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kalign2_advanced_gaps.c

/*
      kalign2_advanced_gaps.c
      
      Released under GPL - see the 'COPYING' file   
      
      Copyright (C) 2006 Timo Lassmann <timolassmann@gmail.com>
      
      This program is free software; you can redistribute it and/or modify
      it under the terms of the GNU General Public License as published by
      the Free Software Foundation; either version 2 of the License, or
      any later version.

      This program is distributed in the hope that it will be useful,
      but WITHOUT ANY WARRANTY; without even the implied warranty of
      MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
      GNU General Public License for more details.

      You should have received a copy of the GNU General Public License
      along with this program; if not, write to the Free Software
      Foundation, Inc., 59 Temple Place, Suite 330, Boston, MA  02111-1307  USA
    
      Please send bug reports, comments etc. to:
      timolassmann@gmail.com
*/

#include "kalign2.h"
#include "kalign2_advanced_gaps.h"


int** advanced_hirschberg_alignment(struct alignment* aln,int* tree,float**submatrix, int** map,int window,float strength,float internal_gap_weight)
{
      struct hirsch_mem* hm = 0;
      int i,j,g,a,b,c;
      int len_a;
      int len_b;
      float** profile = 0;

      profile = malloc(sizeof(float*)*numprofiles);
      for ( i = 0;i< numprofiles;i++){
            profile[i] = 0;
      }

      map = malloc(sizeof(int*)*numprofiles);
      for ( i = 0;i < numprofiles;i++){
            map[i] = 0;
      }
      
      hm = hirsch_mem_alloc(hm,1024);

      fprintf(stderr,"\nAlignment:\n");

      for (i = 0; i < (numseq-1);i++){
            a = tree[i*3];
            b = tree[i*3+1];
            c = tree[i*3+2];
            fprintf(stderr,"\r%8.0f percent done",(float)(i) /(float)numseq * 100);
      //    fprintf(stderr,"Aligning:%d %d->%d  done:%f\n",a,b,c,((float)(i+1)/(float)numseq)*100);
            len_a = aln->sl[a];
            len_b = aln->sl[b];

            
            g = (len_a > len_b)? len_a:len_b;
            map[c] = malloc(sizeof(int) * (g+2));
            if(g > hm->size){
                  hm = hirsch_mem_realloc(hm,g);
            }

            for (j = 0; j < (g+2);j++){
            //    hirsch_path[j] = -1;
                  map[c][j] = -1;
            //    map[c][j] = 0;
            }
      //    map[c][0] = len_a;
            //map[c][len_a+len_b+1] = 3;

            if (a < numseq){
                  profile[a] = advanced_make_profile(profile[a],aln->s[a],len_a,submatrix);
            }
            if (b < numseq){
                  profile[b] = advanced_make_profile(profile[b],aln->s[b],len_b,submatrix);
            }
            
      
            //set_gap_penalties(profile[a],len_a,aln->nsip[b]);
            
            advanced_smooth_gaps(profile[a],len_a,window,strength);
            
            //set_gap_penalties(profile[b],len_b,aln->nsip[a]);
            
            advanced_smooth_gaps(profile[b],len_b,window,strength);
            
            hm->starta = 0;
            hm->startb = 0;
            hm->enda = len_a;
            hm->endb = len_b;
            hm->len_a = len_a;
            hm->len_b = len_b;
            
            hm->f[0].a = 0.0;
            hm->f[0].ga =  -FLOATINFTY;
            hm->f[0].gb = -FLOATINFTY;
            hm->b[0].a = 0.0;
            hm->b[0].ga =  -FLOATINFTY;
            hm->b[0].gb =  -FLOATINFTY;
      //    fprintf(stderr,"LENA:%d LENB:%d     numseq:%d\n",len_a,len_b,numseq);
            if(len_a < len_b){
                  map[c] = advanced_hirsch_pp_dyn(profile[a],profile[b],hm,map[c]);
            }else{
                  hm->enda = len_b;
                  hm->endb = len_a;
                  hm->len_a = len_b;
                  hm->len_b = len_a;
                  map[c] = advanced_hirsch_pp_dyn(profile[b],profile[a],hm,map[c]);
                  map[c] = mirror_hirsch_path(map[c],len_a,len_b);
            }
                              
            map[c] = add_gap_info_to_hirsch_path(map[c],len_a,len_b);

            if(i != numseq-2){
                  profile[c] = malloc(sizeof(float)*64*(map[c][0]+2));
                  profile[c] = advanced_update(profile[a],profile[b],profile[c],map[c],aln->nsip[a],aln->nsip[b],internal_gap_weight);
            }
                  
            aln->sl[c] = map[c][0];
      
            aln->nsip[c] = aln->nsip[a] + aln->nsip[b];
            aln->sip[c] = malloc(sizeof(int)*(aln->nsip[a] + aln->nsip[b]));
            g =0;
            for (j = aln->nsip[a];j--;){
                  aln->sip[c][g] = aln->sip[a][j];
                  g++;
            }
            for (j = aln->nsip[b];j--;){
                  aln->sip[c][g] = aln->sip[b][j];
                  g++;
            }

            free(profile[a]);
            free(profile[b]);
      }
      fprintf(stderr,"\r%8.0f percent done\n",100.0);
      free(profile);
      hirsch_mem_free(hm);
      for (i = 32;i--;){
            free(submatrix[i]);
      }
      free(submatrix);
      return map;
}


float* advanced_make_profile(float* prof, int* seq,int len,float** subm)
{
      int i,j,c;  
      prof = malloc(sizeof(float)*(len+2)*64);
      prof +=  (64 *(len+1));

      for (i = 0;i < 64;i++){
            prof[i] = 0;
      }
      prof[23+32] = -gpo;
      prof[24+32] = -gpe;
      prof[25+32] = -tgpe;
      prof[26] = 1;

      
      i = len;
      while(i--){
            prof -= 64;

            for (j = 0;j < 64;j++){
                  prof[j] = 0;
            }
            prof[26] = 1;//number of residues // both additive
            c = seq[i];
            
            prof[c] += 1.0;
            
            prof += 32;
            
            for(j = 23;j--;){
                  prof[j] = subm[c][j];
            }
            prof[23] = -gpo;
            prof[24] = -gpe;
            prof[25] = -tgpe;
            
            prof -= 32;
      }
      prof -= 64;
      for (i = 0;i < 64;i++){
            prof[i] = 0;
      }

      prof[23+32] = -gpo;
      prof[24+32] = -gpe;
      prof[25+32] = -tgpe;
      prof[26] = 1;
      return prof;
}



void advanced_smooth_gaps(float* prof,int len,int window,float strength)
{
      float tmp_gpo;
      float tmp_gpe;
      float tmp_tgpe;
      int i,j;
      if(!(window &1)){
            window--;
      }
      for ( i = (window/2); i < len - (window/2);i++){
            tmp_gpo = 0.0;
            tmp_gpe = 0.0;
            tmp_tgpe = 0.0;
            for (j = -(window/2); j < (window/2);j++){
                  tmp_gpo += (float)prof[55+((i+j)*64)]*strength;
                  tmp_gpe += (float) prof[56+((i+j)*64)]*strength;
                  tmp_tgpe += (float) prof[57+((i+j)*64)]*strength;
            }
            tmp_gpo /= window;
            tmp_gpe /= window;
            tmp_tgpe /= window;
            prof[27+(i*64)] =  prof[55+(i*64)]*(1.0-strength) + tmp_gpo;
            prof[28+(i*64)] =  prof[56+(i*64)]*(1.0-strength) + tmp_gpe;
            prof[29+(i*64)] =  prof[57+(i*64)]*(1.0-strength) + tmp_tgpe;
      }
}



float* advanced_update(const float* profa,const float* profb,float* newp,int* path,int sipa,int sipb,float internal_gap_weight)
{
      int i,j,c;
      for (i = 64; i--;){
            newp[i] = profa[i] + profb[i];
      }
      
      profa += 64;
      profb += 64;
      newp += 64;

      c = 1;
      
      while(path[c] != 3){
            //Idea: limit the 'virtual' number of residues of one type to x.
            // i.e. only allow a maximum of 10 alanines to be registered in each column
            // the penalty for aligning a 'G' to this column will stay stable even when many (>10) alanines are present.
            // the difference in score between the 'correct' (all alanine) and incorrect (alanines + glycine) will not increase 
            // with the number of sequences. -> see Durbin pp 140
            
            if (!path[c]){
                  //fprintf(stderr,"Align %d\n",c);
                  for (i = 64; i--;){
                        newp[i] = profa[i] + profb[i];
                  }
                        
                  
                  profa += 64;
                  profb += 64;
            }
            if (path[c] & 1){
                  //fprintf(stderr,"Gap_A:%d\n",c);
                  //printf("open:%d ext:%d      %d    %d\n",si->nsip[a] * gpo,si->nsip[a] * gpe,si->nsip[a] * profb[41],si->nsip[a] * profb[46]);
                  for (i = 64; i--;){
                        newp[i] = profb[i];
                  }
                  profb += 64;
                  if(!(path[c] & 20)){
                        if(path[c] & 32){
                              newp[25] += (profa[26] + ((sipa-  profa[26]) * internal_gap_weight));
                              i = tgpe* (profa[26] + ((sipa-  profa[26]) * internal_gap_weight));
                        }else{
                              newp[24] +=  (profa[26] + ((sipa-  profa[26]) * internal_gap_weight));//1;
                              i = gpe* (profa[26] + ((sipa-  profa[26]) * internal_gap_weight));
                        }
                        
                        for (j = 32; j < 55;j++){
                              newp[j] -=i;
                        }
                  }else{
                  if (path[c] & 16){ 
      //                fprintf(stderr,"close_open");
                        if(path[c] & 32){
                              newp[25] +=  (profa[26] + ((sipa-  profa[26]) * internal_gap_weight));//1;
                              i = tgpe* (profa[26] + ((sipa-  profa[26]) * internal_gap_weight));
                              newp[23] +=  (profa[26] + ((sipa-  profa[26]) * internal_gap_weight));//1;
                              i += gpo* (profa[26] + ((sipa-  profa[26]) * internal_gap_weight));
                        }else{
                              newp[23] +=  (profa[26] + ((sipa-  profa[26]) * internal_gap_weight));
                              i = gpo* (profa[26] + ((sipa-  profa[26]) * internal_gap_weight));
                        }
                                                
                        for (j = 32; j < 55;j++){
                              newp[j] -=i;
                        }
                  }
                  if (path[c] & 4){ 
      //                fprintf(stderr,"Gap_open");
                        if(path[c] & 32){
                              newp[25] +=  (profa[26] + ((sipa-  profa[26]) * internal_gap_weight));
                              i = tgpe* (profa[26] + ((sipa-  profa[26]) * internal_gap_weight));
                              newp[23] +=  (profa[26] + ((sipa-  profa[26]) * internal_gap_weight));
                              i += gpo* (profa[26] + ((sipa-  profa[26]) * internal_gap_weight));
                        }else{
                              newp[23] +=  (profa[26] + ((sipa-  profa[26]) * internal_gap_weight));
                              i = gpo* (profa[26] + ((sipa-  profa[26]) * internal_gap_weight));
                        }
                        for (j = 32; j < 55;j++){
                              newp[j] -=i;
                        }
                  }
                  }
                  
                  
            }
            if (path[c] & 2){
                  //fprintf(stderr,"Gap_B:%d\n",c);
                  //printf("open:%d ext:%d      %d    %d\n",si->nsip[b] * gpo,si->nsip[b] * gpe,profa[26],profa[27]);
                  for (i = 64; i--;){
                        newp[i] = profa[i];
                  }
                  profa+=64;
                  if(!(path[c] & 20)){
                        if(path[c] & 32){
                              newp[25] +=  (profb[26] + ((sipb-  profb[26]) * internal_gap_weight));
                              i = tgpe*(profb[26] + ((sipb-  profb[26]) * internal_gap_weight));
                        }else{
                              newp[24] += (profb[26] + ((sipb-  profb[26]) * internal_gap_weight));//1;
                              i = gpe*(profb[26] + ((sipb-  profb[26]) * internal_gap_weight));
                        }
                        for (j = 32; j < 55;j++){
                              newp[j] -=i;
                        }
                  }else{
                  if (path[c] & 16){
      //                fprintf(stderr,"close_open");
                        if(path[c] & 32){
                              newp[25] += (profb[26] + ((sipb-  profb[26]) * internal_gap_weight));//1;
                              i =  tgpe*(profb[26] + ((sipb-  profb[26]) * internal_gap_weight));
                              newp[23] += (profb[26] + ((sipb-  profb[26]) * internal_gap_weight));//1;
                              i +=  gpo*(profb[26] + ((sipb-  profb[26]) * internal_gap_weight));
                        }else{
                              newp[23] += (profb[26] + ((sipb-  profb[26]) * internal_gap_weight));//1;
                              i =  gpo*(profb[26] + ((sipb-  profb[26]) * internal_gap_weight));
                        }
                        for (j = 32; j < 55;j++){
                              newp[j] -=i;
                        }
                  }
                  if (path[c] & 4){
      //                fprintf(stderr,"Gap_open");
                        if(path[c] & 32){
                              newp[25] +=(profb[26] + ((sipb-  profb[26]) * internal_gap_weight));//1;
                              i = tgpe*(profb[26] + ((sipb-  profb[26]) * internal_gap_weight));
                              newp[23] += (profb[26] + ((sipb-  profb[26]) * internal_gap_weight));//1;
                              i += gpo*(profb[26] + ((sipb-  profb[26]) * internal_gap_weight));
                        }else{
                              newp[23] += (profb[26] + ((sipb-  profb[26]) * internal_gap_weight));//1;
                              i = gpo*(profb[26] + ((sipb-  profb[26]) * internal_gap_weight));
                        }
                        
                        for (j = 32; j < 55;j++){
                              newp[j] -=i;
                        }
                  }
                  }
                  
            }
            newp += 64;
            c++;
      }
      for (i = 64; i--;){
            newp[i] =  profa[i] + profb[i];
      }     
      newp -= (path[0]+1) *64;
      return newp;
}



int* advanced_hirsch_pp_dyn(const float* prof1,const float* prof2,struct hirsch_mem* hm, int* hirsch_path)
{
      int mid = ((hm->enda - hm->starta) / 2)+ hm->starta;
      float input_states[6] = {hm->f[0].a,hm->f[0].ga,hm->f[0].gb,hm->b[0].a,hm->b[0].ga,hm->b[0].gb};
      int old_cor[5] = {hm->starta,hm->enda,hm->startb,hm->endb,mid};

      
      //fprintf(stderr,"starta:%d enda:%d startb:%d endb:%d mid:%d\n",hm->starta,hm->enda,hm->startb,hm->endb,mid);
      
      
      if(hm->starta  >= hm->enda){
            return hirsch_path;
      }
      if(hm->startb  >= hm->endb){
            return hirsch_path;
      }

      hm->enda = mid;
      hm->f = advanced_foward_hirsch_pp_dyn(prof1,prof2,hm);
      /*int i;
      fprintf(stderr,"FOWARD\n");
      for (i = hm->startb; i <= hm->endb;i++){
            fprintf(stderr,"%d      %d    %d\n",hm->f[i].a,hm->f[i].ga,hm->f[i].gb);
      }*/

      hm->starta = mid;
      hm->enda = old_cor[1];
      hm->b = advanced_backward_hirsch_pp_dyn(prof1,prof2,hm);
      /*fprintf(stderr,"BaCKWARD\n");

      for (i = hm->startb; i <= hm->endb;i++){
            fprintf(stderr,"%d      %d    %d\n",hm->b[i].a,hm->b[i].ga,hm->b[i].gb);
      }*/

      hirsch_path = advanced_hirsch_align_two_pp_vector(prof1,prof2,hm,hirsch_path,input_states,old_cor);
      return hirsch_path;
}



int* advanced_hirsch_align_two_pp_vector(const float* prof1,const float* prof2,struct hirsch_mem* hm,int* hirsch_path,float input_states[],int old_cor[])
{
      struct states* f = hm->f;
      struct states* b = hm->b;
      int i,j,c;
      int transition = -1;
      
      
      //code:
      // a -> a = 1
      // a -> ga = 2
      // a -> gb = 3
      // ga ->ga = 4
      // ga -> a = 5
      //gb->gb = 6;
      //gb->a = 7;
      
      //int max = -INFTY;
      float max = -INFTY;     
      float middle =  (hm->endb - hm->startb)/2 + hm->startb;
      float sub = 0.0;
      

      prof1+= (64 * (old_cor[4]+1));
      prof2 += 64 * (hm->startb);
      i = hm->startb;
      c = -1;
      for(i = hm->startb; i < hm->endb;i++){
            sub = abs(middle -i);
            sub /= 1000; 
            prof2 += 64;
            //fprintf(stderr,"%d    %d    %d \n",f[i].a,b[i].a,max);
            if(f[i].a+b[i].a-sub > max){
                  max = f[i].a+b[i].a-sub;
      //          fprintf(stderr,"aligned->aligned:%d + %d = %d\n",f[i].a,b[i].a,f[i].a+b[i].a);
                  transition = 1;
                  c = i;
            }
            if(f[i].a+b[i].ga+prof2[27]*prof1[26]-sub > max){
                  max = f[i].a+b[i].ga+prof2[27]*prof1[26]-sub;
      //          fprintf(stderr,"aligned->gap_a:%d + %d +%d = %d\n",f[i].a,b[i].ga,prof1[27],f[i].a+b[i].ga+prof2[27]);
                  transition = 2;
                  c = i;
            }
            if(f[i].a+b[i].gb+prof1[27]*prof2[26] -sub> max){
                  max = f[i].a+b[i].gb+prof1[27]*prof2[26]-sub;
      //          fprintf(stderr,"aligned->gap_b:%d + %d +%d = %d\n",f[i].a,b[i].gb,prof1[27],f[i].a+b[i].gb+prof1[27]);
                  transition = 3;
                  c = i;
            }
            if(f[i].ga+b[i].a+prof2[27]*prof1[26]-sub > max){
                  max = f[i].ga+b[i].a+prof2[27]*prof1[26]-sub;
      //          fprintf(stderr,"gap_a->aligned:%d + %d + %d(gpo) = %d\n",f[i].ga,b[i].a,prof2[27],f[i].ga+b[i].a+prof2[27]);
                  transition = 5;
                  c = i;
            }


            if(hm->startb == 0){
                  if(f[i].gb+b[i].gb+prof1[29]*prof2[26]-sub > max){
                        max = f[i].gb+b[i].gb+prof1[29]*prof2[26]-sub;
      //                fprintf(stderr,"gap_b->gap_b:%d + %d +%d(gpe) =%d \n",f[i].gb, b[i].gb, prof1[28],f[i].gb+b[i].gb+prof1[28]);
                        transition = 6;
                        c = i;
                  }
            }else{
                  if(f[i].gb+b[i].gb+prof1[28]*prof2[26]-sub > max){
                        max = f[i].gb+b[i].gb+prof1[28]*prof2[26]-sub;
      //                fprintf(stderr,"gap_b->gap_b:%d + %d +%d(gpe) =%d \n",f[i].gb, b[i].gb, prof1[28],f[i].gb+b[i].gb+prof1[28]);
                        transition = 6;
                        c = i;
                  }
            }
            if(f[i].gb+b[i].a+prof1[27]*prof2[26]-sub > max){
                  max = f[i].gb+b[i].a+prof1[27]*prof2[26]-sub;
      //          fprintf(stderr,"gap_b->aligned:%d + %d + %d(gpo) = %d\n",f[i].gb,b[i].a,prof1[27],f[i].gb+b[i].a+prof1[27]);
                  transition = 7;
                  c = i;
            }
      }
      i = hm->endb;
      sub = abs(middle -i);
      sub /= 1000; 
      if(f[i].a+b[i].gb+prof1[27]*prof2[26]-sub > max){
            max = f[i].a+b[i].gb+prof1[27]*prof2[26]-sub;
      //          fprintf(stderr,"aligned->gap_b:%d + %d +%d = %d\n",f[i].a,b[i].gb,prof1[27],f[i].a+b[i].gb+prof1[27]);
            transition = 3;
            c = i;
      }
      if(hm->endb == hm->len_b){
            if(f[i].gb+b[i].gb+prof1[29]*prof2[26]-sub > max){
                  max = f[i].gb+b[i].gb+prof1[29]*prof2[26]-sub;
      //                fprintf(stderr,"gap_b->gap_b:%d + %d +%d(gpe) =%d \n",f[i].gb, b[i].gb, prof1[28],f[i].gb+b[i].gb+prof1[28]);
                  transition = 6;
                  c = i;
            }     
      }else{
            if(f[i].gb+b[i].gb+prof1[28]*prof2[26]-sub > max){
                  max = f[i].gb+b[i].gb+prof1[28]*prof2[26]-sub;
      //                fprintf(stderr,"gap_b->gap_b:%d + %d +%d(gpe) =%d \n",f[i].gb, b[i].gb, prof1[28],f[i].gb+b[i].gb+prof1[28]);
                  transition = 6;
                  c = i;
            }
      }
      
      
      
      prof1-= (64 * (old_cor[4]+1));
      prof2 -= hm->endb << 6;
      
      //fprintf(stderr,"Transition:%d     at:%d\n",transition,c);
      //if(transition == -1){
      //    exit(0);
      //}
      
      j = hirsch_path[0];
      switch(transition){
            case 1: //a -> a = 1
                  
                  hirsch_path[old_cor[4]] = c;
                  hirsch_path[old_cor[4]+1] = c+1;
                  
      //          fprintf(stderr,"Aligning:%d-%d\n",old_cor[4],c);
      //          fprintf(stderr,"Aligning:%d-%d\n",old_cor[4]+1,c+1);
                  //foward:
                  hm->f[0].a = input_states[0];
                  hm->f[0].ga = input_states[1];
                  hm->f[0].gb = input_states[2];
                  hm->b[0].a = 0.0;
                  hm->b[0].ga = -FLOATINFTY;
                  hm->b[0].gb = -FLOATINFTY;
      //          fprintf(stderr,"Using this for start:%d   %d    %d\n",hm->f[0].a,hm->f[0].ga,hm->f[0].gb);
                  
                  hm->starta = old_cor[0];
                  hm->enda = old_cor[4]-1;
                  
                  hm->startb = old_cor[2];
                  hm->endb = c-1;
                  //fprintf(stderr,"Following first: %d  what:%d-%d     %d-%d\n",c-1,hm->starta,hm->enda,hm->startb,hm->endb);
                  hirsch_path = advanced_hirsch_pp_dyn(prof1,prof2,hm,hirsch_path);

                  //backward:
                  hm->starta = old_cor[4]+1;
                  hm->enda = old_cor[1];
                  hm->startb = c+1;
                  hm->endb = old_cor[3];
                  hm->f[0].a = 0.0;
                  hm->f[0].ga = -FLOATINFTY;
                  hm->f[0].gb = -FLOATINFTY;
                  hm->b[0].a = input_states[3];
                  hm->b[0].ga = input_states[4];
                  hm->b[0].gb = input_states[5];
      
                  //fprintf(stderr,"Following last: %d  what:%d-%d      %d-%d\n",c+1,hm->starta,hm->enda,hm->startb,hm->endb);
                  hirsch_path = advanced_hirsch_pp_dyn(prof1,prof2,hm,hirsch_path);
                  break;
            case 2:// a -> ga = 2
                  
                  hirsch_path[old_cor[4]] = c;
      //          fprintf(stderr,"Aligning:%d-%d\n",old_cor[4],c);
                  //foward:
                  hm->f[0].a = input_states[0];
                  hm->f[0].ga = input_states[1];
                  hm->f[0].gb = input_states[2];
                  hm->b[0].a = 0.0;
                  hm->b[0].ga = -FLOATINFTY;
                  hm->b[0].gb = -FLOATINFTY;
                  
                  
                  hm->starta = old_cor[0];
                  hm->enda = old_cor[4]-1;
                  
                  hm->startb = old_cor[2];
                  hm->endb = c-1;
                  //fprintf(stderr,"Following first: %d  what:%d-%d     %d-%d\n",c-1,hm->starta,hm->enda,hm->startb,hm->endb);
                  hirsch_path = advanced_hirsch_pp_dyn(prof1,prof2,hm,hirsch_path);

                  //backward:
                  hm->starta = old_cor[4];
                  hm->enda = old_cor[1];
                  hm->startb = c+1;
                  hm->endb = old_cor[3];
                  hm->f[0].a = -INFTY;
                  hm->f[0].ga = 0.0;
                  hm->f[0].gb = -FLOATINFTY;
                  hm->b[0].a = input_states[3];
                  hm->b[0].ga = input_states[4];
                  hm->b[0].gb = input_states[5];
      
                  //fprintf(stderr,"Following last: %d  what:%d-%d      %d-%d\n",c+1,hm->starta,hm->enda,hm->startb,hm->endb);
                  hirsch_path = advanced_hirsch_pp_dyn(prof1,prof2,hm,hirsch_path);
                  break;
            case 3:// a -> gb = 3
                  
                  hirsch_path[old_cor[4]] = c;
      //          fprintf(stderr,"Aligning:%d-%d\n",old_cor[4],c);
                  //foward:
                  hm->f[0].a = input_states[0];
                  hm->f[0].ga = input_states[1];
                  hm->f[0].gb = input_states[2];
                  hm->b[0].a = 0.0;
                  hm->b[0].ga = -FLOATINFTY;
                  hm->b[0].gb = -FLOATINFTY;
                  
                  hm->starta = old_cor[0];
                  hm->enda = old_cor[4]-1;
                  
                  hm->startb = old_cor[2];
                  hm->endb = c-1;
                  //fprintf(stderr,"Following first: %d  what:%d-%d     %d-%d\n",c-1,hm->starta,hm->enda,hm->startb,hm->endb);
                  hirsch_path = advanced_hirsch_pp_dyn(prof1,prof2,hm,hirsch_path);

                  //backward:
                  hm->starta = old_cor[4]+1;
                  hm->enda = old_cor[1];
                  hm->startb = c;
                  hm->endb = old_cor[3];
                  hm->f[0].a = -FLOATINFTY;
                  hm->f[0].ga = -FLOATINFTY;
                  hm->f[0].gb = 0.0;
                  hm->b[0].a = input_states[3];
                  hm->b[0].ga = input_states[4];
                  hm->b[0].gb = input_states[5];
      
                  //fprintf(stderr,"Following last: %d\n",c+1);
                  hirsch_path = advanced_hirsch_pp_dyn(prof1,prof2,hm,hirsch_path);
                  break;
            case 5://ga -> a = 5
                  hirsch_path[old_cor[4]+1] = c+1;
      //          fprintf(stderr,"Aligning:%d-%d\n",old_cor[4]+1,c+1);

                  //foward:
                  hm->f[0].a = input_states[0];
                  hm->f[0].ga = input_states[1];
                  hm->f[0].gb = input_states[2];
                  hm->b[0].a = -FLOATINFTY;
                  hm->b[0].ga = 0.0;
                  hm->b[0].gb = -FLOATINFTY;
                  
                  hm->starta = old_cor[0];
                  hm->enda = old_cor[4];
                  
                  hm->startb = old_cor[2];
                  hm->endb = c-1;
                  //fprintf(stderr,"Following first: %d  what:%d-%d     %d-%d\n",c-1,hm->starta,hm->enda,hm->startb,hm->endb);
                  hirsch_path = advanced_hirsch_pp_dyn(prof1,prof2,hm,hirsch_path);

                  //backward:
                  hm->starta = old_cor[4]+1;
                  hm->enda = old_cor[1];
                  hm->startb = c+1;
                  hm->endb = old_cor[3];
                  hm->f[0].a = 0.0;
                  hm->f[0].ga = -FLOATINFTY;
                  hm->f[0].gb = -FLOATINFTY;
                  hm->b[0].a = input_states[3];
                  hm->b[0].ga = input_states[4];
                  hm->b[0].gb = input_states[5];
      
                  //fprintf(stderr,"Following last: %d\n",c+1);
                  hirsch_path = advanced_hirsch_pp_dyn(prof1,prof2,hm,hirsch_path);
                  break;
            case 6://gb->gb = 6;
                  
                  //foward:
                  hm->f[0].a = input_states[0];
                  hm->f[0].ga = input_states[1];
                  hm->f[0].gb = input_states[2];
                  hm->b[0].a = -FLOATINFTY;
                  hm->b[0].ga = -FLOATINFTY;
                  hm->b[0].gb = 0.0;
                  
                  hm->starta = old_cor[0];
                  hm->enda = old_cor[4]-1;
                  hm->startb = old_cor[2];
                  hm->endb = c;
                  //fprintf(stderr,"Following first: %d  what:%d-%d     %d-%d\n",c-1,hm->starta,hm->enda,hm->startb,hm->endb);
                  hirsch_path = advanced_hirsch_pp_dyn(prof1,prof2,hm,hirsch_path);

                  //backward:
                  hm->starta = old_cor[4]+1;
                  hm->enda = old_cor[1];
                  hm->startb = c;
                  hm->endb = old_cor[3];
                  hm->f[0].a = -FLOATINFTY;
                  hm->f[0].ga = -FLOATINFTY;
                  hm->f[0].gb = 0.0;
                  hm->b[0].a = input_states[3];
                  hm->b[0].ga = input_states[4];
                  hm->b[0].gb = input_states[5];
      
                  //fprintf(stderr,"Following last: %d\n",c+1);
                  hirsch_path = advanced_hirsch_pp_dyn(prof1,prof2,hm,hirsch_path);
                  break;
            case 7://gb->a = 7;
                  
                  hirsch_path[old_cor[4]+1] = c+1;
      //          fprintf(stderr,"Aligning:%d-%d\n",old_cor[4]+1,c+1);
                  //foward:
                  hm->f[0].a = input_states[0];
                  hm->f[0].ga = input_states[1];
                  hm->f[0].gb = input_states[2];
                  hm->b[0].a = -FLOATINFTY;
                  hm->b[0].ga = -FLOATINFTY;
                  hm->b[0].gb = 0.0;
                  
                  hm->starta = old_cor[0];
                  hm->enda = old_cor[4]-1;
                  hm->startb = old_cor[2];
                  hm->endb = c;
                  //fprintf(stderr,"Following first: %d  what:%d-%d     %d-%d\n",c-1,hm->starta,hm->enda,hm->startb,hm->endb);
                  hirsch_path = advanced_hirsch_pp_dyn(prof1,prof2,hm,hirsch_path);

                  //backward:
                  hm->starta = old_cor[4]+1;
                  hm->enda = old_cor[1];
                  hm->startb = c+1;
                  hm->endb = old_cor[3];
                  hm->f[0].a = 0.0;
                  hm->f[0].ga = -FLOATINFTY;
                  hm->f[0].gb = -FLOATINFTY;
                  hm->b[0].a = input_states[3];
                  hm->b[0].ga = input_states[4];
                  hm->b[0].gb = input_states[5];
      
                  //fprintf(stderr,"Following last: %d\n",c+1);
                  hirsch_path = advanced_hirsch_pp_dyn(prof1,prof2,hm,hirsch_path);
                  break;
      }
            
      return hirsch_path;
}



struct states* advanced_foward_hirsch_pp_dyn(const float* prof1,const float* prof2,struct hirsch_mem* hm)
{
      unsigned int freq[26];
      struct states* s = hm->f;

      register float pa = 0;
      register float pga = 0;
      register float pgb = 0;
      register float ca = 0;
      register int i = 0;
      register int j = 0;
      register int c = 0;
      
      
      
      prof1 += (hm->starta) << 6;
      prof2 +=  (hm->startb) << 6;
      s[hm->startb].a = s[0].a;
      s[hm->startb].ga = s[0].ga;
      s[hm->startb].gb = s[0].gb;
      if(hm->startb == 0){
            for (j = hm->startb+1; j < hm->endb;j++){
                  prof2+=64;
                  s[j].a = -FLOATINFTY;
                  
                  s[j].ga = s[j-1].a+prof2[29]*prof1[26];
                  if (s[j-1].ga+prof2[29]*prof1[26] > s[j].ga){
                        s[j].ga = s[j-1].ga+prof2[29]*prof1[26];
                  }
                  s[j].gb = -FLOATINFTY;
            }     
            prof2+=64;  
      }else{

            for (j = hm->startb+1; j < hm->endb;j++){
                  prof2+=64;
                  s[j].a = -FLOATINFTY;
                  
                  s[j].ga = s[j-1].a+prof2[27]*prof1[26];
                  if (s[j-1].ga+prof2[28]*prof1[26] > s[j].ga){
                        s[j].ga = s[j-1].ga+prof2[28]*prof1[26];
                  }
                  s[j].gb = -FLOATINFTY;
            //    prof2+=64;
            }
            prof2+=64;
      }
      
      prof2 -= (hm->endb-hm->startb) << 6;
      
      s[hm->endb].a = -FLOATINFTY;
      s[hm->endb].ga = -FLOATINFTY;
      s[hm->endb].gb = -FLOATINFTY;


      for (i = hm->starta;i < hm->enda;i++){
            prof1 += 64;
            c = 1;
            for (j = 26; j--;){
                  if(prof1[j]){
                        freq[c] = j;
                        c++;
                  }
            }
            freq[0] = c;
                  
            pa = s[hm->startb].a;
            pga = s[hm->startb].ga;
            pgb = s[hm->startb].gb;
            if(hm->startb == 0){
                  s[hm->startb].a = -FLOATINFTY;
                  s[hm->startb].ga = -FLOATINFTY;
            
                  s[hm->startb].gb = pa+prof1[29] * prof2[26];
                        if(pgb+prof1[29] * prof2[26] > s[hm->startb].gb){
                        s[hm->startb].gb = pgb+prof1[29] * prof2[26];
                  }
            }else{
                  s[hm->startb].a = -FLOATINFTY;
                  s[hm->startb].ga = -FLOATINFTY;
            
                  s[hm->startb].gb = pa+prof1[27]*prof2[26];
                  if(pgb+prof1[28]*prof2[26] > s[hm->startb].gb){
                        s[hm->startb].gb = pgb+prof1[28]*prof2[26];
                  }
            }
            for (j = hm->startb+1; j <= hm->endb;j++){
                  prof2 += 64;
                  ca = s[j].a;
                  
                  if((pga += prof2[27-64]*prof1[26-64]) > pa){ 
                        pa = pga;
                  }

                  if((pgb += prof1[27-64]*prof2[26-64]) > pa){
                        pa = pgb;
                  }
                  
                  prof2 += 32;
                  for (c = freq[0];--c;){
                        pa += prof1[freq[c]]*prof2[freq[c]];
                  }
                  prof2 -= 32;      

                  s[j].a = pa;
                  
                  pga = s[j].ga;
                  
                  s[j].ga = s[j-1].a+prof2[27]*prof1[26];
                  if (s[j-1].ga+prof2[28]*prof1[26] > s[j].ga){
                        s[j].ga = s[j-1].ga+prof2[28]*prof1[26];
                  }
                  
                  pgb = s[j].gb;
                  
                  s[j].gb = ca+prof1[27]*prof2[26];
                  if(pgb+prof1[28]*prof2[26] > s[j].gb){
                        s[j].gb = pgb+prof1[28]*prof2[26];
                  }
                  pa = ca;
            }
            prof2 -= (hm->endb-hm->startb) << 6;
            
      }
      prof1 -= 64 * (hm->enda);
      return s;
}

struct states* advanced_backward_hirsch_pp_dyn(const float* prof1,const float* prof2,struct hirsch_mem* hm)
{
      unsigned int freq[26];
      struct states* s = hm->b;
      
      register float pa = 0;
      register float pga = 0;
      register float pgb = 0;
      register float ca = 0;
      register int i = 0;
      register int j = 0;
      register int c = 0;

      prof1 += (hm->enda+1) << 6;
      prof2 += (hm->endb+1) << 6;
      s[hm->endb].a = s[0].a;
      s[hm->endb].ga = s[0].ga;
      s[hm->endb].gb = s[0].gb;
      
      
      //init of first row;
      //j = endb-startb;
      if(hm->endb == hm->len_b){
            
            for(j = hm->endb-1;j > hm->startb;j--){
                  prof2 -= 64;
                  s[j].a = -FLOATINFTY;
                  
                  s[j].ga = s[j+1].a+prof2[29]*prof1[26];
                  if (s[j+1].ga+prof2[29]*prof1[26] > s[j].ga){
                        s[j].ga = s[j+1].ga+prof2[29]*prof1[26];
                  }
                  s[j].gb = -FLOATINFTY;
            }
            prof2 -= 64;
      }else{
            for(j = hm->endb-1;j > hm->startb;j--){
                  prof2 -= 64;
                  s[j].a = -FLOATINFTY;
                  
                  s[j].ga = s[j+1].a+prof2[27]*prof1[26];
                  if (s[j+1].ga+prof2[28]*prof1[26] > s[j].ga){
                        s[j].ga = s[j+1].ga+prof2[28]*prof1[26];
                  }
                  s[j].gb = -FLOATINFTY;
            //    prof2 -= 64;
            }
            prof2 -= 64;
      }
      
      s[hm->startb].a = -FLOATINFTY;
      s[hm->startb].ga = -FLOATINFTY;
      s[hm->startb].gb = -FLOATINFTY;
//    prof2 -= (endb -startb) << 6;

      i = hm->enda-hm->starta;
      while(i--){
            prof1 -= 64;

            c = 1;
            for (j = 26; j--;){
                  if(prof1[j]){
                        freq[c] = j;
                        c++;
                  }
            }
            freq[0] = c;
            
            pa = s[hm->endb].a;
            pga = s[hm->endb].ga;
            pgb = s[hm->endb].gb;
            s[hm->endb].a = -FLOATINFTY;
            s[hm->endb].ga = -FLOATINFTY;

            if(hm->endb == hm->len_b){
                  s[hm->endb].gb = pa+prof1[29]*prof2[26];
                  if(pgb+prof1[29]*prof2[26] > s[hm->endb].gb){
                        s[hm->endb].gb = pgb+prof1[29]*prof2[26];
                  }
            }else{
                  s[hm->endb].gb = pa+prof1[27]*prof2[26];
                  if(pgb+prof1[28]*prof2[26] > s[hm->endb].gb){
                        s[hm->endb].gb = pgb+prof1[28]*prof2[26];
                  }
            }
            //j = endb-startb;
            prof2 += (hm->endb-hm->startb) << 6;
            //while(j--){
            for(j = hm->endb-1;j >= hm->startb;j--){
                  prof2 -= 64;
                  ca = s[j].a;
                  if((pga += prof2[64+27]*prof1[26]) > pa){
                        pa = pga;
                  }
                  if((pgb += prof1[64+27]*prof2[26]) > pa){
                        pa = pgb;
                  }
                  
                  prof2 += 32;
                  for (c = freq[0];--c;){
                        pa += prof1[freq[c]]*prof2[freq[c]];
                  }
                  prof2 -= 32;

                  s[j].a = pa;
                  
                  pga = s[j].ga;
                  
                  s[j].ga = s[j+1].a+prof2[27]*prof1[26];
                  if (s[j+1].ga+prof2[28]*prof1[26] > s[j].ga){
                        s[j].ga = s[j+1].ga+prof2[28]*prof1[26];
                  }
                  
                  pgb = s[j].gb;
                  
                  s[j].gb = ca+prof1[27]*prof2[26];
                  if(pgb+prof1[28]*prof2[26] > s[j].gb){
                        s[j].gb = pgb+prof1[28]*prof2[26];
                  }
                  pa = ca;
            }
      }           
      return s;
}



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