5 * Created by Pat Schloss on 1/31/11.
6 * Copyright 2011 Schloss Lab. All rights reserved.
10 #include "refchimeratest.h"
11 #include "myPerseus.h"
14 int MAXINT = numeric_limits<int>::max();
16 //***************************************************************************************************************
18 RefChimeraTest::RefChimeraTest(vector<Sequence>& refs, bool aligned) : aligned(aligned){
20 m = MothurOut::getInstance();
22 numRefSeqs = refs.size();
24 referenceSeqs.resize(numRefSeqs);
25 referenceNames.resize(numRefSeqs);
26 for(int i=0;i<numRefSeqs;i++){
27 referenceSeqs[i] = refs[i].getAligned();
28 referenceNames[i] = refs[i].getName();
31 alignLength = referenceSeqs[0].length();
34 //***************************************************************************************************************
36 int RefChimeraTest::printHeader(ofstream& chimeraReportFile){
38 chimeraReportFile << "queryName\tbestRef\tbestSequenceMismatch\tleftParentChi,rightParentChi\tbreakPointChi\tminMismatchToChimera\tdistToBestMera\tnumParents" << endl;
40 }catch(exception& e) {
41 m->errorOut(e, "RefChimeraTest", "execute");
46 //***************************************************************************************************************
48 int RefChimeraTest::analyzeQuery(string queryName, string querySeq, ofstream& chimeraReportFile){
53 numParents = analyzeAlignedQuery(queryName, querySeq, chimeraReportFile);
56 numParents = analyzeUnalignedQuery(queryName, querySeq, chimeraReportFile);
63 //***************************************************************************************************************
65 int RefChimeraTest::analyzeAlignedQuery(string queryName, string querySeq, ofstream& chimeraReportFile){
67 vector<vector<int> > left(numRefSeqs);
68 vector<int> singleLeft, bestLeft;
69 vector<int> singleRight, bestRight;
71 vector<vector<int> > right(numRefSeqs);
72 for(int i=0;i<numRefSeqs;i++){
73 left[i].assign(alignLength, 0);
77 int bestSequenceMismatch = getAlignedMismatches(querySeq, left, right, bestMatch);
81 int leftParentBi, rightParentBi, breakPointBi;
82 int minMismatchToChimera = getChimera(left, right, leftParentBi, rightParentBi, breakPointBi, singleLeft, bestLeft, singleRight, bestRight);
85 string chimeraRefSeq = "";
87 if(bestSequenceMismatch - minMismatchToChimera >= 3){// || (minMismatchToChimera == 0 && bestSequenceMismatch != 0)){
89 chimeraRefSeq = stitchBimera(leftParentBi, rightParentBi, breakPointBi);
93 chimeraRefSeq = referenceSeqs[bestMatch];
96 bestRefAlignment = chimeraRefSeq;
97 bestQueryAlignment = querySeq;
99 double distToChimera = calcDistToChimera(bestQueryAlignment, bestRefAlignment);
101 chimeraReportFile << queryName << '\t' << referenceNames[bestMatch] << '\t' << bestSequenceMismatch << '\t';
102 chimeraReportFile << referenceNames[leftParentBi] << ',' << referenceNames[rightParentBi] << '\t' << breakPointBi << '\t';
103 chimeraReportFile << minMismatchToChimera << '\t';
104 chimeraReportFile << '\t' << distToChimera << '\t' << nMera << endl;
109 //***************************************************************************************************************
111 int RefChimeraTest::analyzeUnalignedQuery(string queryName, string querySeq, ofstream& chimeraReportFile){
115 int seqLength = querySeq.length();
117 vector<string> queryAlign(numRefSeqs);
118 vector<string> refAlign(numRefSeqs);
120 vector<vector<int> > leftDiffs(numRefSeqs);
121 vector<vector<int> > rightDiffs(numRefSeqs);
122 vector<vector<int> > leftMaps(numRefSeqs);
123 vector<vector<int> > rightMaps(numRefSeqs);
125 int bestRefIndex = -1;
126 int bestRefDiffs = numeric_limits<int>::max();
127 double bestRefLength = 0;
129 for(int i=0;i<numRefSeqs;i++){
131 int diffs = alignQueryToReferences(querySeq, referenceSeqs[i], queryAlign[i], refAlign[i], length);
132 if(diffs < bestRefDiffs){
133 bestRefDiffs = diffs;
134 bestRefLength = length;
139 if(bestRefDiffs >= 3){
140 for(int i=0;i<numRefSeqs;i++){
141 leftDiffs[i].assign(seqLength, 0);
142 rightDiffs[i].assign(seqLength, 0);
143 leftMaps[i].assign(seqLength, 0);
144 rightMaps[i].assign(seqLength, 0);
146 getUnalignedDiffs(queryAlign[i], refAlign[i], leftDiffs[i], leftMaps[i], rightDiffs[i], rightMaps[i]);
149 vector<int> singleLeft(seqLength, numeric_limits<int>::max());
150 vector<int> bestLeft(seqLength, -1);
152 for(int l=0;l<seqLength;l++){
154 for(int i=0;i<numRefSeqs;i++){
155 if(leftDiffs[i][l] < singleLeft[l]){
156 singleLeft[l] = leftDiffs[i][l];
162 vector<int> singleRight(seqLength, numeric_limits<int>::max());
163 vector<int> bestRight(seqLength, -1);
165 for(int l=0;l<seqLength;l++){
167 for(int i=0;i<numRefSeqs;i++){
168 if(rightDiffs[i][l] < singleRight[l]){
169 singleRight[l] = rightDiffs[i][l];
175 int bestChimeraMismatches = numeric_limits<int>::max();
180 for(int l=0;l<seqLength-1;l++){
182 int chimera = singleLeft[l] + singleRight[seqLength - l - 2];
183 if(chimera < bestChimeraMismatches){
184 bestChimeraMismatches = chimera;
186 leftParent = bestLeft[l];
187 rightParent = bestRight[seqLength - l - 2];
193 if(bestRefDiffs - bestChimeraMismatches >= 3){// || (minMismatchToChimera == 0 && bestSequenceMismatch != 0)){
196 int breakLeft = leftMaps[leftParent][breakPoint];
197 int breakRight = rightMaps[rightParent][rightMaps[rightParent].size() - breakPoint - 2];
199 string left = refAlign[leftParent];
200 string right = refAlign[rightParent];
202 for(int i=0;i<=breakLeft;i++){
204 if (m->control_pressed) { return 0; }
206 if(left[i] != '-' && left[i] != '.'){
207 reference += left[i];
212 for(int i=breakRight;i<right.length();i++){
214 if (m->control_pressed) { return 0; }
216 if(right[i] != '-' && right[i] != '.'){
217 reference += right[i];
224 reference = referenceSeqs[bestRefIndex];
228 double finalDiffs = alignQueryToReferences(querySeq, reference, bestQueryAlignment, bestRefAlignment, alignLength);
229 double finalDistance = finalDiffs / alignLength;
231 chimeraReportFile << queryName << '\t' << referenceNames[bestRefIndex] << '\t' << bestRefDiffs << '\t';
232 chimeraReportFile << referenceNames[leftParent] << ',' << referenceNames[rightParent] << '\t' << breakPoint << '\t';
233 chimeraReportFile << bestChimeraMismatches << '\t';
234 chimeraReportFile << '\t' << finalDistance << '\t' << nMera << endl;
237 bestQueryAlignment = queryAlign[bestRefIndex];
238 bestRefAlignment = refAlign[bestRefIndex];
241 chimeraReportFile << queryName << '\t' << referenceNames[bestRefIndex] << '\t' << bestRefDiffs << '\t';
242 chimeraReportFile << "NA\tNA\tNA\tNA\t1" << endl;
245 bestMatch = bestRefIndex;
249 /**************************************************************************************************/
251 double RefChimeraTest::alignQueryToReferences(string query, string reference, string& qAlign, string& rAlign, double& length){
257 double MISMATCH = -1;
259 int queryLength = query.length();
260 int refLength = reference.length();
262 vector<vector<double> > alignMatrix(queryLength + 1);
263 vector<vector<char> > alignMoves(queryLength + 1);
265 for(int i=0;i<=queryLength;i++){
266 if (m->control_pressed) { return 0; }
267 alignMatrix[i].resize(refLength + 1, 0);
268 alignMoves[i].resize(refLength + 1, 'x');
271 for(int i=0;i<=queryLength;i++){
272 if (m->control_pressed) { return 0; }
273 alignMatrix[i][0] = 0;//GAP * i;
274 alignMoves[i][0] = 'u';
277 for(int i=0;i<=refLength;i++){
278 if (m->control_pressed) { return 0; }
279 alignMatrix[0][i] = 0;//GAP * i;
280 alignMoves[0][i] = 'l';
283 for(int i=1;i<=queryLength;i++){
285 if (m->control_pressed) { return 0; }
287 for(int j=1;j<=refLength;j++){
290 if(query[i-1] == reference[j-1]){ nogapScore = alignMatrix[i-1][j-1] + MATCH; }
291 else { nogapScore = alignMatrix[i-1][j-1] + MISMATCH; }
294 if(i == queryLength) { leftScore = alignMatrix[i][j-1]; }
295 else { leftScore = alignMatrix[i][j-1] + GAP; }
299 if(j == refLength) { upScore = alignMatrix[i-1][j]; }
300 else { upScore = alignMatrix[i-1][j] + GAP; }
302 if(nogapScore > leftScore){
303 if(nogapScore > upScore){
304 alignMoves[i][j] = 'd';
305 alignMatrix[i][j] = nogapScore;
308 alignMoves[i][j] = 'u';
309 alignMatrix[i][j] = upScore;
313 if(leftScore > upScore){
314 alignMoves[i][j] = 'l';
315 alignMatrix[i][j] = leftScore;
318 alignMoves[i][j] = 'u';
319 alignMatrix[i][j] = upScore;
325 int end = refLength - 1;
327 double maxRowValue = -100000000000;
328 for(int i=0;i<queryLength;i++){
329 if(alignMatrix[i][end] > maxRowValue){
331 maxRowValue = alignMatrix[i][end];
335 end = queryLength - 1;
337 double maxColumnValue = -100000000000;
339 for(int j=0;j<refLength;j++){
340 if(alignMatrix[end][j] > maxColumnValue){
342 maxColumnValue = alignMatrix[end][j];
346 int row = queryLength-1;
347 int column = refLength-1;
349 if(maxColumn == column && maxRow == row){} // if the max values are the lower right corner, then we're good
350 else if(alignMatrix[row][maxColumn] < alignMatrix[maxRow][column]){
351 for(int i=maxRow+1;i<queryLength;i++){ // decide whether sequence A or B needs the gaps at the end either set
352 alignMoves[i][column] = 'u';// the pointer upwards or...
357 for(int i=maxColumn+1;i<refLength;i++){
358 alignMoves[row][i] = 'l'; // ...to the left
372 while(i > 0 && j > 0){
374 if (m->control_pressed) { return 0; }
376 if(alignMoves[i][j] == 'd'){
377 qAlign = query[i-1] + qAlign;
378 rAlign = reference[j-1] + rAlign;
380 if(query[i-1] != reference[j-1]){ diffs++; }
386 else if(alignMoves[i][j] == 'u'){
387 qAlign = query[i-1] + qAlign;
389 if(j != refLength) { rAlign = '-' + rAlign; diffs++; length++; }
390 else { rAlign = '.' + rAlign; }
393 else if(alignMoves[i][j] == 'l'){
394 rAlign = reference[j-1] + rAlign;
396 if(i != queryLength){ qAlign = '-' + qAlign; diffs++; length++; }
397 else { qAlign = '.' + qAlign; }
403 qAlign = query.substr(0, i) + qAlign;
404 rAlign = string(i, '.') + rAlign;
407 qAlign = string(j, '.') + qAlign;
408 rAlign = reference.substr(0, j) + rAlign;
414 catch(exception& e) {
415 m->errorOut(e, "RefChimeraTest", "alignQueryToReferences");
420 /**************************************************************************************************/
422 int RefChimeraTest::getUnalignedDiffs(string qAlign, string rAlign, vector<int>& leftDiffs, vector<int>& leftMap, vector<int>& rightDiffs, vector<int>& rightMap){
424 int alignLength = qAlign.length();
428 for(int l=0;l<alignLength;l++){
430 if (m->control_pressed) { return 0; }
432 if(qAlign[l] == '-'){
435 else if(qAlign[l] != '.'){
437 if(rAlign[l] == '-'){
440 else if(qAlign[l] != rAlign[l]){;// && rAlign[l] != '.'){
443 leftDiffs[lCount] = lDiffs;
452 for(int l=alignLength-1;l>=0;l--){
454 if (m->control_pressed) { return 0; }
456 if(qAlign[l] == '-'){
459 else if(qAlign[l] != '.'){
461 if(rAlign[l] == '-'){
464 else if(qAlign[l] != rAlign[l]){;// && rAlign[l] != '.'){
468 rightDiffs[rCount] = rDiffs;
469 rightMap[rCount] = l;
477 catch(exception& e) {
478 m->errorOut(e, "RefChimeraTest", "getUnalignedDiffs");
483 /**************************************************************************************************/
485 int RefChimeraTest::getAlignedMismatches(string& querySeq, vector<vector<int> >& left, vector<vector<int> >& right, int& bestRefSeq){
487 int bestSequenceMismatch = MAXINT;
489 for(int i=0;i<numRefSeqs;i++){
493 for(int l=0;l<alignLength;l++){
494 if(querySeq[l] != '.' && referenceSeqs[i][l] != '.' && querySeq[l] != referenceSeqs[i][l] && referenceSeqs[i][l] != 'N'){
502 for(int l=alignLength-1;l>=0;l--){
503 if(querySeq[l] != '.' && referenceSeqs[i][l] != '.' && querySeq[l] != referenceSeqs[i][l] && referenceSeqs[i][l] != 'N'){
506 right[i][index++] = rDiffs;
509 if(lDiffs < bestSequenceMismatch){
510 bestSequenceMismatch = lDiffs;
514 return bestSequenceMismatch;
517 /**************************************************************************************************/
519 int RefChimeraTest::getChimera(vector<vector<int> >& left, vector<vector<int> >& right, int& leftParent, int& rightParent, int& breakPoint, vector<int>& singleLeft, vector<int>& bestLeft, vector<int>& singleRight, vector<int>& bestRight){
521 singleLeft.resize(alignLength, MAXINT);
522 bestLeft.resize(alignLength, -1);
524 for(int l=0;l<alignLength;l++){
525 for(int i=0;i<numRefSeqs;i++){
526 if(left[i][l] <= singleLeft[l]){
527 singleLeft[l] = left[i][l];
533 singleRight.resize(alignLength, MAXINT);
534 bestRight.resize(alignLength, -1);
536 for(int l=0;l<alignLength;l++){
537 for(int i=0;i<numRefSeqs;i++){
538 if(right[i][l] <= singleRight[l]){
539 singleRight[l] = right[i][l];
545 int bestChimeraMismatches = MAXINT;
550 for(int l=0;l<alignLength;l++){
551 int chimera = singleLeft[l] + singleRight[alignLength - l - 1];
552 if(chimera < bestChimeraMismatches){
553 bestChimeraMismatches = chimera;
555 leftParent = bestLeft[l];
556 rightParent = bestRight[alignLength - l - 1];
560 return bestChimeraMismatches;
563 /**************************************************************************************************/
565 int RefChimeraTest::getTrimera(vector<vector<int> >& left, vector<vector<int> >& right, int& leftParent, int& middleParent, int& rightParent, int& breakPointA, int& breakPointB, vector<int>& singleLeft, vector<int>& bestLeft, vector<int>& singleRight, vector<int>& bestRight){
567 int bestTrimeraMismatches = MAXINT;
576 vector<vector<int> > minDelta(alignLength);
577 vector<vector<int> > minDeltaSeq(alignLength);
579 for(int i=0;i<alignLength;i++){
580 minDelta[i].assign(alignLength, MAXINT);
581 minDeltaSeq[i].assign(alignLength, -1);
584 for(int x=0;x<alignLength;x++){
585 for(int y=x;y<alignLength-1;y++){
587 for(int i=0;i<numRefSeqs;i++){
588 int delta = left[i][y] - left[i][x];
590 if(delta <= minDelta[x][y]){
591 minDelta[x][y] = delta;
592 minDeltaSeq[x][y] = i;
595 minDelta[x][y] += singleLeft[x] + singleRight[alignLength - y - 2];
597 if(minDelta[x][y] < bestTrimeraMismatches){
598 bestTrimeraMismatches = minDelta[x][y];
603 leftParent = bestLeft[x];
604 middleParent = minDeltaSeq[x][y];
605 rightParent = bestRight[alignLength - y - 2];
609 return bestTrimeraMismatches;
612 /**************************************************************************************************/
614 string RefChimeraTest::stitchBimera(int leftParent, int rightParent, int breakPoint){
616 string chimeraRefSeq = referenceSeqs[leftParent].substr(0, breakPoint) + referenceSeqs[rightParent].substr(breakPoint);
617 return chimeraRefSeq;
621 /**************************************************************************************************/
623 string RefChimeraTest::stitchTrimera(int leftParent, int middleParent, int rightParent, int breakPointA, int breakPointB){
625 string chimeraRefSeq = referenceSeqs[leftParent].substr(0, breakPointA) + referenceSeqs[middleParent].substr(breakPointA, breakPointB-breakPointA) + referenceSeqs[rightParent].substr(breakPointB);
627 return chimeraRefSeq;
630 /**************************************************************************************************/
632 double RefChimeraTest::calcDistToChimera(string& querySeq, string& chimeraRefSeq){
637 for(int i=0;i<alignLength;i++){
638 // if(querySeq[i] != '.' && chimeraRefSeq[i] != '.'){
639 if(chimeraRefSeq[i] != '.' && querySeq[i] != '.'){
640 if(querySeq[i] == '-' && chimeraRefSeq[i] == '-' && chimeraRefSeq[i] != 'N'){ /* do nothing */ }
641 else if(querySeq[i] == chimeraRefSeq[i]){
650 return (double)mismatch / (double)(mismatch + match);
653 //***************************************************************************************************************
655 int RefChimeraTest::getClosestRefIndex(){
661 //***************************************************************************************************************
663 string RefChimeraTest::getQueryAlignment(){
665 return bestQueryAlignment;
669 //***************************************************************************************************************
671 string RefChimeraTest::getClosestRefAlignment(){
673 return bestRefAlignment;
677 //***************************************************************************************************************