File: genestats.dy

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%{
#include "wisebase.h"
#include "seqalign.h"
#include "pwmdna.h"
#include "randommodel.h"
#include "complexsequence.h"
#include "complexevalset.h" /* for the standard evals */


#define DEFAULT_SPLICE_OFFSET_SCORE 1.5


%}

struct SpliceSiteScore
pwmDNAScore * score
int offset
Score min_collar  
Score max_collar
Score score_offset

struct GeneStats
SeqAlign * splice5
int splice5_offset
SeqAlign * splice3
int splice3_offset
RandomModelDNA * intron; !def="NULL"// actually counts
double average_intron
RandomModelDNA * polyp;  !def="NULL"// actually counts
double average_polyp
RandomModelDNA * rnd; !def="NULL" 
double codon[64]
%info
This structure is to hold the
new generation of gene statistics
for the genewise algorithms
%%

struct GeneModelParam
double splice5_pseudo
double splice3_pseudo
double intron_emission_pseudo
double polyp_emission_pseudo
Bits   min_collar
Bits   max_collar
Bits   score_offset
char * gene_stats_file
boolean use_gtag_splice
double  prob_for_gtag
%info
A small helper object containing
the ways of converting the actual
counts/alignments to the model

Here really for convience so we can
keep all the code associated with the
creation of the GeneModel together
%%

struct GeneModel
pwmDNA * splice5
int splice5_offset
pwmDNA * splice3
int splice3_offset
RandomModelDNA * intron
double intron_stay_prob
RandomModelDNA * polyp
double polyp_stay_prob
RandomModelDNA * rnd
SpliceSiteScore * splice5score
SpliceSiteScore * splice3score
double codon[64]
boolean use_gtag_splice
Score   score_for_gtag
%info
This structure is to hold the
new generation of models for the
genewise algorithm

%%


struct GeneralGeneModelScore
RandomCodonScore * start
RandomCodonScore * stop
RandomCodonScore * general


%{
#include "genestats.h"


%func
Shows help
%%
void show_help_GeneModelParam(FILE * ofp)
{

  fprintf(ofp,"New gene model statistics\n");
  fprintf(ofp,"  -splice_max_collar      [5.0]  maximum Bits value for a splice site \n");
  fprintf(ofp,"  -splice_min_collar      [-5.0] minimum Bits value for a splice site \n");
  fprintf(ofp,"  -splice_score_offset    [%.1f]  score offset for splice sites\n",DEFAULT_SPLICE_OFFSET_SCORE);
  fprintf(ofp,"  -[no]splice_gtag        make just gtag splice sites (default is gtag, ie no model)\n");  
  fprintf(ofp,"  -splice_gtag_prob       [0.001] probability for gt/ag \n");
  fprintf(ofp,"  -genestats              [/usr/share/wise/gene.stat]\n");

}

%func
Shows genemodel param for info
%%
void show_info_GeneModelParam(GeneModelParam * p,FILE * ofp)
{
  fprintf(ofp,"Gene Parameter file: %s\n",p->gene_stats_file);
  fprintf(ofp,"Splice site model:   %s\n",p->use_gtag_splice == TRUE ? "GT/AG only" : "Position Weight Matrix");
  if( p->use_gtag_splice == FALSE ) {
    fprintf(ofp,"Pseudo counts 5'SS   %1.2f\n",p->splice5_pseudo);
    fprintf(ofp,"Pseudo counts 3'SS   %1.2f\n",p->splice3_pseudo);
    fprintf(ofp,"Minimum SS collar    %2.2f\n",p->min_collar);
    fprintf(ofp,"Maximum SS collar    %2.2f\n",p->max_collar);
    fprintf(ofp,"Splice site offset   %2.2f\n",p->score_offset);
  } else {

    fprintf(ofp,"GT/AG bits penalty   %2.2f\n",Probability2Bits(p->prob_for_gtag));
  }
  
}

%func
Makes a GeneModelParam from argv
%%
GeneModelParam * new_GeneModelParam_from_argv(int * argc,char ** argv)
{
  GeneModelParam * out;
  char * temp;

  out = std_GeneModelParam();
  
  if( (temp=strip_out_assigned_argument(argc,argv,"splice_min_collar")) != NULL ) {
    if( is_double_string(temp,&out->min_collar) == FALSE ) {
      warn("%s is not a floating point number. Can't be a splice_min_collar",temp);
      free_GeneModelParam(out);
      return NULL;
    } 
  }

  strip_out_boolean_def_argument(argc,argv,"splice_gtag",&out->use_gtag_splice);

  if( (temp=strip_out_assigned_argument(argc,argv,"splice_max_collar")) != NULL ) {
    if( is_double_string(temp,&out->max_collar) == FALSE ) {
      warn("%s is not a floating point number. Can't be a splice_max_collar",temp);
      free_GeneModelParam(out);
      return NULL;
    } 
  }

  if( (temp=strip_out_assigned_argument(argc,argv,"splice_score_offset")) != NULL ) {
    if( is_double_string(temp,&out->score_offset) == FALSE ) {
      warn("%s is not a floating point number. Can't be a splice_score_offset",temp);
      free_GeneModelParam(out);
      return NULL;
    } 
  }

  if( (temp=strip_out_assigned_argument(argc,argv,"genestats")) != NULL ) {
    if( out->gene_stats_file != NULL ) {
      ckfree(out->gene_stats_file);
    }

    out->gene_stats_file = stringalloc(temp);
  }

  if( (temp=strip_out_assigned_argument(argc,argv,"splice_gtag_prob")) != NULL ) {
    if( is_double_string(temp,&out->prob_for_gtag) == FALSE ) {
      warn("%s is not a floating pointer number. Can't be a probability for gtag",temp);
      free_GeneModelParam(out);
      return NULL;
    }
  }


  return out;

}

%func
Makes a vanilla general gene model score
%%
GeneralGeneModelScore * vanilla_GeneralGeneModelScore(CodonTable * ct,Probability start_odds,Probability general_odds,Probability stop_odds)
{
  GeneralGeneModelScore * out;
  RandomCodon * temp;
  out = GeneralGeneModelScore_alloc();

  temp = vanilla_start_RandomCodon(ct,start_odds);
  out->start = RandomCodonScore_from_RandomCodon(temp);
  free_RandomCodon(temp);

  temp  = vanilla_stop_RandomCodon(ct,stop_odds);
  out->stop = RandomCodonScore_from_RandomCodon(temp);
  free_RandomCodon(temp);

  temp  = vanilla_general_RandomCodon(ct,general_odds);
  out->general = RandomCodonScore_from_RandomCodon(temp);
  free_RandomCodon(temp);

  return out;
}

%func
Makes a vanilla (ie, all things equal) Met based
start codon rndscore
%%
RandomCodon * vanilla_start_RandomCodon(CodonTable * ct,Probability start_codon_odd_prob)
{
  int i;
  RandomCodon * out;

  out = RandomCodon_alloc();
  
  for(i=0;i<125;i++) {
    if( aminoacid_from_codon(ct,i) == 'M' ) {
      out->codon[i] = start_codon_odd_prob;
    } else {
      out->codon[i] = 0.0;
    }
  }

  return out;
}

%func
Makes a vanilla (ie, all things equal) * based
stop codon rndscore
%%
RandomCodon * vanilla_stop_RandomCodon(CodonTable * ct,Probability stop_codon_odd_prob)
{
  int i;
  RandomCodon * out;

  out = RandomCodon_alloc();
  
  for(i=0;i<125;i++) {
    if( aminoacid_from_codon(ct,i) == 'X' ) {
      out->codon[i] = stop_codon_odd_prob;
    } else {
      out->codon[i] = 0.0;
    }
  }
  return out;
}

%func
Makes a vanilla (ie, all things equal) general non-stop
%%
RandomCodon * vanilla_general_RandomCodon(CodonTable * ct,Probability coding_odd_prob)
{
  int i;
  RandomCodon * out;

  out = RandomCodon_alloc();
  
  for(i=0;i<125;i++) {
    if( aminoacid_from_codon(ct,i) == 'X' ) {
      out->codon[i] = 0.0;
    } else {
      out->codon[i] = coding_odd_prob;
    }
  }

  return out;
}


%func
Makes a standard GeneModelParam
%%
GeneModelParam * std_GeneModelParam(void)
{
  GeneModelParam * out;

  out = GeneModelParam_alloc();

  out->splice5_pseudo = 1.0;
  out->splice3_pseudo = 1.0;
  out->intron_emission_pseudo = 1.0;
  out->polyp_emission_pseudo  = 1.0;

  out->min_collar   = -5.0;
  out->max_collar   = +5.0;
  out->score_offset = DEFAULT_SPLICE_OFFSET_SCORE;
  out->gene_stats_file = stringalloc("/usr/share/wise/gene.stat");
  out->use_gtag_splice = TRUE;

  out->prob_for_gtag = 0.001;

  return out;
}

%func
Combines GeneStats_from_GeneModelParam and GeneModel_from_GeneStats
%%
GeneModel * GeneModel_from_GeneModelParam(GeneModelParam * p)
{
  GeneStats * st;
  GeneModel * out;

  assert(p);

  st = GeneStats_from_GeneModelParam(p);

  assert(st);

  out = GeneModel_from_GeneStats(st,p);

  assert(out);

  free_GeneStats(st);

  return out;
}


%func
Makes a GeneStats from GeneModelParam - basically just opening the file
%%
GeneStats * GeneStats_from_GeneModelParam(GeneModelParam * p)
{
  GeneStats * gs;
  FILE * ifp;

  assert(p);
  assert(p->gene_stats_file);

  ifp = openfile(p->gene_stats_file,"r");
  if( ifp == NULL ) {
    warn("Unable to open %s  as gene stats file",p->gene_stats_file);
    return NULL;
  }

  gs = read_GeneStats(ifp);

  return gs;
}
  

%func
Makes a model from the stats file
%%
GeneModel * GeneModel_from_GeneStats(GeneStats * gs,GeneModelParam * p)
{
  GeneModel * out;
  int i;
  double total;

  out = GeneModel_alloc();

  assert(gs);
  assert(gs->splice5);
  assert(gs->splice3);
  assert(gs->intron);
  assert(gs->rnd);
  

  for(i=0;i<64;i++) {
     out->codon[i] = gs->codon[i];
  }
  
  out->splice5 = pwmDNA_from_SeqAlign(gs->splice5,p->splice5_pseudo);
  
  /*  fprintf(stdout,"GS splice5 %d splice3 %d\n",gs->splice5,gs->splice3);*/

  fold_randommodel_pwmDNA(out->splice5,gs->rnd);

  out->splice5score = SpliceSiteScore_alloc();
  out->splice5score->score = pwmDNAScore_from_pwmDNA(out->splice5);
  out->splice5score->offset = gs->splice5_offset;
  out->splice5score->min_collar   = Probability2Score(Bits2Probability(p->min_collar));
  out->splice5score->max_collar   = Probability2Score(Bits2Probability(p->max_collar));
  out->splice5score->score_offset = Probability2Score(Bits2Probability(p->score_offset));
 

  out->splice3 = pwmDNA_from_SeqAlign(gs->splice3,p->splice3_pseudo);
  fold_randommodel_pwmDNA(out->splice3,gs->rnd);

  out->splice3score = SpliceSiteScore_alloc();
  out->splice3score->score = pwmDNAScore_from_pwmDNA(out->splice3);
  out->splice3score->offset = gs->splice3_offset;
  out->splice3score->min_collar   = Probability2Score(Bits2Probability(p->min_collar));
  out->splice3score->max_collar   = Probability2Score(Bits2Probability(p->max_collar));
  out->splice3score->score_offset = Probability2Score(Bits2Probability(p->score_offset));

  out->use_gtag_splice = p->use_gtag_splice;
  out->score_for_gtag  = Probability2Score(p->prob_for_gtag);

  out->intron  = RandomModelDNA_alloc();
  for(total = 0.0,i=0;i<4;i++)
    total += gs->intron->base[i] + p->intron_emission_pseudo;

  for(i=0;i<4;i++)
    out->intron->base[i] = (gs->intron->base[i] + p->intron_emission_pseudo)/total;

  out->intron->base[4] = 1.0;

  if( gs->polyp != NULL ) {
    out->polyp  = RandomModelDNA_alloc();
    for(total = 0.0,i=0;i<4;i++)
     total += gs->polyp->base[i] + p->polyp_emission_pseudo;

    for(i=0;i<4;i++)
       out->polyp->base[i] = (gs->polyp->base[i] + p->polyp_emission_pseudo)/total;
  }

  out->rnd = hard_link_RandomModelDNA(gs->rnd);
  return out;
}


%func
shows a genemodel
%%
void show_GeneModel(GeneModel * gm,FILE * ofp)
{
  fprintf(ofp,"Splice5\n");
  show_pwmDNA_col(gm->splice5,ofp);
  fprintf(ofp,"Splice3\n");
  show_pwmDNA_col(gm->splice3,ofp);
}

%func
Makes an entire ComplexSequenceEvalSet for genomic work
%%
ComplexSequenceEvalSet * new_ComplexSequenceEvalSet_from_GeneModel(GeneModel * gm)
{
  ComplexSequenceEvalSet * out;

  assert(gm);
  assert(gm->splice5score);
  assert(gm->splice3score);

  out = ComplexSequenceEvalSet_alloc_len(11);

  add_ComplexSequenceEvalSet(out,base_number_ComplexSequenceEval());
  add_ComplexSequenceEvalSet(out,codon_number_ComplexSequenceEval());
  if( gm->use_gtag_splice == FALSE ) {
    add_ComplexSequenceEvalSet(out,ComplexSequenceEval_from_pwmDNAScore_splice(gm->splice5score));
    add_ComplexSequenceEvalSet(out,ComplexSequenceEval_from_pwmDNAScore_splice(gm->splice3score));
  } else {
    add_ComplexSequenceEvalSet(out,ComplexSequenceEval_for_scored_gt(&gm->score_for_gtag));
    add_ComplexSequenceEvalSet(out,ComplexSequenceEval_for_scored_ag(&gm->score_for_gtag));
  }

  add_ComplexSequenceEvalSet(out,flat_zero());
  add_ComplexSequenceEvalSet(out,flat_zero());


  out->type = SEQUENCE_GENOMIC;

  prepare_ComplexSequenceEvalSet(out);

  return out;
}


%func
Makes a ComplexSequenceEval for a GT rule
%type internal
%%
ComplexSequenceEval * ComplexSequenceEval_for_scored_ag(Score * score_for_ag)
{
  ComplexSequenceEval * out;

  out = ComplexSequenceEval_alloc();

  out->left_window   = 3;
  out->right_window  = 3;
  out->left_lookback = 5;
  out->outside_score = NEGI;

  out->data = (void*) score_for_ag;
  out->type = SEQUENCE_GENOMIC;
  out->eval_func = scored_ag_eval_func;
  out->score_type = CseScoreType_Bits;

  return out;
}

%func
Function which actually does the evaluation for scored doners
%type internal
%arg
%%
int scored_ag_eval_func(int type,void *data,char * seq)
{
  if( *(seq-1) == 'A' && *(seq) == 'G' ) 
    return *(Score *)data;
  else return NEGI;
}

%func
Makes a ComplexSequenceEval for a GT rule
%type internal
%%
ComplexSequenceEval * ComplexSequenceEval_for_scored_gt(Score * score_for_gt)
{
  ComplexSequenceEval * out;

  out = ComplexSequenceEval_alloc();

  out->left_window   = 3;
  out->right_window  = 7;
  out->left_lookback = 8;
  out->outside_score = NEGI;

  out->data = (void*) score_for_gt;
  out->type = SEQUENCE_GENOMIC;
  out->eval_func = scored_gt_eval_func;
  out->score_type = CseScoreType_Bits;

  return out;
}

%func
Function which actually does the evaluation for scored doners
%type internal
%arg
%%
int scored_gt_eval_func(int type,void *data,char * seq)
{
  if( *(seq) == 'G' && *(seq+1) == 'T' ) 
    return *(Score *)data;
  else return NEGI;
}


%func
Makes a ComplexSequenceEval for a splice site
pwmdna
%type internal
%%
ComplexSequenceEval * ComplexSequenceEval_from_pwmDNAScore_splice(SpliceSiteScore * score)
{
  ComplexSequenceEval * out;


  /*  printf("Making CSE from %d\n",score);*/

  out = ComplexSequenceEval_alloc();

  /* shouldn't really add ones, but this is ok anyway. 
     Yukky hack due to not understanding a bug in the window 
     determination
     */

  /**
   *STILL don't know precisely what is going on down here! ***/

  /*  out->left_window  = ssm->offset + ssm->pre_splice_site +1; */
  out->left_window   =10;
  /*  out->right_window = ssm->offset + ssm->post_splice_site +1; */
  out->right_window  =10;
  out->left_lookback =10;

  out->outside_score= NEGI;
  out->data_type    = 245; /* any old key */
  out->data         = (void *) score;
  out->type         = SEQUENCE_GENOMIC;
  out->eval_func    = pwmDNA_splice_ComplexSequence_eval_func;
  out->score_type   = CseScoreType_Bits;

  return out;
}

%func
This function is used as a pointer to function in the eval func

You should never be using this function yourself!
%type internal
%%
int pwmDNA_splice_ComplexSequence_eval_func(int type,void * data,char * seq)
{
  SpliceSiteScore * sc;
  pwmDNAScore * pds;
  int score;

  sc  = (SpliceSiteScore* ) data;
  pds = sc->score;

  /* offset is written in biological coordinates. Need to get c style coordiates */

  /* no idea what is happening here, but it works ;) */


  if( seq[0] == 'N' && seq[1] == 'N' && seq[2] == 'N' ) {
    return NEGI;
  }

  score = score_pwmDNAScore_string(pds,seq-sc->offset+1);

/*  printf("Offset is %d %c%c%c\n",sc->offset,seq[0],seq[1],seq[2]);*/

/*  fprintf(stdout,"Before collaring, %d\n",score);*/

  if( score < sc->min_collar ) {
    score = sc->min_collar;
  }
  if( score > sc->max_collar ) {
    score = sc->max_collar;
  }

/*  fprintf(stdout,"Score %d before offset\n",score);*/

  score -= sc->score_offset;

/*  fprintf(stdout,"Score %d after offset\n",score);*/

  /*  fprintf(stderr,"Scoring %d at some position\n",score);*/

  return score;
}

%func
Reads a GeneStats file
%%
GeneStats * read_GeneStats(FILE * ifp)
{
  char buffer[MAXLINE];
  GeneStats * out;
  SeqAlign * temp;
  char **base;
  char **brk;

  out = GeneStats_alloc();
  out->rnd = NULL;

  while( fgets(buffer,MAXLINE,ifp) != NULL ) {
    /*    fprintf(stderr,"Reading (main loop) %s",buffer); */
    if( buffer[0] == '#' )
      continue;
    
    if( buffer[0] == '%' && buffer[1] == '%' )
      break;
    
    if( strstartcmp(buffer,"splice5") == 0 ) {
      base = brk = breakstring(buffer,spacestr);
      if( *brk == NULL || *(brk+1) == NULL || is_integer_string(*(brk+1),&out->splice5_offset) == 0) {
	warn("Cannot read splice5 offset - must be splice5 <number>");
	return NULL;
      }
      ckfree(base);
      temp = read_selex_SeqAlign(ifp);
      if( temp == NULL ) {
	warn("Could not read in selex alignment for splice5");
	continue;
      }

      out->splice5 = temp;
      continue;
    }

    if( strstartcmp(buffer,"splice3") == 0 ) {

      base = brk = breakstring(buffer,spacestr);
      if( *brk == NULL || *(brk+1) == NULL || is_integer_string(*(brk+1),&out->splice3_offset) == 0) {
	warn("Cannot read splice3 offset - must be splice3 <number>");
	return NULL;
      }
      ckfree(base);

      temp = read_selex_SeqAlign(ifp);
      if( temp == NULL ) {
	warn("Could not read in selex alignment for splice5");
	continue;
      }

      out->splice3 = temp;

      continue;
    }
    
    
    if( strstartcmp(buffer,"intron_emission") == 0 ) {
      if( fgets(buffer,MAXLINE,ifp) == NULL ) {
	warn("Could not read in intron emission line");
	break;
      }
      out->intron = get_genestat_emission(buffer);
      if( fgets(buffer,MAXLINE,ifp) != NULL ) {
	continue;
      } else {
	break;
      }
    }

    if( strstartcmp(buffer,"polyp_emission") == 0 ) {
      if( fgets(buffer,MAXLINE,ifp) == NULL ) {
	warn("Could not read in polyp emission line");
	break;
      }
      out->polyp = get_genestat_emission(buffer);
      if( fgets(buffer,MAXLINE,ifp) != NULL ) {
	continue;
      } else {
	break;
      }
    }

    if( strstartcmp(buffer,"rnd_emission") == 0 ) {
      if( fgets(buffer,MAXLINE,ifp) == NULL ) {
	warn("Could not read in rnd emission line");
	break;
      }
      out->rnd = get_genestat_emission(buffer);
      if( fgets(buffer,MAXLINE,ifp) != NULL ) {
	continue;
      } else {
	break;
      }
    }

    if( strstartcmp(buffer,"rndcodon") == 0 ) {
      if( read_codon_GeneStats(out->codon,buffer,ifp) == FALSE ) {
	warn("Problem in reading codon line!");
      }
      continue;
    }

    if( isalpha(buffer[0]) ) { 
      warn("Could not read line %s in genestats reading\n",buffer);
    }
  
  }

  
  assert(out);
  assert(out->splice5);
  assert(out->splice3);
	
  return out;
}

%func
reads in the emission stuff in a genestats line
%type internal
%%
RandomModelDNA * get_genestat_emission(char * buffer)
{
  RandomModelDNA * out;
  int i;
  char ** base;
  char ** brk;
  double d;

  out = RandomModelDNA_alloc();

  base = brk = breakstring(buffer,spacestr);

  for(i=0;*brk != NULL && i < 5;i++, brk++){
    if( is_double_string(*brk,out->base+i) == FALSE) {
      warn("For genestat word %s, not a double in emission!",*brk);
      return FALSE;
    }
  }

  ckfree(base);

  if( i < 4 ) {
    warn("Did not read in 5 numbers for emission scores in genestats");
  }

  return out;
}

%func
testing function
%%
void dump_GeneStats(GeneStats * st,FILE * ofp)
{
  int i;

  assert(st);
  assert(ofp);

  fprintf(ofp,"#\n# Dumping gene stats, wise2.2 style\n#\n");
  fprintf(ofp,"splice5\n");
  write_selex_SeqAlign(st->splice5,10,70,ofp);
  fprintf(ofp,"//\nsplice3\n");
  write_selex_SeqAlign(st->splice3,10,70,ofp);
  fprintf(ofp,"//\n");

  fprintf(ofp,"intron_emission\n");
  for(i=0;i<4;i++) {
    fprintf(ofp,"%f ",st->intron->base[i]);
  }

  fprintf(ofp,"\n");
  fprintf(ofp,"//\n");
  if( st->polyp != NULL ) {
    fprintf(ofp,"polyp_emission\n");
    for(i=0;i<4;i++) {
      fprintf(ofp,"%f ",st->polyp->base[i]);
    }
  }

  fprintf(ofp,"\n");
  fprintf(ofp,"//\n");

}


%func
assummes codon_array is 64 positions long
  
line should have begin consensus on it and be of MAXLINE length as it will be used as the buffer.

This does **not** check that you have filled up all 64 positions.
%%
boolean read_codon_GeneStats(double * codon_array,char* line,FILE * ifp)
{
  boolean ret = TRUE;
  char * codon;
  char * number;


  if( strwhitestartcmp(line,"rndcodon",spacestr) != 0  ) {
    warn("In reading codon line, got no 'rndcoodon' tag [%s]",line);
    return FALSE;
  }


  while( fgets(line,MAXLINE,ifp) != NULL ) {
    if( line[0] == '#' )
      continue;

    if( strwhitestartcmp(line,"//",spacestr) == 0 )
      break;

    codon = strtok(line,spacestr);
    number = strtok(NULL,spacestr);

    if( codon == NULL ) {
      warn("Found an uncommented line in codon consensus with no leading codon word");
      continue;
    }

    if( number == NULL ) {
      warn("For codon %s, no number found",codon);
      ret = FALSE;
      continue;
    }

    if( strchr(codon,'N') != NULL ) 
      continue;

    if( is_non_ambiguous_codon_seq(codon) == FALSE ) {
      warn("Codon %s is not really a codon... problem!");
      ret = FALSE;
      continue;
    }



    codon_array[base4_codon_from_seq(codon)]= atof(number);

  }

  return ret;
}


%}