segment.h 9.62 KB
Newer Older
Mikaël Salson's avatar
Mikaël Salson committed
1 2 3 4
#ifndef SEGMENT_H
#define SEGMENT_H

#include <string>
5
#include <fstream>
Mikaël Salson's avatar
Mikaël Salson committed
6 7 8 9
#include <iostream>
#include "fasta.h"
#include "dynprog.h"
#include "tools.h"
10
#include "germline.h"
Mikaël Salson's avatar
Mikaël Salson committed
11 12
#include "kmerstore.h"
#include "kmeraffect.h"
Mathieu Giraud's avatar
Mathieu Giraud committed
13
#include "affectanalyser.h"
Marc Duez's avatar
Marc Duez committed
14
#include "../lib/json.hpp"
Mikaël Salson's avatar
Mikaël Salson committed
15 16

#define EXTEND_D_ZONE 5
17

18
#define RATIO_STRAND 2          /* The ratio between the affectations in one
Mikaël Salson's avatar
Mikaël Salson committed
19 20
                                   strand and the other, to safely attribute a
                                   segment to a given strand */
Mikaël Salson's avatar
Mikaël Salson committed
21

22 23 24 25
#define DETECT_THRESHOLD_STRAND 5   /* If the number of total affectations
                                       is above this threshold, then a sequence with no clearly attributed
                                       stranf will be marked as STRAND_NOT_CONSISTEN */

26 27 28 29 30
#define DETECT_THRESHOLD 5      /* This threshold only affects the classification of unsegmented sequences.
                                   If the numbers of both V and J affectations are above this threshold,
                                   then the unsegmented sequence will be marked as AMBIGUOUS.
                                   Otherwise, if the number of either V or J affectations if above this threshold,
                                   then the unsegmented sequence will be marked as either ONLY V or ONLY J. */
31

Mathieu Giraud's avatar
Mathieu Giraud committed
32 33
#define JSON_REMEMBER_BEST  4   /* The number of V/D/J predictions to keep  */

34
#define BAD_EVALUE  1e10
35

36
#define THRESHOLD_NB_EXPECTED 1.0 /* Threshold of the accepted expected value for number of found k-mers */
37
#define THRESHOLD_NB_EXPECTED_D  .05 /* e-value threshold, D-REGION */
38

39 40 41 42
#define BOTTOM_TRIANGLE_SHIFT  20   /* Should equal to (max allowed 'k-band') + (max allowed number of V/J deletions) - (min size to recognize facing J/V)
                                       As we need ~10 bp to recognize the facing V/J, this value should be large enough to handle V/J deletions until ~30 bp,
                                       (and even larger V/J deletions if there is a large facing J or V in the read). */

43

44

Mikaël Salson's avatar
Mikaël Salson committed
45
using namespace std;
Marc Duez's avatar
Marc Duez committed
46
using json = nlohmann::json;
Mikaël Salson's avatar
Mikaël Salson committed
47

48 49 50 51
enum SEGMENTED { NOT_PROCESSED,
		 TOTAL_SEG_AND_WINDOW,
                 SEG_PLUS, SEG_MINUS,
                 UNSEG_TOO_SHORT, UNSEG_STRAND_NOT_CONSISTENT,
52
		 UNSEG_TOO_FEW_ZERO,  UNSEG_TOO_FEW_J, UNSEG_TOO_FEW_V,
53
                 UNSEG_BAD_DELTA_MIN, UNSEG_AMBIGUOUS,
54
		 UNSEG_TOO_SHORT_FOR_WINDOW,
55

Mikaël Salson's avatar
Mikaël Salson committed
56
		 STATS_SIZE } ;
57 58 59

#define STATS_FIRST_UNSEG UNSEG_TOO_SHORT

60 61 62 63
const char* const segmented_mesg[] = { "?",
                                       "SEG",
                                       "SEG_+", "SEG_-",
                                       "UNSEG too short", "UNSEG strand",
64
				       "UNSEG too few V/J", "UNSEG only V/5'", "UNSEG only J/3'",
65
				       "UNSEG < delta_min", "UNSEG ambiguous",
66
                                       "UNSEG too short w",
Mikaël Salson's avatar
Mikaël Salson committed
67
                                      } ;
Mikaël Salson's avatar
Mikaël Salson committed
68

69 70


71 72 73 74
/**
 * An alignment box (AlignBox) gather all parameters for a recombined gene segment (V, D, J, other D...)
 **/

75 76 77
class AlignBox
{
 public:
78 79
  string key;

80 81 82 83 84
  int del_left;
  int start;
  int end;
  int del_right;

85
  AlignBox(string key = "");
86
  string getSequence(string sequence);
87
  void addToJson(json &seg);
88 89

  /* Identifier, label and sequence of the reference sequence (the best one) */
90 91 92 93
  int ref_nb;
  string ref_label;
  string ref;

94 95
  /* Identifiers and scores of other possible reference sequence */
  vector<pair<int, int> > score;
96 97
};

98
ostream &operator<<(ostream &out, const AlignBox &box);
99

100
/**
101
 * Check whether there is an overlap between two boxes,
102 103 104
 * If this is the case, fix this overlap (finding the best split point), and update segmentation accordingly
 * @param seq:                             the read
 * @param seq_begin, seq_end:              the positions to consider on 'seq' for the two sequences that may overlap
105
 * @param *box_left, *box_right            the two boxes
106 107
 * @param segment_cost:                    the cost used by the dynamic programing
 *
108 109
 * @post  box_left->del_left and box_right->del_right are set to the best number of nucleotides to trim in order to remove the overlap.
 *        box_left->end and box_right->start are shifted by the good number of nucleotides
110 111 112 113 114
 *
 * @return                                 the N segment
 */

string check_and_resolve_overlap(string seq, int seq_begin, int seq_end,
115 116
                                 AlignBox *box_left, AlignBox *box_right,
                                 Cost segment_cost);
117

Mikaël Salson's avatar
Mikaël Salson committed
118 119 120
class Segmenter {
protected:
  string sequence;
121
  string sequence_or_rc;
122 123

  int JUNCTIONstart, JUNCTIONend;
124 125
  string JUNCTIONaa;

Marc Duez's avatar
Marc Duez committed
126
  int CDR3start, CDR3end;
127 128
  string CDR3nuc;
  string CDR3aa;
129

Mikaël Salson's avatar
Mikaël Salson committed
130
  bool reversed, segmented, dSegmented;
131
  int because;
Mikaël Salson's avatar
Mikaël Salson committed
132

133 134 135 136 137 138
  /**
   * Compares evalue_left, evalue_right and evalue against the provided threshold
   * @post some evalue is above the threshold ==> because is set to UNSEG_TOO_FEW_ZERO, UNSEG_TOO_FEW_V or UNSEG_TOO_FEW_J
   */
  void checkLeftRightEvaluesThreshold(double threshold, int strand);

Mikaël Salson's avatar
Mikaël Salson committed
139 140 141 142 143
  string removeChevauchement();
  bool finishSegmentation();
  bool finishSegmentationD();

 public:
144
  Germline *segmented_germline;
145
  string label;
Mikaël Salson's avatar
Mikaël Salson committed
146
  string code;
147 148
  string info;        // .vdj.fa header, fixed fields
  string info_extra;  // .vdj.fa header, other information, at the end of the header
149
  string seg_V, seg_N, seg_J, system;
150

151 152
  AlignBox *box_V, *box_D, *box_J;

153
  double evalue;
154 155
  double evalue_left;
  double evalue_right;
Mikaël Salson's avatar
Mikaël Salson committed
156 157 158
  string seg_N1, seg_D, seg_N2;
  Cost segment_cost;

Mathieu Giraud's avatar
Mathieu Giraud committed
159
  virtual ~Segmenter();
Mikaël Salson's avatar
Mikaël Salson committed
160

Mathieu Giraud's avatar
Mathieu Giraud committed
161
  /* Queries */
Mikaël Salson's avatar
Mikaël Salson committed
162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212



  Sequence getSequence() const ;

  /**
   * @param l: length around the junction
   * @return the string centered on the junction (ie. at position
   *         (getLeft() + getRight())/2).
   *         The string has length l unless the original string 
   *         is not long enough.
   *         The junction is revcomp-ed if the original string comes from reverse
   *         strand.
   */
  string getJunction(int l) const;

  /**
   * @return the left position (on forward strand) of the segmentation.
   */
  int getLeft() const;
  
  /**
   * @return the right position (on forward strand) of the segmentation
   */
  int getRight() const;
  
  /**
   * @return the left position (on forward strand) of the D segmentation.
   */
  int getLeftD() const;
  
  /**
   * @return the right position (on forward strand) of the D segmentation
   */
  int getRightD() const;

  /**
   * @return true iff the string comes from reverse strand
   */
  bool isReverse() const;

  /**
   * @return true iff the sequence has been successfully segmented
   */
  bool isSegmented() const;
  
  /**
   * @return true if a D gene was found in the N region
   */
  bool isDSegmented() const;

213 214 215 216 217 218 219 220 221
  /**
   * @return the status of the segmentation. Tells if the Sequence has been segmented
   *         of if it has not, what the reason is.
   * @assert getSegmentationStatus() == SEG_PLUS || getSegmentationStatus() == SEG_MINUS
   *         <==> isSegmented()
   */
  int getSegmentationStatus() const;

  string getInfoLine() const;
Mikaël Salson's avatar
Mikaël Salson committed
222

223 224 225 226 227
  /**
   * @post status == SEG_PLUS || status == SEG_MINUS <==> isSegmented()
   */
  void setSegmentationStatus(int status);

Mikaël Salson's avatar
Mikaël Salson committed
228 229 230 231 232 233 234 235 236 237 238
  friend ostream &operator<<(ostream &out, const Segmenter &s);
};



ostream &operator<<(ostream &out, const Segmenter &s);



class KmerSegmenter : public Segmenter
{
Mathieu Giraud's avatar
Mathieu Giraud committed
239
 private:
240
  KmerAffectAnalyser *kaa;
Mikaël Salson's avatar
Mikaël Salson committed
241 242 243 244
 protected:
  string affects;

 public:
245
  int score;
246 247
  int pvalue_left;
  int pvalue_right;
248
  KmerAffect before, after;
249 250

  KmerSegmenter();
Mikaël Salson's avatar
Mikaël Salson committed
251 252 253
  /**
   * Build a segmenter based on KmerSegmentation
   * @param seq: An object read from a FASTA/FASTQ file
254
   * @param germline: the germline
Mikaël Salson's avatar
Mikaël Salson committed
255
   */
256
  KmerSegmenter(Sequence seq, Germline *germline, double threshold = THRESHOLD_NB_EXPECTED, int multiplier=1);
Mathieu Giraud's avatar
Mathieu Giraud committed
257

258 259
  KmerSegmenter(const KmerSegmenter &seg);

Mathieu Giraud's avatar
Mathieu Giraud committed
260 261 262 263 264
  ~KmerSegmenter();

  /**
   * @return the KmerAffectAnalyser of the current sequence.
   */
265
  KmerAffectAnalyser *getKmerAffectAnalyser() const;
Mathieu Giraud's avatar
Mathieu Giraud committed
266

267
  string getInfoLineWithAffects() const;
Marc Duez's avatar
Marc Duez committed
268
  json toJson();
269

Mathieu Giraud's avatar
Mathieu Giraud committed
270
 private:
271 272
  void computeSegmentation(int strand, KmerAffect left, KmerAffect right,
                           double threshold, int multiplier);
Mikaël Salson's avatar
Mikaël Salson committed
273 274
};

275 276 277

class KmerMultiSegmenter
{
278 279
 private:
  double threshold_nb_expected;
280 281 282
 public:
  /**
   * @param seq: An object read from a FASTA/FASTQ file
283 284 285 286
   * @param multigermline: the multigerm
   * @param threshold: threshold of randomly expected segmentation
   */
  KmerMultiSegmenter(Sequence seq, MultiGermline *multigermline, ostream *out_unsegmented,
287
                     double threshold = THRESHOLD_NB_EXPECTED, int nb_reads_for_evalue = 1);
288

289 290
  ~KmerMultiSegmenter();

291
  KmerSegmenter *the_kseg;
292
  MultiGermline *multi_germline;
293 294 295
};


Mikaël Salson's avatar
Mikaël Salson committed
296 297 298
class FineSegmenter : public Segmenter
{
 public:
Mikaël Salson's avatar
Mikaël Salson committed
299 300 301
   vector<pair<int, int> > score_V;
   vector<pair<int, int> > score_D;
   vector<pair<int, int> > score_J;
302 303

   vector <AlignBox*> boxes ;
Mikaël Salson's avatar
Mikaël Salson committed
304
   
Mikaël Salson's avatar
Mikaël Salson committed
305 306 307
   /**
   * Build a fineSegmenter based on KmerSegmentation
   * @param seq: An object read from a FASTA/FASTQ file
308
   * @param germline: germline used
Mikaël Salson's avatar
Mikaël Salson committed
309
   */
310 311
   FineSegmenter(Sequence seq, Germline *germline, Cost segment_cost,
                 double threshold = THRESHOLD_NB_EXPECTED, int multiplier=1);
312 313 314

   ~FineSegmenter();

Mikaël Salson's avatar
Mikaël Salson committed
315 316
  /**
  * extend segmentation from VJ to VDJ
317
  * @param germline: germline used
Mikaël Salson's avatar
Mikaël Salson committed
318
  */
319
  void FineSegmentD(Germline *germline, bool several_D,
320
                    double threshold = THRESHOLD_NB_EXPECTED_D, int multiplier=1);
321 322

  bool FineSegmentD(Germline *germline,
323
                    AlignBox *box_Y, AlignBox *box_DD, AlignBox *box_Z,
324
                    int forbidden_id,
325
                    int extend_DD_on_Y, int extend_DD_on_Z,
326 327
                    double threshold = THRESHOLD_NB_EXPECTED_D, int multiplier=1);

Marc Duez's avatar
Marc Duez committed
328
  void findCDR3();
Mathieu Giraud's avatar
Mathieu Giraud committed
329

Marc Duez's avatar
Marc Duez committed
330
  json toJson();
Mikaël Salson's avatar
Mikaël Salson committed
331
  
Mikaël Salson's avatar
Mikaël Salson committed
332 333 334 335 336
};



#endif