nast.cpp

   1 /*
   2  *  nast.cpp
   3  *
   4  *
   5  *  Created by Pat Schloss on 12/17/08.
   6  *  Copyright 2008 Patrick D. Schloss. All rights reserved.
   7  *
   8  *      This is my implementation of the NAST (nearest alignment space termination) algorithm as described in:
   9  *
  10  *      DeSantis TZ, Hugenholtz P, Keller K, Brodie EL, Larsen N, Piceno YM, Phan R, & Anderson GL.  2006.  NAST: a multiple
  11  *              sequence alignment server for comparative analysis of 16S rRNA genes.  Nucleic Acids Research.  34:W394-9.
  12  *
  13  *      To construct an object one needs to provide a method of getting a pairwise alignment (alignment) and the template
  14  *      and candidate sequence that are to be aligned to each other.
  15  *
  16  */
  17
  18 #include "sequence.hpp"
  19 #include "alignment.hpp"
  20 #include "nast.hpp"
  21
  22 /**************************************************************************************************/
  23
  24 Nast::Nast(Alignment* method, Sequence* cand, Sequence* temp) : alignment(method), candidateSeq(cand), templateSeq(temp) {
  25         try {
  26                 maxInsertLength = 0;
  27                 pairwiseAlignSeqs();    //      This is part A in Fig. 2 of DeSantis et al.
  28                 regapSequences();               //      This is parts B-F in Fig. 2 of DeSantis et al.
  29
  30         }
  31         catch(exception& e) {
  32                 errorOut(e, "Nast", "Nast");
  33                 exit(1);
  34         }
  35 }
  36
  37 /**************************************************************************************************/
  38
  39 void Nast::pairwiseAlignSeqs(){ //      Here we call one of the pairwise alignment methods to align our unaligned candidate
  40                                                                 //      and template sequences
  41         try {
  42
  43                 alignment->align(candidateSeq->getUnaligned(), templateSeq->getUnaligned());
  44
  45                 string candAln = alignment->getSeqAAln();
  46                 string tempAln = alignment->getSeqBAln();
  47
  48                 if(candAln == ""){
  49
  50                         candidateSeq->setPairwise("");
  51                         templateSeq->setPairwise(templateSeq->getUnaligned());
  52
  53                 }
  54                 else{
  55                         if(tempAln[0] == '-'){
  56                                 int pairwiseAlignmentLength = tempAln.length(); //      we need to make sure that the candidate sequence alignment
  57                                 for(int i=0;i<pairwiseAlignmentLength;i++){             //      starts where the template sequence alignment starts, if it
  58                                         if(isalpha(tempAln[i])){                                        //      starts early, we nuke the beginning of the candidate
  59                                                 candAln = candAln.substr(i);                    //      sequence
  60                                                 tempAln = tempAln.substr(i);
  61                                                 break;
  62                                         }
  63                                 }
  64                         }
  65                         int pairwiseAlignmentLength = tempAln.length();
  66                         if(tempAln[pairwiseAlignmentLength-1] == '-'){          //      we need to make sure that the candidate sequence alignment
  67                                 for(int i=pairwiseAlignmentLength-1; i>=0; i--){//      ends where the template sequence alignment ends, if it runs
  68                                         if(isalpha(tempAln[i])){                                        //      long, we nuke the end of the candidate sequence
  69                                                 candAln = candAln.substr(0,i+1);
  70                                                 tempAln = tempAln.substr(0,i+1);
  71                                                 break;
  72                                         }
  73                                 }
  74                         }
  75
  76                 }
  77
  78                 candidateSeq->setPairwise(candAln);                                     //      set the pairwise sequences in the Sequence objects for
  79                 templateSeq->setPairwise(tempAln);                                      //      the candidate and template sequences
  80         }
  81         catch(exception& e) {
  82                 errorOut(e, "Nast", "pairwiseAlignSeqs");
  83                 exit(1);
  84         }
  85 }
  86
  87 /**************************************************************************************************/
  88
  89 void Nast::removeExtraGaps(string& candAln, string tempAln, string newTemplateAlign){
  90
  91 //      here we do steps C-F of Fig. 2 from DeSantis et al.
  92         try {
  93
  94                 int longAlignmentLength = newTemplateAlign.length();
  95
  96                 for(int i=0; i<longAlignmentLength; i++){                               //      use the long alignment as the standard
  97                         int rightIndex, rightRoom, leftIndex, leftRoom;
  98
  99                         //      Part C of Fig. 2 from DeSantis et al.
 100                         if((isalpha(newTemplateAlign[i]) != isalpha(tempAln[i]))){      //if there is a discrepancy between the regapped
 101
 102                                 rightRoom = 0; leftRoom = 0;
 103
 104                                 //      Part D of Fig. 2 from DeSantis et al.           //      template sequence and the official template sequence
 105                                 for(leftIndex=i-1;leftIndex>0;leftIndex--){     //      then we've got problems...
 106                                         if(!isalpha(candAln[leftIndex])){
 107                                                 leftRoom = 1;   //count how far it is to the nearest gap on the LEFT side of the anomaly
 108                                                 while(leftIndex-leftRoom>=0 && !isalpha(candAln[leftIndex-leftRoom]))   {       leftRoom++;             }
 109                                                 break;
 110                                         }
 111                                 }
 112
 113                                 for(rightIndex=i+1;rightIndex<longAlignmentLength-1;rightIndex++){
 114                                         if(!isalpha(candAln[rightIndex])){
 115                                                 rightRoom = 1;  //count how far it is to the nearest gap on the RIGHT side of the anomaly
 116                                                 while(rightIndex+rightRoom<longAlignmentLength && !isalpha(candAln[rightIndex+rightRoom]))      {       rightRoom++;    }
 117                                                 break;
 118                                         }
 119                                 }
 120
 121                                 int insertLength = 0;                                                   //      figure out how long the anomaly is
 122                                 while(!isalpha(newTemplateAlign[i + insertLength]))     {       insertLength++; }
 123                                 if(insertLength > maxInsertLength){     maxInsertLength = insertLength; }
 124
 125                                 if((leftRoom + rightRoom) >= insertLength){
 126
 127                                         //      Parts D & E from Fig. 2 of DeSantis et al.
 128                                         if((i-leftIndex) <= (rightIndex-i)){            //      the left gap is closer - > move stuff left there's
 129
 130                                                 if(leftRoom >= insertLength){                   //      enough room to the left to move
 131
 132                                                         string leftTemplateString = newTemplateAlign.substr(0,i);
 133                                                         string rightTemplateString = newTemplateAlign.substr(i+insertLength);
 134                                                         newTemplateAlign = leftTemplateString + rightTemplateString;
 135                                                         longAlignmentLength = newTemplateAlign.length();
 136
 137                                                         string leftCandidateString = candAln.substr(0,leftIndex-insertLength+1);
 138                                                         string rightCandidateString = candAln.substr(leftIndex+1);
 139                                                         candAln = leftCandidateString + rightCandidateString;
 140
 141                                                 }
 142                                                 else{                                                                   //      not enough room to the left, have to steal some space to
 143                                                         string leftTemplateString = newTemplateAlign.substr(0,i);       //      the right
 144                                                         string rightTemplateString = newTemplateAlign.substr(i+insertLength);
 145                                                         newTemplateAlign = leftTemplateString + rightTemplateString;
 146                                                         longAlignmentLength = newTemplateAlign.length();
 147
 148                                                         string leftCandidateString = candAln.substr(0,leftIndex-leftRoom+1);
 149                                                         string insertString = candAln.substr(leftIndex+1,rightIndex-leftIndex-1);
 150                                                         string rightCandidateString = candAln.substr(rightIndex+(insertLength-leftRoom));
 151                                                         candAln = leftCandidateString + insertString + rightCandidateString;
 152
 153                                                 }
 154                                         }
 155                                         else{                                                                           //      the right gap is closer - > move stuff right there's
 156                                                 if(rightRoom >= insertLength){                  //      enough room to the right to move
 157
 158                                                         string leftTemplateString = newTemplateAlign.substr(0,i);
 159                                                         string rightTemplateString = newTemplateAlign.substr(i+insertLength);
 160                                                         newTemplateAlign = leftTemplateString + rightTemplateString;
 161                                                         longAlignmentLength = newTemplateAlign.length();
 162
 163                                                         string leftCandidateString = candAln.substr(0,rightIndex);
 164                                                         string rightCandidateString = candAln.substr(rightIndex+insertLength);
 165                                                         candAln = leftCandidateString + rightCandidateString;
 166
 167                                                 }
 168                                                 else{                                                                   //      not enough room to the right, have to steal some
 169
 170                                                         //      space to the left lets move left and then right...
 171                                                         string leftTemplateString = newTemplateAlign.substr(0,i);
 172                                                         string rightTemplateString = newTemplateAlign.substr(i+insertLength);
 173                                                         newTemplateAlign = leftTemplateString + rightTemplateString;
 174                                                         longAlignmentLength = newTemplateAlign.length();
 175
 176                                                         string leftCandidateString = candAln.substr(0,leftIndex-(insertLength-rightRoom)+1);
 177                                                         string insertString = candAln.substr(leftIndex+1,rightIndex-leftIndex-1);
 178                                                         string rightCandidateString = candAln.substr(rightIndex+rightRoom);
 179                                                         candAln = leftCandidateString + insertString + rightCandidateString;
 180
 181                                                 }
 182                                         }
 183                                 }
 184                                 else{
 185                         //      there could be a case where there isn't enough room in
 186                                         string leftTemplateString = newTemplateAlign.substr(0,i);                       //      either direction to move stuff
 187                                         string rightTemplateString = newTemplateAlign.substr(i+leftRoom+rightRoom);
 188                                         newTemplateAlign = leftTemplateString + rightTemplateString;
 189                                         longAlignmentLength = newTemplateAlign.length();
 190
 191                                         string leftCandidateString = candAln.substr(0,leftIndex-leftRoom+1);
 192                                         string insertString = candAln.substr(leftIndex+1,rightIndex-leftIndex-1);
 193                                         string rightCandidateString = candAln.substr(rightIndex+rightRoom);
 194                                         candAln = leftCandidateString + insertString + rightCandidateString;
 195
 196                                 }
 197
 198                                 i -= insertLength;
 199                         }
 200                 }
 201         }
 202         catch(exception& e) {
 203                 errorOut(e, "Nast", "removeExtraGaps");
 204                 exit(1);
 205         }
 206 }
 207
 208 /**************************************************************************************************/
 209
 210 void Nast::regapSequences(){    //This is essentially part B in Fig 2. of DeSantis et al.
 211         try {
 212
 213                 string candPair = candidateSeq->getPairwise();
 214                 string candAln = "";
 215
 216                 string tempPair = templateSeq->getPairwise();
 217                 string tempAln = templateSeq->getAligned();             //      we use the template aligned sequence as our guide
 218
 219                 int pairwiseLength = candPair.length();
 220                 int fullAlignLength = tempAln.length();
 221
 222                 if(candPair == ""){
 223                         for(int i=0;i<fullAlignLength;i++)      {       candAln += '.';         }
 224                         candidateSeq->setAligned(candAln);
 225                         return;
 226                 }
 227
 228                 int fullAlignIndex = 0;
 229                 int pairwiseAlignIndex = 0;
 230                 string newTemplateAlign = "";                                   //      this is going to be messy so we want a temporary template
 231                 //      alignment string
 232                 while(tempAln[fullAlignIndex] == '.' || tempAln[fullAlignIndex]  == '-'){
 233                         candAln += '.';                                                         //      add the initial '-' and '.' to the candidate and template
 234                         newTemplateAlign += tempAln[fullAlignIndex];//  pairwise sequences
 235                         fullAlignIndex++;
 236                 }
 237
 238                 string lastLoop = "";
 239
 240                 while(pairwiseAlignIndex<pairwiseLength){
 241                         if(isalpha(tempPair[pairwiseAlignIndex]) && isalpha(tempAln[fullAlignIndex])
 242                            && isalpha(candPair[pairwiseAlignIndex])){
 243                                 //  the template and candidate pairwise and template aligned have characters
 244                                 //      need to add character onto the candidatSeq.aligned sequence
 245
 246                                 candAln += candPair[pairwiseAlignIndex];
 247                                 newTemplateAlign += tempPair[pairwiseAlignIndex];//
 248
 249                                 pairwiseAlignIndex++;
 250                                 fullAlignIndex++;
 251                         }
 252                         else if(isalpha(tempPair[pairwiseAlignIndex]) && !isalpha(tempAln[fullAlignIndex])
 253                                         && isalpha(candPair[pairwiseAlignIndex])){
 254                                 //      the template pairwise and candidate pairwise are characters and the template aligned is a gap
 255                                 //      need to insert gaps into the candidateSeq.aligned sequence
 256
 257                                 candAln += '-';
 258                                 newTemplateAlign += '-';//
 259                                 fullAlignIndex++;
 260                         }
 261                         else if(!isalpha(tempPair[pairwiseAlignIndex]) && isalpha(tempAln[fullAlignIndex])
 262                                         && isalpha(candPair[pairwiseAlignIndex])){
 263                                 //  the template pairwise is a gap and the template aligned and pairwise sequences have characters
 264                                 //      this is the alpha scenario.  add character to the candidateSeq.aligned sequence without progressing
 265                                 //      further through the tempAln sequence.
 266
 267                                 candAln += candPair[pairwiseAlignIndex];
 268                                 newTemplateAlign += '-';//
 269                                 pairwiseAlignIndex++;
 270                         }
 271                         else if(isalpha(tempPair[pairwiseAlignIndex]) && isalpha(tempAln[fullAlignIndex])
 272                                         && !isalpha(candPair[pairwiseAlignIndex])){
 273                                 //  the template pairwise and full alignment are characters and the candidate sequence has a gap
 274                                 //      should not be a big deal, just add the gap position to the candidateSeq.aligned sequence;
 275
 276                                 candAln += candPair[pairwiseAlignIndex];
 277                                 newTemplateAlign += tempAln[fullAlignIndex];//
 278                                 fullAlignIndex++;
 279                                 pairwiseAlignIndex++;
 280                         }
 281                         else if(!isalpha(tempPair[pairwiseAlignIndex]) && !isalpha(tempAln[fullAlignIndex])
 282                                         && isalpha(candPair[pairwiseAlignIndex])){
 283                                 //      the template pairwise and aligned are gaps while the candidate pairwise has a character
 284                                 //      this would be an insertion, go ahead and add the character->seems to be the opposite of the alpha scenario
 285
 286                                 candAln += candPair[pairwiseAlignIndex];
 287                                 newTemplateAlign += tempAln[fullAlignIndex];//
 288                                 pairwiseAlignIndex++;
 289                                 fullAlignIndex++;
 290                         }
 291                         else if(isalpha(tempPair[pairwiseAlignIndex]) && !isalpha(tempAln[fullAlignIndex])
 292                                         && !isalpha(candPair[pairwiseAlignIndex])){
 293                                 //      template pairwise has a character, but its full aligned sequence and candidate sequence have gaps
 294                                 //      this would happen like we need to add a gap.  basically the opposite of the alpha situation
 295
 296                                 newTemplateAlign += tempAln[fullAlignIndex];//
 297                                 candAln += "-";
 298                                 fullAlignIndex++;
 299                         }
 300                         else if(!isalpha(tempPair[pairwiseAlignIndex]) && isalpha(tempAln[fullAlignIndex])
 301                                         && !isalpha(candPair[pairwiseAlignIndex])){
 302                                 //      template and candidate pairwise are gaps and the template aligned is not a gap this should not be possible
 303                                 //      would skip the gaps and not progress through full alignment sequence
 304                                 //      not tested yet
 305
 306                                 mothurOut("We're into D " + toString(fullAlignIndex) + " " +  toString(pairwiseAlignIndex)); mothurOutEndLine();
 307                                 pairwiseAlignIndex++;
 308                         }
 309                         else{
 310                                 //      everything has a gap - not possible
 311                                 //      not tested yet
 312
 313                                 mothurOut("We're into F " +  toString(fullAlignIndex) + " " +  toString(pairwiseAlignIndex)); mothurOutEndLine();
 314                                 pairwiseAlignIndex++;
 315                                 fullAlignIndex++;
 316                         }
 317                 }
 318
 319                 for(int i=fullAlignIndex;i<fullAlignLength;i++){
 320                         candAln += '.';
 321                         newTemplateAlign += tempAln[i];//
 322                 }
 323
 324                 int start = 0;
 325                 int end = candAln.length()-1;
 326
 327                 for(int i=0;i<candAln.length();i++){
 328                         if(candAln[i] == 'Z' || !isalnum(candAln[i]))   {       candAln[i] = '.';       }       //      if we padded the alignemnt from
 329                         else{                   start = i;                      break;          }                                                       //      blast with Z's, change them to
 330                 }                                                                                                                                                               //      '.' characters
 331
 332                 for(int i=candAln.length()-1;i>=0;i--){                                                                                 //      ditto.
 333                         if(candAln[i] == 'Z' || !isalnum(candAln[i]))   {       candAln[i] = '.';       }
 334                         else{                   end = i;                        break;          }
 335                 }
 336
 337                 for(int i=start;i<=end;i++){                                    //      go through the candidate alignment sequence and make sure that
 338                         candAln[i] = toupper(candAln[i]);                       //      everything is upper case
 339                 }
 340
 341
 342                 if(candAln.length() != tempAln.length()){               //      if the regapped candidate sequence is longer than the official
 343                         removeExtraGaps(candAln, tempAln, newTemplateAlign);//  template alignment then we need to do steps C-F in Fig.
 344                 }                                                                                               //      2 of Desantis et al.
 345
 346                 candidateSeq->setAligned(candAln);
 347         }
 348         catch(exception& e) {
 349                 errorOut(e, "Nast", "regapSequences");
 350                 exit(1);
 351         }
 352 }
 353
 354 /**************************************************************************************************/
 355
 356 float Nast::getSimilarityScore(){
 357         try {
 358
 359                 string cand = candidateSeq->getAligned();
 360                 string temp = templateSeq->getAligned();
 361                 int alignmentLength = temp.length();
 362                 int mismatch = 0;
 363                 int denominator = 0;
 364
 365                 for(int i=0;i<alignmentLength;i++){
 366                         if(cand[i] == '-' && temp[i] == '-'){
 367
 368                         }
 369                         else if(cand[i] != '.' && temp[i] != '.'){
 370                                 denominator++;
 371
 372                                 if(cand[i] != temp[i]){
 373                                         mismatch++;
 374                                 }
 375                         }
 376                 }
 377                 float similarity = 100 * (1. - mismatch / (float)denominator);
 378                 if(denominator == 0){   similarity = 0.0000;    }
 379
 380                 return similarity;
 381
 382         }
 383         catch(exception& e) {
 384                 errorOut(e, "Nast", "getSimilarityScore");
 385                 exit(1);
 386         }
 387 }
 388
 389 /**************************************************************************************************/
 390
 391 int Nast::getMaxInsertLength(){
 392
 393         return maxInsertLength;
 394
 395 }
 396
 397 /**************************************************************************************************/