = string_of_int(Vend + FIRST_POS) + " " + string_of_int(Jstart + FIRST_POS)  ;
270 271
      // removeChevauchement is called once info was already computed: it is only to output info_extra
      info_extra += removeChevauchement();
Mathieu Giraud's avatar
Mathieu Giraud committed
272
      finishSegmentation();
273
      system = germline->code;
274
      return ;
Mathieu Giraud's avatar
Mathieu Giraud committed
275
    } 
276

277
 
Mathieu Giraud's avatar
Mathieu Giraud committed
278
}
Mikaël Salson's avatar
Mikaël Salson committed
279

Mathieu Giraud's avatar
Mathieu Giraud committed
280
KmerSegmenter::~KmerSegmenter() {
281 282
  if (kaa)
    delete kaa;
283 284
}

285
KmerMultiSegmenter::KmerMultiSegmenter(Sequence seq, MultiGermline *multigermline, ostream *out_unsegmented, double threshold)
286
{
287
  int best_score_seg = 0 ; // Best score, segmented sequences
288
  int best_score_unseg = 0 ; // Best score, unsegmented sequences
289
  the_kseg = NULL;
290
  multi_germline = multigermline;
291
  threshold_nb_expected = threshold;
292
  
293 294 295 296 297
  // Iterate over the germlines
  for (list<Germline*>::const_iterator it = multigermline->germlines.begin(); it != multigermline->germlines.end(); ++it)
    {
      Germline *germline = *it ;

298 299
      KmerSegmenter *kseg = new KmerSegmenter(seq, germline);
      bool keep_seg = false;
300

301 302 303 304
      if (out_unsegmented)
        {
          // Debug, display k-mer affectation and segmentation result for this germline
          *out_unsegmented << "#"
305 306
                           << left << setw(4) << kseg->segmented_germline->code << " "
                           << left << setw(20) << segmented_mesg[kseg->getSegmentationStatus()] << " ";
307

308
          *out_unsegmented << right << setw(3) << kseg->score << " ";
309
          
310 311
          if (kseg->getSegmentationStatus() != UNSEG_TOO_SHORT) 
            *out_unsegmented << kseg->getKmerAffectAnalyser()->toString();
312 313 314 315

          *out_unsegmented << endl ;
        }

316 317
      // Always remember the first kseg
      if (the_kseg == NULL)
318
        keep_seg = true;
319
      
320
      if (kseg->isSegmented())
321 322
        {
          // Yes, it is segmented
323
          // Should we keep the kseg ?
324
          if (kseg->score > best_score_seg)
325
            {
326
              keep_seg = true;
327
              best_score_seg = kseg->score ;
328
            }
329
        }
330 331 332 333 334 335 336 337 338 339 340 341
      else
        {
          // It is not segmented
          // Should we keep the kseg (with the unsegmentation cause) ?
            if (kseg->score > best_score_unseg)
            {              
              best_score_unseg = kseg->score ;
              if (!best_score_seg)
                keep_seg = true;
            }
        }
      
342
      if (keep_seg) {
343 344
        if (the_kseg)
          delete the_kseg;
345 346 347 348
        the_kseg = kseg;
      } else {
        delete kseg;
      }
349 350 351 352 353 354 355 356 357 358 359 360 361
    } // end for (Germlines)
  if (the_kseg->isSegmented() && getNbExpected() > threshold_nb_expected)
    the_kseg->setSegmentationStatus(UNSEG_NOISY);
}

double KmerMultiSegmenter::getNbExpected() const {
  int max = the_kseg->score;
  double proba = 0;
  int n = the_kseg->getSequence().sequence.size() - the_kseg->getKmerAffectAnalyser()->getIndex().getS();
  for (int i = max; i<  n; i++) {
    proba += nChoosek(n, i) * pow(the_kseg->getKmerAffectAnalyser()->getIndex().getIndexLoad(), i);
  }
  return multi_germline->germlines.size() * proba;
362 363 364
}

KmerMultiSegmenter::~KmerMultiSegmenter() {
365 366
  if (the_kseg)
    delete the_kseg;
Mathieu Giraud's avatar
Mathieu Giraud committed
367 368
}

369 370
void KmerSegmenter::computeSegmentation(int strand, KmerAffect before, KmerAffect after) {
  // Try to segment, computing 'Vend' and 'Jstart'
371 372
  // If not segmented, put the cause of unsegmentation in 'because'

373
  affect_infos max;
Mikaël Salson's avatar
Mikaël Salson committed
374

375
  max = kaa->getMaximum(before, after); 
376 377 378 379 380

      // We labeled it detected if there were both enough affect_5 and enough affect_3
      detected = (max.nb_before_left + max.nb_before_right >= DETECT_THRESHOLD)
        && (max.nb_after_left + max.nb_after_right >= DETECT_THRESHOLD);
      
381
      if (! max.max_found) {
382 383
        if ((strand == 1 && max.nb_before_left == 0)
            || (strand == -1 && max.nb_after_right == 0)) 
384
          because = detected ? UNSEG_AMBIGUOUS : UNSEG_TOO_FEW_V ;
385 386
        else if ((strand == 1 && max.nb_after_right == 0)
                 || (strand == -1 && max.nb_before_left == 0))
Mikaël Salson's avatar
Mikaël Salson committed
387
	{
388
	  because = detected ? UNSEG_AMBIGUOUS : UNSEG_TOO_FEW_J ;
389
	} else 
390 391 392 393 394 395 396 397 398 399
          because = UNSEG_AMBIGUOUS; 
      } else {
        Vend = max.first_pos_max;
        Jstart = max.last_pos_max + 1;
        if (strand == -1) {
          int tmp = sequence.size() - Vend - 1;
          Vend = sequence.size() - Jstart - 1;
          Jstart = tmp;
        }
      }
Mikaël Salson's avatar
Mikaël Salson committed
400
  
401
    score = max.nb_before_left + max.nb_before_right + max.nb_after_left + max.nb_after_right;  
Mathieu Giraud's avatar
Mathieu Giraud committed
402
}
Mikaël Salson's avatar
Mikaël Salson committed
403

404
KmerAffectAnalyser *KmerSegmenter::getKmerAffectAnalyser() const {
Mathieu Giraud's avatar
Mathieu Giraud committed
405 406
  return kaa;
}
Mikaël Salson's avatar
Mikaël Salson committed
407

408
int Segmenter::getSegmentationStatus() const {
Mathieu Giraud's avatar
Mathieu Giraud committed
409
  return because;
Mikaël Salson's avatar
Mikaël Salson committed
410 411
}

412 413 414 415 416
void Segmenter::setSegmentationStatus(int status) {
  because = status;
  segmented = (status == SEG_PLUS || status == SEG_MINUS);
}

Mikaël Salson's avatar
Mikaël Salson committed
417 418 419 420 421 422 423 424 425 426 427 428 429 430 431 432 433 434 435 436 437 438 439 440 441
// FineSegmenter

void best_align(int overlap, string seq_left, string seq_right,
		string ref_left ,string ref_right, int *b_r, int *b_l, Cost segment_cost)
{
      int score_r[overlap+1];
      int score_l[overlap+1];
      
      //LEFT
      ref_left=string(ref_left.rbegin(), ref_left.rend());
      seq_left=string(seq_left.rbegin(), seq_left.rend()); 
      
      DynProg dp1 = DynProg(seq_left, ref_left,
			   DynProg::Local, segment_cost);
      score_l[0] = dp1.compute();
      dp1.backtrack();
      
      //RIGHT
      DynProg dp = DynProg(seq_right, ref_right,
			   DynProg::Local, segment_cost);
      score_r[0] = dp.compute();
      dp.backtrack();    
      
      for(int i=1; i<=overlap; i++){
	if(dp.best_i-i >0)
442
	score_r[i] = dp.B[dp.best_i-i][dp.best_j].score;
Mikaël Salson's avatar
Mikaël Salson committed
443 444 445
	else
	score_r[i] =0;
	if(dp1.best_i-i >0)
446
	score_l[i] = dp1.B[dp1.best_i-i][dp1.best_j].score;	
Mikaël Salson's avatar
Mikaël Salson committed
447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467 468 469 470 471
	else
	score_l[i] =0;
      }
      int score=-1000000;
      int best_r=0;
      int best_l=0;

      for (int i=0; i<=overlap; i++){
	for (int j=overlap-i; j<=overlap; j++){
	  if ( ((score_r[i]+score_l[j]) == score) && (i+j < best_r+best_l )){
	    best_r=i;
	    best_l=j;
	    score=(score_r[i]+score_l[j]) ;
	  }
	  if ( (score_r[i]+score_l[j]) > score){
	    best_r=i;
	    best_l=j;
	    score=(score_r[i]+score_l[j]) ;
	  }
	}
      }
      *b_r=best_r;
      *b_l=best_l;
}

Mikaël Salson's avatar
Mikaël Salson committed
472 473 474 475 476
bool comp_pair (pair<int,int> i,pair<int,int> j)
{
  return ( i.first > j.first);
}

Mathieu Giraud's avatar
Mathieu Giraud committed
477
int align_against_collection(string &read, Fasta &rep, bool reverse_both, bool local, int *tag, 
Mikaël Salson's avatar
Mikaël Salson committed
478
			     int *del, int *del2, int *begin, int *length, vector<pair<int, int> > *score
Mikaël Salson's avatar
Mikaël Salson committed
479 480 481 482 483 484 485 486 487 488
			    , Cost segment_cost)
{
  
  int best_score = MINUS_INF ;
  int best_r = MINUS_INF ;
  int best_best_i = (int) string::npos ;
  int best_best_j = (int) string::npos ;
  int best_first_i = (int) string::npos ;
  int best_first_j = (int) string::npos ;
  string best_label = "" ;
Mikaël Salson's avatar
Mikaël Salson committed
489
  vector<pair<int, int> > score_r;
Mikaël Salson's avatar
Mikaël Salson committed
490 491 492 493 494 495 496 497 498 499 500

  DynProg::DynProgMode dpMode = DynProg::LocalEndWithSomeDeletions;
  if (local==true) dpMode = DynProg::Local;
  
  for (int r = 0 ; r < rep.size() ; r++)
    {
      DynProg dp = DynProg(read, rep.sequence(r),
			   dpMode, // DynProg::SemiGlobalTrans, 
			   segment_cost, // DNA
			   reverse_both, reverse_both);
      int score = dp.compute();
Mikaël Salson's avatar
Mikaël Salson committed
501
      
Mikaël Salson's avatar
Mikaël Salson committed
502 503 504 505 506 507 508 509 510 511 512 513 514 515
      if (local==true){ 
	dp.backtrack();
      }
      
      if (score > best_score)
	{
	  best_score = score ;
	  best_best_i = dp.best_i ;
	  best_best_j = dp.best_j ;
	  best_first_i = dp.first_i ;
	  best_first_j = dp.first_j ;
	  best_r = r ;
	  best_label = rep.label(r) ;
	}
Mikaël Salson's avatar
Mikaël Salson committed
516 517
	
	score_r.push_back(make_pair(score, r));
Mathieu Giraud's avatar
Mathieu Giraud committed
518 519 520 521 522 523

	// #define DEBUG_SEGMENT      

#ifdef DEBUG_SEGMENT	
	cout << rep.label(r) << " " << score << " " << dp.best_i << endl ;
#endif
Mikaël Salson's avatar
Mikaël Salson committed
524 525

    }
Mikaël Salson's avatar
Mikaël Salson committed
526
    sort(score_r.begin(),score_r.end(),comp_pair);
Mikaël Salson's avatar
Mikaël Salson committed
527 528 529 530

  *del = reverse_both ? best_best_j : rep.sequence(best_r).size() - best_best_j - 1;
  *del2 = best_first_j;
  *begin = best_first_i;
Mathieu Giraud's avatar
Mathieu Giraud committed
531
  *tag = best_r ; 
Mikaël Salson's avatar
Mikaël Salson committed
532 533
  
  *length -= *del ;
Mikaël Salson's avatar
Mikaël Salson committed
534 535
  
  *score=score_r;
Mathieu Giraud's avatar
Mathieu Giraud committed
536 537 538 539 540 541

#ifdef DEBUG_SEGMENT	
  cout << "best: " << best_labels << " " << best_score ;
  cout << "del/del2/begin:" << (*del) << "/" << (*del2) << "/" << (*begin) << endl;
  cout << endl;
#endif
Mikaël Salson's avatar
Mikaël Salson committed
542 543 544 545 546 547 548 549 550
  
  return best_best_i ;
}

string format_del(int deletions)
{
  return deletions ? *"(" + string_of_int(deletions) + " del)" : "" ;
}

551
FineSegmenter::FineSegmenter(Sequence seq, Germline *germline, Cost segment_c)
Mikaël Salson's avatar
Mikaël Salson committed
552
{
553 554
  segmented = false;
  dSegmented = false;
555
  because = 0 ;
556
  segmented_germline = germline ;
557
  info_extra = "" ;
Mikaël Salson's avatar
Mikaël Salson committed
558 559
  label = seq.label ;
  sequence = seq.sequence ;
Mathieu Giraud's avatar
Mathieu Giraud committed
560
  Dend=0;
Mikaël Salson's avatar
Mikaël Salson committed
561 562
  segment_cost=segment_c;

563 564 565
  CDR3start = -1;
  CDR3end = -1;
  
Mikaël Salson's avatar
Mikaël Salson committed
566 567 568 569 570
  // TODO: factoriser tout cela, peut-etre en lancant deux segmenteurs, un +, un -, puis un qui chapote
  
  // Strand +
  
  int plus_score = 0 ;
Mathieu Giraud's avatar
Mathieu Giraud committed
571
  int tag_plus_V, tag_plus_J;
Mikaël Salson's avatar
Mikaël Salson committed
572 573 574 575
  int plus_length = 0 ;
  int del_plus_V, del_plus_J ;
  int del2=0;
  int beg=0;
Mikaël Salson's avatar
Mikaël Salson committed
576 577 578 579
  
  vector<pair<int, int> > score_plus_V;
  vector<pair<int, int> > score_plus_J;
  
580
  int plus_left = align_against_collection(sequence, germline->rep_5, false, false, &tag_plus_V, &del_plus_V, &del2, &beg, 
Mikaël Salson's avatar
Mikaël Salson committed
581 582
					   &plus_length, &score_plus_V
					   , segment_cost);
583
  int plus_right = align_against_collection(sequence, germline->rep_3, true, false, &tag_plus_J, &del_plus_J, &del2, &beg,
Mikaël Salson's avatar
Mikaël Salson committed
584 585
					    &plus_length, &score_plus_J
					    , segment_cost);
Mikaël Salson's avatar
Mikaël Salson committed
586 587
  plus_length += plus_right - plus_left ;

Mikaël Salson's avatar
Mikaël Salson committed
588 589
  plus_score=score_plus_V[0].first + score_plus_J[0].first ;
  
Mikaël Salson's avatar
Mikaël Salson committed
590 591 592
  // Strand -
  string rc = revcomp(sequence) ;
  int minus_score = 0 ;
Mathieu Giraud's avatar
Mathieu Giraud committed
593
  int tag_minus_V, tag_minus_J;
Mikaël Salson's avatar
Mikaël Salson committed
594 595
  int minus_length = 0 ;
  int del_minus_V, del_minus_J ;
Mikaël Salson's avatar
Mikaël Salson committed
596 597 598 599
  
  vector<pair<int, int> > score_minus_V;
  vector<pair<int, int> > score_minus_J;
  
600
  int minus_left = align_against_collection(rc, germline->rep_5, false, false, &tag_minus_V, &del_minus_V, &del2, &beg,
Mikaël Salson's avatar
Mikaël Salson committed
601 602
					    &minus_length, &score_minus_V
					    ,  segment_cost);
603
  int minus_right = align_against_collection(rc, germline->rep_3, true, false, &tag_minus_J, &del_minus_J, &del2, &beg,
Mikaël Salson's avatar
Mikaël Salson committed
604 605
					     &minus_length, &score_minus_J
					     , segment_cost);
Mikaël Salson's avatar
Mikaël Salson committed
606 607
  minus_length += minus_right - minus_left ;

Mikaël Salson's avatar
Mikaël Salson committed
608 609
  minus_score=score_minus_V[0].first + score_minus_J[0].first ;
  
Mikaël Salson's avatar
Mikaël Salson committed
610 611 612 613
  reversed = (minus_score > plus_score) ;

  if (!reversed)
    {
Mathieu Giraud's avatar
Mathieu Giraud committed
614 615 616 617
      Vend = plus_left ;
      Jstart = plus_right ;
      best_V = tag_plus_V ;
      best_J = tag_plus_J ;
Mikaël Salson's avatar
Mikaël Salson committed
618 619
      del_V = del_plus_V ;
      del_J = del_plus_J ;
Mikaël Salson's avatar
Mikaël Salson committed
620 621
      score_V=score_plus_V;
      score_J=score_plus_J;
Mikaël Salson's avatar
Mikaël Salson committed
622 623 624
    }
  else
    {
Mathieu Giraud's avatar
Mathieu Giraud committed
625 626 627 628
      Vend = minus_left ;
      Jstart = minus_right ;
      best_V = tag_minus_V ;
      best_J = tag_minus_J ;
Mikaël Salson's avatar
Mikaël Salson committed
629 630
      del_V = del_minus_V ;
      del_J = del_minus_J ;
Mikaël Salson's avatar
Mikaël Salson committed
631 632
      score_V=score_minus_V;
      score_J=score_minus_J;
Mikaël Salson's avatar
Mikaël Salson committed
633 634
    }

Mathieu Giraud's avatar
Mathieu Giraud committed
635
  segmented = (Vend != (int) string::npos) && (Jstart != (int) string::npos) && 
636
    (Jstart - Vend >= germline->delta_min) && (Jstart - Vend <= germline->delta_max);
Mikaël Salson's avatar
Mikaël Salson committed
637 638 639
    
  if (!segmented)
    {
640
      because = DONT_KNOW;
Mathieu Giraud's avatar
Mathieu Giraud committed
641
      info = " @" + string_of_int (Vend + FIRST_POS) + "  @" + string_of_int(Jstart + FIRST_POS) ;
642
      
643
      if (Jstart - Vend < germline->delta_min)
644 645 646 647
        {
          because = UNSEG_BAD_DELTA_MIN  ;
        }

648
      if (Jstart - Vend > germline->delta_max)
649 650 651 652 653 654 655 656 657 658 659 660 661 662
        {
          because = UNSEG_BAD_DELTA_MAX  ;
        }
        
      if (Vend == (int) string::npos) 
        {
          because = UNSEG_TOO_FEW_V ;
        }
      
      if (Jstart == (int) string::npos)
        {
          because = UNSEG_TOO_FEW_J ;
        }
      
Mikaël Salson's avatar
Mikaël Salson committed
663 664 665
      return ;
    }
    
666 667
    because = reversed ? SEG_MINUS : SEG_PLUS ;
    
Mikaël Salson's avatar
Mikaël Salson committed
668
    //overlap VJ
Mathieu Giraud's avatar
Mathieu Giraud committed
669
    if(Jstart-Vend <=0){
Mikaël Salson's avatar
Mikaël Salson committed
670
      int b_r, b_l;
Mathieu Giraud's avatar
Mathieu Giraud committed
671
      int overlap=Vend-Jstart+1;
Mikaël Salson's avatar
Mikaël Salson committed
672
      
Mathieu Giraud's avatar
Mathieu Giraud committed
673 674
      string seq_left = sequence.substr(0, Vend+1);
      string seq_right = sequence.substr(Jstart);
Mikaël Salson's avatar
Mikaël Salson committed
675 676

      best_align(overlap, seq_left, seq_right, 
677
		 germline->rep_5.sequence(best_V), germline->rep_3.sequence(best_J), &b_r,&b_l, segment_cost);
Mikaël Salson's avatar
Mikaël Salson committed
678
      // Trim V
Mathieu Giraud's avatar
Mathieu Giraud committed
679
      Vend -= b_l;
Mikaël Salson's avatar
Mikaël Salson committed
680 681 682
      del_V += b_l;

      // Trim J
Mathieu Giraud's avatar
Mathieu Giraud committed
683
      Jstart += b_r;
Mikaël Salson's avatar
Mikaël Salson committed
684
      del_J += b_r;
685
      if (Jstart>=(int) sequence.length())
Mathieu Giraud's avatar
Mathieu Giraud committed
686
	  Jstart=sequence.length()-1;
Mikaël Salson's avatar
Mikaël Salson committed
687 688 689
    }

    // string chevauchement = removeChevauchement();
Mikaël Salson's avatar
Mikaël Salson committed
690 691

    /// used only below, then recomputed in finishSegmentation() ;
Mathieu Giraud's avatar
Mathieu Giraud committed
692
    seg_N = revcomp(sequence, reversed).substr(Vend+1, Jstart-Vend-1); 
Mikaël Salson's avatar
Mikaël Salson committed
693

694
  code = germline->rep_5.label(best_V) +
Mikaël Salson's avatar
Mikaël Salson committed
695 696 697 698
    " "+ string_of_int(del_V) + 
    "/" + seg_N + 
    // chevauchement +
    "/" + string_of_int(del_J) +
699
    " " + germline->rep_3.label(best_J); 
Mikaël Salson's avatar
Mikaël Salson committed
700

Mikaël Salson's avatar
Mikaël Salson committed
701
    stringstream code_s;
702
   code_s<< germline->rep_5.label(best_V) <<
Mikaël Salson's avatar
Mikaël Salson committed
703 704 705 706
    " -" << string_of_int(del_V) << "/" 
    << seg_N.size()
    // chevauchement +
    << "/-" << string_of_int(del_J)
707
    <<" " << germline->rep_3.label(best_J);
Mikaël Salson's avatar
Mikaël Salson committed
708 709
    code_short=code_s.str();
    
710 711
  code_light = germline->rep_5.label(best_V) +
    "/ " + germline->rep_3.label(best_J); 
Mikaël Salson's avatar
Mikaël Salson committed
712 713

 
Mathieu Giraud's avatar
Mathieu Giraud committed
714
  info = string_of_int(Vend + FIRST_POS) + " " + string_of_int(Jstart + FIRST_POS) ;
Mikaël Salson's avatar
Mikaël Salson committed
715 716 717 718
  finishSegmentation();
}


719
void FineSegmenter::FineSegmentD(Germline *germline){
Mikaël Salson's avatar
Mikaël Salson committed
720 721 722 723
  
  if (segmented){
    
    int end = (int) string::npos ;
Mathieu Giraud's avatar
Mathieu Giraud committed
724
    int tag_D;
Mikaël Salson's avatar
Mikaël Salson committed
725 726 727 728
    int length = 0 ;
    int begin = 0;
    
    // Create a zone where to look for D, adding at most EXTEND_D_ZONE nucleotides at each side
Mathieu Giraud's avatar
Mathieu Giraud committed
729
    int l = Vend - EXTEND_D_ZONE;
Mikaël Salson's avatar
Mikaël Salson committed
730 731 732
    if (l<0) 
      l=0 ;

Mathieu Giraud's avatar
Mathieu Giraud committed
733
    int r = Jstart + EXTEND_D_ZONE;
Mikaël Salson's avatar
Mikaël Salson committed
734 735 736 737 738 739 740

    if (r > (int)getSequence().sequence.length()) 
      r = getSequence().sequence.length();
      
    string str = getSequence().sequence.substr(l, r-l);

    // Align
741
    end = align_against_collection(str, germline->rep_4, false, true, &tag_D, &del_D_right, &del_D_left, &begin,
Mikaël Salson's avatar
Mikaël Salson committed
742 743
				&length, &score_D, segment_cost);
    
Mathieu Giraud's avatar
Mathieu Giraud committed
744
    best_D = tag_D;
Mikaël Salson's avatar
Mikaël Salson committed
745
    
Mathieu Giraud's avatar
Mathieu Giraud committed
746 747
    Dstart = l + begin;
    Dend = l + end;
Mikaël Salson's avatar
Mikaël Salson committed
748 749
	
    string seq = getSequence().sequence;
750 751 752 753 754 755 756 757 758 759


    // recompute remaining length for D
    length = germline->rep_4.sequence(best_D).length() - del_D_right - del_D_left;

    if (length < MIN_D_LENGTH)
      return ;


    dSegmented=true;
Mikaël Salson's avatar
Mikaël Salson committed
760 761
    
    //overlap VD
Mathieu Giraud's avatar
Mathieu Giraud committed
762
    if(Dstart-Vend <=0){
Mikaël Salson's avatar
Mikaël Salson committed
763
      int b_r, b_l;
Mathieu Giraud's avatar
Mathieu Giraud committed
764 765 766
      int overlap=Vend-Dstart+1;
      string seq_left = seq.substr(0, Vend+1);
      string seq_right = seq.substr(Dstart, Dend-Dstart+1);
Mikaël Salson's avatar
Mikaël Salson committed
767 768

      best_align(overlap, seq_left, seq_right, 
769
		 germline->rep_5.sequence(best_V), germline->rep_4.sequence(best_D), &b_r,&b_l, segment_cost);
Mikaël Salson's avatar
Mikaël Salson committed
770 771

      // Trim V
Mathieu Giraud's avatar
Mathieu Giraud committed
772
      Vend -= b_l;
Mikaël Salson's avatar
Mikaël Salson committed
773 774 775
      del_V += b_l;

      // Trim D
Mathieu Giraud's avatar
Mathieu Giraud committed
776
      Dstart += b_r;
Mikaël Salson's avatar
Mikaël Salson committed
777
    }
Mathieu Giraud's avatar
Mathieu Giraud committed
778
    seg_N1 = seq.substr(Vend+1, Dstart-Vend-1) ; // From Vend+1 to Dstart-1
Mikaël Salson's avatar
Mikaël Salson committed
779 780
    
    //overlap DJ
Mathieu Giraud's avatar
Mathieu Giraud committed
781
    if(Jstart-Dend <=0){
Mikaël Salson's avatar
Mikaël Salson committed
782
      int b_r, b_l;
Mathieu Giraud's avatar
Mathieu Giraud committed
783 784 785
      int overlap=Dend-Jstart+1;
      string seq_right = seq.substr(Dstart, Dend-Dstart+1);
      string seq_left = seq.substr(Jstart, seq.length()-Jstart);
Mikaël Salson's avatar
Mikaël Salson committed
786 787

      best_align(overlap, seq_left, seq_right, 
788
		 germline->rep_4.sequence(best_D), germline->rep_3.sequence(best_J), &b_r,&b_l, segment_cost);
Mikaël Salson's avatar
Mikaël Salson committed
789 790

      // Trim D
Mathieu Giraud's avatar
Mathieu Giraud committed
791
      Dend -= b_l;
Mikaël Salson's avatar
Mikaël Salson committed
792 793

      // Trim J
Mathieu Giraud's avatar
Mathieu Giraud committed
794
      Jstart += b_r;
Mikaël Salson's avatar
Mikaël Salson committed
795 796 797
      del_J += b_r;

    }
Mathieu Giraud's avatar
Mathieu Giraud committed
798
    seg_N2 = seq.substr(Dend+1, Jstart-Dend-1) ; // From Dend+1 to right-1
799
    code = germline->rep_5.label(best_V) +
Mikaël Salson's avatar
Mikaël Salson committed
800 801 802 803
    " "+ string_of_int(del_V) + 
    "/" + seg_N1 + 
    
    "/" + string_of_int(del_D_left) +
804
    " " + germline->rep_4.label(best_D) +
Mikaël Salson's avatar
Mikaël Salson committed
805 806 807 808
    " " + string_of_int(del_D_right) +
    
    "/" + seg_N2 +
    "/" + string_of_int(del_J) +
809
    " " + germline->rep_3.label(best_J); 
Mikaël Salson's avatar
Mikaël Salson committed
810

Mikaël Salson's avatar
Mikaël Salson committed
811
    stringstream code_s;
812
    code_s << germline->rep_5.label(best_V) 
Mikaël Salson's avatar
Mikaël Salson committed
813 814 815 816
    << " -" << string_of_int(del_V) << "/" 
    << seg_N1.size()
    
    << "/-" << string_of_int(del_D_left) 
817
    << " " << germline->rep_4.label(best_D) 
Mikaël Salson's avatar
Mikaël Salson committed
818 819 820 821
    << " -" << string_of_int(del_D_right) << "/"
    
    << seg_N2.size()
    << "/-" << string_of_int(del_J) 
822
    << " " << germline->rep_3.label(best_J);
Mikaël Salson's avatar
Mikaël Salson committed
823 824 825
    code_short=code_s.str();
    
    
826 827 828
    code_light = germline->rep_5.label(best_V) +
    "/ " + germline->rep_4.label(best_D) +
    "/ " + germline->rep_3.label(best_J); 
Mikaël Salson's avatar
Mikaël Salson committed
829 830 831 832
    
    finishSegmentationD();
  }
}
Mikaël Salson's avatar
Mikaël Salson committed
833

Marc Duez's avatar
Marc Duez committed
834 835 836 837 838 839 840 841 842 843 844 845 846 847 848 849 850 851 852
void FineSegmenter::findCDR3(){
    string str = getSequence().sequence;
    
    list<string> codon_start;
    codon_start.push_back("TGT");
    codon_start.push_back("TGC");
    
    list<string> codon_end;
    codon_end.push_back("TTT");
    codon_end.push_back("TTC");
    codon_end.push_back("TGG");
    
    list<int> p_start;
    list<int> p_end;

    size_t loc;
    std::list<string>::const_iterator it;
    for (it = codon_start.begin(); it != codon_start.end(); ++it) {//filter 1 : start codon must be in V
        loc = 0;
853
        while ( loc != string::npos && loc < (size_t)Vend){
Marc Duez's avatar
Marc Duez committed
854
            loc = str.find(*it, loc+3);
855
            if (loc != string::npos && loc < (size_t)Vend) {
Marc Duez's avatar
Marc Duez committed
856 857 858 859 860 861 862 863 864 865 866 867 868 869 870
                p_start.push_front(loc);
            }
        }
    }

    for (it = codon_end.begin(); it != codon_end.end(); ++it) {//filter 2 : end codon must be in J
        loc = Jstart;
        while ( loc != string::npos){
            loc = str.find(*it, loc+3);
            if (loc != string::npos) {
                p_end.push_back(loc);
            }
        }
    }

871 872
    CDR3start = -1;
    CDR3end = -1;
Marc Duez's avatar
Marc Duez committed
873 874 875 876 877 878 879 880 881 882 883 884 885 886 887 888 889 890 891
    
    std::list<int>::const_iterator it1;
    for (it1 = p_start.begin(); it1 != p_start.end(); ++it1) {
        
        std::list<int>::const_iterator it2;
        for (it2 = p_end.begin(); it2 != p_end.end(); ++it2) {
            
            if ( (*it2-*it1)%3 == 0){       //filter 3 : start/stop codon must be seprated by a multiple of 3
                
                if ( fabs((*it2-*it1)-36 ) < fabs((CDR3end-CDR3start)-36) ){ //filter 4 : cdr3 length must be close to 12 AA
                    CDR3start = *it1;
                    CDR3end = *it2;
                }
            }
        }
    }
    
}

892
void FineSegmenter::toJsonList(JsonList *seg){
Tatiana Rocher's avatar
Tatiana Rocher committed
893

Mathieu Giraud's avatar
Mathieu Giraud committed
894
  if (isSegmented()) {
895 896 897
    seg->add("5", segmented_germline->rep_5.label(best_V));
    seg->add("5start", 0);
    seg->add("5end", Vend);
Mathieu Giraud's avatar
Mathieu Giraud committed
898 899
    
    if (score_D.size()>0){
900 901 902
      seg->add("4", segmented_germline->rep_4.label(best_D));
      seg->add("4start", Dstart);
      seg->add("4end", Dend);
Mikaël Salson's avatar
Mikaël Salson committed
903
    }
Mathieu Giraud's avatar
Mathieu Giraud committed
904
    
905 906
    seg->add("3", segmented_germline->rep_3.label(best_J));
    seg->add("3start", Jstart);
907 908 909

    if (CDR3start >= 0)
      {
Marc Duez's avatar
Marc Duez committed
910 911 912 913
    JsonList *json_cdr;
    json_cdr=new JsonList();
    json_cdr->add("start", CDR3start);
    json_cdr->add("stop", CDR3end);
914
    seg->add("cdr3", *json_cdr);
915
      }
Tatiana Rocher's avatar
Tatiana Rocher committed
916

917 918
  }
}
919

920 921
void KmerSegmenter::toJsonList(JsonList *seg)
{
922 923 924 925 926 927
    int sequenceSize = sequence.size();

    JsonList *json_affectValues;
    json_affectValues=new JsonList();
    json_affectValues->add("start", 0);
    json_affectValues->add("stop", sequenceSize); 
928 929
    json_affectValues->add("seq", getKmerAffectAnalyser()->toStringValues());
    seg->add("affectValues", *json_affectValues);
Tatiana Rocher's avatar
Tatiana Rocher committed
930 931
      

932
    JsonList *json_affectSigns;
933 934 935
    json_affectSigns=new JsonList();
    json_affectSigns->add("start", 0);
    json_affectSigns->add("stop", sequenceSize); 
936 937
    json_affectSigns->add("seq", getKmerAffectAnalyser()->toStringSigns());
    seg->add("affectSigns", *json_affectSigns);
938 939 940

    delete json_affectValues;
    delete json_affectSigns;
Mikaël Salson's avatar
Mikaël Salson committed
941 942 943
}