segment.cpp 19.2 KB
Newer Older
Mikaël Salson's avatar
Mikaël Salson committed
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
/*
  This file is part of "Vidjil" <http://bioinfo.lifl.fr/vidjil>
  Copyright (C) 2011, 2012, 2013 by Bonsai bioinformatics at LIFL (UMR CNRS 8022, Université Lille) and Inria Lille
  Contributors: Mathieu Giraud <mathieu.giraud@lifl.fr>, Mikaël Salson <mikael.salson@lifl.fr>, Marc Duez

  "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
19
#include <algorithm>    // std::sort
Mikaël Salson's avatar
Mikaël Salson committed
20 21 22 23
#include <cassert>
#include "segment.h"
#include "tools.h"
#include "affectanalyser.h"
Mikaël Salson's avatar
Mikaël Salson committed
24
#include <sstream>
Mikaël Salson's avatar
Mikaël Salson committed
25

Mathieu Giraud's avatar
Mathieu Giraud committed
26
Segmenter::~Segmenter() {}
Mikaël Salson's avatar
Mikaël Salson committed
27

Mathieu Giraud's avatar
Mathieu Giraud committed
28
Sequence Segmenter::getSequence() const {
Mikaël Salson's avatar
Mikaël Salson committed
29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48
  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
49
  return Vend;
Mikaël Salson's avatar
Mikaël Salson committed
50 51 52
}
  
int Segmenter::getRight() const {
Mathieu Giraud's avatar
Mathieu Giraud committed
53
  return Jstart;
Mikaël Salson's avatar
Mikaël Salson committed
54 55 56
}

int Segmenter::getLeftD() const {
Mathieu Giraud's avatar
Mathieu Giraud committed
57
  return Dstart;
Mikaël Salson's avatar
Mikaël Salson committed
58 59 60
}
  
int Segmenter::getRightD() const {
Mathieu Giraud's avatar
Mathieu Giraud committed
61
  return Dend;
Mikaël Salson's avatar
Mikaël Salson committed
62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83
}

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

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

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

// Chevauchement

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

Mathieu Giraud's avatar
Mathieu Giraud committed
84
  if (Vend >= Jstart)
Mikaël Salson's avatar
Mikaël Salson committed
85
    {
Mathieu Giraud's avatar
Mathieu Giraud committed
86
      int middle = (Vend + Jstart) / 2 ;
87
      chevauchement = " !ov " + string_of_int (Vend - Jstart + 1);
Mathieu Giraud's avatar
Mathieu Giraud committed
88 89
      Vend = middle ;
      Jstart = middle+1 ;
Mikaël Salson's avatar
Mikaël Salson committed
90 91 92 93 94 95 96 97 98 99 100 101 102 103
    }

  return chevauchement ;
}

// Prettyprint


bool Segmenter::finishSegmentation() 
{
  assert(isSegmented());
  
  string seq = getSequence().sequence;
    
Mathieu Giraud's avatar
Mathieu Giraud committed
104 105 106 107 108
  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
109 110 111 112 113 114 115 116 117 118 119 120 121

  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
122 123
  seg_V = seq.substr(0, Vend+1) ; // From pos. 0 to Vend
  seg_J = seq.substr(Jstart) ;
Mikaël Salson's avatar
Mikaël Salson committed
124
  
Mathieu Giraud's avatar
Mathieu Giraud committed
125
  seg_D  = seq.substr(Dstart, Dend-Dstart+1) ; // From Dstart to Dend
Mikaël Salson's avatar
Mikaël Salson committed
126
  
Mathieu Giraud's avatar
Mathieu Giraud committed
127 128 129 130
  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
131 132 133 134 135 136 137 138 139 140 141 142 143
		" " + string_of_int(seq.size()-1+FIRST_POS) ;
		
  info += "\t" + code ;
  
  info = (reversed ? "- " : "+ ") + info ;

  return true ;
}

ostream &operator<<(ostream &out, const Segmenter &s)
{
  out << ">" << s.label << " " ;
  out << (s.segmented ? "" : "! ") << s.info ;
144
  out << " " << s.info_extra ;
Mikaël Salson's avatar
Mikaël Salson committed
145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163
  out << endl ;

  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)

164
KmerSegmenter::KmerSegmenter(Sequence seq, MultiGermline *multigermline)
Mikaël Salson's avatar
Mikaël Salson committed
165 166 167 168
{
  label = seq.label ;
  sequence = seq.sequence ;
  info = "" ;
169
  info_extra = "seed";
Mikaël Salson's avatar
Mikaël Salson committed
170
  segmented = false;
171
  segmented_germline = 0;
172
  reversed = false;
Mathieu Giraud's avatar
Mathieu Giraud committed
173
  Dend=0;
Mikaël Salson's avatar
Mikaël Salson committed
174
  
175 176 177 178 179
  // Iterate over the germlines
  for (list<Germline*>::const_iterator it = multigermline->germlines.begin(); it != multigermline->germlines.end(); ++it)
    {
      Germline *germline = *it ;

180
  int s = (size_t)germline->index->getS() ;
Mikaël Salson's avatar
Mikaël Salson committed
181
  int length = sequence.length() ;
Mikaël Salson's avatar
Mikaël Salson committed
182

183
  if (length < s) 
Mikaël Salson's avatar
Mikaël Salson committed
184
    {
Mathieu Giraud's avatar
Mathieu Giraud committed
185 186
      because = UNSEG_TOO_SHORT;
      kaa = NULL;
187
      continue ;
Mikaël Salson's avatar
Mikaël Salson committed
188 189
    }
 
190
  kaa = new KmerAffectAnalyser<KmerAffect>(*(germline->index), sequence);
Mikaël Salson's avatar
Mikaël Salson committed
191 192
  
  // Check strand consistency among the affectations.
Mikaël Salson's avatar
Mikaël Salson committed
193 194 195 196 197 198 199 200 201
  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
202 203 204
    }
  }

Mikaël Salson's avatar
Mikaël Salson committed
205 206 207 208 209 210 211 212 213 214 215 216 217
  // Test on which strand we are.
  if (nb_strand[0] == 0 && nb_strand[1] == 0) {
    strand = 0;                 // No info
  } else if (nb_strand[0] > RATIO_STRAND * nb_strand[1]) {
    strand = -1;
  } else if (nb_strand[1] > RATIO_STRAND * nb_strand[0]) {
    strand = 1;
  } else {
    // Ambiguous information: we have positive and negative strands
    // and there is not enough difference to put them aparat.
    strand = 2;
  }

218
  computeSegmentation(strand, germline->delta_min, germline->delta_max, s);
Mathieu Giraud's avatar
Mathieu Giraud committed
219 220 221 222

  if (segmented)
    {
      // Yes, it is segmented
223
      segmented_germline = germline;
Mathieu Giraud's avatar
Mathieu Giraud committed
224 225 226 227 228

      reversed = (strand == -1); 
      because = reversed ? SEG_MINUS : SEG_PLUS ;

      info = string_of_int(Vend + FIRST_POS) + " " + string_of_int(Jstart + FIRST_POS)  ;
229 230
      // 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
231
      finishSegmentation();
232 233

      return ;
Mathieu Giraud's avatar
Mathieu Giraud committed
234
    } 
235
  } // end for (Germlines)
Mathieu Giraud's avatar
Mathieu Giraud committed
236
}
Mikaël Salson's avatar
Mikaël Salson committed
237

Mathieu Giraud's avatar
Mathieu Giraud committed
238 239 240 241 242
KmerSegmenter::~KmerSegmenter() {
  if (kaa)
    delete kaa;
}

243 244 245 246
void KmerSegmenter::computeSegmentation(int strand, int delta_min, int delta_max, int s) {
  // Try to segment, computing 'Vend' and 'Jstart', and 'segmented'
  // If not segmented, put the cause of unsegmentation in 'because'

Mikaël Salson's avatar
Mikaël Salson committed
247
  segmented = true ;
Mathieu Giraud's avatar
Mathieu Giraud committed
248
  because = 0 ; // Cause of unsegmentation
Mikaël Salson's avatar
Mikaël Salson committed
249 250 251 252

  // Zero information
  if (strand == 0)
    {
Mikaël Salson's avatar
Mikaël Salson committed
253
      because = UNSEG_TOO_FEW_ZERO ;
Mathieu Giraud's avatar
Mathieu Giraud committed
254 255
    } 
  else if (strand == 2) // Ambiguous
Mikaël Salson's avatar
Mikaël Salson committed
256
    {
Mikaël Salson's avatar
Mikaël Salson committed
257
      because = UNSEG_STRAND_NOT_CONSISTENT ;
Mathieu Giraud's avatar
Mathieu Giraud committed
258
    } 
259
  else
Mikaël Salson's avatar
Mikaël Salson committed
260 261
    {
      // Strand +
262 263 264 265 266 267 268
      affect_infos max;
      if (strand == 1)
        max = kaa->getMaximum(AFFECT_V, AFFECT_J);
      else
        max = kaa->getMaximum(AFFECT_J_BWD, AFFECT_V_BWD);

      if (! max.max_found) {
269 270
        if ((strand == 1 && max.nb_before_left == 0)
            || (strand == -1 && max.nb_after_right == 0)) 
271
          because = UNSEG_TOO_FEW_V ;
272 273
        else if ((strand == 1 && max.nb_after_right == 0)
                 || (strand == -1 && max.nb_before_left == 0))
Mikaël Salson's avatar
Mikaël Salson committed
274
	{
Mikaël Salson's avatar
Mikaël Salson committed
275
	  because = UNSEG_TOO_FEW_J ;
276
	} else 
277 278 279 280 281 282 283 284 285 286
          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
287 288
    } 
  
Mathieu Giraud's avatar
Mathieu Giraud committed
289
  if (! because)
Mikaël Salson's avatar
Mikaël Salson committed
290
    {
Mathieu Giraud's avatar
Mathieu Giraud committed
291
      // Now we check the delta between Vend and right
Mikaël Salson's avatar
Mikaël Salson committed
292
   
Mathieu Giraud's avatar
Mathieu Giraud committed
293
      if (Jstart - Vend < delta_min)
Mikaël Salson's avatar
Mikaël Salson committed
294 295 296
	{
	  because = UNSEG_BAD_DELTA_MIN ;
	}
Mikaël Salson's avatar
Mikaël Salson committed
297

Mathieu Giraud's avatar
Mathieu Giraud committed
298
      if (Jstart - Vend > delta_max)
Mikaël Salson's avatar
Mikaël Salson committed
299 300 301
	{
	  because = UNSEG_BAD_DELTA_MAX ;
	}
Mathieu Giraud's avatar
Mathieu Giraud committed
302 303 304 305
    } 
  if (because)
    segmented = false;
}
Mikaël Salson's avatar
Mikaël Salson committed
306

307
KmerAffectAnalyser<KmerAffect> *KmerSegmenter::getKmerAffectAnalyser() const {
Mathieu Giraud's avatar
Mathieu Giraud committed
308 309
  return kaa;
}
Mikaël Salson's avatar
Mikaël Salson committed
310

Mathieu Giraud's avatar
Mathieu Giraud committed
311 312
int KmerSegmenter::getSegmentationStatus() const {
  return because;
Mikaël Salson's avatar
Mikaël Salson committed
313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369
}

// 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)
	score_r[i] = dp.S[dp.best_i-i][dp.best_j];
	else
	score_r[i] =0;
	if(dp1.best_i-i >0)
	score_l[i] = dp1.S[dp1.best_i-i][dp1.best_j];	
	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
370 371 372 373 374
bool comp_pair (pair<int,int> i,pair<int,int> j)
{
  return ( i.first > j.first);
}

Mathieu Giraud's avatar
Mathieu Giraud committed
375
int align_against_collection(string &read, Fasta &rep, bool reverse_both, bool local, int *tag, 
Mikaël Salson's avatar
Mikaël Salson committed
376
			     int *del, int *del2, int *begin, int *length, vector<pair<int, int> > *score
Mikaël Salson's avatar
Mikaël Salson committed
377 378 379 380 381 382 383 384 385 386
			    , 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
387
  vector<pair<int, int> > score_r;
Mikaël Salson's avatar
Mikaël Salson committed
388 389 390 391 392 393 394 395 396 397 398

  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
399
      
Mikaël Salson's avatar
Mikaël Salson committed
400 401 402 403 404 405 406 407 408 409 410 411 412 413
      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
414 415
	
	score_r.push_back(make_pair(score, r));
Mathieu Giraud's avatar
Mathieu Giraud committed
416 417 418 419 420 421

	// #define DEBUG_SEGMENT      

#ifdef DEBUG_SEGMENT	
	cout << rep.label(r) << " " << score << " " << dp.best_i << endl ;
#endif
Mikaël Salson's avatar
Mikaël Salson committed
422 423

    }
Mikaël Salson's avatar
Mikaël Salson committed
424
    sort(score_r.begin(),score_r.end(),comp_pair);
Mikaël Salson's avatar
Mikaël Salson committed
425 426 427 428

  *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
429
  *tag = best_r ; 
Mikaël Salson's avatar
Mikaël Salson committed
430 431
  
  *length -= *del ;
Mikaël Salson's avatar
Mikaël Salson committed
432 433
  
  *score=score_r;
Mathieu Giraud's avatar
Mathieu Giraud committed
434 435 436 437 438 439

#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
440 441 442 443 444 445 446 447 448
  
  return best_best_i ;
}

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

449
FineSegmenter::FineSegmenter(Sequence seq, Germline *germline, Cost segment_c)
Mikaël Salson's avatar
Mikaël Salson committed
450 451
{

452
  info_extra = "" ;
Mikaël Salson's avatar
Mikaël Salson committed
453 454
  label = seq.label ;
  sequence = seq.sequence ;
Mathieu Giraud's avatar
Mathieu Giraud committed
455
  Dend=0;
Mikaël Salson's avatar
Mikaël Salson committed
456 457 458 459 460 461 462
  segment_cost=segment_c;

  // 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
463
  int tag_plus_V, tag_plus_J;
Mikaël Salson's avatar
Mikaël Salson committed
464 465 466 467
  int plus_length = 0 ;
  int del_plus_V, del_plus_J ;
  int del2=0;
  int beg=0;
Mikaël Salson's avatar
Mikaël Salson committed
468 469 470 471
  
  vector<pair<int, int> > score_plus_V;
  vector<pair<int, int> > score_plus_J;
  
472
  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
473 474
					   &plus_length, &score_plus_V
					   , segment_cost);
475
  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
476 477
					    &plus_length, &score_plus_J
					    , segment_cost);
Mikaël Salson's avatar
Mikaël Salson committed
478 479
  plus_length += plus_right - plus_left ;

Mikaël Salson's avatar
Mikaël Salson committed
480 481
  plus_score=score_plus_V[0].first + score_plus_J[0].first ;
  
Mikaël Salson's avatar
Mikaël Salson committed
482 483 484
  // Strand -
  string rc = revcomp(sequence) ;
  int minus_score = 0 ;
Mathieu Giraud's avatar
Mathieu Giraud committed
485
  int tag_minus_V, tag_minus_J;
Mikaël Salson's avatar
Mikaël Salson committed
486 487
  int minus_length = 0 ;
  int del_minus_V, del_minus_J ;
Mikaël Salson's avatar
Mikaël Salson committed
488 489 490 491
  
  vector<pair<int, int> > score_minus_V;
  vector<pair<int, int> > score_minus_J;
  
492
  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
493 494
					    &minus_length, &score_minus_V
					    ,  segment_cost);
495
  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
496 497
					     &minus_length, &score_minus_J
					     , segment_cost);
Mikaël Salson's avatar
Mikaël Salson committed
498 499
  minus_length += minus_right - minus_left ;

Mikaël Salson's avatar
Mikaël Salson committed
500 501
  minus_score=score_minus_V[0].first + score_minus_J[0].first ;
  
Mikaël Salson's avatar
Mikaël Salson committed
502 503 504 505
  reversed = (minus_score > plus_score) ;

  if (!reversed)
    {
Mathieu Giraud's avatar
Mathieu Giraud committed
506 507 508 509
      Vend = plus_left ;
      Jstart = plus_right ;
      best_V = tag_plus_V ;
      best_J = tag_plus_J ;
Mikaël Salson's avatar
Mikaël Salson committed
510 511
      del_V = del_plus_V ;
      del_J = del_plus_J ;
Mikaël Salson's avatar
Mikaël Salson committed
512 513
      score_V=score_plus_V;
      score_J=score_plus_J;
Mikaël Salson's avatar
Mikaël Salson committed
514 515 516
    }
  else
    {
Mathieu Giraud's avatar
Mathieu Giraud committed
517 518 519 520
      Vend = minus_left ;
      Jstart = minus_right ;
      best_V = tag_minus_V ;
      best_J = tag_minus_J ;
Mikaël Salson's avatar
Mikaël Salson committed
521 522
      del_V = del_minus_V ;
      del_J = del_minus_J ;
Mikaël Salson's avatar
Mikaël Salson committed
523 524
      score_V=score_minus_V;
      score_J=score_minus_J;
Mikaël Salson's avatar
Mikaël Salson committed
525 526
    }

Mathieu Giraud's avatar
Mathieu Giraud committed
527
  segmented = (Vend != (int) string::npos) && (Jstart != (int) string::npos) && 
528
    (Jstart - Vend >= germline->delta_min) && (Jstart - Vend <= germline->delta_max);
Mikaël Salson's avatar
Mikaël Salson committed
529 530 531 532 533
    
  dSegmented=false;

  if (!segmented)
    {
534
      because = DONT_KNOW;
Mathieu Giraud's avatar
Mathieu Giraud committed
535
      info = " @" + string_of_int (Vend + FIRST_POS) + "  @" + string_of_int(Jstart + FIRST_POS) ;
536
      
537
      if (Jstart - Vend < germline->delta_min)
538 539 540 541
        {
          because = UNSEG_BAD_DELTA_MIN  ;
        }

542
      if (Jstart - Vend > germline->delta_max)
543 544 545 546 547 548 549 550 551 552 553 554 555 556
        {
          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
557 558 559
      return ;
    }
    
560 561
    because = reversed ? SEG_MINUS : SEG_PLUS ;
    
Mikaël Salson's avatar
Mikaël Salson committed
562
    //overlap VJ
Mathieu Giraud's avatar
Mathieu Giraud committed
563
    if(Jstart-Vend <=0){
Mikaël Salson's avatar
Mikaël Salson committed
564
      int b_r, b_l;
Mathieu Giraud's avatar
Mathieu Giraud committed
565
      int overlap=Vend-Jstart+1;
Mikaël Salson's avatar
Mikaël Salson committed
566
      
Mathieu Giraud's avatar
Mathieu Giraud committed
567 568
      string seq_left = sequence.substr(0, Vend+1);
      string seq_right = sequence.substr(Jstart);
Mikaël Salson's avatar
Mikaël Salson committed
569 570

      best_align(overlap, seq_left, seq_right, 
571
		 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
572
      // Trim V
Mathieu Giraud's avatar
Mathieu Giraud committed
573
      Vend -= b_l;
Mikaël Salson's avatar
Mikaël Salson committed
574 575 576
      del_V += b_l;

      // Trim J
Mathieu Giraud's avatar
Mathieu Giraud committed
577
      Jstart += b_r;
Mikaël Salson's avatar
Mikaël Salson committed
578
      del_J += b_r;
579
      if (Jstart>=(int) sequence.length())
Mathieu Giraud's avatar
Mathieu Giraud committed
580
	  Jstart=sequence.length()-1;
Mikaël Salson's avatar
Mikaël Salson committed
581 582 583
    }

    // string chevauchement = removeChevauchement();
Mikaël Salson's avatar
Mikaël Salson committed
584 585

    /// used only below, then recomputed in finishSegmentation() ;
Mathieu Giraud's avatar
Mathieu Giraud committed
586
    seg_N = revcomp(sequence, reversed).substr(Vend+1, Jstart-Vend-1); 
Mikaël Salson's avatar
Mikaël Salson committed
587

588
  code = germline->rep_5.label(best_V) +
Mikaël Salson's avatar
Mikaël Salson committed
589 590 591 592
    " "+ string_of_int(del_V) + 
    "/" + seg_N + 
    // chevauchement +
    "/" + string_of_int(del_J) +
593
    " " + germline->rep_3.label(best_J); 
Mikaël Salson's avatar
Mikaël Salson committed
594

Mikaël Salson's avatar
Mikaël Salson committed
595
    stringstream code_s;
596
   code_s<< germline->rep_5.label(best_V) <<
Mikaël Salson's avatar
Mikaël Salson committed
597 598 599 600
    " -" << string_of_int(del_V) << "/" 
    << seg_N.size()
    // chevauchement +
    << "/-" << string_of_int(del_J)
601
    <<" " << germline->rep_3.label(best_J);
Mikaël Salson's avatar
Mikaël Salson committed
602 603
    code_short=code_s.str();
    
604 605
  code_light = germline->rep_5.label(best_V) +
    "/ " + germline->rep_3.label(best_J); 
Mikaël Salson's avatar
Mikaël Salson committed
606 607

 
Mathieu Giraud's avatar
Mathieu Giraud committed
608
  info = string_of_int(Vend + FIRST_POS) + " " + string_of_int(Jstart + FIRST_POS) ;
Mikaël Salson's avatar
Mikaël Salson committed
609 610 611 612 613

  finishSegmentation();
}


614
void FineSegmenter::FineSegmentD(Germline *germline){
Mikaël Salson's avatar
Mikaël Salson committed
615 616 617 618
  
  if (segmented){
    
    int end = (int) string::npos ;
Mathieu Giraud's avatar
Mathieu Giraud committed
619
    int tag_D;
Mikaël Salson's avatar
Mikaël Salson committed
620 621 622 623
    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
624
    int l = Vend - EXTEND_D_ZONE;
Mikaël Salson's avatar
Mikaël Salson committed
625 626 627
    if (l<0) 
      l=0 ;

Mathieu Giraud's avatar
Mathieu Giraud committed
628
    int r = Jstart + EXTEND_D_ZONE;
Mikaël Salson's avatar
Mikaël Salson committed
629 630 631 632 633 634 635

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

    // Align
636
    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
637 638
				&length, &score_D, segment_cost);
    
Mathieu Giraud's avatar
Mathieu Giraud committed
639
    best_D = tag_D;
Mikaël Salson's avatar
Mikaël Salson committed
640
    
Mathieu Giraud's avatar
Mathieu Giraud committed
641 642
    Dstart = l + begin;
    Dend = l + end;
Mikaël Salson's avatar
Mikaël Salson committed
643 644 645 646 647 648
	
    string seq = getSequence().sequence;
    
    if (length>0) dSegmented=true;
    
    //overlap VD
Mathieu Giraud's avatar
Mathieu Giraud committed
649
    if(Dstart-Vend <=0){
Mikaël Salson's avatar
Mikaël Salson committed
650
      int b_r, b_l;
Mathieu Giraud's avatar
Mathieu Giraud committed
651 652 653
      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
654 655

      best_align(overlap, seq_left, seq_right, 
656
		 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
657 658

      // Trim V
Mathieu Giraud's avatar
Mathieu Giraud committed
659
      Vend -= b_l;
Mikaël Salson's avatar
Mikaël Salson committed
660 661 662
      del_V += b_l;

      // Trim D
Mathieu Giraud's avatar
Mathieu Giraud committed
663
      Dstart += b_r;
Mikaël Salson's avatar
Mikaël Salson committed
664
    }
Mathieu Giraud's avatar
Mathieu Giraud committed
665
    seg_N1 = seq.substr(Vend+1, Dstart-Vend-1) ; // From Vend+1 to Dstart-1
Mikaël Salson's avatar
Mikaël Salson committed
666 667
    
    //overlap DJ
Mathieu Giraud's avatar
Mathieu Giraud committed
668
    if(Jstart-Dend <=0){
Mikaël Salson's avatar
Mikaël Salson committed
669
      int b_r, b_l;
Mathieu Giraud's avatar
Mathieu Giraud committed
670 671 672
      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
673 674

      best_align(overlap, seq_left, seq_right, 
675
		 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
676 677

      // Trim D
Mathieu Giraud's avatar
Mathieu Giraud committed
678
      Dend -= b_l;
Mikaël Salson's avatar
Mikaël Salson committed
679 680

      // Trim J
Mathieu Giraud's avatar
Mathieu Giraud committed
681
      Jstart += b_r;
Mikaël Salson's avatar
Mikaël Salson committed
682 683 684
      del_J += b_r;

    }
Mathieu Giraud's avatar
Mathieu Giraud committed
685
    seg_N2 = seq.substr(Dend+1, Jstart-Dend-1) ; // From Dend+1 to right-1
686
    code = germline->rep_5.label(best_V) +
Mikaël Salson's avatar
Mikaël Salson committed
687 688 689 690
    " "+ string_of_int(del_V) + 
    "/" + seg_N1 + 
    
    "/" + string_of_int(del_D_left) +
691
    " " + germline->rep_4.label(best_D) +
Mikaël Salson's avatar
Mikaël Salson committed
692 693 694 695
    " " + string_of_int(del_D_right) +
    
    "/" + seg_N2 +
    "/" + string_of_int(del_J) +
696
    " " + germline->rep_3.label(best_J); 
Mikaël Salson's avatar
Mikaël Salson committed
697

Mikaël Salson's avatar
Mikaël Salson committed
698
    stringstream code_s;
699
    code_s << germline->rep_5.label(best_V) 
Mikaël Salson's avatar
Mikaël Salson committed
700 701 702 703
    << " -" << string_of_int(del_V) << "/" 
    << seg_N1.size()
    
    << "/-" << string_of_int(del_D_left) 
704
    << " " << germline->rep_4.label(best_D) 
Mikaël Salson's avatar
Mikaël Salson committed
705 706 707 708
    << " -" << string_of_int(del_D_right) << "/"
    
    << seg_N2.size()
    << "/-" << string_of_int(del_J) 
709
    << " " << germline->rep_3.label(best_J);
Mikaël Salson's avatar
Mikaël Salson committed
710 711 712
    code_short=code_s.str();
    
    
713 714 715
    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
716 717 718 719
    
    finishSegmentationD();
  }
}
Mikaël Salson's avatar
Mikaël Salson committed
720

721
JsonList FineSegmenter::toJsonList(Germline *germline){
Mathieu Giraud's avatar
Mathieu Giraud committed
722
  JsonList result;
Mikaël Salson's avatar
Mikaël Salson committed
723
  
724
  result.add("status", because);
Mathieu Giraud's avatar
Mathieu Giraud committed
725 726 727 728 729 730 731
  result.add("sequence", revcomp(sequence, reversed) );
  if (isSegmented()) {
    result.add("name", code_short);
    result.add("Jstart", Jstart);
    result.add("Nlength", (del_V+del_J+seg_N.size()) );
    result.add("Vend", Vend);

732

Mathieu Giraud's avatar
Mathieu Giraud committed
733 734 735 736 737
    JsonArray jsonV;
    JsonArray jsonJ;

    // TODO: what is going on if some list is smaller than JSON_REMEMBER_BEST ?
    
738
    for (int i=0; i<JSON_REMEMBER_BEST; i++) jsonV.add( germline->rep_5.label(score_V[i].second) ) ;
Mathieu Giraud's avatar
Mathieu Giraud committed
739 740 741 742 743 744 745 746
    result.add("V", jsonV);
    
    
    if (score_D.size()>0){
      result.add("Dstart", Dstart);
      result.add("Dend", Dend);      
      JsonArray jsonD;

747
      for (int i=0; i<JSON_REMEMBER_BEST; i++) jsonD.add( germline->rep_4.label(score_D[i].second) ) ;
Mathieu Giraud's avatar
Mathieu Giraud committed
748
      result.add("D", jsonD);
Mikaël Salson's avatar
Mikaël Salson committed
749
    }
Mathieu Giraud's avatar
Mathieu Giraud committed
750
    
751
    for (int i=0; i<JSON_REMEMBER_BEST; i++) jsonJ.add( germline->rep_3.label(score_J[i].second) ) ;
Mathieu Giraud's avatar
Mathieu Giraud committed
752
    result.add("J", jsonJ);
Mikaël Salson's avatar
Mikaël Salson committed
753
  }
Mathieu Giraud's avatar
Mathieu Giraud committed
754
  return result;
Mikaël Salson's avatar
Mikaël Salson committed
755 756 757
}