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