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
  40 void Nast::pairwiseAlignSeqs(){ //      Here we call one of the pairwise alignment methods to align our unaligned candidate
  41                                                                 //      and template sequences
  42         try {
  43
  44                 alignment->align(candidateSeq->getUnaligned(), templateSeq->getUnaligned());
  45
  46                 string candAln = alignment->getSeqAAln();
  47                 string tempAln = alignment->getSeqBAln();
  48
  49                 if(candAln == ""){
  50
  51                         candidateSeq->setPairwise("");
  52                         templateSeq->setPairwise(templateSeq->getUnaligned());
  53
  54                 }
  55                 else{
  56
  57                         if(tempAln[0] == '-'){
  58                                 int pairwiseAlignmentLength = tempAln.length(); //      we need to make sure that the candidate sequence alignment
  59                                 for(int i=0;i<pairwiseAlignmentLength;i++){             //      starts where the template sequence alignment starts, if it
  60                                         if(isalpha(tempAln[i])){                                        //      starts early, we nuke the beginning of the candidate
  61                                                 candAln = candAln.substr(i);                    //      sequence
  62                                                 tempAln = tempAln.substr(i);
  63                                                 break;
  64                                         }
  65                                 }
  66                         }
  67
  68                         int pairwiseAlignmentLength = tempAln.length();
  69                         if(tempAln[pairwiseAlignmentLength-1] == '-'){          //      we need to make sure that the candidate sequence alignment
  70                                 for(int i=pairwiseAlignmentLength-1; i>=0; i--){//      ends where the template sequence alignment ends, if it runs
  71                                         if(isalpha(tempAln[i])){                                        //      long, we nuke the end of the candidate sequence
  72                                                 candAln = candAln.substr(0,i+1);
  73                                                 tempAln = tempAln.substr(0,i+1);
  74                                                 break;
  75                                         }
  76                                 }
  77                         }
  78
  79                 }
  80
  81                 candidateSeq->setPairwise(candAln);                                     //      set the pairwise sequences in the Sequence objects for
  82                 templateSeq->setPairwise(tempAln);                                      //      the candidate and template sequences
  83
  84         }
  85         catch(exception& e) {
  86                 errorOut(e, "Nast", "pairwiseAlignSeqs");
  87                 exit(1);
  88         }
  89 }
  90
  91 /**************************************************************************************************/
  92
  93 void Nast::removeExtraGaps(string& candAln, string tempAln, string newTemplateAlign){
  94
  95 //      here we do steps C-F of Fig. 2 from DeSantis et al.
  96         try {
  97
  98                 int longAlignmentLength = newTemplateAlign.length();
  99
 100                 for(int i=0; i<longAlignmentLength; i++){                               //      use the long alignment as the standard
 101                         int rightIndex, rightRoom, leftIndex, leftRoom;
 102
 103                         //      Part C of Fig. 2 from DeSantis et al.
 104                         if((isalpha(newTemplateAlign[i]) != isalpha(tempAln[i]))){      //if there is a discrepancy between the regapped
 105
 106                                 rightRoom = 0; leftRoom = 0;
 107
 108                                 //      Part D of Fig. 2 from DeSantis et al.           //      template sequence and the official template sequence
 109                                 for(leftIndex=i-1;leftIndex>0;leftIndex--){     //      then we've got problems...
 110                                         if(!isalpha(candAln[leftIndex])){
 111                                                 leftRoom = 1;   //count how far it is to the nearest gap on the LEFT side of the anomaly
 112                                                 while(leftIndex-leftRoom>=0 && !isalpha(candAln[leftIndex-leftRoom]))   {       leftRoom++;             }
 113                                                 break;
 114                                         }
 115                                 }
 116
 117
 118                                 for(rightIndex=i+1;rightIndex<longAlignmentLength-1;rightIndex++){
 119                                         if(!isalpha(candAln[rightIndex])){
 120                                                 rightRoom = 1;  //count how far it is to the nearest gap on the RIGHT side of the anomaly
 121                                                 while(rightIndex+rightRoom<longAlignmentLength && !isalpha(candAln[rightIndex+rightRoom]))      {       rightRoom++;    }
 122                                                 break;
 123                                         }
 124                                 }
 125
 126                                 int insertLength = 0;                                                   //      figure out how long the anomaly is
 127                                 while(!isalpha(newTemplateAlign[i + insertLength]))     {       insertLength++; }
 128                                 if(insertLength > maxInsertLength){     maxInsertLength = insertLength; }
 129
 130                                 if((leftRoom + rightRoom) >= insertLength){
 131
 132                                         //      Parts D & E from Fig. 2 of DeSantis et al.
 133                                         if((i-leftIndex) <= (rightIndex-i)){            //      the left gap is closer - > move stuff left there's
 134
 135                                                 if(leftRoom >= insertLength){                   //      enough room to the left to move
 136
 137                                                         string leftTemplateString = newTemplateAlign.substr(0,i);
 138                                                         string rightTemplateString = newTemplateAlign.substr(i+insertLength);
 139                                                         newTemplateAlign = leftTemplateString + rightTemplateString;
 140                                                         longAlignmentLength = newTemplateAlign.length();
 141
 142                                                         string leftCandidateString = candAln.substr(0,leftIndex-insertLength+1);
 143                                                         string rightCandidateString = candAln.substr(leftIndex+1);
 144                                                         candAln = leftCandidateString + rightCandidateString;
 145
 146                                                 }
 147                                                 else{                                                                   //      not enough room to the left, have to steal some space to
 148                                                         string leftTemplateString = newTemplateAlign.substr(0,i);       //      the right
 149                                                         string rightTemplateString = newTemplateAlign.substr(i+insertLength);
 150                                                         newTemplateAlign = leftTemplateString + rightTemplateString;
 151                                                         longAlignmentLength = newTemplateAlign.length();
 152
 153                                                         string leftCandidateString = candAln.substr(0,leftIndex-leftRoom+1);
 154                                                         string insertString = candAln.substr(leftIndex+1,rightIndex-leftIndex-1);
 155                                                         string rightCandidateString = candAln.substr(rightIndex+(insertLength-leftRoom));
 156                                                         candAln = leftCandidateString + insertString + rightCandidateString;
 157
 158                                                 }
 159                                         }
 160                                         else{                                                                           //      the right gap is closer - > move stuff right there's
 161                                                 if(rightRoom >= insertLength){                  //      enough room to the right to move
 162
 163                                                         string leftTemplateString = newTemplateAlign.substr(0,i);
 164                                                         string rightTemplateString = newTemplateAlign.substr(i+insertLength);
 165                                                         newTemplateAlign = leftTemplateString + rightTemplateString;
 166                                                         longAlignmentLength = newTemplateAlign.length();
 167
 168                                                         string leftCandidateString = candAln.substr(0,rightIndex);
 169                                                         string rightCandidateString = candAln.substr(rightIndex+insertLength);
 170                                                         candAln = leftCandidateString + rightCandidateString;
 171
 172                                                 }
 173                                                 else{                                                                   //      not enough room to the right, have to steal some
 174                                                         //      space to the left lets move left and then right...
 175                                                         string leftTemplateString = newTemplateAlign.substr(0,i);
 176                                                         string rightTemplateString = newTemplateAlign.substr(i+insertLength);
 177                                                         newTemplateAlign = leftTemplateString + rightTemplateString;
 178                                                         longAlignmentLength = newTemplateAlign.length();
 179
 180                                                         string leftCandidateString = candAln.substr(0,leftIndex-(insertLength-rightRoom)+1);
 181                                                         string insertString = candAln.substr(leftIndex+1,rightIndex-leftIndex-1);
 182                                                         string rightCandidateString = candAln.substr(rightIndex+rightRoom);
 183                                                         candAln = leftCandidateString + insertString + rightCandidateString;
 184
 185                                                 }
 186                                         }
 187                                 }
 188                                 else{
 189                                                                                                         //      there could be a case where there isn't enough room in
 190                                         string leftTemplateString = newTemplateAlign.substr(0,i);                       //      either direction to move stuff
 191                                         string rightTemplateString = newTemplateAlign.substr(i+leftRoom+rightRoom);
 192                                         newTemplateAlign = leftTemplateString + rightTemplateString;
 193                                         longAlignmentLength = newTemplateAlign.length();
 194
 195                                         string leftCandidateString = candAln.substr(0,leftIndex-leftRoom+1);
 196                                         string insertString = candAln.substr(leftIndex+1,rightIndex-leftIndex-1);
 197                                         string rightCandidateString = candAln.substr(rightIndex+rightRoom);
 198                                         candAln = leftCandidateString + insertString + rightCandidateString;
 199
 200                                 }
 201
 202                                 i -= insertLength;
 203                         }
 204                 }
 205         }
 206         catch(exception& e) {
 207                 errorOut(e, "Nast", "removeExtraGaps");
 208                 exit(1);
 209         }
 210
 211 }
 212
 213 /**************************************************************************************************/
 214
 215 void Nast::regapSequences(){    //This is essentially part B in Fig 2. of DeSantis et al.
 216         try {
 217
 218                 string candPair = candidateSeq->getPairwise();
 219                 string candAln = "";
 220
 221                 string tempPair = templateSeq->getPairwise();
 222                 string tempAln = templateSeq->getAligned();             //      we use the template aligned sequence as our guide
 223
 224                 int pairwiseLength = candPair.length();
 225                 int fullAlignLength = tempAln.length();
 226
 227                 if(candPair == ""){
 228                         for(int i=0;i<fullAlignLength;i++)      {       candAln += '.';         }
 229                         candidateSeq->setAligned(candAln);
 230                         return;
 231                 }
 232
 233                 int fullAlignIndex = 0;
 234                 int pairwiseAlignIndex = 0;
 235                 string newTemplateAlign = "";                                   //      this is going to be messy so we want a temporary template
 236                 //      alignment string
 237                 while(tempAln[fullAlignIndex] == '.' || tempAln[fullAlignIndex]  == '-'){
 238                         candAln += '.';                                                         //      add the initial '-' and '.' to the candidate and template
 239                         newTemplateAlign += tempAln[fullAlignIndex];//  pairwise sequences
 240                         fullAlignIndex++;
 241                 }
 242
 243                 string lastLoop = "";
 244
 245                 while(pairwiseAlignIndex<pairwiseLength){
 246                         if(isalpha(tempPair[pairwiseAlignIndex]) && isalpha(tempAln[fullAlignIndex])
 247                            && isalpha(candPair[pairwiseAlignIndex])){
 248                                 //  the template and candidate pairwise and template aligned have characters
 249                                 //      need to add character onto the candidatSeq.aligned sequence
 250
 251                                 candAln += candPair[pairwiseAlignIndex];
 252                                 newTemplateAlign += tempPair[pairwiseAlignIndex];//
 253
 254                                 pairwiseAlignIndex++;
 255                                 fullAlignIndex++;
 256                         }
 257                         else if(isalpha(tempPair[pairwiseAlignIndex]) && !isalpha(tempAln[fullAlignIndex])
 258                                         && isalpha(candPair[pairwiseAlignIndex])){
 259                                 //      the template pairwise and candidate pairwise are characters and the template aligned is a gap
 260                                 //      need to insert gaps into the candidateSeq.aligned sequence
 261
 262                                 candAln += '-';
 263                                 newTemplateAlign += '-';//
 264                                 fullAlignIndex++;
 265                         }
 266                         else if(!isalpha(tempPair[pairwiseAlignIndex]) && isalpha(tempAln[fullAlignIndex])
 267                                         && isalpha(candPair[pairwiseAlignIndex])){
 268                                 //  the template pairwise is a gap and the template aligned and pairwise sequences have characters
 269                                 //      this is the alpha scenario.  add character to the candidateSeq.aligned sequence without progressing
 270                                 //      further through the tempAln sequence.
 271
 272                                 candAln += candPair[pairwiseAlignIndex];
 273                                 newTemplateAlign += '-';//
 274                                 pairwiseAlignIndex++;
 275                         }
 276                         else if(isalpha(tempPair[pairwiseAlignIndex]) && isalpha(tempAln[fullAlignIndex])
 277                                         && !isalpha(candPair[pairwiseAlignIndex])){
 278                                 //  the template pairwise and full alignment are characters and the candidate sequence has a gap
 279                                 //      should not be a big deal, just add the gap position to the candidateSeq.aligned sequence;
 280
 281                                 candAln += candPair[pairwiseAlignIndex];
 282                                 newTemplateAlign += tempAln[fullAlignIndex];//
 283                                 fullAlignIndex++;
 284                                 pairwiseAlignIndex++;
 285                         }
 286                         else if(!isalpha(tempPair[pairwiseAlignIndex]) && !isalpha(tempAln[fullAlignIndex])
 287                                         && isalpha(candPair[pairwiseAlignIndex])){
 288                                 //      the template pairwise and aligned are gaps while the candidate pairwise has a character
 289                                 //      this would be an insertion, go ahead and add the character->seems to be the opposite of the alpha scenario
 290
 291                                 candAln += candPair[pairwiseAlignIndex];
 292                                 newTemplateAlign += tempAln[fullAlignIndex];//
 293                                 pairwiseAlignIndex++;
 294                                 fullAlignIndex++;
 295                         }
 296                         else if(isalpha(tempPair[pairwiseAlignIndex]) && !isalpha(tempAln[fullAlignIndex])
 297                                         && !isalpha(candPair[pairwiseAlignIndex])){
 298                                 //      template pairwise has a character, but its full aligned sequence and candidate sequence have gaps
 299                                 //      this would happen like we need to add a gap.  basically the opposite of the alpha situation
 300
 301                                 newTemplateAlign += tempAln[fullAlignIndex];//
 302                                 candAln += "-";
 303                                 fullAlignIndex++;
 304                         }
 305                         else if(!isalpha(tempPair[pairwiseAlignIndex]) && isalpha(tempAln[fullAlignIndex])
 306                                         && !isalpha(candPair[pairwiseAlignIndex])){
 307                                 //      template and candidate pairwise are gaps and the template aligned is not a gap this should not be possible
 308                                 //      would skip the gaps and not progress through full alignment sequence
 309                                 //      not tested yet
 310
 311                                 mothurOut("We're into D " + toString(fullAlignIndex) + " " +  toString(pairwiseAlignIndex)); mothurOutEndLine();
 312                                 pairwiseAlignIndex++;
 313                         }
 314                         else{
 315                                 //      everything has a gap - not possible
 316                                 //      not tested yet
 317
 318                                 mothurOut("We're into F " +  toString(fullAlignIndex) + " " +  toString(pairwiseAlignIndex)); mothurOutEndLine();
 319                                 pairwiseAlignIndex++;
 320                                 fullAlignIndex++;
 321                         }
 322                 }
 323
 324                 for(int i=fullAlignIndex;i<fullAlignLength;i++){
 325                         candAln += '.';
 326                         newTemplateAlign += tempAln[i];//
 327                 }
 328
 329                 int start, end;
 330                 for(int i=0;i<candAln.length();i++){
 331                         if(candAln[i] == 'Z' || !isalnum(candAln[i]))   {       candAln[i] = '.';       }       //      if we padded the alignemnt from
 332                         else{                   start = i;                      break;          }                                                       //      blast with Z's, change them to
 333                 }                                                                                                                                                               //      '.' characters
 334
 335                 for(int i=candAln.length()-1;i>=0;i--){                                                                                 //      ditto.
 336                         if(candAln[i] == 'Z' || !isalnum(candAln[i]))   {       candAln[i] = '.';       }
 337                         else{                   end = i;                        break;          }
 338                 }
 339
 340                 for(int i=start;i<=end;i++){                                    //      go through the candidate alignment sequence and make sure that
 341                         candAln[i] = toupper(candAln[i]);                       //      everything is upper case
 342                 }
 343
 344
 345                 if(candAln.length() != tempAln.length()){               //      if the regapped candidate sequence is longer than the official
 346                         removeExtraGaps(candAln, tempAln, newTemplateAlign);//  template alignment then we need to do steps C-F in Fig.
 347                 }                                                                                               //      2 of Desantis et al.
 348
 349
 350                 candidateSeq->setAligned(candAln);
 351         }
 352         catch(exception& e) {
 353                 errorOut(e, "Nast", "regapSequences");
 354                 exit(1);
 355         }
 356 }
 357
 358 /**************************************************************************************************/
 359
 360 float Nast::getSimilarityScore(){
 361         try {
 362
 363                 string cand = candidateSeq->getAligned();
 364                 string temp = templateSeq->getAligned();
 365                 int alignmentLength = temp.length();
 366                 int mismatch = 0;
 367                 int denominator = 0;
 368
 369                 for(int i=0;i<alignmentLength;i++){
 370                         if(cand[i] == '-' && temp[i] == '-'){
 371
 372                         }
 373                         else if(cand[i] != '.' && temp[i] != '.'){
 374                                 denominator++;
 375
 376                                 if(cand[i] != temp[i]){
 377                                         mismatch++;
 378                                 }
 379                         }
 380                 }
 381                 float similarity = 100 * (1. - mismatch / (float)denominator);
 382                 if(denominator == 0){   similarity = 0.0000;    }
 383
 384                 return similarity;
 385
 386         }
 387         catch(exception& e) {
 388                 errorOut(e, "Nast", "getSimilarityScore");
 389                 exit(1);
 390         }
 391 }
 392
 393 /**************************************************************************************************/
 394
 395 int Nast::getMaxInsertLength(){
 396
 397         return maxInsertLength;
 398
 399 }
 400
 401 /**************************************************************************************************/