QPalmaDP/fill_matrix.cpp

   1 /*********************************************************************************************/
   2 // Version of fill_matrix with fills several alignment matrices (best, second_best ...)
   3 // nr_paths det. number of these matrices
   4 //
   5 // est_len: Number of columns in alignment matrix: length(EST) +1 (for the gap) (variable: i)
   6 // dna_len: Number of lines in alignment matrix: length(DNA) +1 (for the gap) (variable: j)
   7 //
   8 // !!! IMPORTANT !!! The pictures and equations in the paper/poster etc. describe the algorithm
   9 // for an alignment matrix where DNA and EST changed places !!! IMPORTANT !!!
  10 /*********************************************************************************************/
  11
  12 /*
  13   matchmatrix: columnwise
  14     - A C G T N (dna)
  15   - x x x x x x
  16   A x x x x x x
  17   C x x x x x x
  18   G x x x x x x
  19   T x x x x x x
  20   N x x x x x x
  21 (est)
  22 */
  23
  24 /*
  25   alignment matrix: columnwise
  26    |-EST . . .
  27   -+------------
  28   -|00 ...
  29   D|0.
  30   N|. .
  31   A|.  .
  32   .|.
  33   .|
  34   .|
  35 */
  36
  37
  38 /* TODO
  39    - max_len = 10000 for elegans!
  40    - do not use double
  41
  42 */
  43
  44
  45 #include "fill_matrix.h"
  46
  47 using namespace std;
  48
  49 int check_char(char base)
  50 {
  51   switch(base)
  52   {
  53   case 'A':
  54   case 'a': return 1;
  55   case 'C':
  56   case 'c': return 2;
  57   case 'G':
  58   case 'g': return 3;
  59   case 'T':
  60   case 't': return 4;
  61   case 'N':
  62   case 'n': return 5;
  63   default : return 0;
  64   }
  65
  66 }
  67
  68
  69
  70 void fill_matrix(int nr_paths, Pre_score* matrices[], int est_len /*counter var: i*/, int dna_len /*counter var: j*/, char* est, char* dna, penalty_struct* functions , double* matchmatrix, double* donor, double* acceptor, bool remove_duplicate_scores, int nr_donor_sites, int* donor_sites, int* max_score_positions)
  71 {
  72
  73   /*********************************************************************************************/
  74   // variables
  75   /*********************************************************************************************/
  76   const int mlen = 6; // length of matchmatrix
  77   int estChar, dnaChar; // 0:'-', 1:'a', 2:'c', 3:'g', 4:'t', 5:'n'
  78   double prevValue ;
  79   double tempValue;
  80   int max_len = (int)functions->limits[functions->len-1] ; //last (len) supporting point of h
  81   //printf("max_len: %d\n", max_len) ;
  82
  83   int num_elem ; // counter variable
  84
  85   const int max_num_elem = (4+nr_paths+max_len) * nr_paths ; // upper bound on num_elem
  86   double *scores=new double[max_num_elem] ; //are sorted later
  87   struct ArrayElem *array=new ArrayElem[max_num_elem] ;
  88   //printf("%d\n", max_num_elem*sizeof(ArrayElem)) ;
  89
  90   int max_ss_element[nr_paths*nr_paths]; //position on dna with max ss score for introns of length greater than max_len
  91   int splice_pos ; //splice position get from donor_sites
  92   int start_splice_pos ; //where to start looking in donor_sites
  93
  94   double max_scores[nr_paths] ;
  95
  96   /*********************************************************************************************/
  97   // Initialisation of all alignment matrices, columnwise
  98   /*********************************************************************************************/
  99   for (int z=0; z<nr_paths; z++) /* matrice z */
 100   {
 101     max_scores[z] = log(0.0) ;
 102     max_score_positions[2*z]    = 0; // pos i
 103     max_score_positions[2*z +1] = 0; // pos j
 104
 105     for (int i=0; i<est_len; i++) /* i.column */
 106     {
 107       for (int j=0; j<dna_len; j++) /* j.line */
 108       {
 109         ((Pre_score*)matrices[z] +(i*dna_len) +j)->value = log(0.0); // -inf
 110         ((Pre_score*)matrices[z] +(i*dna_len) +j)->prev_i = 0;
 111         ((Pre_score*)matrices[z] +(i*dna_len) +j)->prev_j = 0;
 112         ((Pre_score*)matrices[z] +(i*dna_len) +j)->prev_matrix_no = 0;
 113         ((Pre_score*)matrices[z] +(i*dna_len) +j)->issplice = 0;
 114       }
 115     }
 116   }
 117
 118
 119   /*********************************************************************************************/
 120   // Element (0,0) for first/best matrice (z=0)
 121   /*********************************************************************************************/
 122   ((Pre_score*)matrices[0])->value = 0;
 123   ((Pre_score*)matrices[0])->prev_i = 0;
 124   ((Pre_score*)matrices[0])->prev_j = 0;
 125   ((Pre_score*)matrices[0])->prev_matrix_no = 0;
 126   ((Pre_score*)matrices[0])->issplice = 0;
 127
 128
 129   /*********************************************************************************************/
 130   // Line Zero for first/best matrice (z=0)
 131   /*********************************************************************************************/
 132   for (int i=1; i<est_len; i++) /* 0.line, all columns (DNA='-') */
 133   {
 134     ((Pre_score*)matrices[0] +(i*dna_len))->value = 0 ;
 135     ((Pre_score*)matrices[0] +(i*dna_len))->prev_i = i-1;
 136     ((Pre_score*)matrices[0] +(i*dna_len))->prev_j = 0;
 137     ((Pre_score*)matrices[0] +(i*dna_len))->prev_matrix_no = 0;
 138     ((Pre_score*)matrices[0] +(i*dna_len))->issplice = 0;
 139   }
 140
 141
 142   /*********************************************************************************************/
 143   // Column Zero for first/best matrice (z=0)
 144   /*********************************************************************************************/
 145   for (int j=1; j<dna_len; j++) // 0.column, all lines
 146   {
 147     ((Pre_score*)matrices[0] +j)->value =  0 ;
 148     ((Pre_score*)matrices[0] +j)->prev_i = 0 ;
 149     ((Pre_score*)matrices[0] +j)->prev_j = j-1 ;
 150     ((Pre_score*)matrices[0] +j)->prev_matrix_no = 0 ;
 151     ((Pre_score*)matrices[0] +j)->issplice = 0;
 152   }
 153
 154
 155   /*********************************************************************************************/
 156   // !!!! Column Zero and line Zero for all other matrices except the best one (z>0): -INF !!!!
 157   /*********************************************************************************************/
 158
 159
 160
 161   /*********************************************************************************************/
 162   // all other entries for all matrices, last column and row treated seperately
 163   /*********************************************************************************************/
 164
 165   /* columnwise, 0.column and 0.line already filled */
 166   for (int i=1; i<est_len; i++) /* i.column */
 167   {
 168
 169     start_splice_pos = 0 ; //where to start looking in donor_sites
 170     for (int zz=0; zz<nr_paths*nr_paths; zz++) {max_ss_element[zz]=0 ;} // initializing
 171
 172     for (int j=1; j<dna_len; j++) //j.line
 173     {
 174       dnaChar = check_char(dna[j-1]) ; // -1 because of of the gaps in the 0.line/column of the al-matrix
 175       estChar = check_char(est[i-1]) ;
 176
 177
 178       //if introns of length greater than max_len possible
 179       if (j > max_len)
 180       {
 181         //storing highest ss_score (the position) and NOT -INF
 182         int new_ss_pos = j-max_len ;
 183         double donor_score = donor[new_ss_pos-1] ;
 184         if (isfinite(donor_score)) //splice site!
 185         {
 186           if (max_ss_element[nr_paths-1] != 0)
 187           {
 188             for (int zz=0; zz<nr_paths; zz++) //for each alignment matrix
 189             {
 190               int pos_with_minscore = nr_paths ; //assuming, the new score is the worst score
 191               double new_intron_score = donor_score+((Pre_score*)matrices[zz]+(i*dna_len)+new_ss_pos-1)->value ; //could be -INF
 192               if (!(isfinite(new_intron_score))) {printf("new_intron_score is -INF\n") ;}
 193               for (int pos=0; pos<nr_paths; pos++) //find worst score of all nr_paths+1 scores
 194               {
 195                 int act_splice_position = max_ss_element[zz*nr_paths+pos] ;
 196                 assert(isfinite(donor[act_splice_position-1])) ;
 197                 double act_intron_score = donor[act_splice_position-1]+((Pre_score*)matrices[zz]+(i*dna_len)+act_splice_position-1)->value ;
 198                 if (new_intron_score >= act_intron_score)
 199                 {
 200                   new_intron_score = act_intron_score ;
 201                   pos_with_minscore = pos ;
 202                 } //else nothing happens, new intron score still the worst one
 203               }
 204               if (pos_with_minscore != nr_paths)
 205               {
 206                 max_ss_element[zz*nr_paths+pos_with_minscore] = new_ss_pos ; //replacing
 207               }
 208             }
 209           }
 210           else
 211           {
 212             for (int pos=0; pos<nr_paths; pos++)
 213             {
 214               if (max_ss_element[pos]==0)  //no previous splice site at this pos
 215               {
 216                 for (int zz=0; zz<nr_paths; zz++) {max_ss_element[zz*nr_paths+pos]=j-max_len ;}
 217                 break ;
 218               }
 219             }
 220           }
 221         }
 222         //start_pos in donor_sites so that only introns shorter then max_length are seen
 223         if ((start_splice_pos < nr_donor_sites) && donor_sites[start_splice_pos] == j-max_len)
 224         {
 225           start_splice_pos++ ;
 226         }
 227       }
 228
 229
 230       /* Computing all possible scores */
 231       num_elem = 0 ; /* number of different scores/possibilities so far */
 232       for (int z=0; z<nr_paths; z++) /* matrice z */
 233       {
 234         Pre_score* actMatrix = (Pre_score*)matrices[z]; /* hm, why?  */
 235
 236         /***************************************/
 237         // 0. Zero (local alignment version)
 238         /***************************************/
 239         assert(num_elem<max_num_elem) ;
 240         array[num_elem].prev_i = 0;
 241         array[num_elem].prev_j = 0;
 242         array[num_elem].prev_matrix_no = z;
 243         array[num_elem].isSplice = false; /* no splice site */
 244         scores[num_elem] = 0 ;
 245         num_elem++ ;
 246
 247
 248         /***************************************/
 249         // 1. gap on EST (j-1,i) -> (j,i)
 250         /***************************************/
 251         prevValue = ((Pre_score*)actMatrix +(i*dna_len)+j-1)->value ; /* (j-1,i) -> (j,i) */
 252         if (isfinite(prevValue))
 253         {
 254           tempValue = prevValue +(matchmatrix[mlen* dnaChar]); /* score(gap,DNA) */
 255           if (isfinite(tempValue))
 256           {
 257             assert(num_elem<max_num_elem) ;
 258             array[num_elem].prev_i = i;
 259             array[num_elem].prev_j = j-1; /* predecessor */
 260             array[num_elem].prev_matrix_no = z;
 261             array[num_elem].isSplice = false; /* no splice site */
 262             scores[num_elem] = -tempValue ;
 263             num_elem++ ;
 264           }
 265         }
 266
 267
 268         /***************************************/
 269         // 2. match/mismatch (j-1,i-1) -> (j,i)
 270         /***************************************/
 271         prevValue = ((Pre_score*)actMatrix +(i-1)*dna_len + j-1)->value ; /* (j-1,i-1) -> (j,i) */
 272         if (isfinite(prevValue))
 273         {
 274           tempValue = prevValue +(matchmatrix[mlen* dnaChar +estChar]);//DNA mit EST
 275           if (isfinite(tempValue))
 276           {
 277             assert(num_elem<max_num_elem) ;
 278             array[num_elem].prev_i = i-1; /* predecessor */
 279             array[num_elem].prev_j = j-1; /* predecessor */
 280             array[num_elem].prev_matrix_no = z;
 281             array[num_elem].isSplice = false; /* no splice site */
 282             scores[num_elem] = -tempValue ;
 283             num_elem++ ;
 284           }
 285         }
 286
 287
 288         /***************************************/
 289         // 3. gap on DNA (j,i-1) -> (j,i)
 290         /***************************************/
 291         prevValue = ((Pre_score*)actMatrix +(i-1)*dna_len + j)->value ;
 292         if (isfinite(prevValue))
 293         {
 294           tempValue = prevValue +(matchmatrix[estChar]); /* score(EST,gap) */
 295           if (isfinite(tempValue))
 296           {
 297             assert(num_elem<max_num_elem) ;
 298             array[num_elem].prev_i = i-1; /* predecessor */
 299             array[num_elem].prev_j = j;
 300             array[num_elem].prev_matrix_no = z;
 301             array[num_elem].isSplice = false;  /* no splice site */
 302             scores[num_elem]=-tempValue ;
 303             num_elem++ ;
 304           }
 305
 306         }
 307
 308
 309         /***************************************/
 310         // 4. all possible splice sites/introns
 311         /***************************************/
 312         // acceptor[j-1]: g of ag (-1 because cpp starts counting at 0)
 313         // donor[splice_pos-1]: g of gt/gc (-1 because cpp starts counting at 0)
 314         // donor_sites: the g's of the gt/gc
 315
 316         if (isfinite(acceptor[j-1]))
 317         {
 318
 319           //the nr_paths many introns of length greater than max_len
 320           for (int pos=0; pos<nr_paths; pos++)
 321           {
 322             if (max_ss_element[z*nr_paths+pos]>0)
 323             {
 324               assert((j-max_ss_element[z*nr_paths+pos]+1) > max_len) ;
 325               splice_pos = max_ss_element[z*nr_paths+pos] ; //the g of the gt
 326               prevValue = ((Pre_score*)actMatrix + (i*dna_len) +splice_pos-1)->value ; //one before the _gt
 327               if (isfinite(prevValue) && (((Pre_score*)actMatrix + (i*dna_len) +splice_pos-1)->issplice!=1))
 328               {
 329                 int dist = j -(splice_pos-1); //_gt...ag: dist from g to g
 330                 assert(dist>max_len) ;
 331                 tempValue = lookup_penalty(functions,dist, NULL, 0) +donor[splice_pos-1] +acceptor[j-1] +prevValue;
 332                 if (isfinite(tempValue))
 333                 {
 334                   assert(num_elem<max_num_elem) ;
 335                   array[num_elem].prev_i = i;
 336                   array[num_elem].prev_j = splice_pos-1; // predecessor
 337                   array[num_elem].prev_matrix_no = z;
 338                   array[num_elem].isSplice = true; // splice site
 339                   scores[num_elem]=-tempValue ;
 340                   num_elem++ ;
 341                 }
 342                 else if (isfinite(lookup_penalty(functions,dist, NULL, 0)))
 343                 {
 344                   printf("Something wrong with donor_sites(1000er) (intron_length: %d)\n", dist) ;
 345                   sleep(5000) ;
 346                 }
 347               }
 348             }
 349           }
 350
 351
 352
 353           //all introns of length <= max_len
 354           for (int k=start_splice_pos; k < nr_donor_sites; k++)
 355           //for (int k=0; k < nr_donor_sites; k++) //also intron of length greater than 1000
 356           {
 357             splice_pos = donor_sites[k] ;
 358             if (splice_pos > j-4) { break ;}
 359             prevValue = ((Pre_score*)actMatrix + (i*dna_len) +splice_pos-1)->value ; //one before the _gt
 360
 361             if (isfinite(prevValue) && (((Pre_score*)actMatrix + (i*dna_len) +splice_pos-1)->issplice!=1))
 362             {
 363               int dist = j -(splice_pos-1); //_gt...ag: dist from g to g
 364               assert(dist<=max_len) ;
 365               tempValue = lookup_penalty(functions,dist, NULL, 0) +donor[splice_pos-1] +acceptor[j-1] +prevValue;
 366               if (isfinite(tempValue))
 367               {
 368                 assert(num_elem<max_num_elem) ;
 369                 array[num_elem].prev_i = i;
 370                 array[num_elem].prev_j = splice_pos-1; /* predecessor */
 371                 array[num_elem].prev_matrix_no = z;
 372                 array[num_elem].isSplice = true; /* splice site */
 373                 scores[num_elem]=-tempValue ;
 374                 num_elem++ ;
 375               }
 376               else if (isfinite(lookup_penalty(functions,dist, NULL, 0)))
 377               {
 378                 printf("Something wrong with donor_sites (intron_length: %d)\n", dist) ;
 379                 sleep(5000) ;
 380               }
 381             }
 382           }
 383         }
 384
 385       } //end of z
 386
 387       CMath::nmin<struct ArrayElem>(scores, array, num_elem, nr_paths);
 388
 389       /* the nr_paths many highest scores are written in the nr_paths many matrices*/
 390       for (int z=0; z<nr_paths; z++) {
 391         if (z>=num_elem) {
 392           //nothing happens, entry in matrices[z] at pos. (i,j) still -inf
 393         }
 394         else {
 395           ((Pre_score*)matrices[z] + (i*dna_len) +j)->value = -scores[z] ;
 396           ((Pre_score*)matrices[z] + (i*dna_len) +j)->prev_i = array[z].prev_i ;
 397           ((Pre_score*)matrices[z] + (i*dna_len) +j)->prev_j = array[z].prev_j ;
 398           ((Pre_score*)matrices[z] + (i*dna_len) +j)->issplice = array[z].isSplice ;
 399           ((Pre_score*)matrices[z] + (i*dna_len) +j)->prev_matrix_no = array[z].prev_matrix_no;
 400
 401           if (-scores[z]>=max_scores[z]) { //storing the postion of the highest alignment score yet
 402             max_scores[z] = -scores[z] ;
 403             max_score_positions[2*z]    = i; // pos i
 404             max_score_positions[2*z +1] = j; // pos j
 405           }
 406         }
 407       } //end of z
 408
 409     } //end of j
 410   } // end of i
 411
 412
 413
 414   //free memory
 415   delete[] array;
 416   delete[] scores;
 417
 418   return;
 419 }
 420
 421