Summary

Bio::Tools::HMMER::Results - Object representing HMMER output results

Package variables

Included modules

Inherit

Bio::Root::IO Bio::Root::Root Bio::SeqAnalysisParserI

Synopsis

   # parse a hmmsearch file (can also parse a hmmpfam file)
   $res = new Bio::Tools::HMMER::Results( -file => 'output.hmm' ,
                                          -type => 'hmmsearch');

   # print out the results for each sequence
   foreach $seq ( $res->each_Set ) {
       print "Sequence bit score is",$seq->bits,"\n";
       foreach $domain ( $seq->each_Domain ) {
           print " Domain start ",$domain->start," end ",$domain->end,
	   " score ",$domain->bits,"\n";
       }
   }

   # new result object on a sequence/domain cutoff of
   # 25 bits sequence, 15 bits domain
   $newresult = $res->filter_on_cutoff(25,15);

   # alternative way of getting out all domains directly
   foreach $domain ( $res->each_Domain ) {
       print "Domain on ",$domain->seq_id," with score ",
       $domain->bits," evalue ",$domain->evalue,"\n";
   }

Description

This object represents HMMER output, either from hmmsearch or
hmmpfam. For hmmsearch, a series of HMMER::Set objects are made, one
for each sequence, which have the the bits score for the object. For
hmmpfam searches, only one Set object is made.
These objects come from the original HMMResults modules used
internally in Pfam, written by Ewan Birney. Ewan then converted them to
BioPerl objects in 1999. That conversion is meant to be backwardly
compatible, but may not be (caveat emptor).

Methods

Methods description

 Title   : next_feature
 Usage   : while( my $feat = $res->next_feature ) { # do something }
 Function: SeqAnalysisParserI implementing function
 Example :
 Returns : A Bio::SeqFeatureI compliant object, in this case,
           each DomainUnit object, ie, flattening the Sequence
           aspect of this.
 Args    : None

 Title   : number
 Usage   : print "There are ",$res->number," domains hit\n";
 Function: provides the number of domains in the HMMER report

 Title   : seqfile
 Usage   : $obj->seqfile($newval)
 Function:
 Example :
 Returns : value of seqfile
 Args    : newvalue (optional)

 Title   : hmmfile
 Usage   : $obj->hmmfile($newval)
 Function:
 Example :
 Returns : value of hmmfile
 Args    : newvalue (optional)

 Title   : add_Domain
 Usage   : $res->add_Domain($unit)
 Function: adds a domain to the results array. Mainly used internally.
 Args    : A Bio::Tools::HMMER::Domain

 Title   : each_Domain
 Usage   : foreach $domain ( $res->each_Domain() )
 Function: array of Domain units which are held in this report
 Returns : array
 Args    : none

 Title   : domain_bits_cutoff_from_evalue
 Usage   : $cutoff = domain_bits_cutoff_from_evalue(0.01);
 Function: return a bits cutoff from an evalue using the
           scores here. Somewhat interesting logic:
            Find the two bit score which straddle the evalue
            if( 25 is between these two points) return 25
            else return the midpoint.

           This logic tries to ensure that with large signal to
           noise separation one still has sensible 25 bit cutoff
 Returns :
 Args    :

 Title   : write_FT_output
 Usage   : $res->write_FT_output(\*STDOUT,'DOMAIN')
 Function: writes feature table output ala swissprot
 Returns :
 Args    :

 Title   : filter_on_cutoff
 Usage   : $newresults = $results->filter_on_cutoff(25,15);
 Function: Produces a new HMMER::Results module which has
           been trimmed at the cutoff.
 Returns : a Bio::Tools::HMMER::Results module
 Args    : sequence cutoff and domain cutoff. in bits score
           if you want one cutoff, simply use same number both places

 Title   : write_ascii_out
 Usage   : $res->write_ascii_out(\*STDOUT)
 Function: writes as
           seq seq_start seq_end model-acc model_start model_end model_name
 Returns :
 Args    :

  FIXME: Now that we have no modelacc, this is probably a bad thing.

 Title   : write_GDF_bits
 Usage   : $res->write_GDF_bits(25,15,\*STDOUT)
 Function: writes GDF format with a sequence,domain threshold
 Returns :
 Args    :

 Title   : add_Set
 Usage   : Mainly internal function
 Function:
 Returns :
 Args    :

 Title   : each_Set
 Usage   :
 Function:
 Returns :
 Args    :

 Title   : get_Set
 Usage   : $set = $res->get_Set('sequence-name');
 Function: returns the Set for a particular sequence
 Returns : a HMMER::Set object
 Args    : name of the sequence

 Title   : _parse_hmmpfam
 Usage   : $res->_parse_hmmpfam($filehandle)
 Function:
 Returns :
 Args    :

 Title   : _parse_hmmsearch
 Usage   : $res->_parse_hmmsearch($filehandle)
 Function:
 Returns :
 Args    :

 Title   : parsetype
 Usage   : $obj->parsetype($newval)
 Function:
 Returns : value of parsetype
 Args    : newvalue (optional)

Methods code

sub new {

  my($class,@args) = @_;

  my $self = $class->SUPER::new(@args);

  $self->{'domain'} = []; # array of HMMUnits
  $self->{'seq'} = {};

  my ($parsetype) = $self->_rearrange([qw(TYPE)],@args);
  $self->_initialize_io(@args);
  if( !defined $parsetype ) {
      $self->throw("No parse type provided. should be hmmsearch or hmmpfam");
  }
  $self->parsetype($parsetype);
  if( defined $self->_fh() ) {
      if( $parsetype eq 'hmmsearch' ) {
	  $self->_parse_hmmsearch($self->_fh());
      } elsif ( $parsetype eq 'hmmpfam' ) {
	  $self->_parse_hmmpfam($self->_fh());
      } else {
	  $self->throw("Did not recoginise type $parsetype");
      }
  }

  return $self; # success - we hope!

}

sub next_feature {

   my ($self) = @_;

   if( $self->{'_started_next_feature'} == 1 ) {
       return shift @{$self->{'_next_feature_array'}};
   } else {
       $self->{'_started_next_feature'} = 1;
       my @array;
       foreach my $seq ( $self->each_Set() ) {
	   foreach my $unit ( $seq->each_Domain() ) {
	       push(@array,$unit);
	   }
       }
       my $res = shift @array;
       $self->{'_next_feature_array'} =\@ array;
       return $res;
   }

   $self->throw("Should not reach here! Error!");

}

sub number {

    my $self = shift;
    my @val;
    my $ref;
    $ref = $self->{'domain'};


    @val = @{$self->{'domain'}};
    return scalar @val;

}

sub seqfile {

   my ($self,$value) = @_;
   if( defined $value) {
      $self->{'seqfile'} = $value;
    }
    return $self->{'seqfile'};

}

sub hmmfile {

   my ($self,$value) = @_;
   if( defined $value) {
      $self->{'hmmfile'} = $value;
    }
    return $self->{'hmmfile'};

}

sub add_Domain {

    my $self = shift;
    my $unit = shift;
    my $name;

    $name = $unit->seq_id();

    if( ! exists $self->{'seq'}->{$name} ) {
	$self->warn("Adding a domain of $name but with no HMMSequence. Will be kept in domain array but not added to a HMMSequence");
    } else {
	$self->{'seq'}->{$name}->add_Domain($unit);
    }
    push(@{$self->{'domain'}},$unit);

}

sub each_Domain {

    my $self = shift;
    my (@arr,$u);

    foreach $u ( @{$self->{'domain'}} ) {
	push(@arr,$u);
    }

    return @arr;

}

sub domain_bits_cutoff_from_evalue {

    my $self = shift;
    my $eval = shift;
    my ($dom,$prev,@doms,$cutoff,$sep,$seen);

    @doms = $self->each_Domain;


    @doms = map { $_->[0] }
            sort { $b->[1] <=> $a->[1] }
            map { [ $_, $_->bits] } @doms;
    $seen = 0;
    foreach $_ ( @doms ) {
	if( $_->evalue > $eval ) {
	    $seen = 1;
	    $dom = $_;
	    last;
	}
	$prev = $_;
    }

    if( ! defined $prev || $seen == 0) {
	$self->throw("Evalue is either above or below the list...");
	return;
    }

    $sep = $prev->bits - $dom->bits ;

    if( $sep < 1 ) {
	return $prev->bits();
    }
    if( $dom->bits < 25 && $prev->bits > 25 ) {
	return 25;
    }

    return int( $dom->bits + $sep/2 ) ;

}

sub dictate_hmm_acc {

    my $self = shift;
    my $acc = shift;
    my ($unit);


    foreach $unit ( $self->eachHMMUnit() ) {
	$unit->hmmacc($acc);
    }

}

sub write_FT_output {

    my $self = shift;
    my $file = shift;
    my $idt  = shift;
    my ($seq,$unit);

    if( !defined $idt ) {
	$idt = "DOMAIN";
    }

    foreach $seq ( $self->each_Set() ) {
	print $file sprintf("ID   %s\n",$seq->name());
	foreach $unit ( $seq->each_Domain() ) {
	    print $file sprintf("FT   %s   %d %d %s\n",$idt,
				$unit->start,$unit->end,$unit->hmmname);
	}
	print $file "//\n";
    }

}

sub filter_on_cutoff {

    my $self = shift;
    my $seqthr = shift;
    my $domthr = shift;
    my ($new,$seq,$unit,@array,@narray);

    if( !defined $domthr ) {
       $self->throw("hmmresults filter on cutoff needs two arguments");
    }

    $new = Bio::Tools::HMMER::Results->new(-type => $self->parsetype);

    foreach $seq ( $self->each_Set()) {
	next if( $seq->bits() < $seqthr );
	$new->add_Set($seq);
	foreach $unit ( $seq->each_Domain() ) {
	    next if( $unit->bits() < $domthr );
	    $new->add_Domain($unit);
	}
    }
    $new;

}

sub write_ascii_out {

    my $self = shift;
    my $fh = shift;
    my ($unit,$seq);

    if( !defined $fh) {
	$fh =\* STDOUT;
    }


    foreach $seq ( $self->each_Set()) {
	foreach $unit ( $seq->each_Domain()) {
	    print $fh sprintf("%s %4d %4d %s %4d %4d %4.2f %4.2g %s\n",
			      $unit->seq_id(),$unit->start(),$unit->end(),
			      $unit->hmmacc,$unit->hstart,$unit->hend,
			      $unit->bits,$unit->evalue,$unit->hmmname);
	}
    }

}

sub write_GDF_bits {

    my $self = shift;
    my $seqt = shift;
    my $domt = shift;
    my $file = shift;
    my $seq;
    my $unit;
    my (@array,@narray);

    if( !defined $file ) {
	$self->throw("Attempting to use write_GDF_bits without passing in correct arguments!");
	return;
    }

    foreach $seq ( $self->each_Set()) {

	if( $seq->bits() < $seqt ) {
	    next;
	}

	foreach $unit ( $seq->each_Domain() ) {
	    if( $unit->bits() < $domt ) {
		next;
	    }
	    push(@array,$unit);
	}

    }

    @narray = sort { my ($aa,$bb,$st_a,$st_b);
		     $aa = $a->seq_id();
		     $bb = $b->seq_id();
		     if ( $aa eq $bb) {
			 $st_a = $a->start();
			 $st_b = $b->start();
			 return $st_a <=> $st_b;
			 }
		     else {
			 return $aa cmp $bb;
		     } } @array;

    foreach $unit ( @narray ) {
	print $file sprintf("%-24s\t%6d\t%6d\t%15s\t%.1f\t%g\n",$unit->get_nse(),$unit->start(),$unit->end(),$unit->seq_id(),$unit->bits(),$unit->evalue);
    }

}

sub write_scores_bits {

    my $self = shift;
    my $seqt = shift;
    my $domt = shift;
    my $file = shift;
    my $seq;
    my $unit;
    my (@array,@narray);

    if( !defined $file ) {
	$self->warn("Attempting to use write_scores_bits without passing in correct arguments!");
	return;
    }

    foreach $seq ( $self->eachHMMSequence()) {

	if( $seq->bits() < $seqt ) {
	    next;
	}

	foreach $unit ( $seq->eachHMMUnit() ) {
	    if( $unit->bits() < $domt ) {
		next;
	    }
	    push(@array,$unit);
	}

    }

    @narray = sort { my ($aa,$bb,$st_a,$st_b);
		     $aa = $a->bits();
		     $bb = $b->bits();
		     return $aa <=> $bb;
		     } @array;

    foreach $unit ( @narray ) {
	print $file sprintf("%4.2f %s\n",$unit->bits(),$unit->get_nse());
    }

}

sub write_GDF {

    my $self = shift;
    my $file = shift;
    my $unit;

    if( !defined $file ) {
	$file =\* STDOUT;
    }


    foreach $unit ( $self->eachHMMUnit() ) {
	print $file sprintf("%-24s\t%6d\t%6d\t%15s\t%.1f\t%g\n",$unit->get_nse(),$unit->start(),$unit->end(),$unit->seq_id(),$unit->bits(),$unit->evalue);
    }

}

sub highest_noise {

    my $self = shift;
    my $seqt = shift;
    my $domt = shift;
    my ($seq,$unit,$hseq,$hdom,$noiseseq,$noisedom);

    $hseq = $hdom = -100000;

    foreach $seq ( $self->eachHMMSequence()) {
	if( $seq->bits() < $seqt && $seq->bits() > $hseq  ) {
	    $hseq = $seq->bits();
	    $noiseseq = $seq;
	}
	foreach $unit ( $seq->eachHMMUnit() ) {
	    if( (($seq->bits() < $seqt) || ($seq->bits() > $seqt && $unit->bits < $domt)) && $unit->bits() > $hdom ) {
		$hdom  = $unit->bits();
		$noisedom = $unit;
	    }
	}
    }


    return ($noiseseq,$noisedom);

}

sub lowest_true {

    my $self = shift;
    my $seqt = shift;
    my $domt = shift;
    my ($seq,$unit,$lowseq,$lowdom,$trueseq,$truedom);

    if( ! defined $domt ) {
	$self->warn("lowest true needs at least a domain threshold cut-off");
	return (0,0);
    }

    $lowseq = $lowdom = 100000;

    foreach $seq ( $self->eachHMMSequence()) {

	if( $seq->bits() >= $seqt && $seq->bits() < $lowseq  ) {
	    $lowseq = $seq->bits();
	    $trueseq = $seq;
	}
	if( $seq->bits() < $seqt ) {
	    next;
	}

	foreach $unit ( $seq->eachHMMUnit() ) {
	    if( $unit->bits() >= $domt && $unit->bits() < $lowdom ) {
		$lowdom  = $unit->bits();
		$truedom = $unit;
	    }
	}
    }


    return ($trueseq,$truedom);

}

sub add_Set {

    my $self = shift;
    my $seq  = shift;
    my $name;

    $name = $seq->name();

    if( exists $self->{'seq'}->{$name} ) {
	$self->throw("You alredy have $name in HMMResults!");
    }
    $self->{'seq'}->{$name} = $seq;

}

sub each_Set {

    my $self = shift;
    my (@array,$name);


    foreach $name ( keys %{$self->{'seq'}} ) {
	push(@array,$self->{'seq'}->{$name});
    }
    return @array;

}

sub get_Set {

    my $self = shift;
    my $name = shift;

    return $self->{'seq'}->{$name};

}

sub _parse_hmmpfam {

    my $self = shift;
    my $file = shift;

    my ($id,$sqfrom,$sqto,$hmmf,$hmmt,$sc,$ev,
	$unit,$nd,$seq,$name,$seqname,$from,
	$to,%hash,%acc,$acc);
    my $count = 0;

    while(<$file>) {
        if( /^HMM file:\s+(\S+)/ ) { $self->hmmfile($1); next; }
	elsif( /^Sequence file:\s+(\S+)/ ) { $self->seqfile($1); next }
	elsif( /^Query(\s+sequence)?:\s+(\S+)/ ) {

	    $seqname = $2;

	    $seq     = Bio::Tools::HMMER::Set->new();

	    $seq ->name($seqname);
	    $self->add_Set($seq);
	    %hash = ();

	    while(<$file>){

		if( /Accession:\s+(\S+)/ ) { $seq->accession($1); next }
		elsif( s/^Description:\s+// ) { chomp; $seq->desc($_); next }
		/^Parsed for domains/ && last;

		# This is to parse out the accession numbers in old Pfam format.
		# now not support due to changes in HMMER.

		if( (($id,$acc, $sc, $ev, $nd) = /^\s*(\S+)\s+(\S+).+?\s(\S+)\s+(\S+)\s+(\d+)\s*$/)) {
		    $hash{$id} = $sc; # we need this for the sequence
		                      # core of the domains below!
		    $acc {$id} = $acc;

		    # this is the more common parsing routine
		} elsif ( (($id,$sc, $ev, $nd) =
			   /^\s*(\S+).+?\s(\S+)\s+(\S+)\s+(\d+)\s*$/) ) {

		    $hash{$id} = $sc; # we need this for the
		                      # sequence score of hte domains below!

		}
	    }

	    while(<$file>) {
		/^Align/ && last;
		m{^//} && last;
		# this is meant to match

		#Sequence Domain  seq-f seq-t    hmm-f hmm-t      score  E-value
		#-------- ------- ----- -----    ----- -----      -----  -------
		#PF00621    1/1     198   372 ..     1   207 []   281.6    1e-80

		if( (($id, $sqfrom, $sqto, $hmmf,$hmmt,$sc, $ev) =
		     /(\S+)\s+\S+\s+(\d+)\s+(\d+).+?(\d+)\s+(\d+)\s+\S+\s+(\S+)\s+(\S+)\s*$/)) {
		    $unit = Bio::Tools::HMMER::Domain->new();
		    $unit->seq_id  ($seqname);
		    $unit->hmmname  ($id);
		    $unit->start    ($sqfrom);
		    $unit->end      ($sqto);
		    $unit->hstart($hmmf);
		    $unit->hend  ($hmmt);
		    $unit->bits     ($sc);
		    $unit->evalue   ($ev);

		    if( !exists($hash{$id}) ) {
			$self->throw("HMMResults parsing error in hmmpfam for $id - can't find sequecne score");
		    }

		    $unit->seqbits($hash{$id});

		    if( defined $acc{$id} ) {
			$unit->hmmacc($acc{$id});
		    }

		    # this should find it's own sequence!
		    $self->add_Domain($unit);
		}
	    }
	    if( m{^//} ) { next; }

	    $_ = <$file>;
	    # parses alignment lines. Icky as we have to break on the same line
	    # that we need to read to place the alignment lines with the unit.

	    while(1) {
		(!defined $_ || m{^//}) && last;

		# matches:
		# PF00621: domain 1 of 1, from 198 to 372
		if( /^\s*(\S+):.*from\s+(\d+)\s+to\s+(\d+)/ ) {

		    $name = $1;
		    $from = $2;
		    $to   = $3;

		    # find the HMMUnit which this alignment is from

		    $unit = $self->get_unit_nse($seqname,$name,$from,$to);
		    if( !defined $unit ) {
			$self->warn("Could not find $name $from $to unit even though I am reading it in. ugh!");
			$_ = <$file>;
			next;
		    }
		    while(<$file>) {
			m{^//} && last;
			/^\s*\S+:.*from\s+\d+\s+to\s+\d+/ && last;
			$unit->add_alignment_line($_);
		    }
		} else {
		    $_ = <$file>;
		}
	    }

	    # back to main 'Query:' loop
	}
    }

}

sub get_unit_nse {

    my $self    = shift;
    my $seqname = shift;
    my $domname = shift;
    my $start   = shift;
    my $end     = shift;

    my($seq,$unit);

    $seq = $self->get_Set($seqname);

    if( !defined $seq ) {
	$self->throw("Could not get sequence name $seqname - so can't get its unit");
    }

    foreach $unit ( $seq->each_Domain() ) {
	if( $unit->hmmname() eq $domname && $unit->start() == $start &&  $unit->end() == $end ) {
	    return $unit;
	}
    }

    return;

}

sub _parse_hmmsearch {

    my $self = shift;
    my $file = shift;
    my ($id,$sqfrom,$sqto,$sc,$ev,$unit,$nd,$seq,$hmmf,$hmmt,
	$hmmfname,$hmmacc, $hmmid, %seqh);
    my $count = 0;

    while(<$file>) {
        /^HMM file:\s+(\S+)/ and do { $self->hmmfile($1); $hmmfname = $1 };
	/^Accession:\s+(\S+)/ and do { $hmmacc = $1 };
	/^Query HMM:\s+(\S+)/ and do { $hmmid = $1 };
	/^Sequence database:\s+(\S+)/ and do { $self->seqfile($1) };
        /^Scores for complete sequences/ && last;
    }

    $hmmfname = "given" if not $hmmfname;

    while(<$file>) {
	/^Parsed for domains/ && last;
	if( (($id, $sc, $ev, $nd) = /(\S+).+?\s(\S+)\s+(\S+)\s+(\d+)\s*$/)) {
	    $seq = Bio::Tools::HMMER::Set->new();
	    $seq->name($id);
	    $seq->bits($sc);
	    $seqh{$id} = $sc;
	    $seq->evalue($ev);
	    $self->add_Set($seq);
	    $seq->accession($hmmacc);
	}
    }

    while(<$file>) {
	/^Alignments of top-scoring domains/ && last;
	if( (($id, $sqfrom, $sqto, $hmmf, $hmmt, $sc, $ev) = /(\S+)\s+\S+\s+(\d+)\s+(\d+).+?(\d+)\s+(\d+)\s+\S+\s+(\S+)\s+(\S+)\s*$/)) {
	    $unit = Bio::Tools::HMMER::Domain->new();

	    $unit->seq_id($id);
	    $unit->hmmname($hmmfname);
	    $unit->start($sqfrom);
	    $unit->end($sqto);
	    $unit->bits($sc);
	    $unit->hstart($hmmf);
	    $unit->hend($hmmt);
	    $unit->evalue($ev);
	    $unit->seqbits($seqh{$id});
	    $self->add_Domain($unit);
	    $count++;
	}
    }

    $_ = <$file>;

    ## Recognize and store domain alignments

    while(1) {
	if( !defined $_ ) {
	    last;
	}
        /^Histogram of all scores/ && last;

        # matches:
        # PF00621: domain 1 of 1, from 198 to 372
        if( /^\s*(\S+):.*from\s+(\d+)\s+to\s+(\d+)/ ) {
            my $name = $1;
            my $from = $2;
            my $to   = $3;

            # find the HMMUnit which this alignment is from
            $unit = $self->get_unit_nse($name,$hmmfname,$from,$to);

            if( !defined $unit ) {
                $self->warn("Could not find $name $from $to unit even though I am reading it in. ugh!");
                next;
            }
            while(<$file>) {
                /^Histogram of all scores/ && last;
                /^\s*\S+:.*from\s+\d+\s+to\s+\d+/ && last;
                $unit->add_alignment_line($_);
            }
        }
        else {
            $_ = <$file>;
        }
    }

    return $count;

}

sub parsetype {

   my ($self,$value) = @_;
   if( defined $value) {
      $self->{'_parsetype'} = $value;
    }
    return $self->{'_parsetype'};

}

General documentation

User feedback is an integral part of the evolution of this and other
Bioperl modules. Send your comments and suggestions preferably to one
of the Bioperl mailing lists. Your participation is much appreciated.

  bioperl-l@bioperl.org                  - General discussion
  http://bioperl.org/wiki/Mailing_lists  - About the mailing lists

Report bugs to the Bioperl bug tracking system to help us keep track
the bugs and their resolution. Bug reports can be submitted via the
web:

  http://bugzilla.open-bio.org/

Email birney@ebi.ac.uk

Jason Stajich, jason-at-bioperl.org

The rest of the documentation details each of the object
methods. Internal methods are usually preceded with a _