hmmpostal.c

hmmer源程序

/************************************************************
 * HMMER - Biological sequence analysis with profile HMMs
 * Copyright (C) 1992-1999 Washington University School of Medicine
 * All Rights Reserved
 * 
 *     This source code is distributed under the terms of the
 *     GNU General Public License. See the files COPYING and LICENSE
 *     for details.
 ************************************************************/

/* Derived from code developed by Ian Holmes (Sanger Centre and UC Berkeley)
 * Copyright (C) 1998 Ian Holmes
 * Distributed under the GNU General Public License
 */

#include <stdio.h>
#include <stdlib.h>
#include <string.h>

#include "structs.h"		/* data structures, macros, #define's   */
#include "config.h"		/* compile-time configuration constants */
#include "funcs.h"		/* function declarations                */
#include "globals.h"		/* alphabet global variables            */
#include "squid.h"		/* general sequence analysis library    */

static char banner[] = "hmmbuild - build a hidden Markov model from an alignment";

static char usage[]  = "\
Usage: hmmbuildpost [-options] <alignment file>\n\
  Available options are:\n\
   -h           : help; print brief help on version and usage\n\
   -n <s>       : name; name this HMM <s>\n\
   -r <hmmfile> : read HMM from <file> instead of building\n\
   -m <hmmfile> : save HMM to <file>\n\
   -o <file>    : re-save annotated alignment to <file>\n\
   -A           : append; append this HMM to <hmmfile>\n\
   -F           : force; allow overwriting of <hmmfile>\n\
\n\
  Alternative search algorithm styles: (default: hmmls domain alignment)\n\
   -f        : multi-hit local (hmmfs style)\n\
   -g        : global alignment (hmms style, Needleman/Wunsch)\n\
   -s        : local alignment (hmmsw style, Smith/Waterman)\n\
";

static char experts[] = "\
  Optional re-alignment of sequences to model:\n\
   --viterbi : standard max-likelihood (Viterbi) algorithm\n\
   --optacc  : optimal accuracy algorithm\n\
\n\
  Alternative model construction strategies: (default: MAP)\n\
   --fast    : Krogh/Haussler fast heuristic construction (see --gapmax)\n\
   --hand    : manual construction (requires SELEX file, #=RF annotation)\n\
\n\
  Expert customization of parameters and priors:\n\
   --null  <file> : read null (random sequence) model from <file>\n\
   --pam <file>   : heuristic PAM-based prior, using BLAST PAM matrix in <file>\n\
   --prior <file> : read Dirichlet prior parameters from <file>\n\
\n\
  Alternative sequence weighting strategies: (default: GSC weights)\n\
   --wblosum     : Henikoff simple filter weights (see --idlevel)\n\
   --wgsc        : Gerstein/Sonnhammer/Chothia tree weights (default)\n\
   --wme         : maximum entropy (ME)\n\
   --wvoronoi    : Sibbald/Argos Voronoi weights\n\
   --wnone       : don't do any weighting\n\
   --noeff       : don't use effective sequence number; just use nseq\n\
\n\
  Forcing an alphabet: (normally autodetected)\n\
   --amino   : override autodetection, assert that seqs are protein\n\
   --nucleic : override autodetection, assert that seqs are DNA/RNA\n\
\n\
  Other expert options:\n\
   --archpri <x> : set architecture size prior to <x> {0.85} [0..1]\n\
   --binary      : save the model in binary format, not ASCII text\n\
   --cfile <file>: save count vectors to <file>\n\
   --gapmax <x>  : max fraction of gaps in mat column {0.50} [0..1]\n\
   --idlevel <x> : set frac. id level used by eff. nseq and --wblosum {0.62}\n\
   --informat <s>: input alignment is in format <s>, not Stockholm\n\
   --pamwgt <x>  : set weight on PAM-based prior to <x> {20.}[>=0]\n\
   --swentry <x> : set S/W aggregate entry prob. to <x> {0.5}\n\
   --swexit <x>  : set S/W aggregate exit prob. to <x>  {0.5}\n\
   --verbose     : print a lot of boring information\n\
\n";

static struct opt_s OPTIONS[] = {
  { "-f", TRUE, sqdARG_NONE },
  { "-g", TRUE, sqdARG_NONE }, 
  { "-h", TRUE, sqdARG_NONE }, 
  { "-n", TRUE, sqdARG_STRING},  
  { "-r", TRUE, sqdARG_STRING},
  { "-m", TRUE, sqdARG_STRING},
  { "-o", TRUE, sqdARG_STRING},
  { "-s", TRUE, sqdARG_NONE }, 
  { "-A", TRUE, sqdARG_NONE },
  { "-F", TRUE, sqdARG_NONE },
  { "--amino",   FALSE, sqdARG_NONE  },
  { "--archpri", FALSE, sqdARG_FLOAT }, 
  { "--binary",  FALSE, sqdARG_NONE  }, 
  { "--cfile",   FALSE, sqdARG_STRING},
  { "--fast",    FALSE, sqdARG_NONE},
  { "--gapmax",  FALSE, sqdARG_FLOAT },
  { "--hand",    FALSE, sqdARG_NONE},
  { "--idlevel", FALSE, sqdARG_FLOAT },
  { "--informat",FALSE, sqdARG_STRING },
  { "--noeff",   FALSE, sqdARG_NONE },
  { "--nucleic", FALSE, sqdARG_NONE },
  { "--null",    FALSE, sqdARG_STRING },
  { "--optacc",  FALSE, sqdARG_NONE  },
  { "--pam",     FALSE, sqdARG_STRING },
  { "--pamwgt",  FALSE, sqdARG_FLOAT },
  { "--prior",   FALSE, sqdARG_STRING },
  { "--swentry", FALSE, sqdARG_FLOAT },
  { "--swexit",  FALSE, sqdARG_FLOAT },
  { "--verbose", FALSE, sqdARG_NONE  },
  { "--viterbi", FALSE, sqdARG_NONE  },
  { "--wgsc",    FALSE, sqdARG_NONE },
  { "--wblosum", FALSE, sqdARG_NONE },
  { "--wme",     FALSE, sqdARG_NONE },
  { "--wnone",   FALSE, sqdARG_NONE },
  { "--wvoronoi",FALSE, sqdARG_NONE },
};
#define NOPTIONS (sizeof(OPTIONS) / sizeof(struct opt_s))

static void save_model(struct plan7_s *hmm, char *hmmfile, int do_append, int do_binary);
static void print_all_scores(FILE *fp, struct plan7_s *hmm, 
			     AINFO *ainfo, char **dsq, int nseq, 
			     struct p7trace_s **tr);
static void save_countvectors(char *cfile, struct plan7_s *hmm);
static void position_average_score(struct plan7_s *hmm, char **seq, float *wgt,
				   int nseq, struct p7trace_s **tr, float *pernode,
				   float *ret_avg);
static float frag_trace_score(struct plan7_s *hmm, char *dsq, struct p7trace_s *tr, 
			      float *pernode, float expected);
static void maximum_entropy(struct plan7_s *hmm, char **dsq, AINFO *ainfo, 
			    int nseq, float eff_nseq, 
			    struct p7prior_s *prior, struct p7trace_s **tr);

extern void Postcode(int L, struct dpmatrix_s *mx, struct p7trace_s *tr);

int
main(int argc, char **argv) 
{
  char            *seqfile;     /* seqfile to read alignment from          */ 
  int              format;	/* format of seqfile                       */
  MSAFILE         *afp;         /* open alignment file                     */
  MSA             *msa;         /* a multiple sequence alignment           */
  char           **dsq;         /* digitized unaligned aseq's              */ 
  struct plan7_s  *hmm;         /* constructed HMM; written to hmmfile     */
  struct p7prior_s *pri;        /* Dirichlet priors to use                 */
  struct p7trace_s **tr;        /* fake tracebacks for aseq's              */ 
  char            *readfile;    /* file to read HMM from                   */
  HMMFILE         *hmmfp;       /* opened hmmfile for reading              */
  char            *hmmfile;     /* file to write HMM to                    */
  FILE            *fp;          /* OUTPUT file handle (misc.)              */
  char            *name;        /* name of the HMM                         */
  int              idx;		/* counter for sequences                   */
  float  randomseq[MAXABET];	/* null sequence model                     */
  float            p1;		/* null sequence model p1 transition       */

  char *optname;                /* name of option found by Getopt()      */
  char *optarg;                 /* argument found by Getopt()            */
  int   optind;                 /* index in argv[]                       */
  enum p7_construction c_strategy; /* construction strategy choice        */
  enum p7_weight {		/* weighting strategy */
    WGT_NONE, WGT_GSC, WGT_BLOSUM, WGT_VORONOI, WGT_ME} w_strategy;
  enum p7_config {              /* algorithm configuration strategy      */
    P7_BASE_CONFIG, P7_LS_CONFIG, P7_FS_CONFIG, P7_SW_CONFIG } cfg_strategy;
  float gapmax;			/* max frac gaps in mat col for -k       */
  int   overwrite_protect;	/* TRUE to prevent overwriting HMM file  */
  enum  realignment_strategy {  /* re-alignment strategy                 */
    REALIGN_NONE, REALIGN_VITERBI, REALIGN_OPTACC } r_strategy;
  int   verbose;		/* TRUE to show a lot of output          */
  char *align_ofile;            /* name of output alignment file         */
  char *rndfile;		/* random sequence model file to read    */
  char *prifile;		/* Dirichlet prior file to read          */
  char *pamfile;		/* PAM matrix file for heuristic prior   */
  char *cfile;			/* output file for count vectors         */
  float archpri;		/* "architecture" prior on model size    */
  float pamwgt;			/* weight on PAM for heuristic prior     */
  int   do_append;		/* TRUE to append to hmmfile             */
  int   do_binary;		/* TRUE to write in binary format        */
  float blosumlevel;		/* BLOSUM frac id filtering level [0.62] */
  float swentry;		/* S/W aggregate entry probability       */
  float swexit;			/* S/W aggregate exit probability        */
  int   do_eff;			/* TRUE to set an effective seq number   */
  float eff_nseq;		/* effective sequence number             */
  int   checksum;
  int   len;

  struct dpmatrix_s *forward_mx;   /* Forward matrix                        */
  struct dpmatrix_s *backward_mx;  /* Backward matrix                       */
  struct dpmatrix_s *posterior_mx; /* Posterior matrix                      */
  struct dpmatrix_s *optacc_mx;    /* Optimal accuracy matrix               */

  /*********************************************** 
   * Parse command line
   ***********************************************/
  
  format            = MSAFILE_UNKNOWN;
  c_strategy        = P7_MAP_CONSTRUCTION;
  w_strategy        = WGT_GSC;
  blosumlevel       = 0.62;
  cfg_strategy      = P7_LS_CONFIG;
  gapmax            = 0.5;
  overwrite_protect = TRUE;
  r_strategy        = REALIGN_NONE;
  verbose           = FALSE;
  readfile          = NULL;
  hmmfile           = NULL;
  align_ofile       = NULL;
  rndfile           = NULL;
  prifile           = NULL;
  pamfile           = NULL;
  cfile             = NULL;
  archpri           = 0.85;
  pamwgt            = 20.;
  Alphabet_type     = hmmNOTSETYET;	/* initially unknown */
  name              = NULL;
  do_append         = FALSE; 
  swentry           = 0.5;
  swexit            = 0.5;
  do_eff            = TRUE;
  do_binary         = FALSE;
  
  while (Getopt(argc, argv, OPTIONS, NOPTIONS, usage,
                &optind, &optname, &optarg))  {
    if      (strcmp(optname, "-f") == 0) cfg_strategy      = P7_FS_CONFIG;
    else if (strcmp(optname, "-g") == 0) cfg_strategy      = P7_BASE_CONFIG;
    else if (strcmp(optname, "-n") == 0) name              = Strdup(optarg); 
    else if (strcmp(optname, "-r") == 0) readfile          = optarg;
    else if (strcmp(optname, "-m") == 0) hmmfile           = optarg;
    else if (strcmp(optname, "-o") == 0) align_ofile       = optarg;
    else if (strcmp(optname, "-r") == 0) rndfile           = optarg;
    else if (strcmp(optname, "-s") == 0) cfg_strategy      = P7_SW_CONFIG;
    else if (strcmp(optname, "-A") == 0) do_append         = TRUE; 
    else if (strcmp(optname, "-F") == 0) overwrite_protect = FALSE;
    else if (strcmp(optname, "--amino")   == 0) SetAlphabet(hmmAMINO);
    else if (strcmp(optname, "--archpri") == 0) archpri       = atof(optarg);
    else if (strcmp(optname, "--binary")  == 0) do_binary     = TRUE;
    else if (strcmp(optname, "--cfile")   == 0) cfile         = optarg;
    else if (strcmp(optname, "--fast")    == 0) c_strategy    = P7_FAST_CONSTRUCTION;
    else if (strcmp(optname, "--hand")    == 0) c_strategy    = P7_HAND_CONSTRUCTION;
    else if (strcmp(optname, "--gapmax")  == 0) gapmax        = atof(optarg);
    else if (strcmp(optname, "--idlevel") == 0) blosumlevel   = atof(optarg);
    else if (strcmp(optname, "--noeff")   == 0) do_eff        = FALSE;
    else if (strcmp(optname, "--nucleic") == 0) SetAlphabet(hmmNUCLEIC);
    else if (strcmp(optname, "--optacc")  == 0) r_strategy    = REALIGN_OPTACC;
    else if (strcmp(optname, "--pam")     == 0) pamfile       = optarg;
    else if (strcmp(optname, "--pamwgt")  == 0) pamwgt        = atof(optarg);
    else if (strcmp(optname, "--prior")   == 0) prifile       = optarg;
    else if (strcmp(optname, "--swentry") == 0) swentry       = atof(optarg); 
    else if (strcmp(optname, "--swexit")  == 0) swexit        = atof(optarg); 
    else if (strcmp(optname, "--verbose") == 0) verbose       = TRUE;
    else if (strcmp(optname, "--viterbi") == 0) r_strategy    = REALIGN_VITERBI;
    else if (strcmp(optname, "--wgsc")    == 0) w_strategy    = WGT_GSC;
    else if (strcmp(optname, "--wblosum") == 0) w_strategy    = WGT_BLOSUM; 
    else if (strcmp(optname, "--wme")     == 0) w_strategy    = WGT_ME;  
    else if (strcmp(optname, "--wnone")   == 0) w_strategy    = WGT_NONE; 
    else if (strcmp(optname, "--wvoronoi")== 0) w_strategy    = WGT_VORONOI;
    else if (strcmp(optname, "--informat") == 0) {
      format = String2SeqfileFormat(optarg);
      if (format == MSAFILE_UNKNOWN) 
	Die("unrecognized sequence file format \"%s\"", optarg);
      if (! IsAlignmentFormat(format))
	Die("%s is an unaligned format, can't read as an alignment", optarg);
    }
    else if (strcmp(optname, "-h") == 0) {
      Banner(stdout, banner);
      puts(usage);
      puts(experts);
      exit(0);
    }
  }
  if (argc - optind != 1)
    Die("Incorrect number of arguments.\n%s\n", usage);

  seqfile = argv[optind++]; 

  if (readfile != NULL && r_strategy == REALIGN_NONE)
    r_strategy = REALIGN_VITERBI;

  if (gapmax < 0. || gapmax > 1.) 
    Die("--gapmax must be a value from 0 to 1\n%s\n", usage);
  if (archpri < 0. || archpri > 1.)
    Die("--archpri must be a value from 0 to 1\n%s\n", usage);
  if (overwrite_protect && hmmfile && !do_append && FileExists(hmmfile))
    Die("HMM file %s already exists. Rename or delete it.", hmmfile); 
  if (overwrite_protect && align_ofile != NULL && FileExists(align_ofile))
    Die("Alignment resave file %s exists. Rename or delete it.", align_ofile); 

  /*********************************************** 
   * Get sequence data
   ***********************************************/

				/* Open the alignment */
  if ((afp = MSAFileOpen(seqfile, format, NULL)) == NULL)
    Die("Alignment file %s could not be opened for reading", seqfile);

                                /* read the alignment from file */
  if ((msa = MSAFileRead(afp)) == NULL) 
    Die("Failed to read aligned sequence file %s", seqfile);
  for (idx = 0; idx < msa->nseq; idx++)
    s2upper(msa->aseq[idx]);
  MSAFileClose(afp);
				/* Set up the alphabet globals */
  if (Alphabet_type == hmmNOTSETYET) 
    DetermineAlphabet(msa->aseq, msa->nseq);

				/* Set up Dirichlet priors */
  if (prifile == NULL)  pri = P7DefaultPrior();
  else                  pri = P7ReadPrior(prifile);

  if (pamfile != NULL)  PAMPrior(pamfile, pri, pamwgt);

				/* Set up the null/random seq model */
  if (rndfile == NULL)  P7DefaultNullModel(randomseq, &p1);
  else                  P7ReadNullModel(rndfile, randomseq, &p1);

				/* Prepare sequences for internal use */
  DigitizeAlignment(msa, &dsq);
  
				/* In some respects we treat DNA more crudely... */
  if (Alphabet_type == hmmNUCLEIC)
    {
      do_eff     = FALSE;	/* don't do effective seq #; it's calibrated for protein */
    }

 /*********************************************** 
  * Either read in an HMM or build from alignment,
  * depending on user specifications.
  ***********************************************/

  if (readfile != NULL) {

    /*********************************************** 
     * Open HMM file (might be in HMMERDB or current directory).
     * Read a single HMM from it.
     ***********************************************/
    
    if ((hmmfp = HMMFileOpen(readfile, "HMMERDB")) == NULL)
      Die("Failed to open HMM file %s\n%s", readfile, usage);
    if (!HMMFileRead(hmmfp, &hmm)) 
      Die("Failed to read any HMMs from %s\n", readfile);
    HMMFileClose(hmmfp);
    if (hmm == NULL) 
      Die("HMM file %s corrupt or in incorrect format? Parse failed", readfile);

    tr = (struct p7trace_s **) MallocOrDie (sizeof(struct p7trace_s *) * msa->nseq);
    for (idx = 0; idx < msa->nseq; idx++)
      tr[idx] = 0;

  } else {

    /*********************************************** 
     * Build an HMM
     ***********************************************/
    
    /* Determine the effective sequence number to use (optional)
     */
    eff_nseq = (float) msa->nseq;
    if (do_eff)
      {
	float *wgt;
	printf("%-40s ... ", "Determining effective sequence number");
	fflush(stdout);
				/* dummy weights array to feed BlosumWeights*/
	wgt = MallocOrDie(sizeof(float) * msa->nseq);
	BlosumWeights(msa->aseq, msa->nseq, msa->alen, blosumlevel, wgt);
	eff_nseq = FSum(wgt, msa->nseq);

	free(wgt);