src/ClustalOmega/src/hhalign/hhalignment-C.h
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 /* -*- mode: c; tab-width: 4; c-basic-offset: 4; indent-tabs-mode: nil -*- */
 
 /*********************************************************************
  * Clustal Omega - Multiple sequence alignment
  *
  * Copyright (C) 2010 University College Dublin
  *
  * Clustal-Omega 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 (at your option) any later version.
  *
  * This file is part of Clustal-Omega.
  *
  ********************************************************************/
 
 /*
  *  RCS $Id: hhalignment-C.h 236 2011-04-14 11:30:04Z fabian $
  */
 
 
 /*
  * Changelog: Michael Remmert made changes to hhalign stand-alone code
  * FS implemented some of the changes on 2010-10-28 -> MR1
  *
  * Note: MR seems to have changed all [aijk]++ to ++[aijk],
  * FS did not do that on 2010-10-28
  */
 
 // hhalignment.C
 
 //////////////////////////////////////////////////////////////////////////////
 //// Class Alignment
 //////////////////////////////////////////////////////////////////////////////
 
 // hhalignment.C
 
 #ifndef MAIN
 #define MAIN
 #include <iostream> // cin, cout, cerr
 #include <fstream> // ofstream, ifstream
 #include <stdio.h> // printf
 using std::cout;
 using std::cerr;
 using std::endl;
 using std::ios;
 using std::ifstream;
 using std::ofstream;
 #include <stdlib.h> // exit
 #include <string> // strcmp, strstr
 #include <math.h> // sqrt, pow
 #include <limits.h> // INT_MIN
 #include <float.h> // FLT_MIN
 #include <time.h> // clock
 #include <ctype.h> // islower, isdigit etc
 #include "util-C.h" // imax, fmax, iround, iceil, ifloor, strint, strscn, strcut, substr, uprstr, uprchr, Basename etc.
 #include "list.h" // list data structure
 #include "hash.h" // hash data structure
 #include "hhdecl-C.h"
 #include "hhutil-C.h" // imax, fmax, iround, iceil, ifloor, strint, strscn, strcut, substr, uprstr, uprchr, Basename etc.
 #include "hhhmm.h"
 #endif
 
 
 enum {KEEP_NOT = 0, KEEP_CONDITIONALLY, KEEP_ALWAYS};
 
 //////////////////////////////////////////////////////////////////////////////
 // Class Alignment
 //////////////////////////////////////////////////////////////////////////////
 
 
 //////////////////////////////////////////////////////////////////////////////
 // Object constructor
 //////////////////////////////////////////////////////////////////////////////
 Alignment::Alignment(int maxseq, int maxres)
 {
 
     //printf(">>>>>>>>%s:%s:%d: maxseq=%d, maxres=%d\n", __FUNCTION__, __FILE__, __LINE__, maxseq, maxres); /* (FS) */
   longname = new(char[DESCLEN]);
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   sname = new char*[maxseq+2]; /* MR1 */
   seq = new char*[maxseq+2]; /* MR1 */
   l = new int[maxres];
   X = new char*[maxseq+2];  /* MR1 */
   I = new short unsigned int*[maxseq+2]; /* MR1 */
   keep = new char[maxseq+2]; /* MR1 */
   display = new char[maxseq+2]; /* MR1 */
   wg = new float[maxseq+2]; /* MR1 */
   nseqs = new int[maxres+2]; /* MR1 */
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   N_in=L=0;
   nres=NULL; // number of residues per sequence k
   first=NULL; // first residue in sequence k
   last=NULL; // last residue in sequence k
   ksort=NULL; // sequence indices sorted by descending nres[k]
   name[0]='\0'; // no name defined yet
   longname[0]='\0'; // no name defined yet
   fam[0]='\0'; // no name defined yet
   file[0]='\0'; // no name defined yet
   readCommentLine = '0'; /* MR1 */
 }
 
 //////////////////////////////////////////////////////////////////////////////
 // Object destructor
 //////////////////////////////////////////////////////////////////////////////
 Alignment::~Alignment()
 {
   delete[] longname; longname = NULL;
   for(int k=0; k<N_in; k++)
     {
       delete[] sname[k]; sname[k] = NULL;
       delete[] seq[k]; seq[k] = NULL;
       delete[] X[k]; X[k] = NULL;
       delete[] I[k]; I[k] = NULL;
     }
   delete[] sname; sname = NULL;
   delete[] seq; seq = NULL;
   delete[] X; X = NULL;
   delete[] I; I = NULL;
   delete[] l; l = NULL;
   delete[] keep; keep = NULL;
   delete[] display; display = NULL;
   delete[] wg; wg = NULL;
   delete[] nseqs; nseqs = NULL;
   delete[] nres; nres = NULL;
   delete[] first; first = NULL;
   delete[] last; last = NULL;
   delete[] ksort; ksort = NULL;
 }
 
 
 /**
  * @brief Reads in an alignment from file into matrix seq[k][l] as ASCII
  */
 void 
 Alignment::Read(FILE* inf, char infile[], char* firstline)
 {
   int l; // Postion in alignment incl. gaps (first=1)
   int h; // Position in input line (first=0)
   int k; // Index of sequence being read currently (first=0)
   char line[LINELEN]=""; // input line
   //char cur_seq[MAXCOL]; // Sequence currently read in
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   char *cur_seq=new char[par.maxColCnt];
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   char* cur_name; // Sequence currently read in
   int linenr=0; // current line number in input file
   char skip_sequence=0;
   RemoveExtension(file,infile); //copy rootname (w/o path) of infile into file variable of class object
 
   kss_dssp=ksa_dssp=kss_pred=kss_conf=kfirst=-1;
   n_display=0;
   N_in=0;
   N_filtered=0;
   N_ss=0;
   cur_seq[0]=' '; // overwrite '\0' character at beginning to be able to do strcpy(*,cur_seq)
   l=1; k=-1;
 
   // Does firstline already contain first line of file?
   if (firstline!= NULL) strcpy(line,firstline);
 
   /////////////////////////////////////////////////////////////////////////
   // Read infile line by line
   /* FIXME: not safe to use MAXSEQ, however, don't think we ever get here (FS) */
   while(firstline || (fgetline(line,LINELEN,inf) && (k<MAXSEQ))) /* FIXME: FS introduced () around &&, precedence! MR1 */
       {
           linenr++;
           firstline=NULL;
           if (line[0]=='>') //line contains sequence name
               {
                   if (k>=MAXSEQ-1)
                       {
                           if (v>=1 && k>=MAXSEQ)
                               cerr<<endl<<"WARNING: maximum number "<<MAXSEQ<<" of sequences exceded in file "<<infile<<"\n";
                           break;
                       }
                   cur_name=line+1; //beginning of current sequence name
                   if (k>=0) //if this is at least the second name line
                       {
                           if (strlen(cur_seq)==0)
                               {
                                   cerr<<endl<<"Error: sequence "<<sname[k]<<" contains no residues."<<endl;
                                   throw 1;
                               }
 
                           // Create space for residues and paste new sequence in
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                           seq[k]=new char[strlen(cur_seq)+2];
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                           if (!seq[k]) MemoryError("array for input sequences");
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                           X[k]=new char[strlen(cur_seq)+2];
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                           if (!X[k]) MemoryError("array for input sequences");
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                           I[k]=new short unsigned int[strlen(cur_seq)+2];
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                           if (!I[k]) MemoryError("array for input sequences");
                           strcpy(seq[k],cur_seq);
                       }
                   skip_sequence=0;
 
                   k++;
                   l=1; //position in current sequence (first=1)
 
                   // display[k]= 0: do not show in Q-T alignments 1: show if not filtered out later 2: show in any case (do not filter out)
                   // keep[k] = 0: do not include in profile 1: include if not filtered out later 2: include in any case (do not filter out)
                   /* {KEEP_NOT=0, KEEP_CONDITIONALLY=1, KEEP_ALWAYS=2} */
                   if (line[1]=='@') cur_name++; //skip @-character in name
                   if (!strncmp(line,">ss_dssp",8)) {
                       if (kss_dssp<0) {display[k]=2; n_display++; keep[k]=KEEP_NOT; kss_dssp=k; N_ss++;} else {skip_sequence=1; k--; continue;}
                   }
                   else if (!strncmp(line,">sa_dssp",8)) {
                       if (ksa_dssp<0) {display[k]=KEEP_ALWAYS; n_display++; keep[k]=KEEP_NOT; ksa_dssp=k; N_ss++;} else {skip_sequence=1; k--; continue;}
                   }
                   else if (!strncmp(line,">ss_pred",8)) {
                       if (kss_pred<0) {display[k]=KEEP_ALWAYS; n_display++; keep[k]=KEEP_NOT; kss_pred=k; N_ss++;} else {skip_sequence=1; k--; continue;}
                   }
                   else if (!strncmp(line,">ss_conf",8)) {
                       if (kss_conf<0) {display[k]=KEEP_ALWAYS; n_display++; keep[k]=KEEP_NOT; kss_conf=k; N_ss++;} else {skip_sequence=1; k--; continue;}
                   }
                   else if (!strncmp(line,">ss_",4) || !strncmp(line,">sa_",4)) {
                       display[k]=KEEP_ALWAYS; n_display++; keep[k]=KEEP_NOT; N_ss++;
                   }
                   else if (!strncmp(line,">aa_",4)) { // ignore sequences beginning with ">aa_"
                       skip_sequence=1; k--; continue;
                   }
                   //store first real seq
                   else if (kfirst<0)
                       {
                           char word[NAMELEN];
                           strwrd(word,line); // Copies first word in ptr to str
                           if (strstr(word,"_consensus"))
                               {display[k]=2; keep[k]=0; n_display++; kfirst=k;} /* MR1 */
                           else
                               {display[k]=keep[k]=KEEP_ALWAYS; n_display++; kfirst=k;}
                       }
                   //store all sequences
                   else if (par.mark==0) {display[k]=keep[k]=KEEP_CONDITIONALLY; n_display++;}
                   //store sequences up to nseqdis
                   else if (line[1]=='@'&& n_display-N_ss<par.nseqdis) {display[k]=keep[k]=KEEP_ALWAYS; n_display++;}
                   else {display[k]=KEEP_NOT; keep[k]=KEEP_CONDITIONALLY;}
 
                   // store sequence name
                   if (v>=4) printf("Reading seq %-16.16s k=%3i n_displ=%3i display[k]=%i keep[k]=%i\n",cur_name,k,n_display,display[k],keep[k]);
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                   sname[k] = new char[strlen(cur_name)+1];
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                   if (!sname[k]) {MemoryError("array for sequence names");}
                   strcpy(sname[k],cur_name);
               } // end if(line contains sequence name)
 
           else if (line[0]=='#') // Commentary line?
               {
                   // #PF01367.9 5_3_exonuc: 5'-3' exonuclease, C-terminal SAM fold; PDB 1taq, 1bgx (T:271-174), 1taq (271-174)
                   if (name[0]) continue; // if already name defined: skip commentary line
                   char *ptr1, *ptr2;
                   ptr1=strscn_(line+1); // set ptr1 to first non-whitespace character after '#' -> AC number
                   strncpy(longname,ptr1,DESCLEN-1); // copy whole commentary line after '# ' into longname
                   longname[DESCLEN-1]='\0';
                   strtr(longname,""," ");
                   ptr2=strcut_(ptr1); // cut after AC number and set ptr2 to first non-whitespace character after AC number
                   // strcpy(fam,ptr1); // copy AC number to fam
                   // if (!strncmp(fam,"PF",2)) strcut_(fam,'.'); // if PFAM identifier contains '.' cut it off
                   // strcut_(ptr2); // cut after first word ...
                   strcpy(name,ptr1); // ... and copy first word into name
                   readCommentLine = '1'; /* MR1 */
               }
 
           //line contains sequence residues or SS information and does not belong to a >aa_ sequence
           else if (!skip_sequence)
               {
                   if (v>=4) cout<<line<<"\n"; //DEBUG
                   if (k==-1 && v)
                       {
                           cerr<<endl<<"WARNING: No sequence name preceding following line in "<<infile<<":\n\'"<<line<<"\'\n";
                           continue;
                       }
 
                   h=0; //counts characters in current line
 
                   // Check whether all characters are correct; store into cur_seq
                   if (keep[k] || (k == kfirst) ) // normal line containing residues /* MR1 */
                       {
                           while (h<LINELEN && line[h]>'\0' && l</*MAXCOL*/par.maxColCnt-1)
                               {
                                   if (aa2i(line[h])>=0) // ignore white-space characters ' ', \t and \n (aa2i()==-1)
                                       {cur_seq[l]=line[h]; l++;}
                                   else if (aa2i(line[h])==-2 && v)
                                       cerr<<endl<<"WARNING: invalid symbol \'"<<line[h]<<"\' at pos. "<<h<<" in line "<<linenr<<" of "<<infile<<"\n";
                                   h++;
                               }
                       }
                   else if (k==kss_dssp) // lines with dssp secondary structure states (. - H E C S T G B)
                       {
                           while (h<LINELEN && line[h]>'\0' && l</*MAXCOL*/par.maxColCnt-1)
                               {
                                   if (ss2i(line[h])>=0 && ss2i(line[h])<=7)
                                       {cur_seq[l]=ss2ss(line[h]); l++;}
                                   else if (v)
                                       cerr<<endl<<"WARNING: invalid symbol \'"<<line[h]<<"\' at pos. "<<h<<" in line "<<linenr<<" of "<<infile<<"\n";
                                   h++;
                               }
                       }
                   else if (k==ksa_dssp) // lines with dssp solvent accessibility states (. - ???)
                       {
                           while (h<LINELEN && line[h]>'\0' && l</*MAXCOL*/par.maxColCnt-1)
                               {
                                   if (sa2i(line[h])>=0)
                                       cur_seq[l++]=line[h];
                                   else if (v)
                                       cerr<<endl<<"WARNING: invalid symbol \'"<<line[h]<<"\' at pos. "<<h<<" in line "<<linenr<<" of "<<infile<<"\n";
                                   h++;
                               }
                       }
                   else if (k==kss_pred) // lines with predicted secondary structure (. - H E C)
                       {
                           while (h<LINELEN && line[h]>'\0' && l</*MAXCOL*/par.maxColCnt-1)
                               {
                                   if (ss2i(line[h])>=0 && ss2i(line[h])<=3)
                                       {cur_seq[l]=ss2ss(line[h]); l++;}
                                   else if (v)
                                       cerr<<endl<<"WARNING: invalid symbol \'"<<line[h]<<"\' at pos. "<<h<<" in line "<<linenr<<" of "<<infile<<"\n";
                                   h++;
                               }
                       }
                   else if (k==kss_conf) // lines with confidence values should contain only 0-9, '-', or '.'
                       {
                           while (h<LINELEN && line[h]>'\0' && l</*MAXCOL*/par.maxColCnt-1)
                               {
                                   if (line[h]=='-' || line[h]=='.' || (line[h]>='0' && line[h]<='9'))
                                       {cur_seq[l]=line[h]; l++;}
                                   else if (v)
                                       cerr<<endl<<"WARNING: invalid symbol \'"<<line[h]<<"\' at pos. "<<l<<" in line "<<linenr<<" of "<<infile<<"\n";
                                   h++;
                               }
                       }
                   else if (display[k]) // other lines such as >sa_pred etc
                       {
                           while (h<LINELEN && line[h]>'\0' && l</*MAXCOL*/par.maxColCnt-1)
                               {
                                   if (line[h]=='-' || line[h]=='.' || (line[h]>='0' && line[h]<='9') || (line[h]>='A' && line[h]<='B'))
                                       {cur_seq[l]=line[h]; l++;}
                                   else if (v)
                                       cerr<<endl<<"WARNING: invalid symbol \'"<<line[h]<<"\' at pos. "<<l<<" in line "<<linenr<<" of "<<infile<<"\n";
                                   h++;
                               }
                       }
                   if (v && l>=/*MAXCOL*/par.maxColCnt-1) 
                       {
                           cerr<<endl<<"WARNING: maximum number of residues "<</*MAXCOL*/par.maxColCnt-2<<" exceded in sequence "<<sname[k]<<"\n";
                           skip_sequence=1;
                       }
                   cur_seq[l]='\0'; //Ensure that cur_seq ends with a '\0' character
               } //end else
 
       }
   /////////////////////////////////////////////////////////////////////////
 
 
   if (k>=0) //if at least one sequence was read in
       {
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           seq[k]=new char[strlen(cur_seq)+2];
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           if (!seq[k]) MemoryError("array for input sequences");
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           X[k]=new char[strlen(cur_seq)+2];
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           if (!X[k]) MemoryError("array for input sequences");
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           I[k]=new short unsigned int[strlen(cur_seq)+2];
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           if (!I[k]) MemoryError("array for input sequences");
           strcpy(seq[k],cur_seq);
       }
   else
       {cerr<<endl<<"Error: no sequences found in file "<<infile<<"\n"; throw 1;}
 
   N_in = k+1;
 
   // Set name, longname, fam
   if (!*name) // longname, name and family were not set by '#...' line yet -> extract from first sequence
       {
           char* ptr;
           // strtr(sname[kfirst],"~"," "); // 'transpose': replaces the tilde with a blanc everywhere in sname[kfirst]
           strncpy(longname,sname[kfirst],DESCLEN-1); // longname is name of first sequence
           longname[DESCLEN-1]='\0';
           strncpy(name,sname[kfirst],NAMELEN-1); // Shortname is first word of longname...
           name[NAMELEN-1]='\0';
           ptr = strcut(name); // ...until first white-space character
           if (ptr && islower(ptr[0]) && ptr[1]=='.' && isdigit(ptr[2])) //Scop family code present as second word?
               {
                   lwrstr(name); // Transform upper case to lower case
                   strcut(ptr); // Non-white-space characters until next white-space character..
                   strcpy(fam,ptr); // ...are the SCOP familiy code
               }
           else if (name[0]=='P' && name[1]=='F' && isdigit(name[2]) && isdigit(name[3]) ) //Pfam code
               {
                   strcpy(fam,name); // set family name = Pfam code
               }
       }
   
   
   
   delete[] cur_seq; cur_seq = NULL;
   
   // Checking for warning messages
   if (v==0) return;
   if (v>=2) cout<<"Read "<<infile<<" with "<<N_in<<" sequences\n";
   if (v>=3) cout<<"Query sequence for alignment has number "<<kfirst<<" (0 is first)\n";
   return;
 }
 
 /*
  * At this point GetSeqsFromHMM() slots in, however,
  * only needed in hhbliys.C, so will skip it for moment, MR1
  */
 
 
 /////////////////////////////////////////////////////////////////////////////
 /**
  * @brief  Convert ASCII in seq[k][l] to int (0-20) in X[k][i],
  *  throw out all insert states, record their number in I[k][i]
  *  and store sequences to be displayed in seq[k] */
 /////////////////////////////////////////////////////////////////////////////
 void 
 Alignment::Compress(const char infile[])
 {
     int i; // Index for match state (first=1)
     int l; // Postion in alignment incl. gaps (first=1)
     int k; // Index for sequences (first=0)
     int a; // amino acid index
     char c;
     int unequal_lengths=0; /* k: seq k doesn't have same number
                               of match states as seq 0 => WARNING */
     /* points to next character in seq[k] to be written */
     /*static short unsigned int h[MAXSEQ];*/
     /*short*/ unsigned int *h = NULL; /* short may lead to overflow for long alignments, FS, r235 -> r236 */
 
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     h = new /*short*/ unsigned int[N_in+2]; /* short -> overflow, FS, r235 -> r236 */
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     float *percent_gaps = NULL; /* FS, 2010-Nov */
     char *match_state = NULL;  /* FS, 2010-Nov */
 
 
     // Initialize 
     for (k=0;k<N_in; k++) 
         {I[k][0]=0;}
 
     if (v>=3)
         {
             if (par.M==1)
                 cout<<"Using match state assignment by capital letters (a2m format)\n";
             else if (par.M==2) cout<<"Using percentage-rule match state assignment\n";
             else if (par.M==3) cout<<"Using residues of first sequence as match states\n";
         }
 
     // Create matrices X and I with amino acids represented by integer numbers
     switch(par.M)
         {
 
             /////////////////////////////////////////////////////////////////////////
             /* a2m/a3m format: match states capital case,
                inserts lower case, delete states '-', inserted gaps '.'
                The confidence values for ss prediction are interpreted as follows:
                0-9:match states(!) '-' :match state '.':insert */
         case 1:
         default:
 
             // Warn if alignment is ment to be -M first or -M NN instead of A2M/A3M
             if (v>=2 && strchr(seq[kfirst],'-') ) // Seed/query sequence contains a gap ...
                 {
                     for (k=1; k<N_in; k++)
                         if (strpbrk(seq[k],"abcdefghiklmnpqrstuvwxyz.")) break;
                     if (k==N_in) // ... but alignment contains no lower case residue
                         printf("WARNING: input alignment %s looks like aligned FASTA instead of A2M/A3M format. Consider using '-M first' or '-M 50'\n",infile);
                 }
 
             // Remove '.' characters from seq[k]
             for(k=0; k<N_in; k++)
                 {
                     char* ptrS=seq[k]; // pointer to source: character in seq[k]
                     char* ptrD=seq[k]; // pointer to destination: seq[k]
                     while(1) // omit '.' symbols
                         {
                             if (*ptrS!='.') {*ptrD=*ptrS; ptrD++;} //leave out '.' symbols
                             if (!*ptrS) break;
                             ptrS++;
                         }
                 }
             L=/*MAXRES*/par.maxResLen-2; // needed because L=imin(L,i)
             for (k=0; k<N_in; k++)
                 {
                     i=1; l=1; // start at i=1, not i=0!
                     if (keep[k]) //skip >ss_dssp, >ss_pred, >ss_conf, >aa_... sequences
                         {
                             while((c=seq[k][l++])) // assign residue to c at same time
                                 {
                                     if (c>='a' && c<='z') I[k][i-1]++;//insert state = lower case character
                                     else if (c!='.') //match state = upper case character
                                         {
                                             X[k][i]=aa2i(c);
                                             I[k][i]=0;
                                             i++;
                                         }
                                 }
                         }
                     else if (k==kss_dssp || k==kss_pred) // does alignment contain sequence of secondary structure states?
                         {
                             while((c=seq[k][l++])) // assign residue to c at same time
                                 if (c!='.' && !(c>='a' && c<='z')) X[k][i++]=ss2i(c); //match state = upper case character
                         }
                     else if (k==ksa_dssp) // does alignment contain sequence of prediction confidence values?
                         {
                             while((c=seq[k][l++])) // assign residue to c at same time
                                 if (c!='.' && !(c>='a' && c<='z')) X[k][i++]=sa2i(c); //match state = upper case character
                         }
                     else if (k==kss_conf) // does alignment contain sequence of prediction confidence values?
                         {
                             while((c=seq[k][l++])) // assign residue to c at same time
                                 if (c!='.') X[k][i++]=cf2i(c); //match state = 0-9 or '-'
                         }
                     else if (k==kfirst)        // does alignment contain sequence of prediction confidence values?
                         {
                             while((c=seq[k][l++]))  // assign residue to c at same time
                                 if (c!='.')
                                     {
                                         X[k][i]=aa2i(c);
                                         I[k][i]=0;
                                         ++i;
                                     }
                         }
                     else continue;
                     i--;
                     if (L!=i && L!=/*MAXRES*/par.maxResLen-2 && !unequal_lengths) unequal_lengths=k; //sequences have different lengths
                     L=imin(L,i);
                 }
             if (unequal_lengths) break;
 
             //Replace GAP with ENDGAP for all end gaps /* MR1 */
             for (k=0; k<N_in; ++k)
                 {
                     if (!keep[k]) continue;
                     for (i=1; i<=L && X[k][i]==GAP; i++) X[k][i]=ENDGAP; /* MR1: NOTE i++ <- ++i */
                     for (i=L; i>=1 && X[k][i]==GAP; i--) X[k][i]=ENDGAP; /* MR1 */
                 }
 
             for (i=1; i<=L; i++) this->l[i]=i; //assign column indices to match states
             if (L<=0)
                 {
                     cout<<"\nError: Alignment in "<<infile<<" contains no match states. Consider using -M first or -M <int> option"<<endl;
                     throw 1;
                 }
             
             if (L==/*MAXRES*/par.maxResLen-2 && v>=2) 
                 {
                     printf("WARNING: Number of match columns too large. Only first %i match columns will be kept!\n",L);
                     break;
                 }
             if (v>=2) cout<<"Alignment in "<<infile<<" contains "<<L<<" match states\n";
             break;
 
             /////////////////////////////////////////////////////////////////////////
             // gap-rule assignment of match states
         case 2:
             int nl[NAA+2]; //nl[a] = number of seq's with amino acid a at position l
             /* Note: allocating statically is fine most of the time 
                but when the sequences/profiles get really long 
                we might run out of memory, so must really do it dynamically. 
                had to move declaration of float *percent_gaps out of switch()
             */
             //float percent_gaps[MAXCOL]; //percentage of gaps in column k (with weighted sequences)
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             percent_gaps = new float[par.maxColCnt];
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             //determine number of columns L in alignment
             L=strlen(seq[kfirst])-1;
 
             // Conversion to integer representation, checking for unequal lengths and initialization
b5f31f05
             if (nres==NULL) nres=new int[N_in];
dafeef0b
             for (k=0; k<N_in; k++)
                 {
                     if (!keep[k]) continue;
                     int nr=0;
                     wg[k]=0; nres[k]=0;
                     for (l=1; l<=L; l++)
                         {
                             X[k][l]=aa2i(seq[k][l]);
                             if (X[k][l]<NAA) nr++;
                         }
                     nres[k]=nr;
                     if (seq[k][L+1]!='\0' && !unequal_lengths) unequal_lengths=k;
                 }
             if (unequal_lengths) break;
 
             // Quick and dirty calculation of the weight per sequence wg[k]
             for (l=1; l<=L; l++) // for all positions l in alignment
                 {
                     int naa=0; //number of different amino acids
                     for (a=0; a<20; a++) nl[a]=0;
                     for (k=0; k<N_in; k++) if (keep[k]) nl[ (int)X[k][l]]++;
                     for (a=0; a<20; a++) if(nl[a]) naa++;
                     if (!naa) naa=1; //naa=0 when column consists of only gaps and Xs (=ANY)
                     for (k=0; k<N_in; k++)
                         if (keep[k] && (X[k][l]<20) )
                             {
                                 //wg[k]+=1.0/float(nl[ (int)X[k][l]]*naa*nres[k]+30.0); /* original version */
                                 wg[k] += 1.0/float(nl[ (int)X[k][l]]*naa*(nres[k]+30.0)); /* MR1 */
                                 // wg[k] += 1.0/float(nl[ (int)X[k][l]]*(nres[k]+30.0)); /* MR1 commented out */
                                 // wg[k] += (naa-1.0)/float(nl[ (int)X[k][l]]*(nres[k]+30.0)); /* MR1 commented out */
                             }
                 } /* 1=l<=L*/
 
             //Replace GAP with ENDGAP for all end gaps
             for (k=0; k<N_in; ++k)
                 {
                     if (!keep[k]) continue;
                     for (i=1; i<=L && X[k][i]==GAP; i++) X[k][i]=ENDGAP; /* MR1: NOTE i++ <- ++i */
                     for (i=L; i>=1 && X[k][i]==GAP; i--) X[k][i]=ENDGAP; /* MR1 */
                 }
 
             // Add up percentage of gaps
             for (l=1; l<=L; l++)
                 {
                     float res=0;
                     float gap=0;
                     for (k=0; k< N_in; k++){
                         if (keep[k]){
                             if ( X[k][l]<GAP) res+=wg[k]; /* MR1, AA or ANY, changed from <ANY */
                             else if ( X[k][l] != ENDGAP) gap+=wg[k];  /* MR1, else: GAP. ENDGAPs are ignored for counting percentage */
                         }
                     }
                     percent_gaps[l]=100.*gap/(res+gap);
                     if (v>=4) cout<<"percent gaps["<<l<<"]="<<percent_gaps[l]<<" first seq:"<<seq[0][l]<<"\n";
                 }
 
             /* Insert states 'bloat' the HMM,
                throwing them out 'slims' down the HMM.
                A slimmer HMM takes less time to construct.
                However, the marriage of Clustal and Hhalign
                is particularly sensitive to residues
                at the very end of the profile; these I call
                'telomeres'. Telomeres must not be shed when
                throwing out insert states, for the telomeres
                we set the match threshold to 100%.
              */
 #define MGAP_LOGIC 0
 #define TELOMERE_LOGIC 1
 #define TELOMERE_DYNAMIC 0
 
 #define ALWAYS_ACCEPT 101.0 /* do NOT change this parameter, must be >=100,
                                make slightly bigger than 100% -- to be sure to be sure */
 #define DEFAULT_MGAPS 100.0 /* Soeding's default is 50, omega default prior to telomere logic was 100
                                FIXME: this used to be par.Mgaps,
                                in a later version re-introduce par.Mgaps to keep this value flexible */
 #define TELOMER_LENGTH 10   /* this parameter must be > 0 (unless DEFAULT_MGAPS=100),
                                if it is too big (L/2) then telomere logic has no effect,
                                don't think it should be changed (much) */
 #define TELOMER_FRACTION 0.10
             //#define HMM_MIN_LENGTH 0.923
 #define HMM_MIN_LENGTH 0.950
 #define FORTRAN_OFFSET 1
             double dDefaultMgaps;
             dDefaultMgaps = DEFAULT_MGAPS;
 
 #if TELOMERE_LOGIC /* turn telomere logic on (1) or off (0) */
             int iTelomereLength;
 
 #if TELOMERE_DYNAMIC /* keep telomere length 'dynamic' */
             iTelomereLength = TELOMER_LENGTH > (int)(L*TELOMER_FRACTION) ? TELOMER_LENGTH : (int)(L*TELOMER_FRACTION);
 #else
             iTelomereLength = TELOMER_LENGTH;
 #endif /* this was dynamic telomere */
 #endif /* this was telomere logic */
 
             /* if HMMs get too small (much smaller than profile length L)
                then one is liable to get a back-tracking error.
                So we should ensure that the DEFAULT_MGAPS parameter does NOT
                shrink the HMM too much.
                take percentage-gap vector, sort it, and fix dDefaultMgaps,
                such that at least (HMM_MIN_LENGTH)*(L) are left
              */
 #if MGAP_LOGIC /* try to adapt Mgaps to size of final HMM */
             {
                 float *pfPercentGaps = NULL;
                 if (NULL == (pfPercentGaps = (float *)malloc((L+1)*sizeof(float)))){
                     printf("%s:%s:%d: could not malloc %d float for sorted percent-gaps\n",
                            __FUNCTION__, __FILE__, __LINE__, L+1);
                     dDefaultMgaps = DEFAULT_MGAPS;
                 }
                 else {
                     for (l = 0; l < L; l++) {
                         pfPercentGaps[l] = percent_gaps[l+FORTRAN_OFFSET];
                     }
                     qsort(pfPercentGaps, L, sizeof(float), CompFltAsc);
 
                     dDefaultMgaps = pfPercentGaps[(int)(HMM_MIN_LENGTH*L)];
                     if (dDefaultMgaps < DEFAULT_MGAPS){
                         //printf("Mgaps = %f <- %f\n", DEFAULT_MGAPS, dDefaultMgaps);
                         dDefaultMgaps = DEFAULT_MGAPS;
                     }
                     else {
                         //printf("Mgaps = %f\n", dDefaultMgaps);
                     }
 
                     free(pfPercentGaps); pfPercentGaps = NULL;
                 }
             }
 #endif /* tried to adapt Mgaps to size of final HMM */
 
             // Throw out insert states and keep only match states
             i=0;
             for (k=0; k<N_in; k++) {h[k]=1; seq[k][0]='-';}
             for (l=1; l<=L; l++)
                 {
 #if TELOMERE_LOGIC
                     float fMgaps = ALWAYS_ACCEPT;
                     if ( (l < iTelomereLength) || (L-l < iTelomereLength) ){
                         /* residue is in telomere, always retain this position */
                         fMgaps = ALWAYS_ACCEPT;
                     }
                     else if (0){
                         /* FIXME: would like to put a transition phase in here,
                            where the Mgap value gradually goes down from 100 to DEFAULT_MGAPS,
                            however, may not be necessary and will make code more clunky */
                     }
                     else {
                         /* position is in centre of sequence,
                            retain position if less than DEFAULT_MGAPS% gaps at this position,
                            for example, if DEFAULT_MGAPS=30 throw out if more than 30% gap.
                            conversely, if DEFAULT_MGAPS=100 throw out if more than 100% gaps,
                            which can never happen, so always retain */
                         fMgaps = dDefaultMgaps;
                     }
                     if (percent_gaps[l] <= fMgaps)
 #else /* this was telomere logic */
                     if (percent_gaps[l]<=float(par.Mgaps))
 #endif /* this was Soeding default */
                         {
                             if (i>=/*MAXRES*/par.maxResLen-2) {
                                 if (v>=1)
                                     printf("WARNING: Number of match columns too large. Only first %i match columns will be kept!\n",i);
                                 break;
                             }
                             i++;
                             this->l[i]=l;
                             for (k=0; k<N_in; k++)
                                 {
                                     if (keep[k])
                                         {
                                             seq[k][h[k]++]=MatchChr(seq[k][l]);
                                             X[k][i]=X[k][l];
                                             I[k][i]=0;
                                         }
                                     else if (k==kss_dssp || k==kss_pred)
                                         {
                                             seq[k][h[k]++]=MatchChr(seq[k][l]);
                                             X[k][i]=ss2i(seq[k][l]);
                                         }
                                     else if (k==ksa_dssp)
                                         {
                                             seq[k][h[k]++]=MatchChr(seq[k][l]);
                                             X[k][i]=sa2i(seq[k][l]);
                                         }
                                     else if (k==kss_conf)
                                         {
                                             seq[k][h[k]++]=seq[k][l];
                                             X[k][i]=cf2i(seq[k][l]);
                                         }
                                 }
                         }
                     else
                         {
                             for (k=0; k<N_in; k++)
                                 if (keep[k] && X[k][l]<GAP)
                                     {
                                         I[k][i]++;
                                         seq[k][h[k]++]=InsertChr(seq[k][l]);
                                     }
                         }
                 }
             for (k=0; k<N_in; k++) seq[k][h[k]]='\0';
 
             //printf("%d\t%d\t%d\tN/L/M\n", N_in, L, i); /* -------- FIXME  */
 
             if (v>=2) cout<<"Alignment in "<<infile<<" contains "<<L<<" columns and "<<i<<" match states\n";
             L = i; //Number of match states
 
             delete[] percent_gaps; percent_gaps = NULL;
             break;
 
 
             ////////////////////////////////////////////////////////////////////////
             // Using residues of first sequence as match states
         case 3:
             /* Note: allocating statically is fine most of the time 
                but when the sequences/profiles get really long 
                we might run out of memory, so must really do it dynamically. 
                had to move declaration of float *percent_gaps out of switch()
             */
             //char match_state[MAXCOL]; //1: column assigned to match state 0: insert state
b5f31f05
             match_state = new char[par.maxColCnt];
dafeef0b
 
             // Determine number of columns L in alignment
             L=strlen(seq[0]+1);
             if (v>=3) printf("Length of first seq = %i\n",L);
             // Check for sequences with unequal lengths
             for (k=1; k<N_in; k++)
                 if (int(strlen(seq[k]+1))!=L) {unequal_lengths=k; break;}
             if (unequal_lengths) break;
 
             // Determine match states: seq kfirst has residue at pos l -> match state
             for (l=1; l<=L; l++)
                 if (isalpha(seq[kfirst][l])) match_state[l]=1; else match_state[l]=0;
             // Throw out insert states and keep only match states
             for (k=0; k<N_in; k++) {h[k]=1; seq[k][0]='-';}
             i=0;
             for (l=1; l<=L; l++)
                 {
                     if (match_state[l]) // does sequence 0 have residue at position l?
                         {
                             if (i>=/*MAXRES*/par.maxResLen-2) {
                                 if (v>=1)
                                     printf("WARNING: Number of match columns too large. Only first %i match columns will be kept!\n",i);
                                 break;
                             }
                             i++;
                             this->l[i]=l;
                             for (k=0; k<N_in; k++)
                                 {
                                     if (keep[k])
                                         {
                                             seq[k][h[k]++]=MatchChr(seq[k][l]);
                                             X[k][i]=aa2i(seq[k][l]);
                                             I[k][i]=0;
                                         }
                                     else if (k==kss_dssp || k==kss_pred)
                                         {
                                             seq[k][h[k]++]=MatchChr(seq[k][l]);
                                             X[k][i]=ss2i(seq[k][l]);
                                         }
                                     else if (k==ksa_dssp)
                                         {
                                             seq[k][h[k]++]=MatchChr(seq[k][l]);
                                             X[k][i]=sa2i(seq[k][l]);
                                         }
                                     else if (k==kss_conf)
                                         {
                                             seq[k][h[k]++]=seq[k][l];
                                             X[k][i]=cf2i(seq[k][l]);
                                         }
                                 }
                         }
                     else
                         {
                             for (k=0; k<N_in; k++)
                                 if (keep[k] && aa2i(seq[k][l])<GAP)
                                     {
                                         I[k][i]++;
                                         seq[k][h[k]++]=InsertChr(seq[k][l]);
                                     }
                         }
                 }
             for (k=0; k<N_in; k++) seq[k][h[k]]='\0';
 
             //Replace GAP with ENDGAP for all end gaps /* MR1 */
             for (k=0; k<N_in; ++k)
                 {
                     if (!keep[k]) continue;
                     for (i=1; i<=L && X[k][i]==GAP; i++) X[k][i]=ENDGAP; /* MR1, note i++ <- ++i */
                     for (i=L; i>=1 && X[k][i]==GAP; i--) X[k][i]=ENDGAP; /* MR1 */
                 }
 
             if (v>=2) cout<<"Alignment in "<<infile<<" contains "<<L<<" columns and "<<i<<" match states\n";
             L = i; //Number of match states
 
             delete[] match_state; match_state = NULL;
             break;
 
         } //end switch()
     ///////////////////////////////////////////////////////////////////////////
 
 
     // Error
     if (unequal_lengths)
         {
             strcut(sname[unequal_lengths]);
             cerr<<endl<<"Error: sequences in "<<infile<<" do not all have the same number of columns, \ne.g. first sequence and sequence "<<sname[unequal_lengths]<<".\n";
             if(par.M==1) cerr<<".\nCheck input format for '-M a2m' option and consider using '-M first' or '-M 50'\n";
             throw 1;
         }
 
     // Avert user about -cons option?
     if (v>=2 && !par.cons)
         {
             for (i=1; i<=L; i++)
                 if (X[kfirst][i]==GAP)
                     {
                         printf("NOTE: Use the '-cons' option to calculate a consensus sequence as first sequence of the alignment.\n");
                         break;
                     }
         }
     /* MR1
     //Replace GAP with ENDGAP for all end gaps
     for (k=0; k<N_in; k++)
     {
     if (!keep[k]) continue;
     for (i=1; i<=L && X[k][i]==GAP; i++) X[k][i]=ENDGAP;
     for (i=L; i>=1 && X[k][i]==GAP; i--) X[k][i]=ENDGAP;
     }*/
 
     // DEBUG
     if (v>=4)
         for (k=0; k<N_in; k++)
             {
                 if (!display[k]) continue;
                 cout<<">"<<sname[k]<<"\n";
                 if (k==kss_dssp || k==kss_pred) {for (i=1; i<=L; i++) cout<<char(i2ss(X[k][i]));}
                 else if (k==kss_conf) {for (i=1; i<=L; i++) cout<<char(i2cf(X[k][i]));}
                 else if (k==ksa_dssp) {for (i=1; i<=L; i++) cout<<char(i2sa(X[k][i]));}
                 else
                     {
                         for (i=1; i<=L; i++) cout<<char(i2aa(X[k][i]));
                         cout<<"\n";
                         for (i=1; i<=L; i++)
                             if (I[k][i]==0) cout<<"-"; else if (I[k][i]>9) cout<<"X"; else cout<<I[k][i];
                     }
                 cout<<"\n";
             }
 
     delete[](h); h = NULL;
 }
 
 
 /**
  * @brief Remove sequences with seq. identity larger than seqid percent
  *(remove the shorter of two) or coverage<cov_thr
  *
  * FIXME: originally max_seqid is a variable that is the cutoff
  *  above which sequences are thrown out. We want to throw out sequences
  *  when building the HMM but not for display, there we want to keep all.
  *  This should be really easy, but there is some hidden stuff going on
  *  in this function, so I did a minimal-invasive change and just stuck
  *  (effectively) a hard-wired 100 instead of the variable.
  *  At a later stage we should get rid of this function alltogether
  *  as it does gobble up some time (and is quadratic in noof sequences, I think)
  *  FS, 2010-10-04
  */
 ////////////////////////////////////////////////////////////////////////////
 /*
  */
 inline int 
 Alignment::FilterForDisplay(int max_seqid, int coverage, int qid, float qsc, int N)
 {
 
     /* FIXME
      * by just returning n_display and not doing anything
      * I think we display everything and not do any work for it
      */
     return n_display; /* FS, 2010-10-04*/
 
 
     if (par.mark) return n_display;
b5f31f05
     char *dummy = new char[N_in+1];
dafeef0b
     int vtmp=v, seqid;
     v=0;
     n_display=0;
     if (kss_dssp>=0) display[kss_dssp]=KEEP_NOT;
     if (ksa_dssp>=0) display[ksa_dssp]=KEEP_NOT;
     if (kss_pred>=0) display[kss_pred]=KEEP_NOT;
     if (kss_conf>=0) display[kss_conf]=KEEP_NOT;
     for (seqid=imin(10,max_seqid); n_display<N && seqid<=max_seqid; seqid++)
         {
             for (int k=0; k<N_in; k++) dummy[k]=display[k];
             n_display = Filter2(dummy,coverage,qid,qsc,20,seqid,0);
             // printf("Seqid=%3i n_display=%4i\n",seqid,n_display);
         }
     if (n_display>N)
         {
             for (int k=0; k<N_in; k++) dummy[k]=display[k];
             n_display = Filter2(dummy,coverage,qid,qsc,20,--(--seqid),0);
         }
     v=vtmp;
     for (int k=0; k<N_in; k++) display[k]=dummy[k];
     if (kss_dssp>=0) {display[kss_dssp]=KEEP_CONDITIONALLY; n_display++;}
     if (ksa_dssp>=0) {display[ksa_dssp]=KEEP_CONDITIONALLY; n_display++;}
     if (kss_pred>=0) {display[kss_pred]=KEEP_CONDITIONALLY; n_display++;}
     if (kss_conf>=0) {display[kss_conf]=KEEP_CONDITIONALLY; n_display++;}
     delete[] dummy; dummy = NULL;
     return n_display;
 }
 
 /////////////////////////////////////////////////////////////////////////////////////
 // Remove sequences with seq. identity larger than seqid percent (remove the shorter of two) or coverage<cov_thr
 /////////////////////////////////////////////////////////////////////////////////////
 inline int Alignment::Filter(int max_seqid, int coverage, int qid, float qsc, int N)
 {
     return Filter2(keep,coverage,qid,qsc,20,max_seqid,N);
 }
 
 /////////////////////////////////////////////////////////////////////////////
 /*
  * @brief Select set of representative sequences in the multiple sequence alignment
  *
  * Filter criteria:
  * Remove sequences with coverage of query less than "coverage" percent
  * Remove sequences with sequence identity to query of less than "qid" percent
  * If Ndiff==0, remove sequences with seq. identity larger than seqid2(=max_seqid) percent
  * If Ndiff>0, remove sequences with minimum-sequence-identity filter of between seqid1
  * and seqid2 (%), where the minimum seqid threshold is determined such that,
  * in all column blocks of at least WMIN=25 residues, at least Ndiff sequences are left.
  * This ensures that in multi-domain proteins sequences covering one domain are not
  * removed completely because sequences covering other domains are more diverse.
  *
  * Allways the shorter of two compared sequences is removed (=> sort sequences by length first).
  * Please note: sequence identity of sequence x with y when filtering x is calculated as
  * number of residues in sequence x that are identical to an aligned residue in y / number of residues in x
  * Example: two sequences x and y are 100% identical in their overlapping region but one overlaps by 10% of its
  * length on the left and the other by 20% on the right. Then x has 10% seq.id with y and y has 20% seq.id. with x.
  */
 //////////////////////////////////////////////////////////////////////////////
 int 
 Alignment::Filter2(char keep[], int coverage, int qid, float qsc, int seqid1, int seqid2, int Ndiff)
 {
     // In the beginnning, keep[k] is 1 for all regular amino acid sequences and 0 for all others (ss_conf, ss_pred,...)
     // In the end, keep[k] will be 1 for all regular representative sequences kept in the alignment, 0 for all others
b5f31f05
     char* in=new char[N_in+1]; // in[k]=1: seq k has been accepted; in[k]=0: seq k has not yet been accepted at current seqid
     char* inkk=new char[N_in+1]; // inkk[k]=1 iff in[ksort[k]]=1 else 0;
     int* Nmax=new int[L+2]; // position-dependent maximum-sequence-identity threshold for filtering /* MR1, used to be called idmax*/
     int* idmaxwin=new int[L+2]; // minimum value of idmax[i-WFIL,i+WFIL]
     int* seqid_prev=new int[N_in+1]; // maximum-sequence-identity threshold used in previous round of filtering (with lower seqid)
     int* N=new int[L+2]; // N[i] number of already accepted sequences at position i
dafeef0b
     const int WFIL=25; // see previous line
 
     int diffNmax=Ndiff;       // current  maximum difference of Nmax[i] and Ndiff /* MR1 */
     int diffNmax_prev=0;      // previous maximum difference of Nmax[i] and Ndiff /* MR1 */
 
     int seqid; // current maximum value for the position-dependent maximum-sequence-identity thresholds in idmax[]
     int seqid_step=0;         // previous increment of seqid /* MR1 */
 
     float diff_min_frac; // minimum fraction of differing positions between sequence j and k needed to accept sequence k
     float qdiff_max_frac=0.9999-0.01*qid; // maximum allowable number of residues different from query sequence
     int diff; // number of differing positions between sequences j and k (counted so far)
     int diff_suff; // number of differing positions between sequences j and k that would be sufficient
     int qdiff_max; // maximum number of residues required to be different from query
     int cov_kj; // upper limit of number of positions where both sequence k and j have a residue
     int first_kj; // first non-gap position in sequence j AND k
     int last_kj; // last non-gap position in sequence j AND k
     int kk, jj; // indices for sequence from 1 to N_in
     int k, j; // kk=ksort[k], jj=ksort[j]
     int i; // counts residues
     int n; // number of sequences accepted so far
 
 
     // Initialize in[k]
     for (n=k=0; k<N_in; k++) if (keep[k]==KEEP_ALWAYS) {in[k]=2/*KEEP_ALWAYS??*/; n++;} else in[k]=0;
 
     // Determine first[k], last[k]?
     if (first==NULL)
         {
b5f31f05
             first=new int[N_in];// first non-gap position in sequence k
             last =new int[N_in];// last  non-gap position in sequence k
dafeef0b
             for (k=0; k<N_in; k++) // do this for ALL sequences, not only those with in[k]==1 (since in[k] may be display[k])
                 {
                     for (i=1; i<=L; i++) if (X[k][i]<NAA) break;
                     first[k]=i;
                     for (i=L; i>=1; i--) if (X[k][i]<NAA) break;
                     last[k]=i;
                 }
         }
 
     // Determine number of residues nres[k]?
     if ( (nres==NULL)  || (sizeof(nres)<N_in*sizeof(int)) )
         {
     	 if (nres) delete[] nres;
b5f31f05
     		nres=new int[N_in];
dafeef0b
             for (k=0; k<N_in; k++) // do this for ALL sequences, not only those with in[k]==1 (since in[k] may be display[k])
                 {
                     int nr=0;
                     for (i=first[k]; i<=last[k]; i++)
                         if (X[k][i]<NAA) nr++;
                     nres[k]=nr;
                     // printf("%20.20s nres=%3i first=%3i last=%3i\n",sname[k],nr,first[k],last[k]);
                 }
         }
 
     // Sort sequences according to length; afterwards, nres[ksort[kk]] is sorted by size
     if (ksort==NULL)
         {
b5f31f05
             ksort=new int[N_in]; // never reuse alignment object for new alignment with more sequences
dafeef0b
             for (k=0; k<N_in; k++) ksort[k]=k;
             QSortInt(nres,ksort,kfirst+1,N_in-1,-1); //Sort sequences after kfirst (query) in descending order
         }
     for (kk=0; kk<N_in; kk++) inkk[kk]=in[ksort[kk]];
 
     // Initialize N[i], idmax[i], idprev[i]
     for (i=1; i<first[kfirst]; i++) N[i]=0;
     for (i=first[kfirst]; i<=last[kfirst]; i++) N[i]=1;
     for (i=last[kfirst]+1; i<=L; i++) N[i]=0;
     //for (i=1; i<=L; i++) {idmax[i]=seqid1; idmaxwin[i]=-1;}
     for (i=1; i<=L; ++i) {Nmax[i]=0; idmaxwin[i]=-1;} /* MR1 */
     for (k=0; k<N_in; k++) seqid_prev[k]=-1;
     if (Ndiff<=0 || Ndiff>=N_in) {seqid1=seqid2; Ndiff=N_in; diffNmax=Ndiff;}
 
     // Check coverage and sim-to-query criteria for each sequence k
     for (k=0; k<N_in; k++)
         {
             if (keep[k]==KEEP_NOT || keep[k]==KEEP_ALWAYS) continue; // seq k not regular sequence OR is marked sequence
             if (100*nres[k]<coverage*L) {keep[k]=KEEP_NOT; continue;} // coverage too low? => reject once and for all
 
             float qsc_sum=0.0;
 
             // Check if score-per-column with query is at least qsc
             if (qsc>-10)
                 {
                     float qsc_min = qsc*nres[k]; // minimum total score of seq k with query
 
                     int gapq=0, gapk=0; // number of consecutive gaps in query or k'th sequence at position i
                     for (int i=first[k]; i<=last[k]; i++)
                         {
                             if (X[k][i]<20)
                                 {
                                     gapk=0;
                                     if (X[kfirst][i]<20)
                                         {
                                             gapq=0;
                                             qsc_sum += S[(int)X[kfirst][i]][(int)X[k][i]];
                                         }
                                     else if (gapq++) qsc_sum-=par.gapExtension; else qsc_sum-=par.gapOpening;
                                 }
                             else if (X[kfirst][i]<20)
                                 {
                                     gapq=0;
                                     if (gapk++) qsc_sum-=par.gapExtension; else qsc_sum-=par.gapOpening;
                                 }
                         }
                     // printf("k=%3i qsc=%6.2f\n",k,qsc_sum);
                     if (qsc_sum<qsc_min) {keep[k]=KEEP_NOT; continue;} // too different from query? => reject once and for all
                 }
 
             //Check if sequence similarity with query at least qid?
             if (qdiff_max_frac<0.999)
                 {
                     qdiff_max=int(qdiff_max_frac*nres[k]+0.9999);
                     // printf("k=%-4i nres=%-4i qdiff_max=%-4i first=%-4i last=%-4i",k,nres[k],qdiff_max,first[k],last[k]);
                     diff=0;
                     for (int i=first[k]; i<=last[k]; i++)
                         // enough different residues to reject based on minimum qid with query? => break
                         if (X[k][i]<20 && X[k][i]!=X[kfirst][i] && ++diff>=qdiff_max) break;
                     // printf(" diff=%4i\n",diff);
                     if (diff>=qdiff_max) {keep[k]=KEEP_NOT; continue;} // too different from query? => reject once and for all
                 }
             // printf(" qsc=%6.2f qid=%6.2f \n",qsc_sum/nres[k],100.0*(1.0-(float)(diff)/nres[k]));
         }
 
     if (seqid1>seqid2)
         {
             for (n=k=0; k<N_in; k++) if (keep[k]>KEEP_NOT) n++;
             return n;
         }
 
     // Successively increment idmax[i] at positons where N[i]<Ndiff
     //for (seqid=seqid1; seqid<=seqid2; seqid+=1+(seqid>=50)) /* MR1 */
     seqid=seqid1;
     while (seqid<=seqid2)
         {
             /*
             // Update idmax[i]
             for (i=1; i<=L; i++) if (N[i]<Ndiff) idmax[i]=seqid;
 
             // Update idmaxwin[i] as minimum of idmax[i-WFIL,i+WFIL]. If idmaxwin[] has not changed then stop
             char stop=1;
             for (i=1; i<=L; i++)
             {
             int idmax_min=seqid2;
             for (j=imax(1,imin(L-2*WFIL+1,i-WFIL)); j<=imin(L,imax(2*WFIL,i+WFIL)); j++)
             if (idmax[j]<idmax_min) idmax_min=idmax[j];
             if (idmax_min>idmaxwin[i]) stop=0; // idmaxwin[i] has changed => do not stop
             idmaxwin[i]=idmax_min;
             }
             */
             char stop=1;
             // Update Nmax[i]
             diffNmax_prev = diffNmax;
             diffNmax = 0;
             for (i=1; i<=L; ++i)
                 {
                     int max=0;
                     for (j=imax(1,imin(L-2*WFIL+1,i-WFIL)); j<=imin(L,imax(2*WFIL,i+WFIL)); ++j)
                         if (N[j]>max) max=N[j];
                     if (Nmax[i]<max) Nmax[i]=max;
                     if (Nmax[i]<Ndiff)
                         {
                             stop=0;
                             idmaxwin[i]=seqid;
                             if (diffNmax<Ndiff-Nmax[i]) diffNmax=Ndiff-Nmax[i];
                         }
 
                 }
 
             //printf("seqid=%3i  diffNmax_prev= %-4i   diffNmax= %-4i   n=%-5i  N_in-N_ss=%-5i\n",seqid,diffNmax_prev,diffNmax,n,N_in-N_ss);
 
             if (stop) break;
 
             // // DEBUG
             // printf("idmax ");
             // for (i=1; i<=L; i++) printf("%2i ",idmax[i]);
             // printf("\n");
             // printf("idmaxwin ");
             // for (i=1; i<=L; i++) printf("%2i ",idmaxwin[i]);
             // printf("\n");
             // printf("N[i] ");
             // for (i=1; i<=L; i++) printf("%2i ",N[i]);
             // printf("\n");
 
             // Loop over all candidate sequences kk (-> k)
             for (kk=0; kk<N_in; kk++)
                 {
                     if (inkk[kk]) continue; // seq k already accepted
                     k=ksort[kk];
                     if (!keep[k]) continue; // seq k is not regular aa sequence or already suppressed by coverage or qid criterion
                     if (keep[k]==KEEP_ALWAYS) {inkk[kk]=2; continue;} // accept all marked sequences (no n++, since this has been done already)
 
                     // Calculate max-seq-id threshold seqidk for sequence k (as maximum over idmaxwin[i])
                     if (seqid>=100) {in[k]=inkk[kk]=1; n++; continue;}
                     float seqidk=seqid1;
                     for (i=first[k]; i<=last[k]; i++)
                         if (idmaxwin[i]>seqidk) seqidk=idmaxwin[i];
                     if (seqid==seqid_prev[k]) continue; // sequence has already been rejected at this seqid threshold => reject this time
                     seqid_prev[k]=seqid;
                     diff_min_frac =0.9999-0.01*seqidk; // min fraction of differing positions between sequence j and k needed to accept sequence k
 
                     // Loop over already accepted sequences
                     for (jj=0; jj<kk; jj++)
                         {
                             if (!inkk[jj]) continue;
                             j=ksort[jj];
                             first_kj=imax(first[k],first[j]);
                             last_kj =imin(last[k],last[j]);
                             cov_kj = last_kj-first_kj+1;
                             diff_suff=int(diff_min_frac*imin(nres[k],cov_kj)+0.999); // nres[j]>nres[k] anyway because of sorting /* MR1 0.999 */
                             diff=0;
                             for (int i=first_kj; i<=last_kj; i++)
                                 {
                                     // enough different residues to accept? => break
                                     if (X[k][i]>=NAA || X[j][i]>=NAA)
                                         cov_kj--;
                                     else
                                         if (X[k][i]!=X[j][i] && ++diff>=diff_suff) break; // accept (k,j)
                                 }
                             // // DEBUG
                             // printf("%20.20s with %20.20s: diff=%i diff_min_frac*cov_kj=%f diff_suff=%i nres=%i cov_kj=%i\n",sname[k],sname[j],diff,diff_min_frac*cov_kj,diff_suff,nres[k],cov_kj);
                             // printf("%s\n%s\n\n",seq[k],seq[j]);
 
                             //if (float(diff)<fmin(diff_min_frac*cov_kj,diff_suff)) break; //similarity > acceptace threshold? Reject! /* MR1 */
                             if (diff<diff_suff && float(diff)<=diff_min_frac*cov_kj) break; //dissimilarity < acceptace threshold? Reject! /* MR1 */
 
 
                         }
                     if (jj>=kk) // did loop reach end? => accept k. Otherwise reject k (the shorter of the two)
                         {
                             in[k]=inkk[kk]=1;
                             n++;
                             for (i=first[k]; i<=last[k]; i++) N[i]++; // update number of sequences at position i
                             // printf("%i %20.20s accepted\n",k,sname[k]);
                         }
                     // else
                     // {
                     // printf("%20.20s rejected: too similar with seq %20.20s diff=%i diff_min_frac*cov_kj=%f diff_suff=%i nres=%i cov_kj=%i\n",sname[k],sname[j],diff,diff_min_frac*cov_kj,diff_suff,nres[k],cov_kj);
                     // printf("%s\n%s\n\n",seq[k],seq[j]);
                     // }
 
                 } // End Loop over all candidate sequences kk
 
             // // DEBUG
             // printf("\n");
             // printf("seqid_prev[k]= \n");
             // for (k=0; k<N_in; k++) printf("%2i ",seqid_prev[k]);
             // printf("\n");
 
             // Increment seqid /* MR1 */
             seqid_step = imax(1,imin(5,diffNmax/(diffNmax_prev-diffNmax+1)*seqid_step/2));
             seqid += seqid_step;
 
         } // End Loop over seqid
 
     if (v>=2)
         {
             printf("%i out of %i sequences passed filter (",n,N_in-N_ss);
             if (par.coverage)
                 printf("%i%% min coverage, ",coverage);
             if (qid)
                 printf("%i%% min sequence identity to query, ",qid);
             if (qsc>-10)
                 printf("%.2f bits min score per column to query, ",qsc);
             if (Ndiff<N_in && Ndiff>0)
                 printf("up to %i%% position-dependent max pairwise sequence identity)\n",seqid);
             else
                 printf("%i%% max pairwise sequence identity)\n",seqid1);
         }
 
     for (k=0; k<N_in; k++) keep[k]=in[k];
     delete[] in; in = NULL;
     delete[] inkk; inkk = NULL;
     //delete[] idmax; idmax = NULL;
     delete[] Nmax; /* MR1 */
     delete[] idmaxwin; idmaxwin = NULL;
     delete[] seqid_prev; seqid_prev = NULL;
     delete[] N; N = NULL;
 #if 0
     printf("%s:%s:%d: sequences accepted = %d/%d\n", __FUNCTION__, __FILE__, __LINE__, n, N_in-N_ss);
 #endif
     return n;
 }
 
 
 
 /* MR1: the Alignment::HomologyFilter is no longer needed in hhalign-stand-alone */
 /////////////////////////////////////////////////////////////////////////////
 /**
  * @brief Filter for min score per column coresc with core query profile,
  *   defined by coverage_core and qsc_core 
  */
 /////////////////////////////////////////////////////////////////////////////
 int 
 Alignment::HomologyFilter(int coverage_core, float qsc_core, float coresc)
 {
     const int seqid_core=90; //maximum sequence identity in core alignment
     const int qid_core=0;
     const int Ndiff_core=0;
     int n;
     HMM qcore;
b5f31f05
     char* coreseq=new char[N_in]; // coreseq[k]=1 if sequence belongs to core of alignment (i.e. it is very similar to query)
dafeef0b
     for (int k=0; k<N_in; k++) coreseq[k]=keep[k]; // Copy keep[] into coreseq[]
 
     // Remove sequences with seq. identity larger than seqid percent (remove the shorter of two)
     int v1=v; v=1;
     n = Filter2(coreseq,coverage_core,qid_core,qsc_core,seqid_core,seqid_core,Ndiff_core);
     v=v1;
     if (v>=2)
         {
             printf("%i out of %i core alignment sequences passed filter (",n,N_in-N_ss);
             if (par.coverage_core)
                 printf("%i%% min coverage, ",coverage_core);
             if (qid_core)
                 printf("%i%% min sequence identity to query, ",qid_core);
             if (qsc_core>-10)
                 printf("%.2f bits min score per column to query, ",qsc_core);
             printf("%i%% max pairwise sequence identity)\n",seqid_core);
         }
 
     // Calculate bare AA frequencies and transition probabilities -> qcore.f[i][a], qcore.tr[i][a]
     FrequenciesAndTransitions(qcore,coreseq);
 
     // Add transition pseudocounts to query -> q.p[i][a] (gapd=1.0, gape=0.333, gapf=gapg=1.0, gaph=gapi=1.0, gapb=1.0
     qcore.AddTransitionPseudocounts(1.0,0.333,1.0,1.0,1.0,1.0,1.0);
 
     // Generate an amino acid frequency matrix from f[i][a] with full pseudocount admixture (tau=1) -> g[i][a]
     qcore.PreparePseudocounts();
 
     // Add amino acid pseudocounts to query: qcore.p[i][a] = (1-tau)*f[i][a] + tau*g[i][a]
     qcore.AddAminoAcidPseudocounts(2,1.5,2.0,1.0); // pcm=2, pca=1.0, pcb=2.5, pcc=1.0
 
     // Filter out all sequences below min score per column with qcore
     n=FilterWithCoreHMM(keep, coresc, qcore);
 
     if (v>=2) cout<<n<<" out of "<<N_in-N_ss<<" sequences filtered by minimum score-per-column threshold of "<<qsc_core<<"\n";
     delete[] coreseq; coreseq = NULL;
     return n;
 }
 
 
 /////////////////////////////////////////////////////////////////////////////////////
 /**
  * @brief Filter out all sequences below a minimum score per column with profile qcore
  */
 int 
 Alignment::FilterWithCoreHMM(char in[], float coresc, HMM& qcore)
 {
     int k; // count sequences in alignment
     int i; // column in query alignment
     int a; // amino acid (0..19)
     int n=1; // number of sequences that passed filter
b5f31f05
     float** logodds=new float*[L+1]; // log-odds ratios for HMM qcore
dafeef0b
     char gap; // 1: previous state in seq k was a gap 0: previous state in seq k was an amino acid
     float score; // score of sequence k aligned with qcore
 
     for (i=1; i<=L; i++) logodds[i]=new(float[21]);
 
     // Determine first[k], last[k]?
     if (first==NULL)
         {
b5f31f05
             first=new int[N_in];// first non-gap position in sequence k
             last =new int[N_in];// last non-gap position in sequence k
dafeef0b
             for (k=0; k<N_in; k++) // do this for ALL sequences, not only those with in[k]==1 (since in[k] may be display[k])
                 {
                     for (i=1; i<=L; i++) if (X[k][i]<NAA) break;
                     first[k]=i;
                     for (i=L; i>=1; i--) if (X[k][i]<NAA) break;
                     last[k]=i;
                 }
         }
 
     // Determine number of residues nres[k]?
     if (nres==NULL)
         {
b5f31f05
             nres=new int[N_in];
dafeef0b
             for (k=0; k<N_in; k++) // do this for ALL sequences, not only those with in[k]==1 (since in[k] may be display[k])
                 {
                     int nr=0;
                     for (i=first[k]; i<=last[k]; i++)
                         if (X[k][i]<NAA) nr++;
                     nres[k]=nr;
                     // printf("%20.20s nres=%3i first=%3i last=%3i\n",sname[k],nr,f,l);
                 }
         }
 
     // Precalculate the log-odds for qcore
     for (i=1; i<=L; i++)
         {
             for (a=0; a<NAA; a++)
                 logodds[i][a]=fast_log2(qcore.p[i][a]/pb[a]);
             logodds[i][ANY]=-0.5; // half a bit penalty for X
 
             // printf(" A R N D C Q E G H I L K M F P S T W Y V\n");
             // printf("%6i ",i);
             // for (a=0; a<20; ++a) fprintf(stdout,"%5.1f ",100*qcore.f[i][a]);
             // printf("\n");
             // printf(" ");
             // for (a=0; a<20; ++a) fprintf(stdout,"%5.1f ",100*qcore.g[i][a]);
             // printf("\n");
             // printf(" ");
             // for (a=0; a<20; ++a) fprintf(stdout,"%5.1f ",100*qcore.p[i][a]);
             // printf("\n");
             // printf(" ");
             // for (a=0; a<20; ++a) fprintf(stdout,"%5.1f ",100*pb[a]);
             // printf("\n");
             // printf(" ");
             // for (a=0; a<20; ++a) fprintf(stdout,"%5.2f ",fast_log2(qcore.p[i][a]/pb[a]));
             // printf("\n");
         }
 
     // Main loop: test all sequences k
     for (k=kfirst+1; k<N_in; k++)
         {
             if (!in[k]) continue; // if in[k]==0 sequence k will be suppressed directly
 
             float score_M=0.0;
             float score_prev=0.0;
 
             // Calculate score of sequence k with core HMM
             score=0; gap=0;
             for (i=first[k]; i<=last[k]; i++)
                 {
                     score_M=0.0;
                     if (X[k][i]<=ANY) // current state is Match
                         {
                             score_M=logodds[i][ (int)X[k][i]];
                             score+=logodds[i][ (int)X[k][i]];
                             if (gap) score+=qcore.tr[i][D2M]; else score+=qcore.tr[i][M2M];
                             gap=0;
                         }
                     else if (X[k][i]==GAP) // current state is Delete (ignore ENDGAPs)
                         {
                             if (gap) score+=qcore.tr[i][D2D]; else score+=qcore.tr[i][M2D];
                             gap=1;
                         }
                     if (I[k][i]) score+=qcore.tr[i][M2I]+(I[k][i]-1)*qcore.tr[i][I2I]+qcore.tr[i][I2M];
                     // if (k==2) printf("i=%3i %c:%c score_M=%6.2f score=%6.2f score_sum=%6.2f \n",i,i2aa(X[kfirst][i]),i2aa(X[k][i]),score_M,score-score_prev,score);
                     score_prev=score;
                 }
 
             printf("k=%3i score=%6.2f\n",k,score);
             if (score<nres[k]*coresc) in[k]=0; else n++;// reject sequence k?
         }
     for (i=1; i<=L; i++){
         delete[] logodds[i]; logodds[i] = NULL;
     }
     delete[] logodds; logodds = NULL;
     return n;
 }
 
 
 /* MR1 */
 #if 0
 /////////////////////////////////////////////////////////////////////////////////////
 /**
  * @brief Filter alignment to given diversity/Neff
  */
 bool 
 Alignment::FilterNeff()
 {
     int v1=v;
     v=v1-1;
     const float TOLX=0.001;
     const float TOLY=0.02;
     char dummy[N_in+1];
     for (int k=0; k<N_in; ++k) dummy[k]=keep[k];
     float x=0.0,y=0.0;
     float x0=-1.0;
     float x1=+2.0;
     float y0=filter_by_qsc(x0,dummy);
     float y1=filter_by_qsc(x1,dummy);
     int i=2;
     while (y0-par.Neff>0 && par.Neff-y1>0)
         {
             x = x0 + (par.Neff-y0)*(x1-x0)/(y1-y0); // linear interpolation between (x0,y0) and (x1,y1)
             y = filter_by_qsc(x,dummy);
             if (v>=2) printf(" %3i  x0=%6.3f -> %6.3f     x=%6.3f -> %6.3f     x1=%6.3f -> %6.3f \n",++i,x0,y0,x,y,x1,y1);
             if (y>par.Neff) {x0=x; y0=y;} else {x1=x; y1=y;}
             if (fabs(par.Neff-y)<TOLY || x1-x0<TOLX) break;
         }
     v=v1;
 
     if (y0>=par.Neff && y1<=par.Neff)
         {
             // Write filtered alignment WITH insert states (lower case) to alignment file
             if (v>=2) printf("Found Neff=%6.3f at filter threshold qsc=%6.3f\n",y,x);
             return true;
         }
     else if (v>=1)
         printf("Diversity of unfiltered alignment %.2f is below target diversity %.2f. No alignment written\n",y0,par.Neff);
 
     return false;
 }
 
 float Alignment::filter_by_qsc(float qsc, char* dummy)
 {
     HMM q;
     for (int k=0; k<N_in; ++k) keep[k]=dummy[k];
     Filter2(keep,par.coverage,0,qsc,par.max_seqid+1,par.max_seqid,0);
     FrequenciesAndTransitions(q);
     //   printf("qsc=%4.1f  N_filtered=%-3i  Neff=%6.3f\n",qsc,n,q.Neff_HMM);
     return q.Neff_HMM;
 }
 #endif
 
 /////////////////////////////////////////////////////////////////////////////////////
 /**
  * @brief  Calculate AA frequencies q.p[i][a] and transition probabilities q.tr[i][a] from alignment
  */
 void 
 Alignment::FrequenciesAndTransitions(HMM& q, char* in)
 {
     int k; // index of sequence
     int i; // position in alignment
     int a; // amino acid (0..19)
     int ni[NAA+3]; // number of times amino acid a occurs at position i
     int naa; // number of different amino acids
 
     if (v>=3)
         cout<<"Calculating position-dependent weights on subalignments\n";
 
     if (in==NULL) in=keep; // what's this good for?
 
     if (N_filtered>1)
         {
             for (k=0; k<N_in; k++) wg[k]=0.0; // initialized wg[k]
             // Calculate global weights
             for (i=1; i<=L; i++) // for all positions i in alignment
                 {
                     for (a=0; a<20; a++) ni[a]=0;
                     for (k=0; k<N_in; k++) if (in[k]) ni[ (int)X[k][i]]++;
                     naa=0; for (a=0; a<20; a++) if(ni[a]) naa++;
                     if (!naa) naa=1; //naa=0 when column consists of only gaps and Xs (=ANY)
                     for (k=0; k<N_in; k++)
                         if (in[k] && X[k][i]<20)
                             wg[k] += 1.0/float(ni[ (int)X[k][i]]*naa*(nres[k]+30));
                     // ensure that each residue of a short sequence contributes as much as a residue of a long sequence:
                     // contribution is proportional to one over sequence length nres[k] plus 30.
                 }
             NormalizeTo1(wg,N_in);
 
 
             // Do pos-specific sequence weighting and calculate amino acid frequencies and transitions
             for (k=0; k<N_in; k++) X[k][0]=ENDGAP; // make sure that sequences ENTER subalignment j for j=1
             for (k=0; k<N_in; k++) X[k][L+1]=ENDGAP; // does it have an influence?
 
 #ifdef HAVE_OPENMP
             if(par.wg != 1)
             {
                 #pragma omp parallel sections
                 {
                     #pragma omp section
                     Amino_acid_frequencies_and_transitions_from_M_state(q,in); // use subalignments of seqs with residue in i
                     #pragma omp section
                     Transitions_from_I_state(q,in); // use subalignments of seqs with insert in i
                     #pragma omp section
                     Transitions_from_D_state(q,in); // use subalignments of seqs with delete in i. Must be last of these three calls if par.wg==1!
                 }
             }
             else
             {
                 #pragma omp parallel sections
                 {
                     #pragma omp section
                     Amino_acid_frequencies_and_transitions_from_M_state(q,in); // use subalignments of seqs with residue in i
                     #pragma omp section
                     Transitions_from_I_state(q,in); // use subalignments of seqs with insert in i
                 }
                 Transitions_from_D_state(q,in); // use subalignments of seqs with delete in i. Must be last of these three calls if par.wg==1!
             }
 #else
             Amino_acid_frequencies_and_transitions_from_M_state(q,in);
             Transitions_from_I_state(q,in);
             Transitions_from_D_state(q,in);
 #endif
         }
     else // N_filtered==1
         {
             X[kfirst][0]=X[kfirst][L+1]=ANY; // (to avoid anallowed access within loop)
             q.Neff_HMM=1.0f;
             for (i=0; i<=L+1; i++) // for all positions i in alignment
                 {
                     q.Neff_M[i]=1.0f;
                     q.Neff_I[i]=q.Neff_D[i]=0.0f;
                     for (a=0; a<20; a++) q.f[i][a]=0.0;
                     /* this is the crucial change that makes terminal-X work */
                     //q.f[i][ (int)(X[kfirst][i]) ] = 1.0; /* MR1 */
                     if (X[kfirst][i] < ANY) /* MR1 */
                         q.f[i][(unsigned int) X[kfirst][i] ] = 1.0;
                     else
                         for (a=0; a<20; ++a) q.f[i][a]=pb[a];
                     q.tr[i][M2M]=0;
                     q.tr[i][M2I]=-100000.0;
                     q.tr[i][M2D]=-100000.0;
                     q.tr[i][I2M]=-100000.0;
                     q.tr[i][I2I]=-100000.0;
                     q.tr[i][D2M]=-100000.0;
                     q.tr[i][D2D]=-100000.0;
                 }
             q.tr[0][I2M]=0;
             q.tr[L][I2M]=0;
             q.tr[0][D2M]=0;
             q.Neff_M[0]=q.Neff_I[0]=q.Neff_D[0]=99.999; // Neff_av[0] is used for calculation of transition pseudocounts for the start state
         }
 
     if (v>=3)
         {
             printf("\nMatches:\n");
             printf("col Neff nseqs\n");
             for (i=1; i<=imin(L,100); i++)
                 printf("%3i %5.2f %3i\n",i,q.Neff_M[i],nseqs[i]);
 
             printf("\nInserts:\n");
             printf("col Neff nseqs\n");
             for (i=1; i<=imin(L,100); i++)
                 printf("%3i %5.2f %3i\n",i,q.Neff_I[i],nseqs[i]);
 
             printf("\nDeletes:\n");
             printf("col Neff nseqs\n");
             for (i=1; i<=imin(L,100); i++)
                 printf("%3i %5.2f %3i\n",i,q.Neff_D[i],nseqs[i]);
         }
 
     // Copy column information into HMM q
     q.L=L;
     q.N_in=N_in;
     q.N_filtered=N_filtered;
     for (i=1; i<=L; i++) q.l[i]=l[i];
 
     // Set names in HMM q
     if (strlen(q.name)==0) strcpy(q.name,name);
     if (strlen(q.longname)==0) strcpy(q.longname,longname);
     if (strlen(q.fam)==0) strcpy(q.fam,fam);
     ScopID(q.cl,q.fold,q.sfam,q.fam); // derive superfamily, fold and class code from family name
     strcpy(q.file,file); // Store basename of alignment file name in q.file
 
     // Copy sequences to be displayed into HMM
     q.nss_dssp=q.nsa_dssp=q.nss_pred=q.nss_conf=q.nfirst=-1;
     int n=0;
     if (kss_dssp>=0) q.nss_dssp=n++; // copy dssp sequence?
     if (ksa_dssp>=0) q.nsa_dssp=n++; // copy dssp sequence?
     if (kss_pred>=0) q.nss_pred=n++; // copy psipred sequence?
     if (kss_conf>=0) q.nss_conf=n++; // copy confidence value sequence?
 
     // Calculate consensus sequence?
     if (par.showcons || par.cons)
         {
             float maxw;
             int maxa;
             if (par.showcons)
                 {
                     // Reserve space for consensus/conservation sequence as Q-T alignment mark-up
                     q.ncons=n++;
                     q.sname[q.ncons]=new(char[10]);
                     if (!q.sname[q.ncons]) {MemoryError("array of names for displayed sequences");}
                     strcpy(q.sname[q.ncons],"Consensus");
b5f31f05
                     q.seq[q.ncons]=new char[L+2];
dafeef0b
                     if (!q.seq[q.ncons]) {MemoryError("array of names for displayed sequences");}
                 }
             if (par.cons)
                 {
                     // Reserve space for consensus sequence as first sequence in alignment
                     q.nfirst=n++; kfirst=-1;
b5f31f05
                     q.sname[q.nfirst]=new char[strlen(name)+11];
dafeef0b
                     if (!q.sname[q.nfirst]) {MemoryError("array of names for displayed sequences");}
                     strcpy(q.sname[q.nfirst],name);
                     strcat(q.sname[q.nfirst],"_consensus");
b5f31f05
                     q.seq[q.nfirst]=new char[L+2];
dafeef0b
                     if (!q.seq[q.nfirst]) {MemoryError("array of names for displayed sequences");}
                 }
             // Calculate consensus amino acids using similarity matrix
             for (i=1; i<=L; i++)
                 {
                     maxw=0.0; maxa=0;
                     for (a=0; a<20; a++)
                         if (q.f[i][a]-pb[a]>maxw) {maxw = q.f[i][a]-pb[a]; maxa = a;}
 
                     if (par.showcons)
                         {
                             maxw =0.0;
                             for (int b=0; b<20; b++) maxw += q.f[i][b]*Sim[maxa][b]*Sim[maxa][b];
                             maxw *= q.Neff_M[i]/(q.Neff_HMM+1); // columns with many gaps don't get consensus symbol
                             if (maxw>0.6) q.seq[q.ncons][i] = uprchr(i2aa(maxa));
                             else if (maxw>0.4) q.seq[q.ncons][i] = lwrchr(i2aa(maxa));
                             else q.seq[q.ncons][i] = 'x';
                         }
                     if (par.cons) q.seq[q.nfirst][i] = uprchr(i2aa(maxa));
                 }
             if (par.showcons)
                 {
                     q.seq[q.ncons][0]='-';
                     q.seq[q.ncons][L+1]='\0';
                 }
             if (par.cons)
                 {
                     q.seq[q.nfirst][0]='-';
                     q.seq[q.nfirst][L+1]='\0';
                 }
         }
 
     // Copy sequences to be displayed from alignment to HMM
     for (k=0; k<N_in; k++)
         {
             int nn;
             if (display[k])
                 {
                     if (0 && (n>=MAXSEQDIS)) {
                         /* FIXME: the test was if(n>=MAXSEQDIS),
                            this test was necessary because alignment memory was static,
                            now it should be dynamic, and should always have the right size,
                            there are at least number-of-sequences plus a 'bit' more
                            however, I do not know what that 'bit' is likely to be (in the future).
                            at the moment it is 1 for the consnseus and 1 for structure,
                            but this might change (FS)
                          */
                         if (par.mark) cerr<<"WARNING: maximum number "<<MAXSEQDIS<<" of sequences for display of alignment exceeded\n";
                         break;
                     }
                     if (k==kss_dssp) nn=q.nss_dssp; // copy dssp sequence to nss_dssp
                     else if (k==ksa_dssp) nn=q.nsa_dssp;
                     else if (k==kss_pred) nn=q.nss_pred;
                     else if (k==kss_conf) nn=q.nss_conf;
                     else if (k==kfirst) nn=q.nfirst=n++;
                     else nn=n++;
                     // strcut(sname[k]," "); // delete rest of name line beginning with two spaces " " // Why this?? Problem for pdb seqs without chain
b5f31f05
                     q.sname[nn]=new char[strlen(sname[k])+1];
dafeef0b
                     if (!q.sname[nn]) {MemoryError("array of names for displayed sequences");}
                     strcpy(q.sname[nn],sname[k]);
b5f31f05
                     q.seq[nn]=new char[strlen(seq[k])+1];
dafeef0b
                     if (!q.seq[nn]) {MemoryError("array of names for displayed sequences");}
                     strcpy(q.seq[nn],seq[k]);
                 }
         }
     q.n_display=n; // how many sequences to be displayed in alignments?
 
     // Copy secondary structure information into HMM
     if (kss_dssp>=0)
         for (i=1; i<=L; i++) q.ss_dssp[i]=X[kss_dssp][i];
     if (ksa_dssp>=0)
         for (i=1; i<=L; i++) q.sa_dssp[i]=X[ksa_dssp][i];
     if (kss_pred>=0)
         {
             for (i=1; i<=L; i++) q.ss_pred[i]=X[kss_pred][i];
             if (kss_conf>=0)
                 for (i=1; i<=L; i++) q.ss_conf[i]=X[kss_conf][i];
             else
                 for (i=1; i<=L; i++) q.ss_conf[i]=5;
         }
 
     q.lamda=0.0;
     q.mu=0.0;
 
     // Debug: print occurence of amino acids for each position i
     if (v>=2) printf("Effective number of sequences exp(entropy) = %-4.1f\n",q.Neff_HMM); //PRINT
     if (v>=3)
         {
             cout<<"\nMatr: ";
             for (a=0; a<20; a++) printf("%4.1f ",100*pb[a]);
             cout<<"\nAmino acid frequencies without pseudocounts:\n";
             cout<<" A R N D C Q E G H I L K M F P S T W Y V\n";
             for (i=1; i<=L; i++)
                 {
                     printf("%3i: ",i);
                     for (a=0; a<20; a++) printf("%4.0f ",100*q.f[i][a]);
                     cout<<endl;
                 }
             cout<<"\n";
 
             printf("\nListing transition probabilities without pseudocounts:\n");
             printf(" i M->M M->I M->D I->M I->I D->M D->D Neff_M Neff_I Neff_D\n");
             for (i=0; i<=L; i++)
                 {
                     printf("%4i %6.3f %6.3f %6.3f ",i,pow(2.0,q.tr[i][M2M]),pow(2.0,q.tr[i][M2I]),pow(2.0,q.tr[i][M2D]));
                     printf("%6.3f %6.3f ",pow(2.0,q.tr[i][I2M]),pow(2.0,q.tr[i][I2I]));
                     printf("%6.3f %6.3f ",pow(2.0,q.tr[i][D2M]),pow(2.0,q.tr[i][D2D]));
                     printf("%6.3f %6.3f %6.3f\n",q.Neff_M[i],q.Neff_I[i],q.Neff_D[i]);
                 }
         }
     q.trans_lin=0;
     q.has_pseudocounts=false; /* MR1 */
 
     return;
 }
 
 
 /////////////////////////////////////////////////////////////////////////////////////
 /*
  * FIXME: one of the most time consuming routines (according to gprof on r112)
  */
 /**
  * @brief Calculate freqs q.f[i][a] and transitions q.tr[i][a] (a=MM,MI,MD) with pos-specific subalignments
  * Pos-specific weights are calculated like in "GetPositionSpecificWeights()"
  */
 void 
 Alignment::Amino_acid_frequencies_and_transitions_from_M_state(HMM& q, char* in)
 {
   // Calculate position-dependent weights wi[k] for each i.
   // For calculation of weights in column i use sub-alignment
   // over sequences which have a *residue* in column i (no gap, no end gap)
   // and over columns where none of these sequences has an end gap.
   // This is done by updating the arrays n[j][a] at each step i-1->i while letting i run from 1 to L.
   // n[j][a] = number of occurences of amino acid a at column j of the subalignment,
   // => only columns with n[j][ENDGAP]=0 are contained in the subalignment!
   // If no sequences enter or leave the subalignment at the step i-1 -> i (i.e. change=0)
   // then the old values wi[k], Neff[i-1], and ncol are used for the new position i.
   // Index a can be an amino acid (0-19), ANY=20, GAP=21, or ENDGAP=22
 
   int k; // index of sequence
   int i,j; // position in alignment
   int a; // amino acid (0..19)
   int naa; // number of different amino acids
   int** n; // n[j][a] = number of seq's with some residue at column i AND a at position j
   //float wi[MAXSEQ]; // weight of sequence k in column i, calculated from subalignment i
   float *wi=NULL; // weight of sequence k in column i, calculated from subalignment i
   //float Neff[MAXRES]; // diversity of subalignment i
b5f31f05
   float *Neff = new float[par.maxResLen]; // diversity of subalignment i
dafeef0b
   int nseqi=0; // number of sequences in subalignment i
   int ncol=0; // number of columns j that contribute to Neff[i]
   char change; // has the set of sequences in subalignment changed? 0:no 1:yes
   float fj[NAA+3]; // to calculate entropy
   float sum;
 
b5f31f05
   wi = new float[N_in+2];
dafeef0b
 
   // Global weights?
   if (par.wg==1)
     for (k=0; k<N_in; k++) wi[k]=wg[k];
 
   // Initialization
   q.Neff_HMM=0.0f;
   Neff[0]=0.0; // if the first column has no residues (i.e. change==0), Neff[i]=Neff[i-1]=Neff[0]
b5f31f05
   n = new int*[L+2];
dafeef0b
   for (j=1; j<=L; j++) n[j]=new(int[NAA+3]);
   for (j=1; j<=L; j++)
     for (a=0; a<NAA+3; a++) n[j][a]=0;
 
 
   //////////////////////////////////////////////////////////////////////////////////////////////
   // Main loop through alignment columns
   for (i=1; i<=L; i++) // Calculate wi[k] at position i as well as Neff[i]
     {
 
       if (par.wg==0)
 	{
 
 	  change=0;
 	  // Check all sequences k and update n[j][a] and ri[j] if necessary
 	  for (k=0; k<N_in; k++)
 	    {
 	      if (!in[k]) continue;
 	      if (X[k][i-1]>=ANY && X[k][i]<ANY)
 		{ // ... if sequence k was NOT included in i-1 and has to be included for column i
 		  change=1;
 		  nseqi++;
 		  for (int j=1; j<=L; j++) n[j][ (int)X[k][j]]++;
 		}
 	      else if (X[k][i-1]<ANY && X[k][i]>=ANY)
 		{ // ... if sequence k WAS included in i-1 and has to be thrown out for column i
 		  change=1;
 		  nseqi--;
 		  for (int j=1; j<=L; j++) n[j][ (int)X[k][j]]--;
 		}
 	    } //end for (k)
 	  nseqs[i]=nseqi;
 
 	  // If subalignment changed: update weights wi[k] and Neff[i]
 	  if (change)
 	    {
 	      // Initialize weights and numbers of residues for subalignment i
 	      ncol=0;
 	      for (k=0; k<N_in; k++) wi[k]=1E-8; // for pathological alignments all wi[k] can get 0; /* MR1 */
 
 	      // sum wi[k] over all columns j and sequences k of subalignment
 	      for (j=1; j<=L; j++)
 		{
 		  // do at least a fraction MAXENDGAPFRAC of sequences in subalignment contain an end gap in j?
 		  if (n[j][ENDGAP]>MAXENDGAPFRAC*nseqi) continue;
 		  naa=0; for (a=0; a<20; a++) if(n[j][a]) naa++;
 		  if (naa==0) continue;
 		  ncol++;
 		  for (k=0; k<N_in; k++)
 		    {
 		      if (in[k] && X[k][i]<ANY && X[k][j]<ANY)
 			{
 			  // if (!n[j][ (int)X[k][j]]) {fprintf(stderr,"Error: Mi=%i: n[%i][X[%i]]=0! (X[%i]=%i)\n",i,j,k,k,X[k][j]);}
 			  wi[k]+=1.0/float(n[j][ (int)X[k][j] ]*naa);
 			}
 		    }
 		}
 
 	      // Check whether number of columns in subalignment is sufficient
 	      if (ncol<NCOLMIN)
 		// Take global weights
 		for (k=0; k<N_in; k++)
 		  if(in[k] && X[k][i]<ANY) wi[k]=wg[k]; else wi[k]=0.0;
 
 	      // Calculate Neff[i]
 	      Neff[i]=0.0;
 	      for (j=1; j<=L; j++)
 		{
 		  // do at least a fraction MAXENDGAPFRA of sequences in subalignment contain an end gap in j?
 		  if (n[j][ENDGAP]>MAXENDGAPFRAC*nseqi) continue;
 		  for (a=0; a<20; a++) fj[a]=0;
 		  for (k=0; k<N_in; k++)
 		    if (in[k] && X[k][i]<ANY && X[k][j]<ANY)
 		      fj[ (int)X[k][j] ]+=wi[k];
 		  NormalizeTo1(fj,NAA);
 		  for (a=0; a<20; a++)
 		    if (fj[a]>1E-10) Neff[i]-=fj[a]*fast_log2(fj[a]);
 		}
 	      if (ncol>0) Neff[i]=pow(2.0,Neff[i]/ncol); else Neff[i]=1.0;
 
 	    }
 
 	  else //no update was necessary; copy values for i-1
 	    {
 	      Neff[i]=Neff[i-1];
 	    }
 	}
 
 
       // Calculate amino acid frequencies q.f[i][a] from weights wi[k]
       for (a=0; a<20; a++) q.f[i][a]=0;
       for (k=0; k<N_in; k++) if (in[k]) q.f[i][ (int)X[k][i] ]+=wi[k];
       NormalizeTo1(q.f[i],NAA,pb);
 
       // Calculate transition probabilities from M state
       q.tr[i][M2M]=q.tr[i][M2D]=q.tr[i][M2I]=0.0;
       for (k=0; k<N_in; k++) //for all sequences
 	{
 	  if (!in[k]) continue;
 	  //if input alignment is local ignore transitions from and to end gaps
 	  if (X[k][i]<ANY) //current state is M
 	    {
 	      if (I[k][i]) //next state is I
 		q.tr[i][M2I]+=wi[k];
 	      else if (X[k][i+1]<=ANY) //next state is M
 		q.tr[i][M2M]+=wi[k];
 	      else if (X[k][i+1]==GAP) //next state is D
 		q.tr[i][M2D]+=wi[k];
 	    }
 	} // end for(k)
       // Normalize and take log
       sum = q.tr[i][M2M]+q.tr[i][M2I]+q.tr[i][M2D]+FLT_MIN;
       q.tr[i][M2M]=log2(q.tr[i][M2M]/sum);
       q.tr[i][M2I]=log2(q.tr[i][M2I]/sum);
       q.tr[i][M2D]=log2(q.tr[i][M2D]/sum);
 
       // for (k=0; k<N_in; k++) if (in[k]) w[k][i]=wi[k];
     }
     // DD TODO:fill in all the missing Neff values
 
 
   // end loop through alignment columns i
   //////////////////////////////////////////////////////////////////////////////////////////////
 
   delete[](wi); wi=NULL;
   // delete n[][]
   for (j=1; j<=L; j++){
     delete[](n[j]); (n[j]) = NULL;
   }
   delete[](n); (n) = NULL;
 
   q.tr[0][M2M]=0;
   q.tr[0][M2I]=-100000;
   q.tr[0][M2D]=-100000;
   q.tr[L][M2M]=0;
   q.tr[L][M2I]=-100000; 
   q.tr[L][M2D]=-100000;
   q.Neff_M[0]=99.999; // Neff_av[0] is used for calculation of transition pseudocounts for the start state
 
   // Set emission probabilities of zero'th (begin) state and L+1st (end) state to background probabilities
   for (a=0; a<20; a++) q.f[0][a]=q.f[L+1][a]=pb[a];
 
   // Assign Neff_M[i] and calculate average over alignment, Neff_M[0]
   if (par.wg==1)
     {
       for (i=1; i<=L; i++)
 	{
 	  float sum=0.0f;
 	  for (a=0; a<20; a++)
 	    if (q.f[i][a]>1E-10) sum -= q.f[i][a]*fast_log2(q.f[i][a]);
 	  q.Neff_HMM+=pow(2.0,sum);
 	}
       q.Neff_HMM/=L;
       float Nlim=fmax(10.0,q.Neff_HMM+1.0); // limiting Neff
       float scale=log2((Nlim-q.Neff_HMM)/(Nlim-1.0)); // for calculating Neff for those seqs with inserts at specific pos
       for (i=1; i<=L; i++)
 	{
 	  float w_M=-1.0/N_filtered;
 	  for (k=0; k<N_in; k++)
 	    if (in[k] && X[k][i]<=ANY) w_M+=wg[k];
 	  if (w_M<0) q.Neff_M[i]=1.0;
 	  else q.Neff_M[i] = Nlim - (Nlim-1.0)*fpow2(scale*w_M);
 	  // fprintf(stderr,"M i=%3i ncol=--- Neff_M=%5.2f Nlim=%5.2f w_M=%5.3f Neff_M=%5.2f\n",i,q.Neff_HMM,Nlim,w_M,q.Neff_M[i]);
 	}
     }
   else
     {
       for (i=1; i<=L; i++)
 	{
 	  q.Neff_HMM+=Neff[i];
 	  q.Neff_M[i]=Neff[i];
       if (q.Neff_M[i] == 0) { q.Neff_M[i] = 1; } /* MR1 */
 	}
       q.Neff_HMM/=L;
     }
 
   delete[] Neff; Neff = NULL;
 
   return;
 
 } /* this is the end of Alignment::Amino_acid_frequencies_and_transitions_from_M_state() */
 
 
 /////////////////////////////////////////////////////////////////////////////////////
 /**
  * @brief Calculate transitions q.tr[i][a] (a=DM,DD) with pos-specific subalignments
  */
 void 
 Alignment::Transitions_from_I_state(HMM& q, char* in)
 {
     // Calculate position-dependent weights wi[k] for each i.
     // For calculation of weights in column i use sub-alignment
     // over sequences which have a INSERT in column i
     // and over columns where none of these sequences has an end gap.
     // This is done by calculating the arrays n[j][a] and rj[j] at each step i-1->i while letting i run from 1 to L.
     // n[j][a] = number of occurences of amino acid a at column j of the subalignment,
     // => only columns with n[j][ENDGAP]=0 are contained in the subalignment!
     // If no sequences enter or leave the subalignment at the step i-1 -> i (i.e. change=0)
     // then the old values wi[k], Neff[i-1], and ncol are used for the new position i.
     // Index a can be an amino acid (0-19), ANY=20, GAP=21, or ENDGAP=22
 
     int k; // index of sequence
     int i,j; // position in alignment
     int a; // amino acid (0..19)
     int naa; // number of different amino acids
     int** n; // n[j][a] = number of seq's with some residue at column i AND a at position j
     //float wi[MAXSEQ]; // weight of sequence k in column i, calculated from subalignment i
     float *wi = NULL; // weight of sequence k in column i, calculated from subalignment i
     //float Neff[MAXRES]; // diversity of subalignment i
b5f31f05
     float *Neff = new float[par.maxResLen]; // diversity of subalignment i
dafeef0b
     int nseqi; // number of sequences in subalignment i
     int ncol; // number of columns j that contribute to Neff[i]
     float fj[NAA+3]; // to calculate entropy
     float sum;
     float Nlim=0.0; // only for global weights
     float scale=0.0; // only for global weights
 
b5f31f05
     wi = new float[N_in+2];
dafeef0b
 
     // Global weights?
     if (par.wg==1)
         {
             for (k=0; k<N_in; k++) wi[k]=wg[k];
             Nlim=fmax(10.0,q.Neff_HMM+1.0); // limiting Neff
             scale=log2((Nlim-q.Neff_HMM)/(Nlim-1.0)); // for calculating Neff for those seqs with inserts at specific pos
         }
 
     // Initialization
b5f31f05
     n = new int*[L+2];
dafeef0b
     for (j=1; j<=L; j++) n[j]=new(int[NAA+3]);
 
     //////////////////////////////////////////////////////////////////////////////////////////////
     // Main loop through alignment columns
     for (i=1; i<=L; i++) // Calculate wi[k] at position i as well as Neff[i]
         {
             if (par.wg==0) // local weights?
                 {
 
                     // Calculate n[j][a] and ri[j]
                     nseqi=0;
                     for (k=0; k<N_in; k++)
                         {
                             if (in[k] && I[k][i]>0)
                                 {
                                     if (nseqi==0) // Initialize only if inserts present! Otherwise O(L*L) even for single sequences!
                                         {
                                             // Initialization of n[j][a]
                                             for (j=1; j<=L; j++)
                                                 for (a=0; a<NAA+3; a++) n[j][a]=0;
                                         }
                                     nseqi++;
                                     for (int j=1; j<=L; j++) n[j][ (int)X[k][j]]++;
                                 }
                         } //end for (k)
                     nseqs[i]=nseqi;
 
                     // If there is no sequence in subalignment j ...
                     if (nseqi==0)
                         {
                             ncol=0;
                             Neff[i]=0.0; // effective number of sequence = 0!
                             q.tr[i][I2M]=-100000;
                             q.tr[i][I2I]=-100000;
                             continue;
                         }
 
                     // update weights wi[k] and Neff[i]
                     // if (1)
                     {
                         // Initialize weights and numbers of residues for subalignment i
                         ncol=0;
                         for (k=0; k<N_in; k++) wi[k]=0.0;
 
                         // sum wi[k] over all columns j and sequences k of subalignment
                         for (j=1; j<=L; j++)
                             {
                                 if (n[j][ENDGAP]>MAXENDGAPFRAC*nseqi) continue;
                                 naa=0; for (a=0; a<20; a++) if(n[j][a]) naa++;
                                 if (naa==0) continue;
                                 ncol++;
                                 for (k=0; k<N_in; k++)
                                     {
                                         if (in[k] && I[k][i]>0 && X[k][j]<ANY)
                                             {
                                                 if (!n[j][ (int)X[k][j]]) {fprintf(stderr,"Error: Ii=%i: n[%i][X[%i]]=0! (X[%i]=%i)\n",i,j,k,k,X[k][j]);}
                                                 wi[k]+=1.0/float(n[j][ (int)X[k][j] ]*naa);
                                             }
                                     }
                             }
 
                         // Check whether number of columns in subalignment is sufficient
                         if (ncol>=NCOLMIN)
                             // Take global weights
                             for (k=0; k<N_in; k++)
                                 if(in[k] && I[k][i]>0) wi[k]=wg[k]; else wi[k]=0.0;
 
                         // Calculate Neff[i]
                         Neff[i]=0.0;
                         for (j=1; j<=L; j++)
                             {
                                 if (n[j][ENDGAP]>MAXENDGAPFRAC*nseqi) continue;
                                 for (a=0; a<20; a++) fj[a]=0;
                                 for (k=0; k<N_in; k++)
                                     if (in[k] && I[k][i]>0 && X[k][j]<ANY)
                                         fj[ (int)X[k][j] ]+=wi[k];
                                 NormalizeTo1(fj,NAA);
                                 for (a=0; a<20; a++)
                                     if (fj[a]>1E-10) Neff[i]-=fj[a]*fast_log2(fj[a]);
                             }
                         if (ncol>0) Neff[i]=pow(2.0,Neff[i]/ncol); else Neff[i]=1.0;
 
                     }
                     // Calculate transition probabilities from I state
                     q.tr[i][I2M]=q.tr[i][I2I]=0.0;
                     for (k=0; k<N_in; k++) //for all sequences
                         {
                             if (in[k] && I[k][i]>0) //current state is I
                                 {
                                     q.tr[i][I2M]+=wi[k];
                                     q.tr[i][I2I]+=wi[k]*(I[k][i]-1);
                                 }
                         } // end for(k)
                 }
 
             else // fast global weights?
                 {
                     float w_I=-1.0/N_filtered;
                     ncol=0;
                     q.tr[i][I2M]=q.tr[i][I2I]=0.0;
                     // Calculate amino acid frequencies fj[a] from weights wg[k]
                     for (k=0; k<N_in; k++)
                         if (in[k] && I[k][i]>0)
                             {
                                 ncol++;
                                 w_I+=wg[k];
                                 q.tr[i][I2M]+=wi[k];
                                 q.tr[i][I2I]+=wi[k]*(I[k][i]-1);
                             }
                     if (ncol>0)
                         {
                             if (w_I<0) Neff[i]=1.0;
                             else Neff[i] = Nlim - (Nlim-1.0)*fpow2(scale*w_I);
                             // fprintf(stderr,"I i=%3i ncol=%3i Neff_M=%5.2f Nlim=%5.2f w_I=%5.3f Neff_I=%5.2f\n",i,ncol,q.Neff_HMM,Nlim,w_I,Neff[i]);
                         }
                     else
                         {
                             Neff[i]=0.0;
                             q.tr[i][I2M]=-100000;
                             q.tr[i][I2I]=-100000;
                             continue;
                         }
                 }
 
             // Normalize and take log
             sum = q.tr[i][I2M]+q.tr[i][I2I];
             q.tr[i][I2M]=log2(q.tr[i][I2M]/sum);
             q.tr[i][I2I]=log2(q.tr[i][I2I]/sum);
 
         }
     // end loop through alignment columns i
     //////////////////////////////////////////////////////////////////////////////////////////////
 
     delete[](wi); wi = NULL;
     // delete n[][]
     for (j=1; j<=L; j++){
         delete[](n[j]); (n[j]) = NULL;
     }
     delete[](n); (n) = NULL;
 
     q.tr[0][I2M]=0;
     q.tr[0][I2I]=-100000;
     q.tr[L][I2M]=0;
     q.tr[L][I2I]=-100000;
     q.Neff_I[0]=99.999;
 
     // Assign Neff_I[i]
     for (i=1; i<=L; i++) // Calculate wi[k] at position i as well as Neff[i] and Neff[i]
         q.Neff_I[i]=Neff[i];
 
     delete[] Neff; Neff = NULL;
     return;
 
 } /* this is the end of Alignment::Transitions_from_I_state() */
 
 
 /////////////////////////////////////////////////////////////////////////////////////
 /**
  * @brief Calculate transitions q.tr[i][a] (a=DM,DD) with pos-specific subalignments
  */
 void 
 Alignment::Transitions_from_D_state(HMM& q, char* in)
 {
     // Calculate position-dependent weights wi[k] for each i.
     // For calculation of weights in column i use sub-alignment
     // over sequences which have a DELETE in column i
     // and over columns where none of these sequences has an end gap.
     // This is done by updating the arrays n[j][a] and rj[j] at each step i-1->i while letting i run from 1 to L.
     // n[j][a] = number of occurences of index a at column j of the subalignment,
     // => only columns with n[j][ENDGAP]=0 are contained in the subalignment!
     // If no sequences enter or leave the subalignment at the step i-1 -> i (i.e. change=0)
     // then the old values wi[k], Neff[i-1], and ncol are used for the new position i.
     // Index a can be an amino acid (0-19), ANY=20, GAP=21, or ENDGAP=22
 
     int k; // index of sequence
     int i,j; // position in alignment
     int a; // amino acid (0..19)
     int naa; // number of different amino acids
     int** n; // n[j][a] = number of seq's with some residue at column i AND a at position j
     //float wi[MAXSEQ]; // weight of sequence k in column i, calculated from subalignment i
     float *wi=NULL; // weight of sequence k in column i, calculated from subalignment i
     //float Neff[MAXRES]; // diversity of subalignment i 
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     float *Neff = new float[par.maxResLen]; // diversity of subalignment i
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     int nseqi=0; // number of sequences in subalignment i (for DEBUGGING)
     int ncol=0; // number of columns j that contribute to Neff[i]
     char change; // has the set of sequences in subalignment changed? 0:no 1:yes
     float fj[NAA+3]; // to calculate entropy
     float sum;
     float Nlim=0.0; // only for global weights
     float scale=0.0; // only for global weights
 
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     wi = new float[N_in+2]; /* FIXME: FS */
dafeef0b
     // Global weights?
     if (par.wg==1)
         {
             for (k=0; k<N_in; k++) wi[k]=wg[k];
             Nlim=fmax(10.0,q.Neff_HMM+1.0); // limiting Neff
             scale=log2((Nlim-q.Neff_HMM)/(Nlim-1.0)); // for calculating Neff for those seqs with dels at specific pos
         }
 
     // Initialization
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     n = new int*[L+2];
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     for (j=1; j<=L; j++) n[j]=new(int[NAA+3]);
     for (j=1; j<=L; j++)
         for (a=0; a<NAA+3; a++) n[j][a]=0;
 
 
 
     //////////////////////////////////////////////////////////////////////////////////////////////
     // Main loop through alignment columns
     for (i=1; i<=L; i++) // Calculate wi[k] at position i as well as Neff[i]
         {
             if (par.wg==0) // if local weights
                 {
                     change=0;
                     // Check all sequences k and update n[j][a] and ri[j] if necessary
                     for (k=0; k<N_in; k++)
                         {
                             if (!in[k]) continue;
                             if (X[k][i-1]!=GAP && X[k][i]==GAP)
                                 { // ... if sequence k was NOT included in i-1 and has to be included for column i
                                     change=1;
                                     nseqi++;
                                     for (int j=1; j<=L; j++) n[j][ (int)X[k][j]]++;
                                 }
                             else if (X[k][i-1]==GAP && X[k][i]!=GAP)
                                 { // ... if sequence k WAS included in i-1 and has to be thrown out for column i
                                     change=1;
                                     nseqi--;
                                     for (int j=1; j<=L; j++) n[j][ (int)X[k][j]]--;
                                 }
                         } //end for (k)
                     nseqs[i]=nseqi;
 
                     // If there is no sequence in subalignment j ...
                     if (nseqi==0)
                         {
                             ncol=0;
                             Neff[i]=0.0; // effective number of sequences = 0!
                             q.tr[i][D2M]=-100000;
                             q.tr[i][D2D]=-100000;
                             continue;
                         }
 
                     // If subalignment changed: update weights wi[k] and Neff[i]
                     if (change)
                         {
                             // Initialize weights and numbers of residues for subalignment i
                             ncol=0;
                             for (k=0; k<N_in; k++) wi[k]=0.0;
 
                             // sum wg[k][i] over all columns j and sequences k of subalignment
                             for (j=1; j<=L; j++)
                                 {
                                     if (n[j][ENDGAP]>MAXENDGAPFRAC*nseqi) continue;
                                     naa=0; for (a=0; a<20; a++) if(n[j][a]) naa++;
                                     if (naa==0) continue;
                                     ncol++;
                                     for (k=0; k<N_in; k++)
                                         {
                                             if (in[k] && X[k][i]==GAP && X[k][j]<ANY)
                                                 {
                                                     if (!n[j][ (int)X[k][j]]) {fprintf(stderr,"Error: Di=%i: n[%i][X[%i]]=0! (X[%i]=%i)\n",i,j,k,k,X[k][j]);}
                                                     wi[k]+=1.0/float(n[j][ (int)X[k][j] ]*naa);
                                                 }
                                         }
                                 }
 
                             // Check whether number of columns in subalignment is sufficient
                             if (ncol<NCOLMIN)
                                 // Take global weights
                                 for (k=0; k<N_in; k++)
                                     if(in[k] && X[k][i]==GAP) wi[k]=wg[k]; else wi[k]=0.0;
 
                             // Calculate Neff[i]
                             Neff[i]=0.0;
                             for (j=1; j<=L; j++)
                                 {
                                     if (n[j][ENDGAP]>MAXENDGAPFRAC*nseqi) continue;
                                     for (a=0; a<20; a++) fj[a]=0;
                                     for (k=0; k<N_in; k++)
                                         if (in[k] && X[k][i]==GAP && X[k][j]<ANY)
                                             fj[ (int)X[k][j] ]+=wi[k];
                                     NormalizeTo1(fj,NAA);
                                     for (a=0; a<20; a++)
                                         if (fj[a]>1E-10) Neff[i]-=fj[a]*fast_log2(fj[a]);
                                 }
                             if (ncol>0) Neff[i]=pow(2.0,Neff[i]/ncol); else Neff[i]=1.0;
 
                         }
 
                     else //no update was necessary; copy values for i-1
                         {
                             Neff[i]=Neff[i-1];
                         }
 
                     // Calculate transition probabilities from D state
                     q.tr[i][D2M]=q.tr[i][D2D]=0.0;
                     for (k=0; k<N_in; k++) //for all sequences
                         {
                             if (in[k] && X[k][i]==GAP) //current state is D
                                 {
                                     if (X[k][i+1]==GAP) //next state is D
                                         q.tr[i][D2D]+=wi[k];
                                     else if (X[k][i+1]<=ANY) //next state is M
                                         q.tr[i][D2M]+=wi[k];
                                 }
                         } // end for(k)
                 }
 
             else // fast global weights?
                 {
                     float w_D=-1.0/N_filtered;
                     ncol=0;
                     q.tr[i][D2M]=q.tr[i][D2D]=0.0;
                     // Calculate amino acid frequencies fj[a] from weights wg[k]
                     for (k=0; k<N_in; k++) //for all sequences
                         if (in[k] && X[k][i]==GAP) //current state is D
                             {
                                 ncol++;
                                 w_D+=wg[k];
                                 if (X[k][i+1]==GAP) //next state is D
                                     q.tr[i][D2D]+=wi[k];
                                 else if (X[k][i+1]<=ANY) //next state is M
                                     q.tr[i][D2M]+=wi[k];
                             }
                     if (ncol>0)
                         {
                             if (w_D<0) Neff[i]=1.0;
                             else Neff[i] = Nlim - (Nlim-1.0)*fpow2(scale*w_D);
                             // fprintf(stderr,"D i=%3i ncol=%3i Neff_M=%5.2f Nlim=%5.2f w_D=%5.3f Neff_D=%5.2f\n",i,ncol,q.Neff_HMM,Nlim,w_D,Neff[i]);
                         }
                     else
                         {
                             Neff[i]=0.0; // effective number of sequences = 0!
                             q.tr[i][D2M]=-100000;
                             q.tr[i][D2D]=-100000;
                             continue;
                         }
                 }
 
             // Normalize and take log
             sum = q.tr[i][D2M]+q.tr[i][D2D];
             q.tr[i][D2M]=log2(q.tr[i][D2M]/sum);
             q.tr[i][D2D]=log2(q.tr[i][D2D]/sum);
 
         }
     // end loop through alignment columns i
     //////////////////////////////////////////////////////////////////////////////////////////////
 
     q.tr[0][D2M]=0;
     q.tr[0][D2D]=-100000;
     q.Neff_D[0]=99.999;
 
     // Assign Neff_D[i]
     for (i=1; i<=L; i++)
         q.Neff_D[i]=Neff[i];
 
     delete[](wi); wi = NULL;/* FIXME: FS */
     // delete n[][]
     for (j=1; j<=L; j++){
         delete[](n[j]); (n[j]) = NULL;
     }
     delete[](n); (n) = NULL;
 
     delete[] Neff; Neff = NULL;
     return;
 
 } /* this is the end of Alignment::Transitions_from_D_state() */
 
 
 
 /////////////////////////////////////////////////////////////////////////////////////
 /**
  * @brief Write alignment without insert states (lower case) to alignment file?
  */
 void 
 Alignment::WriteWithoutInsertsToFile(char* alnfile)
 {
     if (v>=2) cout<<"Writing alignment to "<<alnfile<<"\n";
     FILE* alnf;
     if (!par.append) alnf = fopen(alnfile,"w"); else alnf = fopen(alnfile,"a");
     if (!alnf) OpenFileError(alnfile);
     // If alignment name is different from that of query: write name into commentary line
     if (strncmp(longname,sname[kfirst],DESCLEN-1)) fprintf(alnf,"#%s\n",longname);
     if (v>=2) cout<<"Writing alignment to "<<alnfile<<"\n";
     for (int k=0; k<N_in; k++)
         if (keep[k] || display[k]==KEEP_ALWAYS) // print if either in profile (keep[k]>0) or display is obligatory (display[k]==2)
             {
                 fprintf(alnf,">%s\n",sname[k]);
                 for (int i=1; i<=L; i++) fprintf(alnf,"%c",i2aa(X[k][i]));
                 fprintf(alnf,"\n");
             }
     fclose(alnf);
 }
 
 /////////////////////////////////////////////////////////////////////////////////////
 // Write stored,filtered sequences WITH insert states (lower case) to alignment file?
 /////////////////////////////////////////////////////////////////////////////////////
 void Alignment::WriteToFile(char* alnfile, const char format[])
 {
     FILE* alnf;
     if (!par.append) alnf = fopen(alnfile,"w"); else alnf = fopen(alnfile,"a");
     if (!alnf) OpenFileError(alnfile);
     // If alignment name is different from that of query: write name into commentary line
     if (strncmp(longname,sname[kfirst],DESCLEN-1)) fprintf(alnf,"#%s\n",longname);
     if (!format || !strcmp(format,"a3m"))
         {
             if (v>=2) cout<<"Writing A3M alignment to "<<alnfile<<"\n";
             for (int k=0; k<N_in; k++)
                 if (keep[k] || display[k]==KEEP_ALWAYS) // print if either in profile (keep[k]>0) or display obligatory (display[k]==2)
                     fprintf(alnf,">%s\n%s\n",sname[k],seq[k]+1);
         }
     else // PSI-BLAST format
         {
             if (v>=2) cout<<"Writing PSI-BLAST-formatted alignment to "<<alnfile<<"\n";
             for (int k=kfirst; k<N_in; k++) // skip sequences before kfirst!!
                 if (keep[k] || display[k]==KEEP_ALWAYS) // print if either in profile (keep[k]>0) or display obligatory (display[k]==2)
                     {
                         strcut(sname[k]);
                         fprintf(alnf,"%-20.20s ",sname[k]);
                         // for (int i=1; i<=L; i++) fprintf(alnf,"%c",i2aa(X[k][i]));
                         // fprintf(alnf,"\n");
                         char* ptr=seq[k];
                         for (; *ptr!='\0'; ptr++)
                             if (*ptr==45 || (*ptr>=65 && *ptr<=90)) fprintf(alnf,"%c",*ptr);
                         fprintf(alnf,"\n");
                     }
         }
 
     fclose(alnf);
 }
 
 
 
 /* 
  * FIXME: this function contains a reference to MAXSEQ & MAXCOL
  * however, this may not be accessed  (FS) 
  */
 /////////////////////////////////////////////////////////////////////////////////////
 /**
  * @brief Read a3m slave alignment of hit from file and merge into (query) master alignment
  */
 void 
 Alignment::MergeMasterSlave(Hit& hit, char ta3mfile[])
 {
  Alignment Tali;
  char* cur_seq = new(char[MAXCOL]); // Sequence currently read in
  int maxcol=MAXCOL;
  int l,ll; // position in unaligned template (T) sequence Tali.seq[l]
  int i; // counts match states in query (Q) HMM
  int j; // counts match states in T sequence Tali.seq[l]
  int h; // position in aligned T sequence cur_seq[h]
  int k; // sequence index
  char c; //
  printf("****************%s:%s:%d: did get into MergeMasterSlave\n", __FUNCTION__, __FILE__, __LINE__);
  if (v>=3) printf("Merging %s to query alignment\n",ta3mfile);
 
  // If par.append==1 do not print query alignment
  if (par.append) for (k=0; k<N_in; k++) keep[k]=display[k]=KEEP_NOT;
 
  // Read template alignment into Tali
  FILE* ta3mf=fopen(ta3mfile,"r");
  if (!ta3mf) OpenFileError(ta3mfile);
  Tali.Read(ta3mf,ta3mfile);
  fclose(ta3mf);
 
  // Filter Tali alignment
  Tali.Compress(ta3mfile);
  N_filtered = Tali.Filter(par.max_seqid,par.coverage,par.qid,par.qsc,par.Ndiff);
 
  // Record imatch[j]
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  int* imatch=new int[hit.j2+1];
dafeef0b
  int step = hit.nsteps;
  for (j=hit.j1; j<=hit.j2; j++)
  {
  // Advance to position of next T match state j
  while (hit.j[step]<j) step--;
  imatch[j] = hit.i[step];
 // printf("step=%-3i i=%-3i j=%-3i\n",step,imatch[j],j);
  }
 
  // Determine number of match states of Qali
  for (L=0,l=1; seq[kfirst][l]>'\0'; l++)
  if ((seq[kfirst][l]>='A' && seq[kfirst][l]<='Z') || seq[kfirst][l]=='-') L++;
 
  // For each sequence in T alignment: align to Qali
  for (k=0; k<Tali.N_in; k++)
  {
  if (!Tali.keep[k]) continue;
  if (N_in>=MAXSEQ)
  {
  fprintf(stderr,"WARNING in %s: maximum number of %i sequences exceeded while reading %s. Skipping all following sequences\n",program_name,MAXSEQ,ta3mfile);
  break;
  }
  cur_seq[0]=' '; // 0'th position not used
 
  // Add the hit.i1-1 left end gaps to aligned sequence
  for (h=1; h<hit.i1; h++) cur_seq[h]='-';
 
  // Advance to match state hit.j1 of Tali.seq[k]
  for (j=0, l=1; (c=Tali.seq[k][l])>'\0'; l++)
  if ((c>='A' && c<='Z') || c=='-') // match state at position l?
  if ((++j)==hit.j1) break; // yes: increment j. Reached hit,j1? yes: break
 
  if (j<hit.j1)
  {printf("Error: did not find %i match states in sequence %i of %s. Sequence:\n%s\n",hit.j1,k,Tali.name,Tali.seq[k]); throw 1;}
 
  // Write first match state to cur_seq
  int iprev=hit.i1; // index of previous query match state
  int lprev=l; // previous T match state in Tali.seq[k][l]
  cur_seq[h++] = Tali.seq[k][l]; // first column of alignment is Match-Match state
 
  // For each further match state j in alignment
  step = hit.nsteps;
  for (j=hit.j1+1; j<=hit.j2; j++)
  {
  // Advance to position of next T match state j
  i=imatch[j];
 
  // Advance to position of next T match state j
  while ((c=Tali.seq[k][++l])>'\0' && ((c>='a' && c<='z') || c=='.')) ;
 
  int di=i-iprev; // number of Match states in Q between T match state j-1 and j
  int dl=l-lprev; // 1 + number of inserted residues in T sequence between T match state j-1 and j
  if (di==1)
  {
  // One Q match state for one T match state (treated as special case for speed reasons)
  // i: i-1 i di=1
  // Q: XXXXXX.....XXXXXX
  // T: YYYYYYyyyyyYYYYYY
  // j: j-1 j
  // l: lprev l dl=6
 
  // Inserts in lower case
  for (ll=lprev+1; ll<l; ll++)
  if (Tali.seq[k][ll]!='-' && Tali.seq[k][ll]!='.') cur_seq[h++] = lwrchr(Tali.seq[k][ll]);
 
  // Template Match state -> upper case
  cur_seq[h++] = Tali.seq[k][ll];
  }
  else if (di==0)
  {
  // Gap in query: no Q match state for on T match state (special case for speed reasons)
  // i: i-1 i-1 di=0
  // Q: XXXXXX.....~~~XXX
  // T: YYYYYYyyyyyYYYYYY
  // j: j-1 j
  // l: lprev l dl=6
 
  // All T residues (including T match state) in lower case
  for (ll=lprev+1; ll<=l; ll++)
  if (Tali.seq[k][ll]!='-' && Tali.seq[k][ll]!='.') cur_seq[h++] = lwrchr(Tali.seq[k][ll]);
  }
  else if (di>=dl)
  {
  // More Match states in Q than Inserts in the T sequence
  // => half T inserts y left, half right-aligned in uc, gaps to fill up
  // Number of T insert residues to be left-aligned: (int)(dl/2)
  // i: iprev i di=7
  // Q: XXXXXXXXXXXXXXXXXX
  // T: YYYYYYYyyy-yyYYYYY
  // j: j-1 j
  // l: lprev l dl=6
 
  // Add left-bounded template residues
  for (ll=lprev+1; ll<=lprev+(int)(dl/2); ll++)
  cur_seq[h++]=uprchr(Tali.seq[k][ll]);
 
  // Add central gaps
  for (int gap=1; gap<=di-dl; gap++) cur_seq[h++]='-';
 
  // Add right-bounded residues
  for (; ll<=l; ll++)
  cur_seq[h++]=uprchr(Tali.seq[k][ll]);
  }
  else if (di<dl)
  {
  // Fewer Match states in Q than inserts in T sequence
  // => half of available space di for left- half for right-aligned T inserts, rest in lc
  // number of T inserts to be left-aligned in uc: (int)(di/2),
  // i: iprev i di=5
  // Q: XXXXXXXXX.XXXXXXX
  // T: YYYYYYYyyyyyYYYYY
  // j: j-1 j
  // l: lprev l dl=6
 
  // Add left-bounded template residues
  for (ll=lprev+1; ll<=lprev+(int)(di/2); ll++)
  cur_seq[h++]=uprchr(Tali.seq[k][ll]);
 
  // Add central inserts
  for (int ins=1; ins<=dl-di; ins++,ll++)
  if (Tali.seq[k][ll]!='-' && Tali.seq[k][ll]!='.') cur_seq[h++] = lwrchr(Tali.seq[k][ll]);
 
  // Add right-bounded residues
  for (; ll<=l; ll++)
  cur_seq[h++]=uprchr(Tali.seq[k][ll]);
  }
 // printf("i=%-3i j=%-3i l=%-3i cur_seq=%s\n",i,j,l,cur_seq);
 
  iprev=i; lprev=l;
  if (h>=maxcol-1000) // too few columns? Reserve double space
  {
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  char* new_seq=new char[2*maxcol];
dafeef0b
  strncpy(new_seq,cur_seq,maxcol); //////// check: maxcol-1 ????
  delete[](cur_seq); (cur_seq) = NULL;
  cur_seq=new_seq;
  maxcol*=2;
  }
  }
 
  // Add the remaining gaps '-' to the end of the template sequence
  for (i=hit.i2+1; i<=L; i++) cur_seq[h++]='-';
  cur_seq[h++]='\0';
 
  keep[N_in] = display[N_in] = KEEP_CONDITIONALLY;
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  seq[N_in]=new char[h];
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  if (!seq[N_in]) MemoryError("array for input sequences");
  strcpy(seq[N_in],cur_seq);
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  X[N_in]=new char[h];
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  if (!X[N_in]) MemoryError("array for input sequences");
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  I[N_in]=new short unsigned int[h];
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  if (!I[N_in]) MemoryError("array for input sequences");
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  sname[N_in]=new char[strlen(Tali.sname[k])+1];
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  if (!sname[N_in]) MemoryError("array for input sequences");
  strcpy(sname[N_in],Tali.sname[k]);
  N_in++;
 
 // printf("k=%-3i %s\n",k,Tali.seq[k]);
 // printf("Query %s\n",seq[kfirst]);
 // printf("k=%-3i %s\n\n",k,cur_seq);
 
  } // end for (k)
 
 // printf("N_in=%-5i HMM=%s with %i sequences\n",N_in,ta3mfile,N_filtered);
 
  delete[] cur_seq; cur_seq = NULL;
  delete[] imatch; imatch = NULL;
  delete[] ksort; ksort=NULL; // if ksort already existed it will be to short for merged alignment
  delete[] first; first=NULL; // if first already existed it will be to short for merged alignment
  delete[] last; last=NULL; // if last already existed it will be to short for merged alignment
 
 } /* this is the end of Alignment::MergeMasterSlave() */
 
 
 /////////////////////////////////////////////////////////////////////////////////////
 /**
  * @brief Add a sequence to Qali
  */
 void 
 Alignment::AddSequence(char Xk[], int Ik[])
 {
  int i; // position in query and target
  if (L<=0) InternalError("L is not set in AddSequence()");
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  X[N_in]=new char[L+2];
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  for (i=0; i<=L+1; i++) X[N_in][i]=Xk[i];
  if (Ik==NULL)
  for (i=0; i<=L+1; i++) I[N_in][i]=0;
  else
  for (i=0; i<=L+1; i++) I[N_in][i]=Ik[i];
  N_in++;
 }
 
 
 /////////////////////////////////////////////////////////////////////////////////////
 /**
  * @brief Determine matrix of position-specific weights w[k][i] for multiple alignment
  * Pos-specific weights are calculated like in "Amino_acid_frequencies_and_transitions_from_M_state()"
  */
 void 
 Alignment::GetPositionSpecificWeights(float* w[])
 {
  // Calculate position-dependent weights wi[k] for each i.
  // For calculation of weights in column i use sub-alignment
  // over sequences which have a *residue* in column i (no gap, no end gap)
  // and over columns where none of these sequences has an end gap.
  // This is done by updating the arrays n[j][a] at each step i-1->i while letting i run from 1 to L.
  // n[j][a] = number of occurences of amino acid a at column j of the subalignment,
  // => only columns with n[j][ENDGAP]=0 are contained in the subalignment!
  // If no sequences enter or leave the subalignment at the step i-1 -> i (i.e. change=0)
  // then the old values w[k][i] and ncol are used for the new position i.
  // Index a can be an amino acid (0-19), ANY=20, GAP=21, or ENDGAP=22
 
  char* in=keep; // to keep the code similar to Amino_acid_frequencies_and_transitions_from_M_state()
  int k; // index of sequence
  int i,j; // position in alignment
  int a; // amino acid (0..19)
  int naa; // number of different amino acids
  int** n; // n[j][a] = number of seq's with some residue at column i AND a at position j
  int nseqi=0; // number of sequences in subalignment i
  int ncol=0; // number of columns j that contribute to Neff[i]
  char change; // has the set of sequences in subalignment changed? 0:no 1:yes
 
 
  // Global weights?
  if (par.wg==1)
  {
  for (k=0; k<N_in; k++)
  for (i=1; i<=L; i++) w[k][i]=wg[k];
  }
  else
  {
 
  // Initialization
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  n = new int*[L+2];
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  for (j=1; j<=L; j++) n[j]=new(int[NAA+3]);
  for (j=1; j<=L; j++)
  for (a=0; a<NAA+3; a++) n[j][a]=0;
 
  //////////////////////////////////////////////////////////////////////////////////////////////
  // Main loop through alignment columns
  for (i=1; i<=L; i++) // Calculate w[k][i]
  {
  change=0;
  // Check all sequences k and update n[j][a] and ri[j] if necessary
  for (k=0; k<N_in; k++)
  {
  if (!in[k]) continue;
  if (X[k][i-1]>=ANY && X[k][i]<ANY)
  { // ... if sequence k was NOT included in i-1 and has to be included for column i
  change=1;
  nseqi++;
  for (int j=1; j<=L; j++) n[j][ (int)X[k][j]]++;
  }
  else if (X[k][i-1]<ANY && X[k][i]>=ANY)
  { // ... if sequence k WAS included in i-1 and has to be thrown out for column i
  change=1;
  nseqi--;
  for (int j=1; j<=L; j++) n[j][ (int)X[k][j]]--;
  }
  } //end for (k)
  nseqs[i]=nseqi;
 
  // If subalignment changed: update weights w[k][i] and Neff[i]
  if (change)
  {
  // Initialize weights and numbers of residues for subalignment i
  ncol=0;
  for (k=0; k<N_in; k++) w[k][i]=0.0;
 
  // sum wi[k] over all columns j and sequences k of subalignment
  for (j=1; j<=L; j++)
  {
  // do at least a fraction MAXENDGAPFRAC of sequences in subalignment contain an end gap in j?
  if (n[j][ENDGAP]>MAXENDGAPFRAC*nseqi) continue;
  naa=0; for (a=0; a<20; a++) if(n[j][a]) naa++;
  if (naa==0) continue;
  ncol++;
  for (k=0; k<N_in; k++)
  {
  if (in[k] && X[k][i]<ANY && X[k][j]<ANY)
  {
 // if (!n[j][ (int)X[k][j]]) {fprintf(stderr,"Error: Mi=%i: n[%i][X[%i]]=0! (X[%i]=%i)\n",i,j,k,k,X[k][j]);}
  w[k][i]+=1.0/float(n[j][ (int)X[k][j] ]*naa);
  }
  }
  }
 
  // Check whether number of columns in subalignment is sufficient
  if (ncol<NCOLMIN)
  // Take global weights
  for (k=0; k<N_in; k++)
  if(in[k]) {if(X[k][i]<ANY) w[k][i]=wg[k]; else w[k][i]=0.0;}
  }
  }
  // end loop through alignment columns i
  ///////////////////////////////////////////////////////////////////////
 
  // delete n[][]
  for (j=1; j<=L; j++){
  delete[](n[j]); (n[j]) = NULL;
  }
  delete[](n); (n) = NULL;
 
  }
  return;
 }
 
 #ifdef CLUSTALO
 /* @* Transfer
  *
  * take sequence data from Clustal and transfer it into
  * hhalign accessible information (structure/class)
  *
  * Note that hhalign does not see all sequences/profiles
  * but only sequences that are elements of the 2 profiles
  * to be aligned.
  *
  * References to the required sequences are passed into hhalign
  * through auxilliary pointers that are shallow copies of the
  * sequence/profile data available to Clustal.
  *
  * Re-allocating memory for these auxilliary pointers
  * would be desaterous, as it might detach the memory
  * seen by Clustal.
  */
 void 
 Alignment::Transfer(char **ppcProf, int iCnt){
 
     /* @<variables local to Transfer@> */
     int iLen; /* length of profile */
     int k; /* generic iterator */
 
     /* @<initialisation@> */
     N_in = iCnt;
     N_filtered = N_ss = 0;
     kss_dssp = ksa_dssp = kss_pred = kss_conf = -1;
     kfirst = 0;
     strcpy(longname, "unknown_long_seq_name");
     strcpy(name, "unknown_seq_name");
     strcpy(file, "unknown_file_name");
     n_display = iCnt;
 
     /* @<determine length of profile@>
        all sequences in profile should have same length,
        so only do it for 1st */
     for (iLen = 0; '\0' != ppcProf[0][iLen]; iLen++);
 
     /* @<allocate memory for sequences etc@> */
     for (k = 0; k < iCnt; k++){
 #define GOOD_MEASURE 1000 /* Temporary -- can be removed once rest in place */
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         I[k] = new short unsigned int[iLen+2+GOOD_MEASURE];
         X[k] = new char[iLen+2+GOOD_MEASURE];
         seq[k] = new char[iLen+2+GOOD_MEASURE];
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         seq[k][0] = ' ';
         seq[k][1] = '\0';
         if (NULL == ppcProf[k]){
             printf("%s:%d: Arena[%d]=NULL, cnt=%d\n", __FILE__, __LINE__, k, iCnt);
             throw -1;
         }
         strcat(seq[k], ppcProf[k]);
         keep[k] = KEEP_CONDITIONALLY;
         display[k] = KEEP_CONDITIONALLY;
         sname[k] = new(char[GOOD_MEASURE]);
         strcpy(sname[k], "unknown_sname");
     } /* (0 <= k < iCnt) */
     /* FIXME: Soeding always makes 1st sequence permanent */
     /*keep[0] = KEEP_ALWAYS;
       display[k] = KEEP_ALWAYS;*/
 #if 1
     /* Believe that the first and last positions are
        most important in stability of this algorithm.
        Must make sure that at least 2 sequences with
        residues in these positions are kept.
        Think any sequence will do, but better to keep
        the one with the longest 'contig'
     */
     int iSeq; /* sequence iterator */
     int iHeadLen = 0, iHeadID = -1; /* length & ID of longest head contig */
     int iTailLen = 0, iTailID = -1; /* length & ID of longest head contig */
     int iCont = -1;
     char *pcFind = NULL;
 
 #if 0
     printf("%s:%s:%d: NEW PROFILE (%d seq) ================\n",
            __FUNCTION__, __FILE__, __LINE__, iCnt);
 #endif
     for (iSeq = 0; iSeq < iCnt; iSeq++){
 #if 0
         printf("%s:%s:%d: consider seq %d ------------------\n",
                __FUNCTION__, __FILE__, __LINE__, iSeq);
 #endif
         pcFind = strchr(&seq[iSeq][1], '-');
         if (NULL == pcFind){
             /* no gap at all in this sequences, spans entire profile */
             iHeadID = iTailID = iSeq;
             iHeadLen = iTailLen = iLen;
             break;
         }
         iCont = (int)(pcFind - &seq[iSeq][1]);
         if (iCont > iHeadLen){
             iHeadLen = iCont;
             iHeadID  = iSeq;
         }
         pcFind = strrchr(seq[iSeq], '-');
         iCont = iLen - (int)(pcFind - seq[iSeq]);
         if (iCont > iTailLen){
             iTailLen = iCont;
             iTailID  = iSeq;
         }
 
 #if 0
         printf("%s:%s:%d: seq %3d: len = %d(%d) %s\n",
                __FUNCTION__, __FILE__, __LINE__, iSeq, iCont, iLen, seq[iSeq]);
 #endif
     } /* 0 <= iSeq < iCnt */
 #if 0
     printf("%s:%s:%d: seq %d is winner with head contig of %d, seq %d tail contig of %d\n"
            , __FUNCTION__, __FILE__, __LINE__, iHeadID, iHeadLen, iTailID, iTailLen);
 #endif
     if ( (-1 == iHeadID) || (-1 == iTailID) ){
         printf("%s:%s:%d: profile has no leading and/or trailing residues (h=%d:t=%d:#=%d)\n",
                __FUNCTION__, __FILE__, __LINE__, iHeadID, iTailID, iCnt);
     }
     else{
         keep[iHeadID] = KEEP_ALWAYS;
         keep[iTailID] = KEEP_ALWAYS;
     }
 #endif
     /* @= */
     return;
 
 } /* this is the end of Transfer() */
 #endif
 
 #ifdef CLUSTALO
 /* @* Alignment::ClobberGlobal (eg: qali)
  *
  * Note: originally hhalign() was stand-alone code,
  * there are a couple of GLOBAL (!) variables,
  * which would have been destroyed on exit.
  * However, now there is no 'exit' from hhalign(),
  * and on re-entry the global variable must be clean again.
  */
 void 
 Alignment::ClobberGlobal(void){
 
  /* @<essentials@>
  these are essential to re-set (as some of them are used as flags) */
  for(int k=0; k<N_in; k++)
  {
  delete[] sname[k]; sname[k] = NULL;
  delete[] seq[k]; seq[k] = NULL;
  delete[] X[k]; X[k] = NULL;
  delete[] I[k]; I[k] = NULL;
  }
  delete[] nres; nres = NULL;
  delete[] first; first = NULL;
  delete[] last; last = NULL;
  delete[] ksort; ksort = NULL;
  N_in = N_filtered = n_display = 0;
  L = 0;
  kss_dssp = ksa_dssp = kss_pred = kss_conf = kfirst = -1;
 
  /* @<re-set but keep memory@>
  do not free the memory but re-set content */
  longname[0] = '\0'; //delete[] longname; longname = NULL;
  keep[0] = '\0'; //delete[] keep; keep = NULL;
  display[0] = '\0'; //delete[] display; display = NULL;
  wg[0] = 0; //delete[] wg; wg = NULL;
  nseqs[0] = 0; //delete[] nseqs; nseqs = NULL;
  name[0]='\0';
  fam[0]='\0';
  file[0]='\0';
  //delete[] sname; sname = NULL;
  //delete[] seq; seq = NULL;
  //delete[] X; X = NULL;
  //delete[] I; I = NULL;
  //delete[] l; l = NULL;
 
  /* @= */
  return;
 }
 #endif