5 * Created by westcott on 9/23/09.
6 * Copyright 2009 Schloss Lab. All rights reserved.
12 /***********************************************************************/ //int num, int match, int misMatch, , string mode, Database* dataLeft, Database* dataRight
13 Maligner::Maligner(vector<Sequence*> temp, int match, int misMatch, float div, int ms, int minCov) : db(temp), matchScore(match), misMatchPenalty(misMatch), minDivR(div), minSimilarity(ms), minCoverage(minCov) {
14 //numWanted(num), , searchMethod(mode), databaseLeft(dataLeft), databaseRight(dataRight)
16 m = MothurOut::getInstance();
19 /***********************************************************************/
20 string Maligner::getResults(Sequence* q, DeCalculator* decalc) {
23 outputResults.clear();
25 //make copy so trimming doesn't destroy query from calling class - remember to deallocate
26 query = new Sequence(q->getName(), q->getAligned());
30 //copy refSeqs so that filter does not effect original
31 for(int i = 0; i < db.size(); i++) {
32 Sequence* newSeq = new Sequence(db[i]->getName(), db[i]->getAligned());
33 refSeqs.push_back(newSeq);
36 refSeqs = minCoverageFilter(refSeqs);
38 if (refSeqs.size() < 2) {
39 for (int i = 0; i < refSeqs.size(); i++) { delete refSeqs[i]; }
40 percentIdenticalQueryChimera = 0.0;
44 int chimeraPenalty = computeChimeraPenalty();
47 chimera = chimeraMaligner(chimeraPenalty, decalc);
49 if (m->control_pressed) { return chimera; }
54 for (int i = 0; i < refSeqs.size(); i++) { delete refSeqs[i]; }
59 m->errorOut(e, "Maligner", "getResults");
63 /***********************************************************************/
64 string Maligner::chimeraMaligner(int chimeraPenalty, DeCalculator* decalc) {
69 //trims seqs to first non gap char in all seqs and last non gap char in all seqs
70 spotMap = decalc->trimSeqs(query, refSeqs);
72 //you trimmed the whole sequence, skip
73 if (query->getAligned() == "") { return "no"; }
75 vector<Sequence*> temp = refSeqs;
76 temp.push_back(query);
80 //for (int i = 0; i < refSeqs.size(); i++) { cout << refSeqs[i]->getName() << endl << refSeqs[i]->getAligned() << endl; }
82 vector< vector<score_struct> > matrix = buildScoreMatrix(query->getAligned().length(), refSeqs.size()); //builds and initializes
84 if (m->control_pressed) { return chimera; }
86 fillScoreMatrix(matrix, refSeqs, chimeraPenalty);
88 vector<trace_struct> trace = extractHighestPath(matrix);
91 //for(int i=0;i<trace.size();i++){
92 // cout << trace[i].col << '\t' << trace[i].oldCol << '\t' << refSeqs[trace[i].row]->getName() << endl;
95 if (trace.size() > 1) { chimera = "yes"; }
96 else { chimera = "no"; return chimera; }
98 int traceStart = trace[0].col;
99 int traceEnd = trace[trace.size()-1].oldCol;
100 string queryInRange = query->getAligned();
101 queryInRange = queryInRange.substr(traceStart, (traceEnd-traceStart+1));
103 if (m->control_pressed) { return chimera; }
105 //save output results
106 for (int i = 0; i < trace.size(); i++) {
107 int regionStart = trace[i].col;
108 int regionEnd = trace[i].oldCol;
109 int seqIndex = trace[i].row;
113 temp.parent = refSeqs[seqIndex]->getName();
114 temp.parentAligned = db[seqIndex]->getAligned();
115 temp.nastRegionStart = spotMap[regionStart];
116 temp.nastRegionEnd = spotMap[regionEnd];
117 temp.regionStart = regionStart;
118 temp.regionEnd = regionEnd;
120 string parentInRange = refSeqs[seqIndex]->getAligned();
121 parentInRange = parentInRange.substr(traceStart, (traceEnd-traceStart+1));
123 temp.queryToParent = computePercentID(queryInRange, parentInRange);
124 temp.divR = (percentIdenticalQueryChimera / temp.queryToParent);
126 string queryInRegion = query->getAligned();
127 queryInRegion = queryInRegion.substr(regionStart, (regionEnd-regionStart+1));
129 string parentInRegion = refSeqs[seqIndex]->getAligned();
130 parentInRegion = parentInRegion.substr(regionStart, (regionEnd-regionStart+1));
132 temp.queryToParentLocal = computePercentID(queryInRegion, parentInRegion);
134 //cout << temp.parent << '\t' << "NAST:" << temp.nastRegionStart << '-' << temp.nastRegionEnd << " G:" << temp.queryToParent << " L:" << temp.queryToParentLocal << endl;
135 outputResults.push_back(temp);
140 catch(exception& e) {
141 m->errorOut(e, "Maligner", "chimeraMaligner");
145 /***********************************************************************/
146 //removes top matches that do not have minimum coverage with query.
147 vector<Sequence*> Maligner::minCoverageFilter(vector<Sequence*> ref){
149 vector<Sequence*> newRefs;
151 string queryAligned = query->getAligned();
153 for (int i = 0; i < ref.size(); i++) {
155 string refAligned = ref[i]->getAligned();
161 for (int j = 0; j < queryAligned.length(); j++) {
163 if (isalpha(queryAligned[j])) {
166 if (isalpha(refAligned[j])) {
172 int coverage = ((numCovered/(float)numBases)*100);
174 //if coverage above minimum
175 if (coverage > minCoverage) {
176 newRefs.push_back(ref[i]);
184 catch(exception& e) {
185 m->errorOut(e, "Maligner", "minCoverageFilter");
189 /***********************************************************************/
190 // a breakpoint should yield fewer mismatches than this number with respect to the best parent sequence.
191 int Maligner::computeChimeraPenalty() {
194 int numAllowable = ((1.0 - (1.0/minDivR)) * query->getNumBases());
196 // if(numAllowable < 1){ numAllowable = 1; }
198 int penalty = int(numAllowable + 1) * misMatchPenalty;
203 catch(exception& e) {
204 m->errorOut(e, "Maligner", "computeChimeraPenalty");
208 /***********************************************************************/
209 //this is a vertical filter
210 void Maligner::verticalFilter(vector<Sequence*> seqs) {
212 vector<int> gaps; gaps.resize(query->getAligned().length(), 0);
214 string filterString = (string(query->getAligned().length(), '1'));
217 for (int i = 0; i < seqs.size(); i++) {
219 string seqAligned = seqs[i]->getAligned();
221 for (int j = 0; j < seqAligned.length(); j++) {
222 //if this spot is a gap
223 if ((seqAligned[j] == '-') || (seqAligned[j] == '.')) { gaps[j]++; }
227 //zero out spot where all sequences have blanks
228 int numColRemoved = 0;
229 for(int i = 0; i < seqs[0]->getAligned().length(); i++){
230 if(gaps[i] == seqs.size()) { filterString[i] = '0'; numColRemoved++; }
233 map<int, int> newMap;
235 for (int i = 0; i < seqs.size(); i++) {
237 string seqAligned = seqs[i]->getAligned();
238 string newAligned = "";
241 for (int j = 0; j < seqAligned.length(); j++) {
242 //if this spot is not a gap
243 if (filterString[j] == '1') {
244 newAligned += seqAligned[j];
245 newMap[count] = spotMap[j];
250 seqs[i]->setAligned(newAligned);
255 catch(exception& e) {
256 m->errorOut(e, "Maligner", "verticalFilter");
260 //***************************************************************************************************************
261 vector< vector<score_struct> > Maligner::buildScoreMatrix(int cols, int rows) {
264 vector< vector<score_struct> > m(rows);
266 for (int i = 0; i < rows; i++) {
267 for (int j = 0; j < cols; j++) {
269 //initialize each cell
272 temp.score = -9999999;
276 m[i].push_back(temp);
282 catch(exception& e) {
283 m->errorOut(e, "Maligner", "buildScoreMatrix");
288 //***************************************************************************************************************
290 void Maligner::fillScoreMatrix(vector<vector<score_struct> >& ms, vector<Sequence*> seqs, int penalty) {
293 //get matrix dimensions
294 int numCols = query->getAligned().length();
295 int numRows = seqs.size();
297 //initialize first col
298 string queryAligned = query->getAligned();
299 for (int i = 0; i < numRows; i++) {
300 string subjectAligned = seqs[i]->getAligned();
303 if ((!isalpha(queryAligned[0])) && (!isalpha(subjectAligned[0]))) {
305 // ms[i][0].mismatches = 0;
306 }else if (queryAligned[0] == subjectAligned[0]) { //|| subjectAligned[0] == 'N')
307 ms[i][0].score = matchScore;
308 // ms[i][0].mismatches = 0;
311 // ms[i][0].mismatches = 1;
315 //fill rest of matrix
316 for (int j = 1; j < numCols; j++) { //iterate through matrix columns
318 for (int i = 0; i < numRows; i++) { //iterate through matrix rows
320 string subjectAligned = seqs[i]->getAligned();
322 int matchMisMatchScore = 0;
324 if ((!isalpha(queryAligned[j])) && (!isalpha(subjectAligned[j]))) {
326 }else if ((toupper(queryAligned[j]) == 'N') || (toupper(subjectAligned[j]) == 'N')) {
327 //matchMisMatchScore = matchScore;
329 }else if (queryAligned[j] == subjectAligned[j]) {
330 matchMisMatchScore = matchScore;
331 // ms[i][j].mismatches = ms[i][j-1].mismatches;
332 }else if (queryAligned[j] != subjectAligned[j]) {
333 matchMisMatchScore = misMatchPenalty;
334 // ms[i][j].mismatches = ms[i][j-1].mismatches + 1;
337 //compute score based on previous columns scores
338 for (int prevIndex = 0; prevIndex < numRows; prevIndex++) { //iterate through rows
340 int sumScore = matchMisMatchScore + ms[prevIndex][j-1].score;
342 //you are not at yourself
343 if (prevIndex != i) { sumScore += penalty; }
344 if (sumScore < 0) { sumScore = 0; }
346 if (sumScore > ms[i][j].score) {
347 ms[i][j].score = sumScore;
348 ms[i][j].prev = prevIndex;
354 /* for(int i=0;i<numRows;i++){
355 cout << seqs[i]->getName();
356 for(int j=0;j<numCols;j++){
357 cout << '\t' << ms[i][j].mismatches;
362 /*cout << numRows << '\t' << numCols << endl;
363 for(int i=0;i<numRows;i++){
364 cout << seqs[i]->getName() << endl << seqs[i]->getAligned() << endl << endl;
365 if ((seqs[i]->getName() == "S000003470") || (seqs[i]->getName() == "S000383265") || (seqs[i]->getName() == "7000004128191054")) {
366 for(int j=0;j<numCols;j++){
367 cout << '\t' << ms[i][j].score;
373 /*for(int i=0;i<numRows;i++){
374 cout << seqs[i]->getName();
375 for(int j=0;j<numCols;j++){
376 cout << '\t' << ms[i][j].prev;
383 catch(exception& e) {
384 m->errorOut(e, "Maligner", "fillScoreMatrix");
389 //***************************************************************************************************************
391 vector<trace_struct> Maligner::extractHighestPath(vector<vector<score_struct> > ms) {
395 //get matrix dimensions
396 int numCols = query->getAligned().length();
397 int numRows = ms.size();
400 //find highest score scoring matrix
401 vector<score_struct> highestStruct;
402 int highestScore = 0;
404 for (int i = 0; i < numRows; i++) {
405 for (int j = 0; j < numCols; j++) {
406 if (ms[i][j].score > highestScore) {
407 highestScore = ms[i][j].score;
408 highestStruct.resize(0);
409 highestStruct.push_back(ms[i][j]);
411 else if(ms[i][j].score == highestScore){
412 highestStruct.push_back(ms[i][j]);
417 //cout << endl << highestScore << '\t' << highestStruct.size() << '\t' << highestStruct[0].row << endl;
419 vector<trace_struct> maxTrace;
420 double maxPercentIdenticalQueryAntiChimera = 0;
422 for(int i=0;i<highestStruct.size();i++){
424 vector<score_struct> path;
426 int rowIndex = highestStruct[i].row;
427 int pos = highestStruct[i].col;
428 int score = highestStruct[i].score;
430 while (pos >= 0 && score > 0) {
431 score_struct temp = ms[rowIndex][pos];
434 if (score > 0) { path.push_back(temp); }
436 rowIndex = temp.prev;
440 reverse(path.begin(), path.end());
442 vector<trace_struct> trace = mapTraceRegionsToAlignment(path, refSeqs);
444 //cout << "traces\n";
445 //for(int j=0;j<trace.size();j++){
446 // cout << trace[j].col << '\t' << trace[j].oldCol << '\t' << refSeqs[trace[j].row]->getName() << endl;
449 int traceStart = path[0].col;
450 int traceEnd = path[path.size()-1].col;
451 // cout << "traceStart/End\t" << traceStart << '\t' << traceEnd << endl;
453 string queryInRange = query->getAligned();
454 queryInRange = queryInRange.substr(traceStart, (traceEnd-traceStart+1));
455 // cout << "here" << endl;
456 string chimeraSeq = constructChimericSeq(trace, refSeqs);
457 string antiChimeraSeq = constructAntiChimericSeq(trace, refSeqs);
459 percentIdenticalQueryChimera = computePercentID(queryInRange, chimeraSeq);
460 double percentIdenticalQueryAntiChimera = computePercentID(queryInRange, antiChimeraSeq);
461 // cout << i << '\t' << percentIdenticalQueryChimera << '\t' << percentIdenticalQueryAntiChimera << endl;
463 if(percentIdenticalQueryAntiChimera > maxPercentIdenticalQueryAntiChimera){
464 maxPercentIdenticalQueryAntiChimera = percentIdenticalQueryAntiChimera;
468 // cout << maxPercentIdenticalQueryAntiChimera << endl;
473 catch(exception& e) {
474 m->errorOut(e, "Maligner", "extractHighestPath");
479 //***************************************************************************************************************
481 vector<trace_struct> Maligner::mapTraceRegionsToAlignment(vector<score_struct> path, vector<Sequence*> seqs) {
483 vector<trace_struct> trace;
485 int region_index = path[0].row;
486 int region_start = path[0].col;
488 for (int i = 1; i < path.size(); i++) {
490 int next_region_index = path[i].row;
492 if (next_region_index != region_index) {
495 int col_index = path[i].col;
497 temp.col = region_start;
498 temp.oldCol = col_index-1;
499 temp.row = region_index;
501 trace.push_back(temp);
503 region_index = path[i].row;
504 region_start = col_index;
510 temp.col = region_start;
511 temp.oldCol = path[path.size()-1].col;
512 temp.row = region_index;
513 trace.push_back(temp);
516 // cout << trace.size() << endl;
517 // for(int i=0;i<trace.size();i++){
518 // cout << seqs[trace[i].row]->getName() << endl;
525 catch(exception& e) {
526 m->errorOut(e, "Maligner", "mapTraceRegionsToAlignment");
531 //***************************************************************************************************************
533 string Maligner::constructChimericSeq(vector<trace_struct> trace, vector<Sequence*> seqs) {
537 for (int i = 0; i < trace.size(); i++) {
538 // cout << i << '\t' << trace[i].row << '\t' << trace[i].col << '\t' << trace[i].oldCol << endl;
540 string seqAlign = seqs[trace[i].row]->getAligned();
541 seqAlign = seqAlign.substr(trace[i].col, (trace[i].oldCol-trace[i].col+1));
547 catch(exception& e) {
548 m->errorOut(e, "Maligner", "constructChimericSeq");
553 //***************************************************************************************************************
555 string Maligner::constructAntiChimericSeq(vector<trace_struct> trace, vector<Sequence*> seqs) {
557 string antiChimera = "";
559 for (int i = 0; i < trace.size(); i++) {
560 // cout << i << '\t' << (trace.size() - i - 1) << '\t' << trace[i].row << '\t' << trace[i].col << '\t' << trace[i].oldCol << endl;
562 int oppositeIndex = trace.size() - i - 1;
564 string seqAlign = seqs[trace[oppositeIndex].row]->getAligned();
565 seqAlign = seqAlign.substr(trace[i].col, (trace[i].oldCol-trace[i].col+1));
566 antiChimera += seqAlign;
571 catch(exception& e) {
572 m->errorOut(e, "Maligner", "constructChimericSeq");
577 //***************************************************************************************************************
578 float Maligner::computePercentID(string queryAlign, string chimera) {
581 if (queryAlign.length() != chimera.length()) {
582 m->mothurOut("Error, alignment strings are of different lengths: "); m->mothurOutEndLine();
583 m->mothurOut(toString(queryAlign.length())); m->mothurOutEndLine(); m->mothurOutEndLine(); m->mothurOutEndLine(); m->mothurOutEndLine();
584 m->mothurOut(toString(chimera.length())); m->mothurOutEndLine();
590 int numIdentical = 0;
592 for (int i = 0; i < queryAlign.length(); i++) {
593 if ((isalpha(queryAlign[i])) || (isalpha(chimera[i]))) {
595 if (queryAlign[i] == chimera[i]) {
601 if (numBases == 0) { return 0; }
603 float percentIdentical = (numIdentical/(float)numBases) * 100;
605 return percentIdentical;
608 catch(exception& e) {
609 m->errorOut(e, "Maligner", "computePercentID");
613 //***************************************************************************************************************