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(*(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
219
220
  // Are there enoguh V/J to assert that this was the correct germline (and thus that we won't test other ones) ?
  detected = (nb_strand[0] + nb_strand[1] >= DETECT_THRESHOLD);

221
  computeSegmentation(strand, germline);
Mathieu Giraud's avatar
Mathieu Giraud committed
222
223
224
225

  if (segmented)
    {
      // Yes, it is segmented
226
      segmented_germline = germline;
227
      germline->stats.insert(length);
Mathieu Giraud's avatar
Mathieu Giraud committed
228
229
230
231
232

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

      info = string_of_int(Vend + FIRST_POS) + " " + string_of_int(Jstart + FIRST_POS)  ;
233
234
      // 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
235
      finishSegmentation();
236
      system = germline->code;
237
      return ;
Mathieu Giraud's avatar
Mathieu Giraud committed
238
    } 
239

240
241
  // If the germline was detected, do not test other germlines
  if (detected)
242
243
    return ;

244
  } // end for (Germlines)
Mathieu Giraud's avatar
Mathieu Giraud committed
245
}
Mikaël Salson's avatar
Mikaël Salson committed
246

Mathieu Giraud's avatar
Mathieu Giraud committed
247
248
249
250
251
KmerSegmenter::~KmerSegmenter() {
  if (kaa)
    delete kaa;
}

252
void KmerSegmenter::computeSegmentation(int strand, Germline* germline) {
253
254
255
  // 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
256
  segmented = true ;
Mathieu Giraud's avatar
Mathieu Giraud committed
257
  because = 0 ; // Cause of unsegmentation
Mikaël Salson's avatar
Mikaël Salson committed
258
259
260
261

  // Zero information
  if (strand == 0)
    {
Mikaël Salson's avatar
Mikaël Salson committed
262
      because = UNSEG_TOO_FEW_ZERO ;
Mathieu Giraud's avatar
Mathieu Giraud committed
263
264
    } 
  else if (strand == 2) // Ambiguous
Mikaël Salson's avatar
Mikaël Salson committed
265
    {
Mikaël Salson's avatar
Mikaël Salson committed
266
      because = UNSEG_STRAND_NOT_CONSISTENT ;
Mathieu Giraud's avatar
Mathieu Giraud committed
267
    } 
268
  else
Mikaël Salson's avatar
Mikaël Salson committed
269
    {
270
271
      affect_infos max;
      if (strand == 1)
272
273
        max = kaa->getMaximum(KmerAffect(germline->affect_5, 1), 
			      KmerAffect(germline->affect_3, 1));
274
      else
275
276
        max = kaa->getMaximum(KmerAffect(germline->affect_3, -1), 
			      KmerAffect(germline->affect_5, -1));
277
278

      if (! max.max_found) {
279
280
        if ((strand == 1 && max.nb_before_left == 0)
            || (strand == -1 && max.nb_after_right == 0)) 
281
          because = detected ? UNSEG_AMBIGUOUS : UNSEG_TOO_FEW_V ;
282
283
        else if ((strand == 1 && max.nb_after_right == 0)
                 || (strand == -1 && max.nb_before_left == 0))
Mikaël Salson's avatar
Mikaël Salson committed
284
	{
285
	  because = detected ? UNSEG_AMBIGUOUS : UNSEG_TOO_FEW_J ;
286
	} else 
287
288
289
290
291
292
293
294
295
296
          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
297
298
    } 
  
Mathieu Giraud's avatar
Mathieu Giraud committed
299
  if (! because)
Mikaël Salson's avatar
Mikaël Salson committed
300
    {
Mathieu Giraud's avatar
Mathieu Giraud committed
301
      // Now we check the delta between Vend and right
Mikaël Salson's avatar
Mikaël Salson committed
302
   
303
      if (Jstart - Vend < germline->delta_min)
Mikaël Salson's avatar
Mikaël Salson committed
304
305
306
	{
	  because = UNSEG_BAD_DELTA_MIN ;
	}
Mikaël Salson's avatar
Mikaël Salson committed
307

308
      if (Jstart - Vend > germline->delta_max)
Mikaël Salson's avatar
Mikaël Salson committed
309
310
311
	{
	  because = UNSEG_BAD_DELTA_MAX ;
	}
Mathieu Giraud's avatar
Mathieu Giraud committed
312
313
314
315
    } 
  if (because)
    segmented = false;
}
Mikaël Salson's avatar
Mikaël Salson committed
316

317
KmerAffectAnalyser *KmerSegmenter::getKmerAffectAnalyser() const {
Mathieu Giraud's avatar
Mathieu Giraud committed
318
319
  return kaa;
}
Mikaël Salson's avatar
Mikaël Salson committed
320

Mathieu Giraud's avatar
Mathieu Giraud committed
321
322
int KmerSegmenter::getSegmentationStatus() const {
  return because;
Mikaël Salson's avatar
Mikaël Salson committed
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
370
371
372
373
374
375
376
377
378
379
}

// 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
380
381
382
383
384
bool comp_pair (pair<int,int> i,pair<int,int> j)
{
  return ( i.first > j.first);
}

Mathieu Giraud's avatar
Mathieu Giraud committed
385
int align_against_collection(string &read, Fasta &rep, bool reverse_both, bool local, int *tag, 
Mikaël Salson's avatar
Mikaël Salson committed
386
			     int *del, int *del2, int *begin, int *length, vector<pair<int, int> > *score
Mikaël Salson's avatar
Mikaël Salson committed
387
388
389
390
391
392
393
394
395
396
			    , 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
397
  vector<pair<int, int> > score_r;
Mikaël Salson's avatar
Mikaël Salson committed
398
399
400
401
402
403
404
405
406
407
408

  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
409
      
Mikaël Salson's avatar
Mikaël Salson committed
410
411
412
413
414
415
416
417
418
419
420
421
422
423
      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
424
425
	
	score_r.push_back(make_pair(score, r));
Mathieu Giraud's avatar
Mathieu Giraud committed
426
427
428
429
430
431

	// #define DEBUG_SEGMENT      

#ifdef DEBUG_SEGMENT	
	cout << rep.label(r) << " " << score << " " << dp.best_i << endl ;
#endif
Mikaël Salson's avatar
Mikaël Salson committed
432
433

    }
Mikaël Salson's avatar
Mikaël Salson committed
434
    sort(score_r.begin(),score_r.end(),comp_pair);
Mikaël Salson's avatar
Mikaël Salson committed
435
436
437
438

  *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
439
  *tag = best_r ; 
Mikaël Salson's avatar
Mikaël Salson committed
440
441
  
  *length -= *del ;
Mikaël Salson's avatar
Mikaël Salson committed
442
443
  
  *score=score_r;
Mathieu Giraud's avatar
Mathieu Giraud committed
444
445
446
447
448
449

#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
450
451
452
453
454
455
456
457
458
  
  return best_best_i ;
}

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

459
FineSegmenter::FineSegmenter(Sequence seq, Germline *germline, Cost segment_c)
Mikaël Salson's avatar
Mikaël Salson committed
460
461
{

462
  info_extra = "" ;
Mikaël Salson's avatar
Mikaël Salson committed
463
464
  label = seq.label ;
  sequence = seq.sequence ;
Mathieu Giraud's avatar
Mathieu Giraud committed
465
  Dend=0;
Mikaël Salson's avatar
Mikaël Salson committed
466
467
468
469
470
471
472
  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
473
  int tag_plus_V, tag_plus_J;
Mikaël Salson's avatar
Mikaël Salson committed
474
475
476
477
  int plus_length = 0 ;
  int del_plus_V, del_plus_J ;
  int del2=0;
  int beg=0;
Mikaël Salson's avatar
Mikaël Salson committed
478
479
480
481
  
  vector<pair<int, int> > score_plus_V;
  vector<pair<int, int> > score_plus_J;
  
482
  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
483
484
					   &plus_length, &score_plus_V
					   , segment_cost);
485
  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
486
487
					    &plus_length, &score_plus_J
					    , segment_cost);
Mikaël Salson's avatar
Mikaël Salson committed
488
489
  plus_length += plus_right - plus_left ;

Mikaël Salson's avatar
Mikaël Salson committed
490
491
  plus_score=score_plus_V[0].first + score_plus_J[0].first ;
  
Mikaël Salson's avatar
Mikaël Salson committed
492
493
494
  // Strand -
  string rc = revcomp(sequence) ;
  int minus_score = 0 ;
Mathieu Giraud's avatar
Mathieu Giraud committed
495
  int tag_minus_V, tag_minus_J;
Mikaël Salson's avatar
Mikaël Salson committed
496
497
  int minus_length = 0 ;
  int del_minus_V, del_minus_J ;
Mikaël Salson's avatar
Mikaël Salson committed
498
499
500
501
  
  vector<pair<int, int> > score_minus_V;
  vector<pair<int, int> > score_minus_J;
  
502
  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
503
504
					    &minus_length, &score_minus_V
					    ,  segment_cost);
505
  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
506
507
					     &minus_length, &score_minus_J
					     , segment_cost);
Mikaël Salson's avatar
Mikaël Salson committed
508
509
  minus_length += minus_right - minus_left ;

Mikaël Salson's avatar
Mikaël Salson committed
510
511
  minus_score=score_minus_V[0].first + score_minus_J[0].first ;
  
Mikaël Salson's avatar
Mikaël Salson committed
512
513
514
515
  reversed = (minus_score > plus_score) ;

  if (!reversed)
    {
Mathieu Giraud's avatar
Mathieu Giraud committed
516
517
518
519
      Vend = plus_left ;
      Jstart = plus_right ;
      best_V = tag_plus_V ;
      best_J = tag_plus_J ;
Mikaël Salson's avatar
Mikaël Salson committed
520
521
      del_V = del_plus_V ;
      del_J = del_plus_J ;
Mikaël Salson's avatar
Mikaël Salson committed
522
523
      score_V=score_plus_V;
      score_J=score_plus_J;
Mikaël Salson's avatar
Mikaël Salson committed
524
525
526
    }
  else
    {
Mathieu Giraud's avatar
Mathieu Giraud committed
527
528
529
530
      Vend = minus_left ;
      Jstart = minus_right ;
      best_V = tag_minus_V ;
      best_J = tag_minus_J ;
Mikaël Salson's avatar
Mikaël Salson committed
531
532
      del_V = del_minus_V ;
      del_J = del_minus_J ;
Mikaël Salson's avatar
Mikaël Salson committed
533
534
      score_V=score_minus_V;
      score_J=score_minus_J;
Mikaël Salson's avatar
Mikaël Salson committed
535
536
    }

Mathieu Giraud's avatar
Mathieu Giraud committed
537
  segmented = (Vend != (int) string::npos) && (Jstart != (int) string::npos) && 
538
    (Jstart - Vend >= germline->delta_min) && (Jstart - Vend <= germline->delta_max);
Mikaël Salson's avatar
Mikaël Salson committed
539
540
541
542
543
    
  dSegmented=false;

  if (!segmented)
    {
544
      because = DONT_KNOW;
Mathieu Giraud's avatar
Mathieu Giraud committed
545
      info = " @" + string_of_int (Vend + FIRST_POS) + "  @" + string_of_int(Jstart + FIRST_POS) ;
546
      
547
      if (Jstart - Vend < germline->delta_min)
548
549
550
551
        {
          because = UNSEG_BAD_DELTA_MIN  ;
        }

552
      if (Jstart - Vend > germline->delta_max)
553
554
555
556
557
558
559
560
561
562
563
564
565
566
        {
          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
567
568
569
      return ;
    }
    
570
571
    because = reversed ? SEG_MINUS : SEG_PLUS ;
    
Mikaël Salson's avatar
Mikaël Salson committed
572
    //overlap VJ
Mathieu Giraud's avatar
Mathieu Giraud committed
573
    if(Jstart-Vend <=0){
Mikaël Salson's avatar
Mikaël Salson committed
574
      int b_r, b_l;
Mathieu Giraud's avatar
Mathieu Giraud committed
575
      int overlap=Vend-Jstart+1;
Mikaël Salson's avatar
Mikaël Salson committed
576
      
Mathieu Giraud's avatar
Mathieu Giraud committed
577
578
      string seq_left = sequence.substr(0, Vend+1);
      string seq_right = sequence.substr(Jstart);
Mikaël Salson's avatar
Mikaël Salson committed
579
580

      best_align(overlap, seq_left, seq_right, 
581
		 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
582
      // Trim V
Mathieu Giraud's avatar
Mathieu Giraud committed
583
      Vend -= b_l;
Mikaël Salson's avatar
Mikaël Salson committed
584
585
586
      del_V += b_l;

      // Trim J
Mathieu Giraud's avatar
Mathieu Giraud committed
587
      Jstart += b_r;
Mikaël Salson's avatar
Mikaël Salson committed
588
      del_J += b_r;
589
      if (Jstart>=(int) sequence.length())
Mathieu Giraud's avatar
Mathieu Giraud committed
590
	  Jstart=sequence.length()-1;
Mikaël Salson's avatar
Mikaël Salson committed
591
592
593
    }

    // string chevauchement = removeChevauchement();
Mikaël Salson's avatar
Mikaël Salson committed
594
595

    /// used only below, then recomputed in finishSegmentation() ;
Mathieu Giraud's avatar
Mathieu Giraud committed
596
    seg_N = revcomp(sequence, reversed).substr(Vend+1, Jstart-Vend-1); 
Mikaël Salson's avatar
Mikaël Salson committed
597

598
  code = germline->rep_5.label(best_V) +
Mikaël Salson's avatar
Mikaël Salson committed
599
600
601
602
    " "+ string_of_int(del_V) + 
    "/" + seg_N + 
    // chevauchement +
    "/" + string_of_int(del_J) +
603
    " " + germline->rep_3.label(best_J); 
Mikaël Salson's avatar
Mikaël Salson committed
604

Mikaël Salson's avatar
Mikaël Salson committed
605
    stringstream code_s;
606
   code_s<< germline->rep_5.label(best_V) <<
Mikaël Salson's avatar
Mikaël Salson committed
607
608
609
610
    " -" << string_of_int(del_V) << "/" 
    << seg_N.size()
    // chevauchement +
    << "/-" << string_of_int(del_J)
611
    <<" " << germline->rep_3.label(best_J);
Mikaël Salson's avatar
Mikaël Salson committed
612
613
    code_short=code_s.str();
    
614
615
  code_light = germline->rep_5.label(best_V) +
    "/ " + germline->rep_3.label(best_J); 
Mikaël Salson's avatar
Mikaël Salson committed
616
617

 
Mathieu Giraud's avatar
Mathieu Giraud committed
618
  info = string_of_int(Vend + FIRST_POS) + " " + string_of_int(Jstart + FIRST_POS) ;
Mikaël Salson's avatar
Mikaël Salson committed
619
620
621
622
623

  finishSegmentation();
}


624
void FineSegmenter::FineSegmentD(Germline *germline){
Mikaël Salson's avatar
Mikaël Salson committed
625
626
627
628
  
  if (segmented){
    
    int end = (int) string::npos ;
Mathieu Giraud's avatar
Mathieu Giraud committed
629
    int tag_D;
Mikaël Salson's avatar
Mikaël Salson committed
630
631
632
633
    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
634
    int l = Vend - EXTEND_D_ZONE;
Mikaël Salson's avatar
Mikaël Salson committed
635
636
637
    if (l<0) 
      l=0 ;

Mathieu Giraud's avatar
Mathieu Giraud committed
638
    int r = Jstart + EXTEND_D_ZONE;
Mikaël Salson's avatar
Mikaël Salson committed
639
640
641
642
643
644
645

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

    // Align
646
    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
647
648
				&length, &score_D, segment_cost);
    
Mathieu Giraud's avatar
Mathieu Giraud committed
649
    best_D = tag_D;
Mikaël Salson's avatar
Mikaël Salson committed
650
    
Mathieu Giraud's avatar
Mathieu Giraud committed
651
652
    Dstart = l + begin;
    Dend = l + end;
Mikaël Salson's avatar
Mikaël Salson committed
653
654
655
656
657
658
	
    string seq = getSequence().sequence;
    
    if (length>0) dSegmented=true;
    
    //overlap VD
Mathieu Giraud's avatar
Mathieu Giraud committed
659
    if(Dstart-Vend <=0){
Mikaël Salson's avatar
Mikaël Salson committed
660
      int b_r, b_l;
Mathieu Giraud's avatar
Mathieu Giraud committed
661
662
663
      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
664
665

      best_align(overlap, seq_left, seq_right, 
666
		 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
667
668

      // Trim V
Mathieu Giraud's avatar
Mathieu Giraud committed
669
      Vend -= b_l;
Mikaël Salson's avatar
Mikaël Salson committed
670
671
672
      del_V += b_l;

      // Trim D
Mathieu Giraud's avatar
Mathieu Giraud committed
673
      Dstart += b_r;
Mikaël Salson's avatar
Mikaël Salson committed
674
    }
Mathieu Giraud's avatar
Mathieu Giraud committed
675
    seg_N1 = seq.substr(Vend+1, Dstart-Vend-1) ; // From Vend+1 to Dstart-1
Mikaël Salson's avatar
Mikaël Salson committed
676
677
    
    //overlap DJ
Mathieu Giraud's avatar
Mathieu Giraud committed
678
    if(Jstart-Dend <=0){
Mikaël Salson's avatar
Mikaël Salson committed
679
      int b_r, b_l;
Mathieu Giraud's avatar
Mathieu Giraud committed
680
681
682
      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
683
684

      best_align(overlap, seq_left, seq_right, 
685
		 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
686
687

      // Trim D
Mathieu Giraud's avatar
Mathieu Giraud committed
688
      Dend -= b_l;
Mikaël Salson's avatar
Mikaël Salson committed
689
690

      // Trim J
Mathieu Giraud's avatar
Mathieu Giraud committed
691
      Jstart += b_r;
Mikaël Salson's avatar
Mikaël Salson committed
692
693
694
      del_J += b_r;

    }
Mathieu Giraud's avatar
Mathieu Giraud committed
695
    seg_N2 = seq.substr(Dend+1, Jstart-Dend-1) ; // From Dend+1 to right-1
696
    code = germline->rep_5.label(best_V) +
Mikaël Salson's avatar
Mikaël Salson committed
697
698
699
700
    " "+ string_of_int(del_V) + 
    "/" + seg_N1 + 
    
    "/" + string_of_int(del_D_left) +
701
    " " + germline->rep_4.label(best_D) +
Mikaël Salson's avatar
Mikaël Salson committed
702
703
704
705
    " " + string_of_int(del_D_right) +
    
    "/" + seg_N2 +
    "/" + string_of_int(del_J) +
706
    " " + germline->rep_3.label(best_J); 
Mikaël Salson's avatar
Mikaël Salson committed
707

Mikaël Salson's avatar
Mikaël Salson committed
708
    stringstream code_s;
709
    code_s << germline->rep_5.label(best_V) 
Mikaël Salson's avatar
Mikaël Salson committed
710
711
712
713
    << " -" << string_of_int(del_V) << "/" 
    << seg_N1.size()
    
    << "/-" << string_of_int(del_D_left) 
714
    << " " << germline->rep_4.label(best_D) 
Mikaël Salson's avatar
Mikaël Salson committed
715
716
717
718
    << " -" << string_of_int(del_D_right) << "/"
    
    << seg_N2.size()
    << "/-" << string_of_int(del_J) 
719
    << " " << germline->rep_3.label(best_J);
Mikaël Salson's avatar
Mikaël Salson committed
720
721
722
    code_short=code_s.str();
    
    
723
724
725
    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
726
727
728
729
    
    finishSegmentationD();
  }
}
Mikaël Salson's avatar
Mikaël Salson committed
730

731
JsonList FineSegmenter::toJsonList(Germline *germline){
Mathieu Giraud's avatar
Mathieu Giraud committed
732
  JsonList result;
Mikaël Salson's avatar
Mikaël Salson committed
733
  
Mathieu Giraud's avatar
Mathieu Giraud committed
734
735
736
737
  result.add("sequence", revcomp(sequence, reversed) );
  if (isSegmented()) {
    result.add("name", code_short);
    
738
    JsonList seg;
Marc Duez's avatar
Marc Duez committed
739
    seg.add("5", germline->rep_5.label(best_V));
740
741
    seg.add("5start", 0);
    seg.add("5end", Vend);
Mathieu Giraud's avatar
Mathieu Giraud committed
742
743
    
    if (score_D.size()>0){
Marc Duez's avatar
Marc Duez committed
744
      seg.add("4", germline->rep_4.label(best_D));
Marc Duez's avatar
Marc Duez committed
745
746
      seg.add("4start", Dstart);
      seg.add("4end", Dend);      
Mikaël Salson's avatar
Mikaël Salson committed
747
    }
Mathieu Giraud's avatar
Mathieu Giraud committed
748
    
Marc Duez's avatar
Marc Duez committed
749
    seg.add("3", germline->rep_3.label(best_J));
750
751
752
    seg.add("3start", Jstart);
    
    result.add("seg", seg);
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
}