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1 /*
2  *  slayer.cpp
3  *  Mothur
4  *
5  *  Created by westcott on 9/25/09.
6  *  Copyright 2009 Schloss Lab. All rights reserved.
7  *
8  */
9
10 #include "slayer.h"
11
12 /***********************************************************************/
13 Slayer::Slayer(int win, int increment, int parentThreshold, float div, int i, int snp, int mi) :
14                 minBS(mi), windowSize(win), windowStep(increment), parentFragmentThreshold(parentThreshold), divRThreshold(div), iters(i), percentSNPSample(snp){ m = MothurOut::getInstance(); }
15 /***********************************************************************/
16 string Slayer::getResults(Sequence* query, vector<Sequence*> refSeqs) {
17         try {
18                 vector<data_struct> all; all.clear();
19                 myQuery = *query;
20
21                 for (int i = 0; i < refSeqs.size(); i++) {
22                 
23                         for (int j = i+1; j < refSeqs.size(); j++) {
24                         
25                                 if (m->control_pressed) { return "no";  }
26         
27                                 //make copies of query and each parent because runBellerophon removes gaps and messes them up
28                                 Sequence* q = new Sequence(query->getName(), query->getAligned());
29                                 Sequence* leftParent = new Sequence(refSeqs[i]->getName(), refSeqs[i]->getAligned());
30                                 Sequence* rightParent = new Sequence(refSeqs[j]->getName(), refSeqs[j]->getAligned());
31                                 
32                                 //cout << q->getName() << endl << q->getAligned() << endl << endl;      
33                                 //cout << leftParent->getName() << endl << leftParent->getAligned() << endl << endl;            
34                                 //cout << rightParent->getName() << endl << rightParent->getAligned() << endl << endl;  
35                                 //cout << " length = " << rightParent->getAligned().length() << endl;
36         
37                                 map<int, int> spots;  //map from spot in original sequence to spot in filtered sequence for query and both parents
38                                 vector<data_struct> divs = runBellerophon(q, leftParent, rightParent, spots);
39         
40                                 if (m->control_pressed) { delete q; delete leftParent; delete rightParent; return "no"; }
41 //                              cout << "examining:\t" << refSeqs[i]->getName() << '\t' << refSeqs[j]->getName() << endl;
42                                 vector<data_struct> selectedDivs;
43                                 for (int k = 0; k < divs.size(); k++) {
44                                         
45                                         vector<snps> snpsLeft = getSNPS(divs[k].parentA.getAligned(), divs[k].querySeq.getAligned(), divs[k].parentB.getAligned(), divs[k].winLStart, divs[k].winLEnd);
46                                         vector<snps> snpsRight = getSNPS(divs[k].parentA.getAligned(), divs[k].querySeq.getAligned(), divs[k].parentB.getAligned(), divs[k].winRStart, divs[k].winREnd);
47         
48                                         if (m->control_pressed) { delete q; delete leftParent; delete rightParent; return "no"; }
49                                         
50                                         int numSNPSLeft = snpsLeft.size();
51                                         int numSNPSRight = snpsRight.size();
52                                         
53 //                                      cout << numSNPSLeft << '\t' << numSNPSRight << endl;
54                                         //require at least 4 SNPs on each side of the break
55                                         if ((numSNPSLeft >= 4) && (numSNPSRight >= 4)) {
56                                                         
57                                                 float BS_A, BS_B;
58                                                 bootstrapSNPS(snpsLeft, snpsRight, BS_A, BS_B, iters);
59                                                 
60                                                 if (m->control_pressed) { delete q; delete leftParent; delete rightParent; return "no"; }
61
62                                                 divs[k].bsa = BS_A;
63                                                 divs[k].bsb = BS_B;
64                                                 divs[k].bsMax = max(BS_A, BS_B);
65                                                 divs[k].chimeraMax = max(divs[k].qla_qrb, divs[k].qlb_qra);
66                                                 
67                                                 
68                                                 //are we within 10 points of the bootstrap cutoff?
69 //                                              if ((divs[k].bsMax >= (minBS-10)) && (iters < 1000)) {
70 //                                                      bootstrapSNPS(snpsLeft, snpsRight, BS_A, BS_B, 1000);
71 //                                                              
72 //                                                      if (m->control_pressed) { delete q; delete leftParent; delete rightParent; return "no"; }
73 //                                                              
74 //                                                      divs[k].bsa = BS_A;
75 //                                                      divs[k].bsb = BS_B;
76 //                                                      divs[k].bsMax = max(BS_A, BS_B);
77 //                                                      divs[k].chimeraMax = max(divs[k].qla_qrb, divs[k].qlb_qra);
78 //                                              }
79                                                 
80                                                 //so results reflect orignal alignment
81                                                 divs[k].winLStart = spots[divs[k].winLStart];
82                                                 divs[k].winLEnd = spots[divs[k].winLEnd];  
83                                                 divs[k].winRStart = spots[divs[k].winRStart]; 
84                                                 divs[k].winREnd = spots[divs[k].winREnd]; 
85                                                 
86                                                 selectedDivs.push_back(divs[k]);
87                                         }
88                                 }
89
90                                 //save selected
91                                 for (int mi = 0; mi < selectedDivs.size(); mi++) {  all.push_back(selectedDivs[mi]);    }
92                                 
93                                 delete q;
94                                 delete leftParent;
95                                 delete rightParent;
96                         }
97                 }
98                 
99
100                 // compute bootstrap support
101                 if (all.size() > 0) {
102                         //sort them
103                         sort(all.begin(), all.end(), compareDataStruct);
104                         reverse(all.begin(), all.end());
105                                                 
106                         outputResults = all;
107                         return "yes"; 
108                 }else {
109                         outputResults = all;
110                         return "no";
111                 }
112         }
113         catch(exception& e) {
114                 m->errorOut(e, "Slayer", "getResults");
115                 exit(1);
116         }
117 }
118 /***********************************************************************/
119 vector<data_struct> Slayer::runBellerophon(Sequence* q, Sequence* pA, Sequence* pB, map<int, int>& spots) {
120         try{
121                 
122                 vector<data_struct> data;
123                 
124                 //vertical filter
125                 vector<Sequence*> temp;
126                 temp.push_back(q); temp.push_back(pA); temp.push_back(pB);
127                 
128                 //maps spot in new alignment to spot in alignment before filter
129                 spots = verticalFilter(temp);  //fills baseSpots
130                 
131                 //get these to avoid numerous function calls
132                 string query = q->getAligned();
133                 string parentA = pA->getAligned();
134                 string parentB = pB->getAligned();
135                 int length = query.length();
136 //cout << q->getName() << endl << q->getAligned() << endl << endl;      
137 //cout << pA->getName() << endl << pA->getUnaligned() << endl << endl;          
138 //cout << pB->getName() << endl << pB->getUnaligned() << endl << endl;  
139 //cout << " length = " << length << endl;
140         
141                 //check window size
142                 if (length < (2*windowSize+windowStep)) { 
143 //                      m->mothurOut("Your window size is too large for " + q->getName() + ". I will make the window size " + toString(length/4) + " which is 1/4 the filtered length."); m->mothurOutEndLine();        
144                         windowSize = length / 4;
145                 }
146                 
147                 for (int i = windowSize-1; i <= (length - windowSize); i += windowStep) {
148                 
149                         if (m->control_pressed) { return data; }
150                 
151                         int breakpoint = i;
152                         int leftLength = breakpoint + 1;
153                         int rightLength = length - leftLength;
154                                 
155                         float QLA = computePercentID(query, parentA, 0, breakpoint);
156                         float QRB = computePercentID(query, parentB, breakpoint+1, length-1);
157                 
158                         float QLB = computePercentID(query, parentB, 0, breakpoint);
159                         float QRA = computePercentID(query, parentA, breakpoint+1, length-1);
160                 
161                         float LAB = computePercentID(parentA, parentB, 0, breakpoint);
162                         float RAB = computePercentID(parentA, parentB, breakpoint+1, length-1); 
163                         
164                         float AB = ((LAB*leftLength) + (RAB*rightLength)) / (float) length;
165                         float QA = ((QLA*leftLength) + (QRA*rightLength)) / (float) length;
166                         float QB = ((QLB*leftLength) + (QRB*rightLength)) / (float) length;
167                 
168                         float QLA_QRB = ((QLA*leftLength) + (QRB*rightLength)) / (float) length;
169                         float QLB_QRA = ((QLB*leftLength) + (QRA*rightLength)) / (float) length;
170                 
171                         //in original and not used
172                         //float avgQA_QB = ((QA*leftLength) + (QB*rightLength)) / (float) length;
173                 
174                         float divR_QLA_QRB = min((QLA_QRB/QA), (QLA_QRB/QB));
175                         float divR_QLB_QRA = min((QLB_QRA/QA), (QLB_QRA/QB));
176                         
177                         
178                         //cout << q->getName() << '\t';
179                         //cout << pA->getName() << '\t';
180                         //cout << pB->getName() << '\t';
181                     //cout << "bp: " << breakpoint << " CHIM_TYPE_A\t" << divR_QLA_QRB << "\tQLA: " << QLA << "\tQRB: " << QRB << "\tQLA_QRB: " << QLA_QRB;
182                         //cout << "\tCHIM_TYPE_B\t" << divR_QLB_QRA << "\tQLB: " << QLB << "\tQRA: " << QRA << "\tQLB_QRA: " << QLB_QRA << endl;
183 //cout << leftLength << '\t' << rightLength << '\t' << QLA << '\t' << QRB << '\t' << QLB << '\t' << QRA  << '\t' << LAB << '\t' << RAB << '\t' << AB << '\t' << QA << '\t' << QB << '\t' << QLA_QRB << '\t' <<  QLB_QRA <<    endl;             
184
185 //cout << divRThreshold << endl;
186 //cout << breakpoint << '\t' << divR_QLA_QRB << '\t' << divR_QLB_QRA << endl;
187                         //is one of them above the 
188                         if (divR_QLA_QRB >= divRThreshold || divR_QLB_QRA >= divRThreshold) {
189                                 
190                                 if (((QLA_QRB > QA) && (QLA_QRB > QB) && (QLA >= parentFragmentThreshold) && (QRB >= parentFragmentThreshold))  ||
191                                         ((QLB_QRA > QA) && (QLB_QRA > QB) && (QLB >=parentFragmentThreshold) && (QRA >= parentFragmentThreshold)))  {
192                                         
193                                         data_struct member;
194                                         
195                                         member.divr_qla_qrb = divR_QLA_QRB;
196                                         member.divr_qlb_qra = divR_QLB_QRA;
197                                         member.qla_qrb = QLA_QRB;
198                                         member.qlb_qra = QLB_QRA;
199                                         member.qla = QLA;
200                                         member.qrb = QRB;
201                                         member.ab = AB; 
202                                         member.qa = QA;
203                                         member.qb = QB; 
204                                         member.lab = LAB; 
205                                         member.rab = RAB; 
206                                         member.qra = QRA; 
207                                         member.qlb = QLB; 
208                                         member.winLStart = 0;
209                                         member.winLEnd = breakpoint;  
210                                         member.winRStart = breakpoint+1; 
211                                         member.winREnd = length-1; 
212                                         member.querySeq = *(q);
213                                         member.parentA = *(pA);
214                                         member.parentB = *(pB);
215                                         member.bsa = 0;
216                                         member.bsb = 0;
217                                         member.bsMax = 0;
218                                         member.chimeraMax = 0;
219                                         
220                                         data.push_back(member);
221                                         
222                                 }//if
223                         }//if
224                 }//for
225                 
226                 
227                 return data;
228                 
229         }
230         catch(exception& e) {
231                 m->errorOut(e, "Slayer", "runBellerophon");
232                 exit(1);
233         }
234 }
235 /***********************************************************************/
236 vector<snps> Slayer::getSNPS(string parentA, string query, string parentB, int left, int right) {
237         try {
238         
239                 vector<snps> data;
240
241                 for (int i = left; i <= right; i++) {
242                         
243                         char A = parentA[i];
244                         char Q = query[i];
245                         char B = parentB[i];
246                         
247                         if ((A != Q) || (B != Q)) {
248
249                                 //ensure not neighboring a gap. change to 12/09 release of chimeraSlayer - not sure what this adds, but it eliminates alot of SNPS
250
251                                 
252                                 if (
253                                         //did query loose a base here during filter??
254                                         ( i == 0 || abs (baseSpots[0][i] - baseSpots[0][i-1]) == 1) &&
255                                         ( i == query.length()-1 || abs (baseSpots[0][i] - baseSpots[0][i+1]) == 1)
256                                         &&
257                                         //did parentA loose a base here during filter??
258                                         ( i == 0 || abs (baseSpots[1][i] - baseSpots[1][i-1]) == 1) &&
259                                         ( i == parentA.length()-1 || abs (baseSpots[1][i] - baseSpots[1][i+1]) == 1) 
260                                         &&
261                                         //did parentB loose a base here during filter??
262                                         ( i == 0 || abs (baseSpots[2][i] - baseSpots[2][i-1]) == 1) &&
263                                         ( i == parentB.length()-1 || abs (baseSpots[2][i] - baseSpots[2][i+1]) == 1)
264                                         ) 
265                                 { 
266                                         snps member;
267                                         member.queryChar = Q;
268                                         member.parentAChar = A;
269                                         member.parentBChar = B;
270                                         data.push_back(member);
271                                 }
272                         }
273                 }
274                 
275                 return data;
276                 
277         }
278         catch(exception& e) {
279                 m->errorOut(e, "Slayer", "getSNPS");
280                 exit(1);
281         }
282 }
283 /***********************************************************************/
284 int Slayer::bootstrapSNPS(vector<snps> left, vector<snps> right, float& BSA, float& BSB, int numIters) {
285         try {
286
287                 srand((unsigned)time( NULL ));
288
289                 int count_A = 0; // sceneario QLA,QRB supported
290                 int count_B = 0; // sceneario QLB,QRA supported
291         
292                 int numLeft = max(1, int(left.size() * percentSNPSample/(float)100 + 0.5));
293                 int numRight = max(1, int(right.size() * percentSNPSample/(float)100 + 0.5));
294
295                 for (int i = 0; i < numIters; i++) {
296                         //random sampling with replacement.
297                 
298                         if (m->control_pressed) { return 0;  }
299                         
300                         vector<snps> selectedLeft;
301
302                         for (int j = 0; j < numLeft; j++) {
303                                 int index = int(rand() % left.size());
304                                 selectedLeft.push_back(left[index]);
305                         }
306
307                         vector<snps> selectedRight;
308                         for (int j = 0; j < numRight; j++) {
309                                 int index = int(rand() % right.size());
310                                 selectedRight.push_back(right[index]);
311                         }
312                 
313                         /* A  ------------------------------------------
314                         #       QLA                     QRA
315                         # Q  ------------------------------------------
316                         #                      |
317                         #                      |
318                         # Q  ------------------------------------------
319                         #       QLB                     QRB
320                         # B  ------------------------------------------ */
321                 
322                 
323                         float QLA = snpQA(selectedLeft);
324                         float QRA = snpQA(selectedRight);
325                 
326                         float QLB = snpQB(selectedLeft);
327                         float QRB = snpQB(selectedRight);
328         
329                         //in original - not used - not sure why?
330                         //float ALB = snpAB(selectedLeft);
331                         //float ARB = snpAB(selectedRight);
332                 
333                         if ((QLA > QLB) && (QRB > QRA)) {
334                                 count_A++;
335                         }
336                 
337                         if ((QLB > QLA) && (QRA > QRB)) {
338                                 count_B++;
339                         }
340                         
341 //cout << "selected left snp: \n";
342 //for (int j = 0; j < selectedLeft.size(); j++) {  cout << selectedLeft[j].parentAChar;  } 
343 //cout << endl;
344 //for (int j = 0; j < selectedLeft.size(); j++) {  cout << selectedLeft[j].queryChar;  }
345 //cout << endl;
346 //for (int j = 0; j < selectedLeft.size(); j++) {  cout << selectedLeft[j].parentBChar;  }
347 //cout << endl;
348 //cout << "selected right snp: \n";
349 //for (int j = 0; j < selectedRight.size(); j++) {  cout << selectedRight[j].parentAChar;  } 
350 //cout << endl;
351 //for (int i = 0; i < selectedRight.size(); i++) {  cout << selectedRight[i].queryChar;  }
352 //cout << endl;
353 //for (int i = 0; i < selectedRight.size(); i++) {  cout << selectedRight[i].parentBChar;  }
354 //cout << endl;         
355                 }
356
357
358                 //cout << count_A << '\t' << count_B << endl;
359
360                 BSA = (float) count_A / (float) numIters * 100;
361                 BSB = (float) count_B / (float) numIters * 100;
362 //cout << "bsa = " << BSA << " bsb = " << BSB << endl;
363
364                 return 0;
365         
366         }
367         catch(exception& e) {
368                 m->errorOut(e, "Slayer", "bootstrapSNPS");
369                 exit(1);
370         }
371 }
372 /***********************************************************************/
373 float Slayer::snpQA(vector<snps> data) {
374         try {
375         
376                 int numIdentical = 0;
377         
378                 for (int i = 0; i < data.size(); i++) {
379                         if (data[i].parentAChar == data[i].queryChar) {
380                                 numIdentical++;
381                         }
382                 }
383
384                 float percentID = (numIdentical / (float) data.size()) * 100;
385                 
386                 return percentID;
387         }
388         catch(exception& e) {
389                 m->errorOut(e, "Slayer", "snpQA");
390                 exit(1);
391         }
392 }
393 /***********************************************************************/
394 float Slayer::snpQB(vector<snps> data) {
395         try {
396         
397                 int numIdentical = 0;
398         
399                 for (int i = 0; i < data.size(); i++) {
400                         if (data[i].parentBChar == data[i].queryChar) {
401                                 numIdentical++;
402                         }
403                 }
404
405                 float percentID = (numIdentical / (float) data.size()) * 100;
406                 
407                 return percentID;
408
409         }
410         catch(exception& e) {
411                 m->errorOut(e, "Slayer", "snpQB");
412                 exit(1);
413         }
414 }
415 /***********************************************************************/
416 float Slayer::snpAB(vector<snps> data) {
417         try {
418                 int numIdentical = 0;
419         
420                 for (int i = 0; i < data.size(); i++) {
421                         if (data[i].parentAChar == data[i].parentBChar) {
422                                 numIdentical++;
423                         }
424                 }
425
426                 float percentID = (numIdentical / (float) data.size()) * 100;
427                 
428                 return percentID;
429
430         }
431         catch(exception& e) {
432                 m->errorOut(e, "Slayer", "snpAB");
433                 exit(1);
434         }
435 }
436 /***********************************************************************/
437 float Slayer::computePercentID(string queryAlign, string chimera, int left, int right) {
438         try {
439                                 
440                 int numIdentical = 0;
441                 int countA = 0;
442                 int countB = 0;
443                 for (int i = left; i <= right; i++) {
444                         if (((queryAlign[i] != 'G') && (queryAlign[i] != 'T') && (queryAlign[i] != 'A') && (queryAlign[i] != 'C')&& (queryAlign[i] != '.') && (queryAlign[i] != '-')) ||
445                                 ((chimera[i] != 'G') && (chimera[i] != 'T') && (chimera[i] != 'A') && (chimera[i] != 'C')&& (chimera[i] != '.') && (chimera[i] != '-'))) {}
446                         else {
447                                 
448                                 bool charA = false; bool charB = false;
449                                 if ((queryAlign[i] == 'G') || (queryAlign[i] == 'T') || (queryAlign[i] == 'A') || (queryAlign[i] == 'C')) { charA = true; }
450                                 if ((chimera[i] == 'G') || (chimera[i] == 'T') || (chimera[i] == 'A') || (chimera[i] == 'C')) { charB = true; }
451                                 
452                                 if (charA || charB) {
453                                         
454                                         if (charA) { countA++; }
455                                         if (charB) { countB++; }
456                                         
457                                         if (queryAlign[i] == chimera[i]) {
458                                                 numIdentical++;
459                                         }
460                                 }
461                         }
462                         
463                 }
464                 
465                 float numBases = (countA + countB) /(float) 2;
466                 
467                 if (numBases == 0) { return 0; }
468                 
469                 float percentIdentical = (numIdentical/(float)numBases) * 100;
470
471                 return percentIdentical;
472                 
473         }
474         catch(exception& e) {
475                 m->errorOut(e, "Slayer", "computePercentID");
476                 exit(1);
477         }
478 }
479 /***********************************************************************/
480 //remove columns that contain any gaps
481 map<int, int> Slayer::verticalFilter(vector<Sequence*> seqs) {
482         try {
483                 //find baseSpots
484                 baseSpots.clear(); 
485                 baseSpots.resize(3);  //query, parentA, parentB
486         
487                 vector<int> gaps;       gaps.resize(seqs[0]->getAligned().length(), 0);
488                 
489                 string filterString = (string(seqs[0]->getAligned().length(), '1'));
490                 
491                 //for each sequence
492                 for (int i = 0; i < seqs.size(); i++) {
493                 
494                         string seqAligned = seqs[i]->getAligned();
495                         
496                         for (int j = 0; j < seqAligned.length(); j++) {
497                                 //if this spot is a gap
498                                 if ((seqAligned[j] == '-') || (seqAligned[j] == '.') || (toupper(seqAligned[j]) == 'N'))        {   gaps[j]++;  }
499                         }
500                 }
501                 
502                 //zero out spot where any sequences have blanks
503                 int numColRemoved = 0;
504                 int count = 0;
505                 map<int, int> maskMap; maskMap.clear();
506
507                 for(int i = 0; i < seqs[0]->getAligned().length(); i++){
508                         if(gaps[i] != 0)        {       filterString[i] = '0';  numColRemoved++;  }
509                         else {
510                                 maskMap[count] = i;
511                                 count++;
512                         }
513                 }
514
515                 //for each sequence
516                 for (int i = 0; i < seqs.size(); i++) {
517                 
518                         string seqAligned = seqs[i]->getAligned();
519                         string newAligned = "";
520                         
521                         int baseCount = 0;
522                         int count = 0;
523                         for (int j = 0; j < seqAligned.length(); j++) {
524                                 //are you a base
525                                 if ((seqAligned[j] != '-') && (seqAligned[j] != '.') && (toupper(seqAligned[j]) != 'N'))        { baseCount++; }
526                         
527                                 //if this spot is not a gap
528                                 if (filterString[j] == '1') { 
529                                         newAligned += seqAligned[j]; 
530                                         baseSpots[i][count] = baseCount;
531                                         count++;
532                                 }
533                         }
534                         
535                         seqs[i]->setAligned(newAligned);
536                 }
537                 
538                 return maskMap;
539         }
540         catch(exception& e) {
541                 m->errorOut(e, "Slayer", "verticalFilter");
542                 exit(1);
543         }
544 }
545 /***********************************************************************/