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