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Migrated tool version 0.2 from old tool shed archive to new tool shed repository
| author | clustalomega |
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| date | Tue, 07 Jun 2011 16:13:02 -0400 |
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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: 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 */