--- /dev/null
+/* -*- 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: hhhmm-C.h 224 2011-03-23 12:13:33Z fabian $
+ */
+
+
+// hhhmm.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.
+#endif
+
+// #ifndef WNLIB
+// #define WNLIB
+// #include "wnconj.h" // Will Naylor's wnlib for optimization in C
+// #endif
+
+//////////////////////////////////////////////////////////////////////////////
+//// Class HMM
+//////////////////////////////////////////////////////////////////////////////
+
+//////////////////////////////////////////////////////////////////////////////
+// Object constructor
+//////////////////////////////////////////////////////////////////////////////
+HMM::HMM(int maxseqdis, int maxres)
+{
+ sname = new char*[maxseqdis]; // names of stored sequences
+ for (int i = 0; i < maxseqdis; i++){ sname[i] = NULL;}
+ seq = new char*[maxseqdis]; // residues of stored sequences (first at pos 1!)
+ for (int i = 0; i < maxseqdis; i++){ seq[i] = NULL;}
+ Neff_M = new float[maxres]; // Neff_M[i] = diversity of subalignment of seqs that have residue in col i
+ Neff_I = new float[maxres]; // Neff_I[i] = diversity of subalignment of seqs that have insert in col i
+ Neff_D = new float[maxres]; // Neff_D[i] = diversity of subalignment of seqs that have delete in col i
+ longname = new char[DESCLEN]; // Full name of first sequence of original alignment (NAME field)
+ ss_dssp = new char[maxres]; // secondary structure determined by dssp 0:- 1:H 2:E 3:C 4:S 5:T 6:G 7:B
+ sa_dssp = new char[maxres]; // solvent accessibility state determined by dssp 0:- 1:A (absolutely buried) 2:B 3:C 4:D 5:E (exposed)
+ ss_pred = new char[maxres]; // predicted secondary structure 0:- 1:H 2:E 3:C
+ ss_conf = new char[maxres]; // confidence value of prediction 0:- 1:0 ... 10:9
+ Xcons = NULL; // create only when needed: consensus sequence in internal representation (A=0 R=1 N=2 D=3 ...)
+ l = new int[maxres]; // l[i] = pos. of j'th match state in aligment
+ /* FS introduced sentinel, NULL terminates loop in destructor, FS, r221->222 */
+ f = new float*[maxres+1]; f[maxres] = NULL; // f[i][a] = prob of finding amino acid a in column i WITHOUT pseudocounts
+ g = new float*[maxres+1]; g[maxres] = NULL; // f[i][a] = prob of finding amino acid a in column i WITH pseudocounts
+ p = new float*[maxres+1]; p[maxres] = NULL; // p[i][a] = prob of finding amino acid a in column i WITH OPTIMUM pseudocounts
+ tr = new float*[maxres+1]; tr[maxres] = NULL; // log2 of transition probabilities M2M M2I M2D I2M I2I D2M D2D M2M_GAPOPEN GAPOPEN GAPEXTD
+// tr_lin = new float*[maxres]; // linear transition probabilities M2M M2I M2D I2M I2I D2M D2D M2M_GAPOPEN GAPOPEN GAPEXTD
+ for (int i=0; i<maxres; i++) {f[i]=new(float[NAA+3]);}
+ for (int i=0; i<maxres; i++) {g[i]=new(float[NAA]);}
+ for (int i=0; i<maxres; i++) {p[i]=new(float[NAA]);}
+ for (int i=0; i<maxres; i++) {tr[i]=new(float[NTRANS]);}
+// for (int i=0; i<maxres; i++) tr_lin[i]=new(float[NTRANS]);
+ L=0;
+ Neff_HMM=0;
+ n_display=N_in=N_filtered=0;
+ nss_dssp=nsa_dssp=nss_pred=nss_conf=nfirst=ncons=-1;
+// lamda_hash.New(37,0.0); // Set size and NULL element for hash
+// mu_hash.New(37,0.0); // Set size and NULL element for hash
+ lamda=0.0; mu=0.0;
+ name[0]=longname[0]=fam[0]='\0';
+ trans_lin=0; // transition probs in log space
+}
+
+
+//////////////////////////////////////////////////////////////////////////////
+// Object destructor
+//////////////////////////////////////////////////////////////////////////////
+HMM::~HMM()
+{
+ //Delete name and seq matrices
+ if (NULL != sname){
+ for (int k=0; (k < n_display) && (NULL != sname[k]); k++){
+ delete[] sname[k]; sname[k] = NULL;
+ }
+ delete[] sname; sname = NULL;
+ }
+ if (NULL != seq){
+ for (int k=0; (k < n_display) && (NULL != seq[k]); k++){
+ delete[] seq[k]; seq[k] = NULL;
+ }
+ delete[] seq; seq = NULL;
+ }
+ delete[] Neff_M; Neff_M = NULL;
+ delete[] Neff_D; Neff_D = NULL;
+ delete[] Neff_I; Neff_I = NULL;
+ delete[] longname; longname = NULL;
+ delete[] ss_dssp; ss_dssp = NULL;
+ delete[] sa_dssp; sa_dssp = NULL;
+ delete[] ss_pred; ss_pred = NULL;
+ delete[] ss_conf; ss_conf = NULL;
+ delete[] Xcons; Xcons = NULL;
+ delete[] l; l = NULL;
+ for (int i=0; i</*MAXRES*/par.maxResLen; i++){
+ if (f[i]){
+ delete[] f[i]; f[i] = NULL;
+ }
+ else break;
+ }
+ for (int i=0; i</*MAXRES*/par.maxResLen; i++){
+ if (g[i]){
+ delete[] g[i]; g[i] = NULL;
+ }
+ else break;
+ }
+ for (int i=0; i</*MAXRES*/par.maxResLen; i++){
+ if (p[i]){
+ delete[] p[i]; p[i] = NULL;
+ }
+ else break;
+ }
+ for (int i=0; i</*MAXRES*/par.maxResLen; i++){
+ if (tr[i]){
+ delete[] tr[i]; tr[i] = NULL;
+ }
+ else break;
+ }
+ // for (int i=0; i</*MAXRES*/par.maxResLen; i++) if (tr_lin[i]) delete[] tr_lin[i]; else break;
+ delete[] f; f = NULL;
+ delete[] g; g = NULL;
+ delete[] p; p = NULL;
+ delete[] tr; tr = NULL;
+// delete[] tr_lin;
+}
+
+//////////////////////////////////////////////////////////////////////////////
+// Deep-copy constructor
+//////////////////////////////////////////////////////////////////////////////
+HMM& HMM::operator=(HMM& q)
+{
+ L=q.L;
+ for (int i=0; i<=L+1; ++i)
+ {
+ for (int a=0; a<NAA; ++a)
+ {
+ f[i][a]=q.f[i][a];
+ g[i][a]=q.g[i][a];
+ p[i][a]=q.p[i][a];
+ }
+ for (int a=0; a<NTRANS; ++a)
+ tr[i][a]=q.tr[i][a];
+ ss_dssp[i]=q.ss_dssp[i];
+ sa_dssp[i]=q.sa_dssp[i];
+ ss_pred[i]=q.ss_pred[i];
+ ss_conf[i]=q.ss_conf[i];
+ l[i]=q.l[i];
+ }
+ if (q.Xcons)
+ for (int i=0; i<=L+1; ++i)
+ Xcons[i] =q.Xcons[i];
+
+ n_display=q.n_display;
+ for (int k=0; k<n_display; k++) {
+ sname[k]=new(char[strlen(q.sname[k])+1]);
+ if (!sname[k]) MemoryError("array of names for sequences to display");
+ strcpy(sname[k],q.sname[k]);
+ }
+ for (int k=0; k<n_display; k++) {
+ seq[k]=new(char[strlen(q.seq[k])+1]);
+ if (!seq[k]) MemoryError("array of names for sequences to display");
+ strcpy(seq[k],q.seq[k]);
+ }
+ ncons=q.ncons;
+ nfirst=q.nfirst;
+ nss_dssp=q.nss_dssp;
+ nsa_dssp=q.nsa_dssp;
+ nss_pred=q.nss_pred;
+ nss_conf=q.nss_conf;
+
+ for (int i=0; i<=L+1; ++i) Neff_M[i]=q.Neff_M[i];
+ for (int i=0; i<=L+1; ++i) Neff_I[i]=q.Neff_I[i];
+ for (int i=0; i<=L+1; ++i) Neff_D[i]=q.Neff_D[i];
+ Neff_HMM=q.Neff_HMM;
+
+ strcpy(longname,q.longname);
+ strcpy(name,q.name);
+ strcpy(fam,q.fam);
+ strcpy(sfam,q.sfam);
+ strcpy(fold,q.fold);
+ strcpy(cl,q.cl);
+ strcpy(file,q.file);
+
+ lamda=q.lamda;
+ mu=q.mu;
+
+ for (int a=0; a<NAA; ++a) pav[a]=q.pav[a];
+ N_in=q.N_in;
+ N_filtered=q.N_filtered;
+ trans_lin=q.trans_lin;
+ return (HMM&) (*this);
+}
+
+
+///////////////////////////////////////////////////////////////////////////////
+/**
+ * @brief Read an HMM from an HHsearch .hhm file; return 0 at end of file
+ */
+int
+HMM::Read(FILE* dbf, char* path)
+{
+ char line[LINELEN]=""; // input line
+ char str3[8]="",str4[8]=""; // first 3 and 4 letters of input line
+ char* ptr; // pointer for string manipulation
+ int i=0; // index for match state (first=1)
+ int a; // amino acid index
+ static int warn=0;
+
+ trans_lin=0;
+ L=0;
+ Neff_HMM=0;
+ n_display=N_in=N_filtered=0;
+ nss_dssp=nsa_dssp=nss_pred=nss_conf=nfirst=ncons=-1;
+ lamda=mu=0.0;
+ trans_lin=0; // transition probs in log space
+ name[0]=longname[0]=fam[0]='\0';
+ //If at the end of while-loop L is still 0 then we have reached end of db file
+
+ //Do not delete name and seq vectors because their adresses are transferred to hitlist as part of a hit!!
+
+ while (fgetline(line,LINELEN-1,dbf) && !(line[0]=='/' && line[1]=='/'))
+ {
+
+ if (strscn(line)==NULL) continue; // skip lines that contain only white space
+ substr(str3,line,0,2); // copy the first three characters into str3
+ substr(str4,line,0,3); // copy the first four characters into str4
+
+ if (!strncmp("HH",line,2)) continue;
+
+ if (!strcmp("NAME",str4))
+ {
+ ptr=strscn(line+4); //advance to first non-white-space character
+ if (ptr)
+ {
+ strncpy(longname,ptr,DESCLEN-1); //copy full name to longname
+ longname[DESCLEN-1]='\0';
+ strncpy(name,ptr,NAMELEN-1); //copy longname to name...
+ strcut(name); //...cut after first word...
+ }
+ else
+ {
+ strcpy(longname,"undefined");
+ strcpy(name,"undefined");
+ }
+ if (v>=4) cout<<"Reading in HMM "<<name<<":\n";
+ }
+
+ else if (!strcmp("FAM",str3))
+ {
+ ptr=strscn(line+3); //advance to first non-white-space character
+ if (ptr) strncpy(fam,ptr,IDLEN-1); else strcpy(fam,""); //copy family name to basename
+ ScopID(cl,fold,sfam,fam); //get scop classification from basename (e.g. a.1.2.3.4)
+ }
+
+ else if (!strcmp("FILE",str4))
+ {
+ if (path) strncpy(file,path,NAMELEN-1); else *file='\0'; // copy path to file variable
+ ptr=strscn(line+4); //advance to first non-white-space character
+ if (ptr)
+ strncat(file,ptr,NAMELEN-1-strlen(file)); // append file name read from file to path
+ else strcat(file,"*");
+ }
+
+ else if (!strcmp("LENG",str4))
+ {
+ ptr=line+4;
+ L=strint(ptr); //read next integer (number of match states)
+ }
+ else if (!strcmp("FILT",str4) || !strcmp("NSEQ",str4))
+ {
+ ptr=line+4;
+ N_filtered=strint(ptr); //read next integer: number of sequences after filtering
+ N_in=strint(ptr); //read next integer: number of sequences in alignment
+ }
+
+ else if (!strcmp("NEFF",str4) || !strcmp("NAA",str3)) sscanf(line+6,"%f",&Neff_HMM);
+
+ else if (!strcmp("EVD",str3))
+ {
+// char key[IDLEN];
+ sscanf(line+6,"%f %f",&lamda,&mu);
+// sscanf(line+22,"%s",key);
+// lamda_hash.Add(key,lamda);
+// mu_hash.Add(key,mu);
+ }
+
+ else if (!strcmp("DESC",str4)) continue;
+ else if (!strcmp("COM",str3)) continue;
+ else if (!strcmp("DATE",str4)) continue;
+
+ /////////////////////////////////////////////////////////////////////////////////////
+ // Read template sequences that should get displayed in output alignments
+ else if (!strcmp("SEQ",str3))
+ {
+ //char cur_seq[MAXCOL]=""; //Sequence currently read in
+ char *cur_seq = new(char[par.maxColCnt]); //Sequence currently read in
+ int k; // sequence index; start with -1; after reading name of n'th sequence-> k=n
+ int h; // index for character in input line
+ int l=1; // index of character in sequence seq[k]
+ int i=1; // index of match states in ss_dssp[i] and ss_pred[i] sequence
+ int n_seq=0; // number of sequences to be displayed EXCLUDING ss sequences
+ cur_seq[0]='-'; // overwrite '\0' character at beginning to be able to do strcpy(*,cur_seq)
+ k=-1;
+ while (fgetline(line,LINELEN-1,dbf) && line[0]!='#')
+ {
+ if (v>=4) cout<<"Read from file:"<<line<<"\n"; //DEBUG
+ if (line[0]=='>') //line contains sequence name
+ {
+ if (k>=MAXSEQDIS-1) //maximum number of allowable sequences exceeded
+ {while (fgetline(line,LINELEN-1,dbf) && line[0]!='#'); break;}
+ k++;
+ if (!strncmp(line,">ss_dssp",8)) nss_dssp=k;
+ else if (!strncmp(line,">sa_dssp",8)) nsa_dssp=k;
+ else if (!strncmp(line,">ss_pred",8)) nss_pred=k;
+ else if (!strncmp(line,">ss_conf",8)) nss_conf=k;
+ else if (!strncmp(line,">Cons-",6) || !strncmp(line,">Consensus",10)) ncons=k;
+ else
+ {
+ if (nfirst==-1) nfirst=k;
+ if (n_seq>=par.nseqdis)
+ {while (fgetline(line,LINELEN-1,dbf) && line[0]!='#'); k--; break;}
+ n_seq++;
+ }
+
+ //If this is not the first sequence then store residues of previous sequence
+ if (k>0) {
+ seq[k-1]=new(char[strlen(cur_seq)+1]);
+ if (!seq[k-1]) MemoryError("array of sequences to display");
+ strcpy(seq[k-1],cur_seq);
+ }
+
+ // store sequence name
+ strcut(line+1); //find next white-space character and overwrite it with end-of-string character
+ sname[k] = new (char[strlen(line+1)+1]); //+1 for terminating '\0'
+ if (!sname[k]) MemoryError("array of names for sequences to display");
+ strcpy(sname[k],line+1); //store sequence name in **name
+ l=1; i=1;
+ }
+ else //line contains sequence residues
+ {
+ if (k==-1)
+ {
+ cerr<<endl<<"WARNING: Ignoring following line while reading HMM"<<name<<":\n\'"<<line<<"\'\n";
+ continue;
+ }
+
+ h=0; //counts characters in current line
+
+ // Check whether all characters are correct; store into cur_seq
+ if (k==nss_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 && line[h]!='.')
+ {
+ char c=ss2ss(line[h]);
+ cur_seq[l]=c;
+ if (c!='.' && !(c>='a' && c<='z')) ss_dssp[i++]=ss2i(c);
+ l++;
+ }
+ else if (v && ss2i(line[h])==-2)
+ cerr<<endl<<"WARNING: invalid symbol \'"<<line[h]<<"\' at pos. "<<h<<" in line '"<<line<<"' of HMM "<<name<<"\n";
+ h++;
+ }
+ }
+ if (k==nsa_dssp) // lines with dssp secondary solvent accessibility (- A B C D E)
+ {
+ while (h<LINELEN && line[h]>'\0' && l</*MAXCOL*/par.maxColCnt-1)
+ {
+ if (sa2i(line[h])>=0)
+ {
+ char c=line[h];
+ cur_seq[l]=c;
+ if (c!='.' && !(c>='a' && c<='z')) sa_dssp[i++]=sa2i(c);
+ l++;
+ }
+ else if (v && sa2i(line[h])==-2)
+ cerr<<endl<<"WARNING: invalid symbol \'"<<line[h]<<"\' at pos. "<<h<<" in line '"<<line<<"' of HMM "<<name<<"\n";
+ h++;
+ }
+ }
+ else if (k==nss_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 && line[h]!='.')
+ {
+ char c=ss2ss(line[h]);
+ cur_seq[l]=c;
+ if (c!='.' && !(c>='a' && c<='z')) ss_pred[i++]=ss2i(c);
+ l++;
+ }
+ else if (v && ss2i(line[h])==-2)
+ cerr<<endl<<"WARNING: invalid symbol \'"<<line[h]<<"\' at pos. "<<h<<" in line '"<<line<<"' of HMM "<<name<<"\n";
+ h++;
+ }
+ }
+ else if (k==nss_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]>='0' && line[h]<='9'))
+ {
+ cur_seq[l]=line[h];
+ ss_conf[l]=cf2i(line[h]);
+ l++;
+ }
+ else if (v && cf2i(line[h])==-2)
+ cerr<<endl<<"WARNING: invalid symbol \'"<<line[h]<<"\' at pos. "<<h<<" in line '"<<line<<"' of HMM "<<name<<"\n";
+ h++;
+ }
+ }
+ else // normal line containing residues
+ {
+ while (h<LINELEN && line[h]>'\0' && l</*MAXCOL*/par.maxColCnt-1)
+ {
+ if (aa2i(line[h])>=0 && line[h]!='.') // ignore '.' and 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 '"<<line<<"' of HMM "<<name<<"\n";
+ h++;
+ }
+ }
+ cur_seq[l]='\0'; //Ensure that cur_seq ends with a '\0' character
+
+ } //end else
+ } //while(getline)
+ //If this is not the first sequence some residues have already been read in
+ if (k>=0) {
+ seq[k]=new(char[strlen(cur_seq)+1]);
+ if (!seq[k]) MemoryError("array of sequences to display");
+ strcpy(seq[k],cur_seq);
+ }
+ n_display=k+1;
+
+ // DEBUG
+ if (v>=4)
+ {
+ printf("nss_dssp=%i nsa_dssp=%i nss_pred=%i nss_conf=%i nfirst=%i\n",nss_dssp,nsa_dssp,nss_pred,nss_conf,nfirst);
+ for (k=0; k<n_display; k++)
+ {
+ int j;
+ cout<<">"<<sname[k]<<"(k="<<k<<")\n";
+ if (k==nss_dssp) {for (j=1; j<=L; j++) cout<<char(i2ss(ss_dssp[j]));}
+ else if (k==nsa_dssp) {for (j=1; j<=L; j++) cout<<char(i2sa(sa_dssp[j]));}
+ else if (k==nss_pred) {for (j=1; j<=L; j++) cout<<char(i2ss(ss_pred[j]));}
+ else if (k==nss_conf) {for (j=1; j<=L; j++) cout<<int(ss_conf[j]-1);}
+ else {for (j=1; j<=L; j++) cout<<seq[k][j];}
+ cout<<"\n";
+ }
+ }
+
+ } //end if("SEQ")
+
+ /////////////////////////////////////////////////////////////////////////////////////
+ // Read average amino acid frequencies for HMM
+ else if (!strcmp("FREQ",str4))
+ {
+ fprintf(stderr,"Error: hhm file has obsolete format.\n");
+ fprintf(stderr,"Please use hhmake version > 1.1 to generate hhm files.\n");
+ exit(1);
+ }
+
+ else if (!strcmp("AVER",str4)) {} // AVER line scrapped
+ else if (!strcmp("NULL",str4))
+ {
+ ptr=line+4;
+ for (a=0; a<20 && ptr; ++a)
+ //s2[a]: transform amino acids Sorted by alphabet -> internal numbers for amino acids
+ pb[s2a[a]] = (float) fpow2(float(-strinta(ptr))/HMMSCALE);
+ if (!ptr) return Warning(dbf,line,name);
+ if (v>=4)
+ {
+ printf("\nNULL ");
+ for (a=0; a<20; ++a) printf("%5.1f ",100.*pb[s2a[a]]);
+ printf("\n");
+ }
+ }
+
+ /////////////////////////////////////////////////////////////////////////////////////
+ // Read transition probabilities from start state
+ else if (!strcmp("HMM",str3))
+ {
+ fgetline(line,LINELEN-1,dbf); // Skip line with amino acid labels
+ fgetline(line,LINELEN-1,dbf); // Skip line with transition labels
+ ptr=line;
+ for (a=0; a<=D2D && ptr; ++a)
+ tr[0][a] = float(-strinta(ptr))/HMMSCALE; //store transition probabilites as log2 values
+ // strinta returns next integer in string and puts ptr to first char
+ // after the integer. Returns -99999 if '*' is found.
+ // ptr is set to 0 if no integer is found after ptr.
+ Neff_M[0] = float(strinta(ptr))/HMMSCALE; // Read eff. number of sequences with M->? transition
+ Neff_I[0] = float(strinta(ptr))/HMMSCALE; // Read eff. number of sequences with I->? transition
+ Neff_D[0] = float(strinta(ptr))/HMMSCALE; // Read eff. number of sequences with D->? transition
+ if (!ptr) return Warning(dbf,line,name);
+
+ /////////////////////////////////////////////////////////////////////////////////////
+ // Read columns of HMM
+ int next_i=0; // index of next column
+ while (fgetline(line,LINELEN-2,dbf) && !(line[0]=='/' && line[1]=='/') && line[0]!='#')
+ {
+ if (strscn(line)==NULL) continue; // skip lines that contain only white space
+
+ // Read in AA probabilities
+ ptr=line+1;
+ int prev_i = next_i;
+ next_i = strint(ptr); ++i;
+ if (v && next_i!=prev_i+1)
+ if (++warn<=5)
+ {
+ cerr<<endl<<"WARNING: in HMM "<<name<<" state "<<prev_i<<" is followed by state "<<next_i<<"\n";
+ if (warn==5) cerr<<endl<<"WARNING: further warnings while reading HMMs will be suppressed.\n";
+ }
+ if (i>L)
+ {
+ cerr<<endl<<"WARNING: in HMM "<<name<<" there are more columns than the stated length "<<L<<". Skipping HMM\n";
+ return 2;
+ }
+ if (i>=/*MAXRES*/par.maxResLen-2)
+ {
+ fgetline(line,LINELEN-1,dbf); // Skip line
+ continue;
+ }
+
+ for (a=0; a<20 && ptr; ++a)
+// f[i][s2a[a]] = (float)pow(2.,float(-strinta(ptr))/HMMSCALE);
+ f[i][s2a[a]] = fpow2(float(-strinta(ptr))/HMMSCALE); // speed-up ~5 s for 10000 SCOP domains
+
+ //s2a[a]: transform amino acids Sorted by alphabet -> internal numbers for amino acids
+ l[i]=strint(ptr);
+ if (!ptr) return Warning(dbf,line,name);
+ if (v>=4)
+ {
+ printf("%s",line);
+ printf("%6i ",i);
+ for (a=0; a<20; ++a) printf("%5.1f ",100*f[i][s2a[a]]);
+ printf("%5i",l[i]);
+ printf("\n");
+ }
+
+ // Read transition probabilities
+ fgetline(line,LINELEN-1,dbf); // Skip line with amino acid labels
+ if (line[0]!=' ' && line[0]!='\t') return Warning(dbf,line,name);
+ ptr=line;
+ for (a=0; a<=D2D && ptr; ++a)
+ tr[i][a] = float(-strinta(ptr))/HMMSCALE; //store transition prob's as log2-values
+ Neff_M[i] = float(strinta(ptr))/HMMSCALE; // Read eff. number of sequences with M->? transition
+ Neff_I[i] = float(strinta(ptr))/HMMSCALE; // Read eff. number of sequences with I->? transition
+ Neff_D[i] = float(strinta(ptr))/HMMSCALE; // Read eff. number of sequences with D->? transition
+ if (!ptr) return Warning(dbf,line,name);
+ if (v>=4)
+ {
+ printf(" ");
+ for (a=0; a<=D2D; ++a) printf("%5.1f ",100*fpow2(tr[i][a]));
+ printf("%5.1f %5.1f %5.1f \n",Neff_M[i],Neff_I[i],Neff_D[i]);
+ }
+ }
+ if (line[0]=='/' && line[1]=='/') break;
+ }
+ else if (v) cerr<<endl<<"WARNING: Ignoring line\n\'"<<line<<"\'\nin HMM "<<name<<"\n";
+
+ } //while(getline)
+
+ if (L==0) return 0; //End of db file -> stop reading in
+
+ // Set coefficients of EVD (= 0.0 if not calibrated for these parameters)
+// lamda = lamda_hash.Show(par.Key());
+// mu = mu_hash.Show(par.Key());
+ if (lamda && v>=3) printf("HMM %s is already calibrated: lamda=%-5.3f, mu=%-5.2f\n",name,lamda,mu);
+
+ if (v && i!=L) cerr<<endl<<"Warning: in HMM "<<name<<" there are only "<<i<<" columns while the stated length is "<<L<<"\n";
+ if (v && i>/*MAXRES*/par.maxResLen-2) {i=/*MAXRES*/par.maxResLen-2; cerr<<endl<<"WARNING: maximum number "<</*MAXRES*/par.maxResLen-2<<" of residues exceeded while reading HMM "<<name<<"\n";}
+ if (v && !i) cerr<<endl<<"WARNING: HMM "<<name<<" contains no match states. Check the alignment that gave rise to this HMM.\n";
+ if (v>=2) cout<<"Read in HMM "<<name<<" with "<<L<<" match states and effective number of sequences = "<<Neff_HMM<<"\n";
+ L = i;
+
+ // Set emission probabilities of zero'th (begin) state and L+1st (end) state to background probabilities
+ for (a=0; a<20; ++a) f[0][a]=f[L+1][a]=pb[a];
+ Neff_M[L+1]=1.0f;
+ Neff_I[L+1]=Neff_D[L+1]=0.0f;
+
+ return 1; //return status: ok
+
+} /* this is the end of HMM::Read() */
+
+
+/////////////////////////////////////////////////////////////////////////////////////
+/**
+ * @brief Read an HMM from a HMMer .hmm file; return 0 at end of file
+ */
+int
+HMM::ReadHMMer(FILE* dbf, char* filestr)
+{
+ char line[LINELEN]=""; // input line
+ char desc[DESCLEN]=""; // description of family
+ char str4[5]=""; // first 4 letters of input line
+ char* ptr; // pointer for string manipulation
+ int i=0; // index for match state (first=1)
+ int a; // amino acid index
+ char dssp=0; // 1 if a consensus SS has been found in the transition prob lines
+ char annot=0; // 1 if at least one annotation character in insert lines is ne '-' or ' '
+ int k=0; // index for seq[k]
+ static char ignore_hmmer_cal = 0;
+ char* annotchr; // consensus amino acids in ASCII format, or, in HMMER format, the reference annotation character in insert line
+ //annotchr = new char[MAXRES]; // consensus amino acids in ASCII format, or, in HMMER format, the reference annotation character in insert line
+ annotchr = new char[par.maxResLen]; // consensus amino acids in ASCII format, or, in HMMER format, the reference annotation character in insert line
+ static int warn=0;
+ int iAlpha = 20; /* size of alphabet, default is protein = 20 */
+ double dAlphaInv = 1.00 / (double)(iAlpha); /* weight of AA */
+
+ trans_lin=0;
+ L=0;
+ Neff_HMM=0;
+ n_display=N_in=N_filtered=0;
+ nss_dssp=nsa_dssp=nss_pred=nss_conf=nfirst=ncons=-1;
+ lamda=mu=0.0;
+ trans_lin=0; // transition probs in log space
+ name[0]=longname[0]=desc[0]=fam[0]='\0';
+ //If at the end of while-loop L is still 0 then we have reached end of db file
+
+ // Do not delete name and seq vectors because their adresses are transferred to hitlist as part of a hit!!
+
+ while (fgetline(line,LINELEN-1,dbf) && !(line[0]=='/' && line[1]=='/'))
+ {
+
+ if (strscn(line)==NULL) continue; // skip lines that contain only white space
+ if (!strncmp("HMMER",line,5)) continue;
+
+ substr(str4,line,0,3); // copy the first four characters into str4
+
+ if (!strcmp("NAME",str4) && name[0]=='\0')
+ {
+ ptr=strscn(line+4); // advance to first non-white-space character
+ strncpy(name,ptr,NAMELEN-1); // copy full name to name
+ strcut(name); // ...cut after first word...
+ if (v>=4) cout<<"Reading in HMM "<<name<<":\n";
+ }
+
+ else if (!strcmp("ACC ",str4))
+ {
+ ptr=strscn(line+4); // advance to first non-white-space character
+ strncpy(longname,ptr,DESCLEN-1); // copy Accession id to longname...
+ }
+
+ else if (!strcmp("DESC",str4))
+ {
+ ptr=strscn(line+4); // advance to first non-white-space character
+ if (ptr)
+ {
+ strncpy(desc,ptr,DESCLEN-1); // copy description to name...
+ desc[DESCLEN-1]='\0';
+ strcut(ptr); // ...cut after first word...
+ }
+ if (!ptr || ptr[1]!='.' || strchr(ptr+3,'.')==NULL) strcpy(fam,""); else strcpy(fam,ptr); // could not find two '.' in name?
+ }
+
+ else if (!strcmp("LENG",str4))
+ {
+ ptr=line+4;
+ L=strint(ptr); //read next integer (number of match states)
+ }
+
+ else if (!strcmp("ALPH",str4)) {
+
+ ptr=strscn(line+4);
+
+ if (0 == strcmp(ptr, "Amino")){
+ iAlpha = 20;
+ }
+ else if (0 == strcmp(ptr, "Nucleic")){
+ iAlpha = 4;
+ printf("%s:%s:%d: WARNING: HMM reading does not work for DNA/RNA\n",
+ __FUNCTION__, __FILE__, __LINE__);
+ }
+ else {
+ return Warning(dbf,line,name);
+ }
+ dAlphaInv = 1.00 / (double)(iAlpha);
+ //continue;
+ }
+ else if (!strcmp("RF ",str4)) continue;
+ else if (!strcmp("CS ",str4)) continue;
+ else if (!strcmp("MAP ",str4)) continue;
+ else if (!strcmp("COM ",str4)) continue;
+ else if (!strcmp("NSEQ",str4))
+ {
+ ptr=line+4;
+ N_in=N_filtered=strint(ptr); //read next integer: number of sequences after filtering
+ }
+
+ else if (!strcmp("DATE",str4)) continue;
+ else if (!strncmp("CKSUM ",line,5)) continue;
+ else if (!strcmp("GA ",str4)) continue;
+ else if (!strcmp("TC ",str4)) continue;
+ else if (!strcmp("NC ",str4)) continue;
+
+ else if (!strncmp("SADSS",line,5))
+ {
+ if (nsa_dssp<0)
+ {
+ nsa_dssp=k++;
+ seq[nsa_dssp] = new(char[/*MAXRES*/par.maxResLen+2]);
+ sname[nsa_dssp] = new(char[15]);
+ strcpy(seq[nsa_dssp]," ");
+ strcpy(sname[nsa_dssp],"sa_dssp");
+
+ }
+ ptr=strscn(line+5);
+ if (ptr)
+ {
+ strcut(ptr);
+ if (strlen(seq[nsa_dssp])+strlen(ptr)>=(unsigned)(/*MAXRES*/par.maxResLen))
+ printf("\nWARNING: HMM %s has SADSS records with more than %i residues.\n",name,/*MAXRES*/par.maxResLen);
+ else strcat(seq[nsa_dssp],ptr);
+ }
+ }
+
+ else if (!strncmp("SSPRD",line,5))
+ {
+ if (nss_pred<0)
+ {
+ nss_pred=k++;
+ seq[nss_pred] = new(char[/*MAXRES*/par.maxResLen+2]);
+ sname[nss_pred] = new(char[15]);
+ strcpy(seq[nss_pred]," ");
+ strcpy(sname[nss_pred],"ss_pred");
+
+ }
+ ptr=strscn(line+5);
+ if (ptr)
+ {
+ strcut(ptr);
+ if (strlen(seq[nss_pred])+strlen(ptr)>=(unsigned)(/*MAXRES*/par.maxResLen))
+ printf("\nWARNING: HMM %s has SSPRD records with more than %i residues.\n",name,/*MAXRES*/par.maxResLen);
+ else strcat(seq[nss_pred],ptr);
+ }
+ }
+
+ else if (!strncmp("SSCON",line,5))
+ {
+ if (nss_conf<0)
+ {
+ nss_conf=k++;
+ seq[nss_conf] = new(char[/*MAXRES*/par.maxResLen+2]);
+ sname[nss_conf] = new(char[15]);
+ strcpy(seq[nss_conf]," ");
+ strcpy(sname[nss_conf],"ss_conf");
+ }
+ ptr=strscn(line+5);
+ if (ptr)
+ {
+ strcut(ptr);
+ if (strlen(seq[nss_conf])+strlen(ptr)>=(unsigned)(/*MAXRES*/par.maxResLen))
+ printf("\nWARNING: HMM %s has SSPRD records with more than %i residues.\n",name,/*MAXRES*/par.maxResLen);
+ else strcat(seq[nss_conf],ptr);
+ }
+ }
+
+ else if (!strncmp("SSCIT",line,5)) continue;
+ else if (!strcmp("XT ",str4)) continue;
+ else if (!strcmp("NULT",str4)) continue;
+
+ else if (!strcmp("NULE",str4))
+ {
+ ptr=line+4;
+ for (a=0; (a < iAlpha) && ptr; ++a){
+ /* FIXME: FS introduced alphabet size (was '20')
+ and dAlphaInv (was '0.05' = 1/20) */
+ //s2a[a]: transform amino acids Sorted by alphabet -> internal numbers for amino acids
+ pb[s2a[a]] = (float) dAlphaInv * fpow2(float(strinta(ptr,-99999))/HMMSCALE); /* dAlphaInv */
+ }
+ for (a = iAlpha; a < 20; a++){
+ pb[s2a[a]] = 0.0;
+ }
+ if (!ptr) return Warning(dbf,line,name);
+ if (v>=4)
+ {
+ printf("\nNULL ");
+ for (a=0; a<iAlpha; ++a) { /* FIXME: FS introduced iAlpha, was '20' */
+ printf("%5.1f ",100.*pb[s2a[a]]);
+ }
+ printf("\n");
+ }
+ }
+
+ else if (!strcmp("EVD ",str4))
+ {
+ char* ptr=line+4;
+ ptr = strscn(ptr);
+ sscanf(ptr,"%f",&lamda);
+ ptr = strscn(ptr);
+ sscanf(ptr,"%f",&mu);
+ if (lamda<0)
+ {
+ if (v>=2 && ignore_hmmer_cal==0)
+ cerr<<endl<<"Warning: some HMMs have been calibrated with HMMER's 'hmmcalibrate'. These calibrations will be ignored\n";
+ ignore_hmmer_cal=1;
+ mu = lamda = 0.0;
+ }
+ }
+
+ /////////////////////////////////////////////////////////////////////////////////////
+ // Read transition probabilities from start state
+ else if (!strncmp("HMM",line,3))
+ {
+ fgetline(line,LINELEN-1,dbf); // Skip line with amino acid labels
+ fgetline(line,LINELEN-1,dbf); // Skip line with transition labels
+ ptr=line;
+ for (a=0; a<=M2D && ptr; ++a)
+ tr[0][a] = float(strinta(ptr,-99999))/HMMSCALE; //store transition probabilites as log2 values
+ // strinta returns next integer in string and puts ptr to first char
+ // after the integer. Returns -99999 if '*' is found.
+ // ptr is set to 0 if no integer is found after ptr.
+ tr[0][I2M] = tr[0][D2M] = 0.0;
+ tr[0][I2I] = tr[0][D2D] = -99999.0;
+ if (!ptr) return Warning(dbf,line,name);
+ if (v>=4)
+ {
+ printf(" ");
+ for (a=0; a<=D2D && ptr; ++a) printf("%5.1f ",100*fpow2(tr[i][a]));
+ printf("\n");
+ }
+
+ // Prepare to store DSSP states (if there are none, delete afterwards)
+ nss_dssp=k++;
+ seq[nss_dssp] = new(char[/*MAXRES*/par.maxResLen+2]);
+ sname[nss_dssp] = new(char[15]);
+ strcpy(sname[nss_dssp],"ss_dssp");
+
+ /////////////////////////////////////////////////////////////////////////////////////
+ // Read columns of HMM
+ int next_i=0; // index of next column
+ while (fgetline(line,LINELEN-1,dbf) && !(line[0]=='/' && line[1]=='/') && line[0]!='#')
+ {
+ if (strscn(line)==NULL) continue; // skip lines that contain only white space
+
+ // Read in AA probabilities
+ ptr=line;
+ int prev_i = next_i;
+ next_i = strint(ptr); ++i;
+ if (v && next_i!=prev_i+1)
+ if (++warn<5)
+ {
+ cerr<<endl<<"WARNING: in HMM "<<name<<" state "<<prev_i<<" is followed by state "<<next_i<<"\n";
+ if (warn==5) cerr<<endl<<"WARNING: further warnings while reading HMMs will be suppressed.\n";
+ }
+ if (i>L)
+ {
+ cerr<<endl<<"Error: in HMM "<<name<<" there are more columns than the stated length "<<L<<"\n";
+ return 2;
+ }
+ if (i>L && v)
+ cerr<<endl<<"WARNING: in HMM "<<name<<" there are more columns than the stated length "<<L<<"\n";
+ if (i>=/*MAXRES*/par.maxResLen-2)
+ {
+ fgetline(line,LINELEN-1,dbf); // Skip two lines
+ fgetline(line,LINELEN-1,dbf);
+ continue;
+ }
+
+ for (a=0; (a<iAlpha) && ptr; ++a){ /* FIXME: FS introduced iAlpha, was '20' */
+ f[i][s2a[a]] = (float) pb[s2a[a]]*fpow2(float(strinta(ptr,-99999))/HMMSCALE);
+ //s2a[a]: transform amino acids Sorted by alphabet -> internal numbers for amino acids
+ }
+ for (a = iAlpha; a < 20; a++){
+ f[i][s2a[a]] = 0.0;
+ }
+ if (!ptr) return Warning(dbf,line,name);
+ if (v>=4)
+ {
+ printf("%6i ",i);
+ for (a=0; a<iAlpha; ++a) { /* FIXME: FS introduced iAlpha, was '20' */
+ printf("%5.1f ",100*f[i][s2a[a]]);
+ }
+ printf("\n");
+ }
+
+ // Read insert emission line
+ fgetline(line,LINELEN-1,dbf);
+ ptr = strscn(line);
+ if (!ptr) return Warning(dbf,line,name);
+ annotchr[i]=uprchr(*ptr);
+ if (*ptr!='-' && *ptr!=' ') annot=1;
+
+ // Read annotation character and seven transition probabilities
+ fgetline(line,LINELEN-1,dbf);
+ ptr = strscn(line);
+ switch (*ptr)
+ {
+ case 'H':
+ ss_dssp[i]=1;
+ seq[nss_dssp][i]=*ptr;
+ dssp=1;
+ break;
+ case 'E':
+ ss_dssp[i]=2;
+ seq[nss_dssp][i]=*ptr;
+ dssp=1;
+ break;
+ case 'C':
+ ss_dssp[i]=3;
+ seq[nss_dssp][i]=*ptr;
+ dssp=1;
+ break;
+ case 'S':
+ ss_dssp[i]=4;
+ seq[nss_dssp][i]=*ptr;
+ dssp=1;
+ break;
+ case 'T':
+ ss_dssp[i]=5;
+ seq[nss_dssp][i]=*ptr;
+ dssp=1;
+ break;
+ case 'G':
+ ss_dssp[i]=6;
+ seq[nss_dssp][i]=*ptr;
+ dssp=1;
+ break;
+ case 'B':
+ ss_dssp[i]=7;
+ seq[nss_dssp][i]=*ptr;
+ dssp=1;
+ break;
+ case 'I':
+ dssp=1;
+ case '~':
+ ss_dssp[i]=3;
+ seq[nss_dssp][i]=*ptr;
+ break;
+ case '-':
+ default:
+ ss_dssp[i]=0;
+ seq[nss_dssp][i]=*ptr;
+ break;
+
+ }
+
+ ptr+=2;
+ for (a=0; a<=D2D && ptr; ++a)
+ tr[i][a] = float(strinta(ptr,-99999))/HMMSCALE; //store transition prob's as log2-values
+ if (!ptr) return Warning(dbf,line,name);
+ if (v>=4)
+ {
+ printf(" ");
+ for (a=0; a<=D2D; ++a) printf("%5.1f ",100*fpow2(tr[i][a]));
+ printf("\n");
+ }
+ }
+
+ if (line[0]=='/' && line[1]=='/') break;
+
+ } /* strncmp("HMM") */
+
+ } //while(getline)
+
+ if (L==0) return 0; //End of db file -> stop reading in
+
+ // Set coefficients of EVD (= 0.0 if not calibrated for these parameters)
+ // lamda = lamda_hash.Show(par.Key());
+ // mu = mu_hash.Show(par.Key());
+ if (lamda && v>=2) printf("HMM %s is already calibrated: lamda=%-5.3f, mu=%-5.2f\n",name,lamda,mu);
+
+ if (v && i!=L) cerr<<endl<<"Warning: in HMM "<<name<<" there are only "<<i<<" columns while the stated length is "<<L<<"\n";
+ if (v && i>=/*MAXRES*/par.maxResLen-2) {i=/*MAXRES*/par.maxResLen-2; cerr<<endl<<"WARNING: maximum number "<</*MAXRES*/par.maxResLen-2<<" of residues exceeded while reading HMM "<<name<<"\n";}
+ if (v && !i) cerr<<endl<<"WARNING: HMM "<<name<<" contains no match states. Check the alignment that gave rise to this HMM.\n";
+ L = i;
+
+ if (strlen(longname)>0) strcat(longname," ");
+ strncat(longname,name,DESCLEN-strlen(longname)-1); // longname = ACC NAME DESC
+ if (strlen(name)>0) strcat(longname," ");
+ strncat(longname,desc,DESCLEN-strlen(longname)-1);
+ longname[DESCLEN-1]='\0';
+ ScopID(cl,fold,sfam,fam);// get scop classification from basename (e.g. a.1.2.3.4)
+ RemoveExtension(file,filestr); // copy name of dbfile without extension into 'file'
+
+ // Secondary structure
+ if (!dssp)
+ {
+ // remove dssp sequence
+ // memory that had been allocated in case ss_dssp was given needs to be freed
+ delete[] seq[nss_dssp]; seq[nss_dssp] = NULL;
+ // memory that had been allocated in case ss_dssp was given needs to be freed
+ delete[] sname[nss_dssp]; sname[nss_dssp] = NULL;
+ nss_dssp=-1;
+ k--;
+ }
+ if (nss_pred>=0)
+ {
+ for (i=1; i<=L; ++i) ss_pred[i] = ss2i(seq[nss_pred][i]);
+ if (nss_conf>=0)
+ for (i=1; i<=L; ++i) ss_conf[i] = cf2i(seq[nss_conf][i]);
+ else
+ for (i=1; i<=L; ++i) ss_conf[i] = 5;
+ }
+
+ // Copy query (first sequence) and consensus residues?
+ if (par.showcons)
+ {
+ sname[k]=new(char[10]);
+ strcpy(sname[k],"Consensus");
+ sname[k+1]=new(char[strlen(longname)+1]);
+ strcpy(sname[k+1],longname);
+ seq[k]=new(char[L+2]);
+ seq[k][0]=' ';
+ seq[k][L+1]='\0';
+ seq[k+1]=new(char[L+2]);
+ seq[k+1][0]=' ';
+ seq[k+1][L+1]='\0';
+ for (i=1; i<=L; ++i)
+ {
+ float pmax=0.0;
+ int amax=0;
+ for (a=0; a<NAA; ++a)
+ if (f[i][a]>pmax) {amax=a; pmax=f[i][a];}
+ if (pmax>0.6) seq[k][i]=i2aa(amax);
+ else if (pmax>0.4) seq[k][i]=lwrchr(i2aa(amax));
+ else seq[k][i]='x';
+ seq[k+1][i]=i2aa(amax);
+ }
+ ncons=k++; // nfirst is set later!
+ }
+ else
+ {
+ sname[k]=new(char[strlen(longname)+1]);
+ /* FIXME valgrind says bytes get lost here during hmm iteration --
+ fixed in HMM::ClobberGlobal(), I (FS) think */
+ strcpy(sname[k],longname);
+ seq[k]=new(char[L+2]);
+ seq[k][0]=' ';
+ seq[k][L+1]='\0';
+ }
+
+ if (annot) // read in some annotation characters?
+ {
+ annotchr[0]=' ';
+ annotchr[L+1]='\0';
+ strcpy(seq[k],annotchr); // overwrite the consensus sequence with the annotation characters
+ }
+ else if (!par.showcons) // we have not yet calculated the consensus, but we need it now as query (first sequence)
+ {
+ /* FIXME: FS set ncons=k
+ don't understand why it is not set but seem to need it */
+ ncons = k;
+ for (i=1; i<=L; ++i)
+ {
+ float pmax=0.0;
+ int amax=0;
+ for (a=0; a<NAA; ++a)
+ if (f[i][a]>pmax) {amax=a; pmax=f[i][a];}
+ seq[k][i]=i2aa(amax);
+ }
+ }
+// printf("%i query name=%s seq=%s\n",n,sname[n],seq[n]);
+ nfirst=k++;
+
+ n_display=k;
+
+ // Calculate overall Neff_HMM
+ Neff_HMM=0;
+ for (i=1; i<=L; ++i)
+ {
+ float S=0.0;
+ for (a=0; a<iAlpha; ++a) { /* FIXME: FS introduced iAlpha, was '20' */
+ if (f[i][a]>1E-10) S-=f[i][a]*fast_log2(f[i][a]);
+ }
+ Neff_HMM+=(float) fpow2(S);
+ }
+ Neff_HMM/=L;
+ for (i=0; i<=L; ++i) Neff_M[i] = Neff_I[i] = Neff_D[i] = 10.0; // to add only little additional pseudocounts!
+ if (v>=2)
+ cout<<"Read in HMM "<<name<<" with "<<L<<" match states and effective number of sequences = "<<Neff_HMM<<"\n";
+
+ // Set emission probabilities of zero'th (begin) state and L+1st (end) state to background probabilities
+ for (a=0; a<iAlpha; ++a) { /* FIXME: FS introduced iAlpha, was '20' */
+ f[0][a]=f[L+1][a]=pb[a];
+ }
+ delete[] annotchr; annotchr = NULL;
+
+ return 1; //return status: ok
+
+} /* this is the end of HMM::ReadHMMer() */
+
+
+
+/////////////////////////////////////////////////////////////////////////////////////
+/**
+ * @brief Read an HMM from a HMMER3 .hmm file; return 0 at end of file
+ */
+int
+HMM::ReadHMMer3(FILE* dbf, char* filestr)
+{
+ char line[LINELEN]=""; // input line
+ char desc[DESCLEN]=""; // description of family
+ char str4[5]=""; // first 4 letters of input line
+ char* ptr; // pointer for string manipulation
+ int i=0; // index for match state (first=1)
+ int a; // amino acid index
+ char dssp=0; // 1 if a consensus SS has been found in the transition prob lines
+ char annot=0; // 1 if at least one annotation character in insert lines is ne '-' or ' '
+ int k=0; // index for seq[k]
+ char* annotchr; // consensus amino acids in ASCII format, or, in HMMER format, the reference annotation character in insert line
+ //annotchr = new char[MAXRES]; // consensus amino acids in ASCII format, or, in HMMER format, the reference annotation character in insert line
+ annotchr = new char[par.maxResLen]; // consensus amino acids in ASCII format, or, in HMMER format, the reference annotation character in insert line
+ static int warn=0;
+ int iAlpha = 20; /* size of alphabet, default is protein = 20 */
+ double dAlphaInv = 1.00 / (double)(iAlpha); /* weight of AA */
+
+ trans_lin=0;
+ L=0;
+ Neff_HMM=0;
+ n_seqs=n_display=N_in=N_filtered=0;
+ nss_dssp=nsa_dssp=nss_pred=nss_conf=nfirst=ncons=-1;
+ lamda=mu=0.0;
+ trans_lin=0; // transition probs in log space
+ name[0]=longname[0]=desc[0]=fam[0]='\0';
+ //If at the end of while-loop L is still 0 then we have reached end of db file
+
+ // Do not delete name and seq vectors because their adresses are transferred to hitlist as part of a hit!!
+
+
+ while (fgetline(line,LINELEN-1,dbf) && !(line[0]=='/' && line[1]=='/'))
+ {
+
+ if (strscn(line)==NULL) continue; // skip lines that contain only white space
+ if (!strncmp("HMMER",line,5)) continue;
+
+ substr(str4,line,0,3); // copy the first four characters into str4
+
+ if (!strcmp("NAME",str4) && name[0]=='\0')
+ {
+ ptr=strscn(line+4); // advance to first non-white-space character
+ strncpy(name,ptr,NAMELEN-1); // copy full name to name
+ strcut(name); // ...cut after first word...
+ if (v>=4) cout<<"Reading in HMM "<<name<<":\n";
+ }
+
+ else if (!strcmp("ACC ",str4))
+ {
+ ptr=strscn(line+4); // advance to first non-white-space character
+ strncpy(longname,ptr,DESCLEN-1); // copy Accession id to longname...
+ }
+
+ else if (!strcmp("DESC",str4))
+ {
+ ptr=strscn(line+4); // advance to first non-white-space character
+ if (ptr)
+ {
+ strncpy(desc,ptr,DESCLEN-1); // copy description to name...
+ desc[DESCLEN-1]='\0';
+ strcut(ptr); // ...cut after first word...
+ }
+ if (!ptr || ptr[1]!='.' || strchr(ptr+3,'.')==NULL) strcpy(fam,""); else strcpy(fam,ptr); // could not find two '.' in name?
+ }
+
+ else if (!strcmp("LENG",str4))
+ {
+ ptr=line+4;
+ L=strint(ptr); //read next integer (number of match states)
+ }
+
+ else if (!strcmp("ALPH",str4)) {
+
+ ptr=strscn(line+4);
+
+ if (0 == strcmp(ptr, "amino")){
+ iAlpha = 20;
+ }
+ else if (0 == strcmp(ptr, "Nucleic")){
+ iAlpha = 4;
+ printf("%s:%s:%d: WARNING: HMM reading does not work for DNA/RNA\n",
+ __FUNCTION__, __FILE__, __LINE__);
+ }
+ else {
+ return Warning(dbf,line,name);
+ }
+ dAlphaInv = 1.00 / (double)(iAlpha);
+ //continue;
+ }
+ else if (!strcmp("RF ",str4)) continue;
+ else if (!strcmp("CS ",str4)) continue;
+ else if (!strcmp("MAP ",str4)) continue;
+ else if (!strcmp("COM ",str4)) continue;
+ else if (!strcmp("NSEQ",str4))
+ {
+ ptr=line+4;
+ N_in=N_filtered=strint(ptr); //read next integer: number of sequences after filtering
+ }
+
+ else if (!strcmp("DATE",str4)) continue;
+ else if (!strncmp("CKSUM ",line,5)) continue;
+ else if (!strcmp("GA ",str4)) continue;
+ else if (!strcmp("TC ",str4)) continue;
+ else if (!strcmp("NC ",str4)) continue;
+
+ //////////////////////////////////////////////////////////////////////////////////////////////////////
+ // Still needed???
+
+ else if (!strncmp("SADSS",line,5))
+ {
+ if (nsa_dssp<0)
+ {
+ nsa_dssp=k++;
+ seq[nsa_dssp] = new(char[/*MAXRES*/par.maxResLen+2]);
+ sname[nsa_dssp] = new(char[15]);
+ strcpy(seq[nsa_dssp]," ");
+ strcpy(sname[nsa_dssp],"sa_dssp");
+
+ }
+ ptr=strscn(line+5);
+ if (ptr)
+ {
+ strcut(ptr);
+ if (strlen(seq[nsa_dssp])+strlen(ptr)>=(unsigned)(/*MAXRES*/par.maxResLen))
+ printf("\nWARNING: HMM %s has SADSS records with more than %i residues.\n",name,/*MAXRES*/par.maxResLen);
+ else strcat(seq[nsa_dssp],ptr);
+ }
+ }
+
+ else if (!strncmp("SSPRD",line,5))
+ {
+ if (nss_pred<0)
+ {
+ nss_pred=k++;
+ seq[nss_pred] = new(char[/*MAXRES*/par.maxResLen+2]);
+ sname[nss_pred] = new(char[15]);
+ strcpy(seq[nss_pred]," ");
+ strcpy(sname[nss_pred],"ss_pred");
+
+ }
+ ptr=strscn(line+5);
+ if (ptr)
+ {
+ strcut(ptr);
+ if (strlen(seq[nss_pred])+strlen(ptr)>=(unsigned)(/*MAXRES*/par.maxResLen))
+ printf("\nWARNING: HMM %s has SSPRD records with more than %i residues.\n",name,/*MAXRES*/par.maxResLen);
+ else strcat(seq[nss_pred],ptr);
+ }
+ }
+
+ else if (!strncmp("SSCON",line,5))
+ {
+ if (nss_conf<0)
+ {
+ nss_conf=k++;
+ seq[nss_conf] = new(char[/*MAXRES*/par.maxResLen+2]);
+ sname[nss_conf] = new(char[15]);
+ strcpy(seq[nss_conf]," ");
+ strcpy(sname[nss_conf],"ss_conf");
+ }
+ ptr=strscn(line+5);
+ if (ptr)
+ {
+ strcut(ptr);
+ if (strlen(seq[nss_conf])+strlen(ptr)>=(unsigned)(/*MAXRES*/par.maxResLen))
+ printf("\nWARNING: HMM %s has SSPRD records with more than %i residues.\n",name,/*MAXRES*/par.maxResLen);
+ else strcat(seq[nss_conf],ptr);
+ }
+ }
+
+ else if (!strncmp("SSCIT",line,5)) continue;
+ else if (!strcmp("XT ",str4)) continue;
+ //////////////////////////////////////////////////////////////////////////////////////////////////////
+ else if (!strncmp("STATS LOCAL",line,11)) continue;
+
+ else if (!strcmp("EFFN",str4))
+ {
+ ptr=line+4;
+ float effn = strflt(ptr);
+ // Calculate Neff_HMM by using f(x) = ax^0.1 + bx^0.5 + cx + d (fitted with scop25 dataset)
+ Neff_HMM = -1.403534 * pow(effn, 0.1) + 4.428118 * pow(effn, 0.5) - 0.2885410 * effn - 1.108568;
+ }
+
+ /////////////////////////////////////////////////////////////////////////////////////
+ // Read transition probabilities from start state
+ else if (!strncmp("HMM",line,3))
+ {
+ fgetline(line,LINELEN-1,dbf); // Skip line with amino acid labels
+ fgetline(line,LINELEN-1,dbf); // Skip line with transition labels
+ ptr=strscn(line);
+
+ if (!strncmp("COMPO",ptr,5))
+ {
+ ptr=ptr+5;
+ for (a=0; a<20 && ptr; ++a)
+ //s2a[a]: transform amino acids Sorted by alphabet -> internal numbers for amino acids
+ pb[s2a[a]] = (float) exp(-1.0*strflta(ptr,99999));
+ if (!ptr) return Warning(dbf,line,name);
+ if (v>=4)
+ {
+ printf("\nNULL ");
+ for (a=0; a<20; ++a) printf("%6.3g ",100.*pb[s2a[a]]);
+ printf("\n");
+ }
+ fgetline(line,LINELEN-1,dbf); // Read next line
+ }
+
+ fgetline(line,LINELEN-1,dbf); // Skip line with 0-states insert probabilities
+
+ ptr = strscn(line);
+ for (a=0; a<=D2D && ptr; ++a)
+ tr[0][a] = log2((float) exp(-1.0*strflta(ptr,99999))); //store transition probabilites as log2 values
+ // strinta returns next integer in string and puts ptr to first char
+ // after the integer. Returns -99999 if '*' is found.
+ // ptr is set to 0 if no integer is found after ptr.
+ if (!ptr) return Warning(dbf,line,name);
+ if (v>=4)
+ {
+ printf(" ");
+ for (a=0; a<=D2D && ptr; ++a) printf("%6.3g ",100*fpow2(tr[i][a]));
+ printf("\n");
+ }
+
+ // Prepare to store DSSP states (if there are none, delete afterwards)
+ nss_dssp=k++;
+ seq[nss_dssp] = new(char[/*MAXRES*/par.maxResLen+2]);
+ sname[nss_dssp] = new(char[15]);
+ strcpy(sname[nss_dssp],"ss_dssp");
+
+ /////////////////////////////////////////////////////////////////////////////////////
+ // Read columns of HMM
+ int next_i=0; // index of next column
+ while (fgetline(line,LINELEN-1,dbf) && !(line[0]=='/' && line[1]=='/') && line[0]!='#')
+ {
+ if (strscn(line)==NULL) continue; // skip lines that contain only white space
+
+ // Read in AA probabilities
+ ptr=line;
+ int prev_i = next_i;
+ next_i = strint(ptr); ++i;
+ if (v && next_i!=prev_i+1)
+ if (++warn<5)
+ {
+ cerr<<endl<<"WARNING: in HMM "<<name<<" state "<<prev_i<<" is followed by state "<<next_i<<"\n";
+ if (warn==5) cerr<<endl<<"WARNING: further warnings while reading HMMs will be suppressed.\n";
+ }
+ if (i>L)
+ {
+ cerr<<endl<<"Error: in HMM "<<name<<" there are more columns than the stated length "<<L<<"\n";
+ return 2;
+ }
+ if (i>L && v)
+ cerr<<endl<<"WARNING: in HMM "<<name<<" there are more columns than the stated length "<<L<<"\n";
+ if (i>=/*MAXRES*/par.maxResLen-2)
+ {
+ fgetline(line,LINELEN-1,dbf); // Skip two lines
+ fgetline(line,LINELEN-1,dbf);
+ continue;
+ }
+
+ for (a=0; a<iAlpha && ptr; ++a){ /* FIXME: FS introduced iAlpha, was '20' */
+ f[i][s2a[a]] = (float) exp(-1.0*strflta(ptr,99999));
+ //s2a[a]: transform amino acids Sorted by alphabet -> internal numbers for amino acids
+ }
+ for (a = iAlpha; a < 20; a++){
+ f[i][s2a[a]] = 0.0;
+ }
+ if (!ptr) return Warning(dbf,line,name);
+ if (v>=4)
+ {
+ printf("%6i ",i);
+ for (a=0; a<iAlpha; ++a) printf("%6.3g ",100*f[i][s2a[a]]);
+ printf("\n");
+ }
+
+ // Ignore MAP annotation
+ ptr = strscn(line); //find next word
+ ptr = strscn_ws(line); // ignore word
+
+ // Read RF and CS annotation
+ ptr = strscn(line);
+ if (!ptr) return Warning(dbf,line,name);
+ annotchr[i]=uprchr(*ptr);
+ if (*ptr!='-' && *ptr!=' ') annot=1;
+
+ ptr = strscn(line);
+ switch (*ptr)
+ {
+ case 'H':
+ ss_dssp[i]=1;
+ seq[nss_dssp][i]=*ptr;
+ dssp=1;
+ break;
+ case 'E':
+ ss_dssp[i]=2;
+ seq[nss_dssp][i]=*ptr;
+ dssp=1;
+ break;
+ case 'C':
+ ss_dssp[i]=3;
+ seq[nss_dssp][i]=*ptr;
+ dssp=1;
+ break;
+ case 'S':
+ ss_dssp[i]=4;
+ seq[nss_dssp][i]=*ptr;
+ dssp=1;
+ break;
+ case 'T':
+ ss_dssp[i]=5;
+ seq[nss_dssp][i]=*ptr;
+ dssp=1;
+ break;
+ case 'G':
+ ss_dssp[i]=6;
+ seq[nss_dssp][i]=*ptr;
+ dssp=1;
+ break;
+ case 'B':
+ ss_dssp[i]=7;
+ seq[nss_dssp][i]=*ptr;
+ dssp=1;
+ break;
+ case 'I':
+ dssp=1;
+ case '~':
+ ss_dssp[i]=3;
+ seq[nss_dssp][i]=*ptr;
+ break;
+ case '-': // no SS available from any template
+ case '.': // no clear consensus SS structure
+ case 'X': // no clear consensus SS structure
+ ss_dssp[i]=0;
+ seq[nss_dssp][i]='-';
+ break;
+ default:
+ ss_dssp[i]=0;
+ seq[nss_dssp][i]=*ptr;
+ break;
+ }
+
+ // Read insert emission line
+ fgetline(line,LINELEN-1,dbf);
+
+ // Read seven transition probabilities
+ fgetline(line,LINELEN-1,dbf);
+
+ ptr+=2;
+ for (a=0; a<=D2D && ptr; ++a)
+ tr[i][a] = log2((float) exp(-1.0*strflta(ptr,99999))); //store transition prob's as log2-values
+ if (!ptr) return Warning(dbf,line,name);
+ if (v>=4)
+ {
+ printf(" ");
+ for (a=0; a<=D2D; ++a) printf("%6.3g ",100*fpow2(tr[i][a]));
+ printf("\n");
+ }
+ }
+
+ if (line[0]=='/' && line[1]=='/') break;
+
+ } /* strncmp("HMM") */
+
+ } //while(getline)
+
+ if (L==0) return 0; //End of db file -> stop reading in
+
+ if (v && i!=L) cerr<<endl<<"Warning: in HMM "<<name<<" there are only "<<i<<" columns while the stated length is "<<L<<"\n";
+ if (v && i>=/*MAXRES*/par.maxResLen-2) {i=/*MAXRES*/par.maxResLen-2; cerr<<endl<<"WARNING: maximum number "<</*MAXRES*/par.maxResLen-2<<" of residues exceeded while reading HMM "<<name<<"\n";}
+ if (v && !i) cerr<<endl<<"WARNING: HMM "<<name<<" contains no match states. Check the alignment that gave rise to this HMM.\n";
+ L = i;
+
+ if (strlen(longname)>0) strcat(longname," ");
+ strncat(longname,name,DESCLEN-strlen(longname)-1); // longname = ACC NAME DESC
+ if (strlen(name)>0) strcat(longname," ");
+ strncat(longname,desc,DESCLEN-strlen(longname)-1);
+ longname[DESCLEN-1]='\0';
+ ScopID(cl,fold,sfam,fam);// get scop classification from basename (e.g. a.1.2.3.4)
+ RemoveExtension(file,filestr); // copy name of dbfile without extension into 'file'
+
+ // Secondary structure
+ if (!dssp)
+ {
+ // remove dssp sequence
+ delete[] seq[nss_dssp]; // memory that had been allocated in case ss_dssp was given needs to be freed
+ delete[] sname[nss_dssp]; // memory that had been allocated in case ss_dssp was given needs to be freed
+ nss_dssp=-1;
+ k--;
+ }
+ else { seq[nss_dssp][0]='-'; seq[nss_dssp][L+1]='\0'; }
+
+ if (nss_pred>=0)
+ {
+ for (i=1; i<=L; ++i) ss_pred[i] = ss2i(seq[nss_pred][i]);
+ if (nss_conf>=0)
+ for (i=1; i<=L; ++i) ss_conf[i] = cf2i(seq[nss_conf][i]);
+ else
+ for (i=1; i<=L; ++i) ss_conf[i] = 5;
+ }
+
+ // Copy query (first sequence) and consensus residues?
+ if (par.showcons)
+ {
+ sname[k]=new(char[10]);
+ strcpy(sname[k],"Consensus");
+ sname[k+1]=new(char[strlen(longname)+1]);
+ strcpy(sname[k+1],longname);
+ seq[k]=new(char[L+2]);
+ seq[k][0]=' ';
+ seq[k][L+1]='\0';
+ seq[k+1]=new(char[L+2]);
+ seq[k+1][0]=' ';
+ seq[k+1][L+1]='\0';
+ for (i=1; i<=L; ++i)
+ {
+ float pmax=0.0;
+ int amax=0;
+ for (a=0; a<NAA; ++a)
+ if (f[i][a]>pmax) {amax=a; pmax=f[i][a];}
+ if (pmax>0.6) seq[k][i]=i2aa(amax);
+ else if (pmax>0.4) seq[k][i]=lwrchr(i2aa(amax));
+ else seq[k][i]='x';
+ seq[k+1][i]=i2aa(amax);
+ }
+ ncons=k++; // nfirst is set later!
+ }
+ else
+ {
+ sname[k]=new(char[strlen(longname)+1]);
+ strcpy(sname[k],longname);
+ seq[k]=new(char[L+2]);
+ seq[k][0]=' ';
+ seq[k][L+1]='\0';
+ }
+
+ if (annot) // read in some annotation characters?
+ {
+ annotchr[0]=' ';
+ annotchr[L+1]='\0';
+ strcpy(seq[k],annotchr); // overwrite the consensus sequence with the annotation characters
+ }
+ else if (!par.showcons) // we have not yet calculated the consensus, but we need it now as query (first sequence)
+ {
+ for (i=1; i<=L; ++i)
+ {
+ float pmax=0.0;
+ int amax=0;
+ for (a=0; a<NAA; ++a)
+ if (f[i][a]>pmax) {amax=a; pmax=f[i][a];}
+ seq[k][i]=i2aa(amax);
+ }
+ }
+ // printf("%i query name=%s seq=%s\n",n,sname[n],seq[n]);
+ nfirst=k++;
+
+ n_display=k;
+ n_seqs=k;
+
+ // If no effektive number of sequences is given, calculate Neff_HMM by given profile
+ if (Neff_HMM == 0) {
+ for (i=1; i<=L; ++i)
+ {
+ float S=0.0;
+ for (a=0; a<20; ++a)
+ if (f[i][a]>1E-10) S-=f[i][a]*fast_log2(f[i][a]);
+ Neff_HMM+=(float) fpow2(S);
+ }
+ Neff_HMM/=L;
+ }
+
+ for (i=0; i<=L; ++i) Neff_M[i] = Neff_I[i] = Neff_D[i] = 10.0; // to add only little additional pseudocounts!
+ Neff_M[L+1]=1.0f;
+ Neff_I[L+1]=Neff_D[L+1]=0.0f;
+
+ if (v>=2)
+ cout<<"Read in HMM "<<name<<" with "<<L<<" match states and effective number of sequences = "<<Neff_HMM<<"\n";
+
+ ///////////////////////////////////////////////////////////////////
+
+ // Set emission probabilities of zero'th (begin) state and L+1st (end) state to background probabilities
+ for (a=0; a<20; ++a) f[0][a]=f[L+1][a]=pb[a];
+ delete[] annotchr;
+
+ has_pseudocounts=true;
+
+ return 1; //return status: ok
+
+
+} /* this is the end of HMM::ReadHMMer3() */
+
+
+//////////////////////////////////////////////////////////////////////////////
+/**
+ * @brief Add transition pseudocounts to HMM (and calculate lin-space transition probs)
+ */
+void
+HMM::AddTransitionPseudocounts(float gapd, float gape, float gapf, float gapg, float gaph, float gapi, float gapb)
+{
+ int i; //position in alignment
+ float sum;
+ float pM2M, pM2I, pM2D, pI2I, pI2M, pD2D, pD2M;
+ float p0,p1,p2;
+ if (par.gapb<=0) return;
+ if (trans_lin==1) {fprintf(stderr,"Error: Adding transition pseudocounts to linear representation of %s not allowed. Please report this error to the HHsearch developers.\n",name); exit(6);}
+ if (trans_lin==2) {fprintf(stderr,"Error: Adding transition pseudocounts twice is %s not allowed. Please report this error to the HHsearch developers.\n",name); exit(6);}
+ trans_lin=2;
+
+ // Calculate pseudocount transition probabilities
+ pM2D=pM2I=gapd*0.0286; //a-priori probability for inserts and deletions
+ pM2M=1-pM2D-pM2I;
+ // gape=0 -> pI2I=0 gape=1 -> pI2I=0.75 gape=inf -> pI2I=1.
+ pI2I=1.0*gape/(gape-1+1.0/0.75);
+ pI2M=1-pI2I;
+ // gape=0 -> pD2D=0 gape=1 -> pD2D=0.75 gape=inf -> pD2D=1.
+ pD2D=1.0*gape/(gape-1+1.0/0.75);
+ pD2M=1-pD2D;
+
+ for (i=0; i<=L; ++i) //for all columns in HMM
+ {
+ // Transitions from M state
+ p0 = (Neff_M[i]-1)*fpow2(tr[i][M2M]) + gapb*pM2M;
+ p1 = (Neff_M[i]-1)*fpow2(tr[i][M2D]) + gapb*pM2D;
+ p2 = (Neff_M[i]-1)*fpow2(tr[i][M2I]) + gapb*pM2I;
+ if (i==0) p1=p2=0; //from M(0) no transition to D(1) and I(0) possible
+ if (i==L) p1=p2=0; //from M(L) no transition to D(L+1) and I(L+1) possible
+ sum = p0+p1+p2+FLT_MIN;
+
+// p0 = p0/sum ;
+// p1 = pow(p1/sum,gapf);
+// p2 = pow(p2/sum,gapg);
+// sum = p0+p1+p2+FLT_MIN;
+// tr[i][M2M] = fast_log2(p0/sum);
+// tr[i][M2D] = fast_log2(p1/sum);
+// tr[i][M2I] = fast_log2(p2/sum);
+
+ tr[i][M2M] = fast_log2(p0/sum);
+ tr[i][M2D] = fast_log2(p1/sum)*gapf;
+ tr[i][M2I] = fast_log2(p2/sum)*gapg;
+
+ // Transitions from I state
+ p0 = Neff_I[i]*fpow2(tr[i][I2M]) + gapb*pI2M;
+ p1 = Neff_I[i]*fpow2(tr[i][I2I]) + gapb*pI2I;
+ sum = p0+p1+FLT_MIN;
+
+// p0 = pow(p0/sum,gapg);
+// p1 = pow(p1/sum,gapi);
+// sum = p0+p1+FLT_MIN;
+// tr[i][I2M] = fast_log2(p0/sum);
+// tr[i][I2I] = fast_log2(p1/sum);
+
+ tr[i][I2M] = fast_log2(p0/sum);
+ tr[i][I2I] = fast_log2(p1/sum)*gapi;
+
+ // Transitions from D state
+ p0 = Neff_D[i]*fpow2(tr[i][D2M]) + gapb*pD2M;
+ p1 = Neff_D[i]*fpow2(tr[i][D2D]) + gapb*pD2D;
+ if (i==L) p1=0; //from D(L) no transition to D(L+1) possible
+ sum = p0+p1+FLT_MIN;
+
+// p0 = pow(p0/sum,gapf);
+// p1 = pow(p1/sum,gaph);
+// sum = p0+p1+FLT_MIN;
+// tr[i][D2M] = fast_log2(p0/sum);
+// tr[i][D2D] = fast_log2(p1/sum);
+
+ tr[i][D2M] = fast_log2(p0/sum);
+ tr[i][D2D] = fast_log2(p1/sum)*gaph;
+
+ // SS-dependent gap penalties
+ tr[i][M2M_GAPOPEN]=tr[i][M2M];
+ tr[i][GAPOPEN]=0.0;
+ tr[i][GAPEXTD]=0.0;
+ }
+
+ if (v>=4)
+ {
+ printf("\nPseudocount transition probabilities:\n");
+ printf("pM2M=%4.1f%%, pM2I=%4.1f%%, pM2D=%4.1f%%, ",100*pM2M,100*pM2I,100*pM2D);
+ printf("pI2M=%4.1f%%, pI2I=%4.1f%%, ",100*pI2M,100*pI2I);
+ printf("pD2M=%4.1f%%, pD2D=%4.1f%% ",100*pD2M,100*pD2D);
+ printf("tau = %4.1f%%\n\n",100.*gapb/(Neff_HMM-1+gapb));
+ printf("Listing transition probabilities WITH pseudocounts:\n");
+ printf(" i dssp pred sacc M->M M->I M->D I->M I->I D->M D->D\n");
+
+ for (i=1; i<=L; ++i) //for all columns in HMM
+ {
+ printf("%4i %1c %1c %1c %6.3f %6.3f %6.3f ",i,i2ss(ss_dssp[i]),i2ss(ss_pred[i]),i2sa(sa_dssp[i]),fpow2(tr[i][M2M]),fpow2(tr[i][M2I]),fpow2(tr[i][M2D]));
+ printf("%6.3f %6.3f ",fpow2(tr[i][I2M]),fpow2(tr[i][I2I]));
+ printf("%6.3f %6.3f ",fpow2(tr[i][D2M]),fpow2(tr[i][D2D]));
+ printf("%1i %2i %1i\n",ss_pred[i],ss_conf[i],ss_dssp[i]);
+ }
+ printf("\n");
+ printf("nss_dssp=%i nss_pred=%i\n",nss_dssp,nss_pred);
+ }
+ return;
+}
+
+
+//////////////////////////////////////////////////////////////////////////////
+/**
+ * @brief Use secondary structure-dependent gap penalties
+ * on top of the HMM transition penalties
+ */
+void
+HMM::UseSecStrucDependentGapPenalties()
+{
+ int i; // column in HMM
+ int ii;
+ //unsigned char iis[MAXRES]; // inside-integer array
+ unsigned char iis[par.maxResLen]; // inside-integer array
+ float d; // Additional penalty for opening gap whithin SS element
+ float e; // Additional penalty for extending gap whithin SS element
+
+ // Determine inside-integers:
+ // CCSTCCCHHHHHHHHHHHCCCCCEEEEECCSBGGGCCCCEECC
+ // 0000000123444432100000012210000000000001000
+ ii=0;
+ for (i=0; i<=L; ++i) // forward run
+ {
+ if (ss_dssp[i]==1 || ss_dssp[i]==2) {ii+=(ii<par.ssgapi);} else ii=0;
+ iis[i]=ii;
+ } for (i=0; i<=L; ++i)
+ ii=0;
+ iis[0]=iis[L]=0;
+ for (i=L; i>=0; i--) // backward run
+ {
+ if (ss_dssp[i]==1 || ss_dssp[i]==2) {ii+=(ii<par.ssgapi);} else ii=0;
+ iis[i-1]=imin(ii,iis[i-1]);
+ }
+
+ // Add SS-dependent gap penalties to HMM transition penalties
+ for (i=0; i<=L; ++i) //for all columns in HMM
+ {
+ d=-iis[i]*par.ssgapd;
+ e=-iis[i]*par.ssgape;
+ tr[i][GAPOPEN]=d;
+ tr[i][GAPEXTD]=e;
+ tr[i][M2M_GAPOPEN]+=d;
+ tr[i][M2I]+=d;
+ tr[i][I2M]+=d;
+ tr[i][I2I]+=e;
+ tr[i][M2D]+=d;
+ tr[i][D2M]+=d;
+ tr[i][D2D]+=e;
+ }
+
+ if (v>=3)
+ {
+ printf("Col SS II\n");
+ for (i=0; i<=L; ++i) printf("%3i %c %2i\n",i,i2ss(ss_dssp[i]),iis[i]);
+ }
+ return;
+}
+
+/////////////////////////////////////////////////////////////////////////////////////
+/**
+ * @brief Generate an amino acid frequency matrix g[][] with full pseudocount admixture (tau=1)
+ */
+void
+HMM::PreparePseudocounts()
+{
+ for (int i=0; i<=L+1; ++i)
+ for (int a=0; a<20; ++a)
+ g[i][a] = // produces fast code
+ R[a][0]*f[i][0] +R[a][1]*f[i][1] +R[a][2]*f[i][2] +R[a][3]*f[i][3] +R[a][4]*f[i][4]
+ +R[a][5]*f[i][5] +R[a][6]*f[i][6] +R[a][7]*f[i][7] +R[a][8]*f[i][8] +R[a][9]*f[i][9]
+ +R[a][10]*f[i][10]+R[a][11]*f[i][11]+R[a][12]*f[i][12]+R[a][13]*f[i][13]+R[a][14]*f[i][14]
+ +R[a][15]*f[i][15]+R[a][16]*f[i][16]+R[a][17]*f[i][17]+R[a][18]*f[i][18]+R[a][19]*f[i][19];
+}
+
+/////////////////////////////////////////////////////////////////////////////////////
+/**
+ * @brief Add amino acid pseudocounts to HMM and calculate average protein aa probabilities pav[a]
+ * Pseudocounts: t.p[i][a] = (1-tau)*f[i][a] + tau*g[i][a]
+ */
+void
+HMM::AddAminoAcidPseudocounts(char pcm, float pca, float pcb, float pcc)
+{
+ int i; //position in HMM
+ int a; //amino acid (0..19)
+ float sum;
+ float tau; //tau = pseudocount admixture
+
+ for (a=0; a<20; ++a) pav[a]=pb[a]*100.0f/Neff_HMM; // initialize vector of average aa freqs with pseudocounts
+
+ // Calculate amino acid frequencies p[i][a] = (1-tau(i))*f[i][a] + tau(i)*g[i][a]
+ switch (pcm)
+ {
+ case 0: //no pseudocounts whatsoever: tau=0
+ for (i=1; i<=L; ++i)
+ for (a=0; a<20; ++a)
+ pav[a] += ( p[i][a]=f[i][a] );
+ break;
+ case 1: //constant pseudocounts (for optimization): tau = pca
+ tau = pca;
+ for (i=1; i<=L; ++i)
+ for (a=0; a<20; ++a)
+ pav[a] += ( p[i][a] = (1.-tau)*f[i][a] + tau * g[i][a] );
+ break;
+ case 2: //divergence-dependent pseudocounts
+ case 4: //divergence-dependent pseudocounts and rate matrix rescaling
+ if (par.pcc==1.0f)
+ for (i=1; i<=L; ++i)
+ {
+ tau = fmin(1.0, pca/(1. + Neff_M[i]/pcb ) );
+ for (a=0; a<20; ++a)
+ pav[a] += ( p[i][a] = (1.-tau)*f[i][a] + tau * g[i][a] );
+ }
+ else
+ for (i=1; i<=L; ++i)
+ {
+ tau = fmin(1.0, pca/(1. + pow((Neff_M[i])/pcb,pcc)));
+ for (a=0; a<20; ++a)
+ pav[a] += ( p[i][a] = (1.-tau)*f[i][a] + tau * g[i][a] );
+ }
+ break;
+ case 3: // constant-divergence pseudocounts
+ for (i=1; i<=L; ++i)
+ {
+ float x = Neff_M[i]/pcb;
+ pca = 0.793 + 0.048*(pcb-10.0);
+ tau = fmax(0.0, pca*(1-x + pcc*x*(1-x)) );
+ for (a=0; a<20; ++a)
+ pav[a] += ( p[i][a] = (1.-tau)*f[i][a] + tau * g[i][a] );
+ }
+ if (v>=2) { printf("Divergence before / after addition of amino acid pseudocounts: %5.2f / %5.2f\n",Neff_HMM, CalcNeff()); }
+ break;
+ } //end switch (pcm)
+
+
+ // Normalize vector of average aa frequencies pav[a]
+ NormalizeTo1(pav,NAA);
+
+ for (a=0; a<20; ++a)
+ p[0][a] = p[L+1][a] = pav[a];
+
+ // DEBUGGING output
+ if (v>=3)
+ {
+ switch (pcm)
+ {
+ case 0:
+ cout<<"No pseudocounts added (-pcm 0)\n";
+ return;
+ case 1:
+ cout<<"Adding constant AA pseudocount admixture of "<<pca<<" to HMM "<<name<<"\n";
+ break;
+ case 2:
+ cout<<"Adding divergence-dependent AA pseudocounts (-pcm 2) with admixture of "
+ <<pca/(1.+pow((Neff_HMM-1.)/pcb,pcc))<<" to HMM "<<name<<"\n";
+ break;
+ } //end switch (pcm)
+ cout<<"\nAverage amino acid frequencies WITH pseudocounts in HMM: \nProf: ";
+ for (a=0; a<20; ++a) printf("%4.1f ",100*pav[a]);
+ cout<<"\n";
+ if (v>=4)
+ {
+ cout<<"\nAmino acid frequencies WITHOUT pseudocounts:\n 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);
+ sum=0;
+ for (a=0; a<20; ++a)
+ {
+ sum+=f[i][a];
+ printf("%4.1f ",100*f[i][a]);
+ }
+ printf(" sum=%5.3f\n",sum);
+ }
+ cout<<"\nAmino acid frequencies WITH pseudocounts:\n 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);
+ sum=0;
+ for (a=0; a<20; ++a)
+ {
+ sum+=p[i][a];
+ printf("%4.1f ",100*p[i][a]);
+ }
+ printf(" sum=%5.3f\n",sum);
+ }
+ }
+ }
+ return;
+}
+
+
+/////////////////////////////////////////////////////////////////////////////////////
+/**
+ * @brief Factor Null model into HMM t
+ */
+void
+HMM::IncludeNullModelInHMM(HMM& q, HMM& t)
+{
+
+ int i,j; //query and template match state indices
+ int a; //amino acid index
+
+ switch (par.columnscore)
+ {
+ default:
+ case 0: // Null model with background prob. from database
+ for (a=0; a<20; ++a) pnul[a]=pb[a];
+ break;
+
+ case 1: // Null model with background prob. equal average from query and template
+ for (a=0; a<20; ++a) pnul[a]=0.5*(q.pav[a]+t.pav[a]);
+ break;
+
+ case 2: // Null model with background prob. from template protein
+ for (a=0; a<20; ++a) pnul[a]=t.pav[a];
+ break;
+
+ case 3: // Null model with background prob. from query protein
+ for (a=0; a<20; ++a) pnul[a]=q.pav[a];
+ break;
+
+ case 4: // Null model with background prob. equal average from query and template
+ for (a=0; a<20; ++a) pnul[a]=sqrt(q.pav[a]*t.pav[a]);
+ break;
+
+ case 10: // Separated column scoring for Stochastic Backtracing (STILL USED??)
+ for (i=0; i<=q.L+1; ++i)
+ {
+ float sum = 0.0;
+ for (a=0; a<20; ++a) sum += pb[a]*q.p[i][a];
+ sum = 1.0/sqrt(sum);
+ for (a=0; a<20; ++a) q.p[i][a]*=sum;
+ }
+ for (j=0; j<=t.L+1; j++)
+ {
+ float sum = 0.0;
+ for (a=0; a<20; ++a) sum += pb[a]*t.p[j][a];
+ sum = 1.0/sqrt(sum);
+ for (a=0; a<20; ++a) t.p[j][a]*=sum;
+ }
+ break;
+
+ case 11: // log co-emission probability (no null model)
+ for (a=0; a<20; ++a) pnul[a]=0.05;
+ break;
+
+ }
+
+ // !!!!! ATTENTION!!!!!!! after this t.p is not the same as after adding pseudocounts !!!
+ //Introduce amino acid weights into template (for all but SOP scores)
+ if (par.columnscore!=10)
+ for (a=0; a<20; ++a)
+ for (j=0; j<=t.L+1; j++)
+ t.p[j][a]/=pnul[a];
+
+ if (v>=5)
+ {
+ cout<<"\nAverage amino acid frequencies\n";
+ cout<<" A R N D C Q E G H I L K M F P S T W Y V\n";
+ cout<<"Q: ";
+ for (a=0; a<20; ++a) printf("%4.1f ",100*q.pav[a]);
+ cout<<"\nT: ";
+ for (a=0; a<20; ++a) printf("%4.1f ",100*t.pav[a]);
+ cout<<"\nNull: ";
+ for (a=0; a<20; ++a) printf("%4.1f ",100*pnul[a]);
+ cout<<"\npb: ";
+ for (a=0; a<20; ++a) printf("%4.1f ",100*pb[a]);
+ }
+
+
+ return;
+}
+
+
+/////////////////////////////////////////////////////////////////////////////////////
+/**
+ * @brief Write HMM to output file
+ */
+void
+HMM::WriteToFile(char* outfile)
+{
+ const int SEQLEN=100; // number of residues per line for sequences to be displayed
+ int i,a;
+
+ if (trans_lin) {fprintf(stderr,"Error: Writing transition pseudocounts in linear representation not allowed. Please report this error to the HHsearch developers.\n"); exit(6);}
+
+ FILE *outf=NULL;
+ if (strcmp(outfile,"stdout"))
+ {
+ if (par.append) outf=fopen(outfile,"a"); else outf=fopen(outfile,"w");
+ if (!outf) OpenFileError(outfile);
+ }
+ else
+ outf = stdout;
+ if (v>=2) cout<<"Writing HMM to "<<outfile<<"\n";
+
+// fprintf(outf,"HHsearch HHM format 1.5\n");
+ fprintf(outf,"HHsearch 1.5\n"); // format specification
+ fprintf(outf,"NAME %s\n",longname); // name of first sequence
+ fprintf(outf,"FAM %s\n",fam); // family name
+ char file_nopath[NAMELEN];
+ RemovePath(file_nopath,file);
+ fprintf(outf,"FILE %s\n",file_nopath); // base name of alignment file
+
+ // Print command line
+ fprintf(outf,"COM ");
+ for (int i=0; i<par.argc; i++)
+ if (strlen(par.argv[i])<=100)
+ fprintf(outf,"%s ",par.argv[i]);
+ else
+ fprintf(outf,"<%i characters> ",(int)strlen(par.argv[i]));
+ fprintf(outf,"\n");
+
+ // print out date stamp
+ time_t* tp=new(time_t);
+ *tp=time(NULL);
+ fprintf(outf,"DATE %s",ctime(tp));
+ delete tp; tp = NULL; /* really? FS */
+
+ // Print out some statistics of alignment
+ fprintf(outf,"LENG %i match states, %i columns in multiple alignment\n",L,l[L]);
+ fprintf(outf,"FILT %i out of %i sequences passed filter (-id %i -cov %i -qid %i -qsc %.2f -diff %i)\n",N_filtered,N_in,par.max_seqid,par.coverage,par.qid,par.qsc,par.Ndiff);
+ fprintf(outf,"NEFF %-4.1f\n",Neff_HMM);
+
+ // Print selected sequences from alignment (including secondary structure and confidence values, if known)
+ fprintf(outf,"SEQ\n");
+ for (int n=0; n<n_display; n++)
+ {
+ fprintf(outf,">%s\n",sname[n]);
+ //first sequence character starts at 1; 0 not used.
+ for(unsigned int j=0; j<strlen(seq[n]+1); j+=SEQLEN) fprintf(outf,"%-.*s\n",SEQLEN,seq[n]+1+j);
+ }
+ fprintf(outf,"#\n");
+
+ // print null model background probabilities from substitution matrix
+ fprintf(outf,"NULL ");
+ for (a=0; a<20; ++a) fout(outf,-iround(fast_log2(pb[s2a[a]])*HMMSCALE ));
+ fprintf(outf,"\n");
+
+ // print table header line with amino acids
+ fprintf(outf,"HMM ");
+ for (a=0; a<20; ++a) fprintf(outf,"%1c\t",i2aa(s2a[a]));
+ fprintf(outf,"\n");
+
+ // print table header line with state transitions
+ fprintf(outf," M->M\tM->I\tM->D\tI->M\tI->I\tD->M\tD->D\tNeff\tNeff_I\tNeff_D\n");
+
+ // print out transition probabilities from begin state (virtual match state)
+ fprintf(outf," ");
+ for (a=0; a<=D2D; ++a) fout(outf,-iround(tr[0][a]*HMMSCALE));
+ fout(outf,iround(Neff_M[0]*HMMSCALE));
+ fout(outf,iround(Neff_I[0]*HMMSCALE));
+ fout(outf,iround(Neff_D[0]*HMMSCALE));
+ fprintf(outf,"\n");
+
+ // Start loop for printing HMM columns
+ int h=1;
+ for (i=1; i<=L; ++i)
+ {
+
+ while(islower(seq[nfirst][h]) && seq[nfirst][h]) h++;
+ fprintf(outf,"%1c %-4i ",seq[nfirst][h++],i);
+
+ // Print emission probabilities for match state
+ for (a=0; a<20; ++a) fout(outf,-iround(fast_log2(p[i][s2a[a]])*HMMSCALE ));
+ fprintf(outf,"%-i",l[i]);
+ fprintf(outf,"\n");
+
+ // Print transition probabilities
+ fprintf(outf," ");
+ for (a=0; a<=D2D; ++a) fout(outf,-iround(tr[i][a]*HMMSCALE));
+ fout(outf,iround(Neff_M[i]*HMMSCALE));
+ fout(outf,iround(Neff_I[i]*HMMSCALE));
+ fout(outf,iround(Neff_D[i]*HMMSCALE));
+ fprintf(outf,"\n\n");
+ } // end for(i)-loop for printing HMM columns
+
+ fprintf(outf,"//\n");
+ fclose(outf);
+}
+
+/////////////////////////////////////////////////////////////////////////////////////
+/**
+ * @brief Write HMM to output file
+ */
+void
+HMM::InsertCalibration(char* infile)
+{
+ char* line = new(char[LINELEN]); // input line
+ char** lines = new(char*[3*L+100000]);
+ int nline=0;
+ int l;
+ char done=0; // inserted new 'EVD mu sigma' line?
+
+ // Read from infile all lines and insert the EVD line with lamda and mu coefficients
+ ifstream inf;
+ inf.open(infile, ios::in);
+ if (!inf) OpenFileError(infile);
+ if (v>=2) cout<<"Recording calibration coefficients in "<<infile<<"\n";
+
+ while (inf.getline(line,LINELEN) && !(line[0]=='/' && line[1]=='/') && nline<2*/*MAXRES*/par.maxResLen)
+ {
+
+ // Found an EVD lamda mu line? -> remove
+ while (!done && !strncmp(line,"EVD ",3) && !(line[0]=='/' && line[1]=='/') && nline<2*/*MAXRES*/par.maxResLen)
+ inf.getline(line,LINELEN);
+ if ((line[0]=='/' && line[1]=='/') || nline>=2*/*MAXRES*/par.maxResLen)
+ {fprintf(stderr,"Error: wrong format in %s. Expecting hhm format\n",infile); exit(1);}
+
+ // Found the SEQ line? -> insert calibration before this line
+ if (!done && (!strncmp("SEQ",line,3) || !strncmp("HMM",line,3)) && (isspace(line[3]) || line[3]=='\0'))
+ {
+ done=1;
+ lines[nline]=new(char[128]);
+ if (!lines[nline]) MemoryError("space to read in HHM file for calibration");
+ sprintf(lines[nline],"EVD %-7.4f %-7.4f",lamda,mu);
+ nline++;
+ }
+ lines[nline]=new(char[strlen(line)+1]);
+ if (!lines[nline]) MemoryError("space to read in HHM file for calibration");
+ strcpy (lines[nline],line);
+ nline++;
+ }
+ inf.close();
+
+ // Write to infile all lines
+ FILE* infout=fopen(infile,"w");
+ if (!infout) {
+ cerr<<endl<<"WARNING in "<<program_name<<": no calibration coefficients written to "<<infile<<":\n";
+ cerr<<"Could not open file for writing.\n";
+ return;
+ }
+ for (l=0; l<nline; l++) {
+ fprintf(infout,"%s\n",lines[l]);
+ delete[] lines[l]; lines[l] = NULL;
+ }
+ fprintf(infout,"//\n");
+ fclose(infout);
+ delete[] line; line = NULL;
+ delete[] lines; lines = NULL;
+ return;
+}
+
+/////////////////////////////////////////////////////////////////////////////////////
+/**
+ * @brief Write HMM to output file in HMMER format
+ */
+void
+HMM::WriteToFileHMMER(char* outfile)
+{
+ const int INTSCALE=1000; //scaling factor in HMMER files
+ const float pBD=0.50;
+ const int LOG2pBD=iround(fast_log2(pBD)*INTSCALE);
+ const int LOG2pBM=iround(fast_log2(1-pBD)*INTSCALE);
+ const float pJB=1.0/350;
+ const int LOG2pJB=iround(fast_log2(pJB)*INTSCALE);
+ const int LOG2pJJ=iround(fast_log2(1-pJB)*INTSCALE);
+ const float pEJ=0.5;
+ const int LOG2pEJ=iround(fast_log2(pEJ)*INTSCALE);
+ const int LOG2pEC=iround(fast_log2(1-pEJ)*INTSCALE);
+ char c;
+ int i,a;
+
+ if (trans_lin) {fprintf(stderr,"Error: Writing transition pseudocounts in linear representation not allowed. Please report this error to the HHsearch developers.\n"); exit(6);}
+
+ FILE *outf=NULL;
+ if (strcmp(outfile,"stdout"))
+ {
+ if (par.append) outf=fopen(outfile,"a"); else outf=fopen(outfile,"w");
+ if (!outf) OpenFileError(outfile);
+ }
+ else
+ outf = stdout;
+ if (v>=2) cout<<"Writing HMM to "<<outfile<<"\n";
+
+ fprintf(outf,"HMMER2.0 [hhmake %s]\n",VERSION_AND_DATE);
+ fprintf(outf,"NAME %s\n",file); // base name of alignment file
+ fprintf(outf,"DESC %s\n",longname);
+ fprintf(outf,"LENG %i\n",L);
+ fprintf(outf,"ALPH Amino\n"); // amino acid seuqences (not DNA)
+ fprintf(outf,"RF yes\n"); // reference annotation flag
+ fprintf(outf,"CS yes\n"); // consensus structure annotation flag
+ fprintf(outf,"MAP yes\n"); // write MA column number after each line of aa probabilities
+
+ fprintf(outf,"COM "); // print out command line
+ for (i=0; i<=par.argc-1; ++i) fprintf(outf,"%s ",par.argv[i]); fprintf(outf,"\n");
+
+ fprintf(outf,"NSEQ %i\n",N_filtered); // print number of sequences after filtering
+
+ // Date stamp
+ time_t* tp=new(time_t);
+ *tp=time(NULL);
+ fprintf(outf,"DATE %s",ctime(tp));
+ delete tp; tp = NULL; /* really? FS */
+
+ // Print out secondary structure
+ if (nss_dssp>=0)
+ fprintf(outf,"SSDSS %s\n",seq[nss_dssp]);
+ if (nsa_dssp>=0)
+ fprintf(outf,"SADSS %s\n",seq[nsa_dssp]);
+ if (nss_pred>=0)
+ fprintf(outf,"SSPRD %s\n",seq[nss_pred]);
+ if (nss_conf>=0)
+ fprintf(outf,"SSCNF %s\n",seq[nss_conf]);
+
+
+ // Special Plan7 transitions that control repeated detection of profile HMM within sequence
+ fprintf(outf,"XT %6i %6i %6i %6i %6i %6i %6i %6i\n",LOG2pJB,LOG2pJJ,LOG2pEC,LOG2pEJ,LOG2pJB,LOG2pJJ,LOG2pJB,LOG2pJJ);
+ fprintf(outf,"NULT -4 -8455\n");
+
+
+ // Null model background probabilities from substitution matrix
+ fprintf(outf,"NULE ");
+ for (a=0; a<20; ++a)
+ {
+ float lg2=fast_log2(pb[s2a[a]]*20.0);
+ if (lg2<-99.999) fprintf(outf," *"); else fprintf(outf," %6i",iround(lg2*INTSCALE));
+ }
+ fprintf(outf,"\n");
+
+ // Table header line with amino acids
+ fprintf(outf,"HMM ");
+ for (a=0; a<20; ++a) fprintf(outf," %1c ",i2aa(s2a[a]));
+ fprintf(outf,"\n");
+
+ // Table header line with state transitions
+ fprintf(outf," m->m m->i m->d i->m i->i d->m d->d b->m m->e\n");
+
+ // Transition probabilities from begin state
+ fprintf(outf," %6i * %6i\n",LOG2pBM,LOG2pBD);
+
+ // Start loop for printing HMM columns
+ int h=1, hss=1;
+ for (i=1; i<=L; ++i)
+ {
+
+ // Emission probabilities for match state
+ fprintf(outf," %5i",i);
+ for (a=0; a<20; ++a) fprintf(outf," %6i",imax(-9999,iround(fast_log2(p[i][s2a[a]]/pb[s2a[a]])*INTSCALE)));
+ fprintf(outf," %5i",l[i]);
+ fprintf(outf,"\n");
+
+ // Emission probabilities (relative to null model) for insert state
+ while(islower(seq[nfirst][h]) && seq[nfirst][h]) h++;
+ if (i==L)
+ fprintf(outf," %1c * * * * * * * * * * * * * * * * * * * *\n",seq[nfirst][h++]);
+ else
+ fprintf(outf," %1c 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0\n",seq[nfirst][h++]);
+
+ // Transition probabilities
+ if (nss_dssp>=0)
+ {
+ while(islower(seq[nss_dssp][hss]) && seq[nss_dssp][hss]) hss++;
+ c=seq[nss_dssp][hss++];
+ }
+ else c=' ';
+ fprintf(outf," %1c",c);
+ if (i==1)
+ {
+ for (a=0; a<=D2D; ++a) fprintf(outf," %6i",imax(-9999,iround(tr[i][a]*INTSCALE)));
+ fprintf(outf," %6i *\n",LOG2pBM);
+ }
+ else if (i==L)
+ {
+ for (a=0; a<=D2D; ++a) fprintf(outf," *");
+ fprintf(outf," * 0\n");
+ }
+ else
+ {
+ for (a=0; a<=D2D; ++a) fprintf(outf," %6i",imax(-9999,iround(tr[i][a]*INTSCALE)));
+ fprintf(outf," * *\n");
+ }
+ }
+
+ fprintf(outf,"//\n");
+ fclose(outf);
+}
+
+
+/////////////////////////////////////////////////////////////////////////////////////
+/**
+ * @brief Transform log to lin transition probs
+ */
+void
+HMM::Log2LinTransitionProbs(float beta)
+{
+ if (trans_lin==1) return;
+ trans_lin=1;
+ for (int i=0; i<=L; ++i)
+ {
+ for (int a=0; a<NTRANS; ++a)
+ tr[i][a] = fpow2(beta*tr[i][a]);
+/* FIXME valgrind says: "Conditional jump or move depends on
+ * uninitialised value(s)" when using hmm iteration
+ */
+ }
+}
+
+
+/**
+ * @brief Set query columns in His-tags etc to Null model distribution
+ */
+void
+HMM::NeutralizeTags()
+{
+ char* qseq = seq[nfirst];
+ char* pt;
+ int a,i;
+
+ if (NULL == qseq){
+ return;
+ }
+
+ // Neutralize His tag
+ if ( (pt=strstr(qseq,"HHHHH")) )
+ {
+ int i0 = pt-qseq+1;
+ if (v>=2) printf("Neutralized His-tag at position %i\n",i0);
+ for (i=imax(i0-5,1); i<i0; ++i) // neutralize leading 5 columns
+ for (a=0; a<NAA; ++a) p[i][a]=pb[a];
+ for (; (*pt)!='H'; ++i,++pt) // neutralize His columns
+ for (a=0; a<NAA; ++a) p[i][a]=pb[a];
+ i0=i;
+ for (; i<imin(i0+5,L+1); ++i) // neutralize trailing 5 columns
+ for (a=0; a<NAA; ++a) p[i][a]=pb[a];
+ if (v>=3) printf("start:%i end:%i\n",imax(i0-5,1),i-1);
+ }
+
+ // Neutralize C-myc tag
+ if ( (pt=strstr(qseq,"EQKLISEEDL")) )
+ {
+ if (v>=2) printf("Neutralized C-myc-tag at position %i\n",int(pt-qseq)+1);
+ for (i=pt-qseq+1; i<=pt-qseq+10; ++i)
+ for (a=0; a<NAA; ++a) p[i][a]=pb[a];
+ }
+ // Neutralize FLAG tag
+ if ( (pt=strstr(qseq,"DYKDDDDK")) )
+ {
+ if (v>=2) printf("Neutralized FLAG-tag at position %i\n",int(pt-qseq)+1);
+ for (i=pt-qseq+1; i<=pt-qseq+8; ++i)
+ for (a=0; a<NAA; ++a) p[i][a]=pb[a];
+ }
+}
+
+
+
+/////////////////////////////////////////////////////////////////////////////////////
+/**
+ * @brief Calculate effective number of sequences using profiles INCLUDING pseudocounts
+ */
+float
+HMM::CalcNeff()
+{
+ float Neff=0;
+ for (int i=1; i<=L; ++i)
+ for (int a=0; a<20; ++a)
+ if (p[i][a]>1E-10) Neff-=p[i][a]*fast_log2(p[i][a]);
+ return fpow2(Neff/L);
+}
+
+
+/////////////////////////////////////////////////////////////////////////////////////
+/**
+ * @brief Calculate consensus of HMM (needed to merge HMMs later)
+ */
+void
+HMM::CalculateConsensus()
+{
+ int i; // position in query
+ int a; // amino acid
+ if (!Xcons) Xcons = new char[/*MAXRES*/par.maxResLen+2];
+ for (i=1; i<=L; ++i)
+ {
+ float max=f[i][0]-pb[0];
+ for (a=1; a<20; ++a)
+ if (f[i][a]-pb[a]>max) Xcons[i]=a;
+ }
+ Xcons[0]=Xcons[L+1]=ENDGAP;
+}
+
+// /////////////////////////////////////////////////////////////////////////////////////
+// // Store linear transition probabilities
+// /////////////////////////////////////////////////////////////////////////////////////
+// void HMM::StoreLinearTransitionProbs()
+// {
+// int i; // position in query
+// for (i=0; i<=L+1; ++i) if (!tr_lin[i]) tr_lin[i] = new(float[NTRANS]);
+// for (i=0; i<=L+1; ++i)
+// {
+// tr_lin[i][M2M] = fpow2(tr[i][M2M]);
+// tr_lin[i][M2I] = fpow2(tr[i][M2I]);
+// tr_lin[i][M2D] = fpow2(tr[i][M2D]);
+// tr_lin[i][D2M] = fpow2(tr[i][M2D]);
+// tr_lin[i][D2D] = fpow2(tr[i][D2D]);
+// tr_lin[i][I2M] = fpow2(tr[i][I2M]);
+// tr_lin[i][I2I] = fpow2(tr[i][I2I]);
+// }
+// }
+
+
+// #define Weff(Neff) (1.0+par.neffa*(Neff-1.0)+(par.neffb-4.0*par.neffa)/16.0*(Neff-1.0)*(Neff-1.0))
+
+// /////////////////////////////////////////////////////////////////////////////////////
+// // Initialize f[i][a] with query HMM
+// /////////////////////////////////////////////////////////////////////////////////////
+// void HMM::MergeQueryHMM(HMM& q, float wk[])
+// {
+// int i; // position in query
+// int a; // amino acid
+// float Weff_M, Weff_D, Weff_I;
+// for (i=1; i<=L; i++)
+// {
+// Weff_M = Weff(q.Neff_M[i]-1.0);
+// Weff_D = Weff(q.Neff_D[i]-1.0);
+// Weff_I = Weff(q.Neff_I[i]-1.0);
+// for (a=0; a<20; a++) f[i][a] = q.f[i][a]*wk[i]*Weff_M;
+// tr_lin[i][M2M] = q.tr_lin[i][M2M]*wk[i]*Weff_M;
+// tr_lin[i][M2I] = q.tr_lin[i][M2I]*wk[i]*Weff_M;
+// tr_lin[i][M2D] = q.tr_lin[i][M2D]*wk[i]*Weff_M;
+// tr_lin[i][D2M] = q.tr_lin[i][D2M]*wk[i]*Weff_D;
+// tr_lin[i][D2D] = q.tr_lin[i][D2D]*wk[i]*Weff_D;
+// tr_lin[i][I2M] = q.tr_lin[i][I2M]*wk[i]*Weff_I;
+// tr_lin[i][I2I] = q.tr_lin[i][I2I]*wk[i]*Weff_I;
+// }
+// }
+
+
+
+// /////////////////////////////////////////////////////////////////////////////////////
+// // Normalize probabilities in total merged super-HMM
+// /////////////////////////////////////////////////////////////////////////////////////
+// void HMM::NormalizeHMMandTransitionsLin2Log()
+// {
+// int i; // position in query
+// int a; // amino acid
+// for (i=0; i<=L+1; i++)
+// {
+// float sum=0.0;
+// for (a=0; a<20; a++) sum += f[i][a];
+// for (a=0; a<20; a++) f[i][a]/=sum;
+// sum = tr_lin[i][M2M] + tr_lin[i][M2I] + tr_lin[i][M2D];
+// tr_lin[i][M2M] /= sum;
+// tr_lin[i][M2I] /= sum;
+// tr_lin[i][M2D] /= sum;
+// tr[i][M2M] = fast_log2(tr_lin[i][M2M]);
+// tr[i][M2I] = fast_log2(tr_lin[i][M2I]);
+// tr[i][M2D] = fast_log2(tr_lin[i][M2D]);
+// sum = tr_lin[i][D2M] + tr_lin[i][D2D];
+// tr_lin[i][D2M] /= sum;
+// tr_lin[i][D2D] /= sum;
+// tr[i][D2M] = fast_log2(tr_lin[i][D2M]);
+// tr[i][D2D] = fast_log2(tr_lin[i][D2D]);
+// sum = tr_lin[i][I2M] + tr_lin[i][I2I];
+// tr_lin[i][I2M] /= sum;
+// tr_lin[i][I2I] /= sum;
+// tr[i][I2M] = fast_log2(tr_lin[i][I2M]);
+// tr[i][I2I] = fast_log2(tr_lin[i][I2I]);
+// }
+// }
+
+
+// UNCOMMENT TO ACTIVATE COMPOSITIONALLY BIASED PSEUDOCOUNTS BY RESCALING THE RATE MATRIX
+
+// /////////////////////////////////////////////////////////////////////////////////////
+// //// Function to minimize
+// /////////////////////////////////////////////////////////////////////////////////////
+// double RescaleMatrixFunc(double x[])
+// {
+// double sum=0.0;
+// for (int a=0; a<20; ++a)
+// {
+// double za=0.0;
+// for (int b=0; b<20; ++b) za+=P[a][b]*x[b];
+// sum += (x[a]*za-qav[a])*(x[a]*za-qav[a]);
+// }
+// return sum;
+// }
+
+// /////////////////////////////////////////////////////////////////////////////////////
+// //// Gradient of function to minimize
+// /////////////////////////////////////////////////////////////////////////////////////
+// void RescaleMatrixFuncGrad(double grad[], double x[])
+// {
+// double z[20] = {0.0};
+// double w[20];
+// double tmp;
+// for (int a=0; a<20; ++a)
+// for (int b=0; b<20; ++b) z[a] += P[a][b]*x[b];
+
+// for (int a=0; a<20; ++a) w[a] = x[a]*z[a]-qav[a];
+// for (int a=0; a<20; ++a)
+// {
+// tmp = w[a]*z[a];
+// for (int b=0; b<20; ++b) tmp += P[a][b]*x[b]*w[b];
+// grad[a] = 2.0*tmp;
+// }
+// return;
+// }
+
+
+// /////////////////////////////////////////////////////////////////////////////////////
+// //// Rescale a substitution matrix to biased aa frequencies in global vector qav[a]
+// /////////////////////////////////////////////////////////////////////////////////////
+// void HMM::RescaleMatrix()
+// {
+// int a,b;
+// int code;
+// double x[21]; // scaling factor
+// double val_min;
+// const int len=20;
+// const int max_iterations=50;
+
+// if (v>=2) printf("Adjusting rate matrix to query amino acid composition ...\n");
+
+// // Put amino acid frequencies into global array (needed to call WNLIB's conjugate gradient method)
+// for (a=0; a<20; ++a) qav[a] = pav[a];
+
+// // Initialize scaling factors x[a]
+// for (a=0; a<20; ++a) x[a]=pow(qav[a]/pb[a],0.73); // Initialize
+
+// // Call conjugate gradient minimization method from WNLIB
+// wn_conj_gradient_method(&code,&val_min,x,len,&RescaleMatrixFunc,&RescaleMatrixFuncGrad,max_iterations);
+
+
+// // Calculate z[a] = sum_b Pab*xb
+// float sum_err=0.0f;
+// float sum = 0.0f;
+// for (a=0; a<20; ++a)
+// {
+// float za=0.0f; // za = sum_b Pab*xb
+// for (b=0; b<20; ++b) za+=P[a][b]*x[b];
+// sum_err += (x[a]*za/qav[a]-1)*(x[a]*za/qav[a]-1);
+// sum += x[a]*za;
+// }
+// if (sum_err>1e-3 & v>=1) fprintf(stderr,"WARNING: adjusting rate matrix by CG resulted in residual error of %5.3f.\n",sum_err);
+
+// // Rescale rate matrix
+// for (a=0; a<20; ++a)
+// for (b=0; b<20; ++b)
+// {
+// P[a][b] *= x[a]*x[b]/sum;
+// R[a][b] = P[a][b]/qav[b];
+// }
+
+// // How well approximated?
+// if (v>=3)
+// {
+// // Calculate z[a] = sum_b Pab*xb
+// float z[21];
+// for (a=0; a<20; ++a)
+// for (z[a]=0.0, b=0; b<20; ++b) z[a]+=P[a][b];
+// printf("Adjust A R N D C Q E G H I L K M F P S T W Y V\nErr? ");
+// for (a=0; a<20; ++a) printf("%4.0f ",1000*z[a]/qav[a]);
+// cout<<endl<<"xa ";
+// for (a=0; a<20; ++a) fprintf(stdout,"%4.2f ",x[a]);
+// cout<<endl;
+// }
+
+// // Evaluate sequence identity underlying substitution matrix
+// if (v>=3)
+// {
+// float id=0.0f;
+// float entropy=0.0f;
+// float entropy_qav=0.0f;
+// float mut_info=0.0f;
+// for (a=0; a<20; ++a) id += P[a][a];
+// for (a=0; a<20; ++a) entropy_qav-=qav[a]*fast_log2(qav[a]);
+// for (a=0; a<20; ++a)
+// for (b=0; b<20; ++b)
+// {
+// entropy-=P[a][b]*fast_log2(R[a][b]);
+// mut_info += P[a][b]*fast_log2(P[a][b]/qav[a]/qav[b]);
+// }
+
+// fprintf(stdout,"Rescaling rate matrix: sequence identity = %2.0f%%; entropy per column = %4.2f bits (out of %4.2f); mutual information = %4.2f bits\n",100*id,entropy,entropy_qav,mut_info);
+// }
+// return;
+// }
+
+
+/* @* HMM::ClobberGlobal (eg, q,t)
+ */
+void
+HMM::ClobberGlobal(void){
+
+ for (int i = 0; i < n_display; i++){
+ if (sname[i]){
+ delete[] sname[i]; sname[i] = NULL;
+ }
+ if (seq[i]){
+ delete[] seq[i]; seq[i] = NULL;
+ }
+ }
+ Neff_M[0] = Neff_I[0] = Neff_D[0] = 0.0;
+ longname[0] = '\0'; file[0] = '\0';
+ ss_dssp[0] = sa_dssp[0] = ss_pred[0] = ss_conf[0] = '\0';
+ Xcons = NULL;
+ l[0] = 0;
+ L = 0;
+ Neff_HMM = 0;
+ n_display = N_in = N_filtered = 0;
+ nss_dssp = nsa_dssp = nss_pred = nss_conf = nfirst = ncons = -1;
+ lamda = 0.0; mu = 0.0;
+ name[0] = longname[0] = fam[0] = '\0';
+
+ for (int i = 0; i < NAA; i++){
+ pav[i] = 0;
+ }
+
+ /* @= */
+ return;
+
+} /* this is the end of ClobberGlobal() */
+
+
+/*
+ * EOF hhhmm-C.h
+ */
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