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