SliceAdaptor.pm 46.7 KB
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#
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# Ensembl module for Bio::EnsEMBL::DBSQL::SliceAdaptor
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#
# Cared for by Ewan Birney <ensembl-dev@ebi.ac.uk>
#
# Copyright Ewan Birney
#
# You may distribute this module under the same terms as perl itself

# POD documentation - main docs before the code

=head1 NAME

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Bio::EnsEMBL::DBSQL::SliceAdaptor - A database aware adaptor responsible for
the creation of Slice objects.
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=head1 SYNOPSIS

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  my $db = Bio::EnsEMBL::DBSQL::DBAdaptor->new(...);

  my $slice_adaptor = $db->get_SliceAdaptor();

  #get a slice on the entire chromosome X
  my $chr_slice = $slice_adaptor->fetch_by_region('chromosome','X');

  #get a slice for each clone in the database
  foreach my $cln_slice (@{$slice_adaptor->fetch_all('clone')}) {
    #do something with clone
  }

  #get a slice which is part of NT_004321
  my $spctg_slice = $slice_adaptor->fetch_by_region('supercontig','NT_004321',
                                                    200_000, 600_000);
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=head1 DESCRIPTION

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This module is responsible for fetching Slices representing genomic regions
from a database.  Details on how slices can be used are in the
Bio::EnsEMBL::Slice module.
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=head1 AUTHOR - Ewan Birney

This modules is part of the Ensembl project http://www.ensembl.org

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=head1 CONTACT
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Email ensembl-dev@ebi.ac.uk
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=head1 METHODS
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=cut


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package Bio::EnsEMBL::DBSQL::SliceAdaptor;
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use vars qw(@ISA);
use strict;

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use Bio::EnsEMBL::DBSQL::BaseAdaptor;
use Bio::EnsEMBL::Slice;
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use Bio::EnsEMBL::DBSQL::DBAdaptor;
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use Bio::EnsEMBL::Mapper;
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use POSIX qw(ceil floor);

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use Bio::EnsEMBL::Utils::Exception qw(throw deprecate warning);
use Bio::EnsEMBL::Utils::Cache; #CPAN LRU cache
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@ISA = ('Bio::EnsEMBL::DBSQL::BaseAdaptor');
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my $SEQ_REGION_CACHE_SIZE = 1000;
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sub new {
  my $caller = shift;
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  my $class = ref($caller) || $caller;
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  my $self = $class->SUPER::new(@_);
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  my %name_cache;
  my %id_cache;
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  tie(%name_cache, 'Bio::EnsEMBL::Utils::Cache', $SEQ_REGION_CACHE_SIZE);
  tie(%id_cache, 'Bio::EnsEMBL::Utils::Cache', $SEQ_REGION_CACHE_SIZE);

  $self->{'_name_cache'} = \%name_cache;
  $self->{'_id_cache'} = \%id_cache;

  return $self;
}


=head2 fetch_by_region

  Arg [1]    : string $coord_system_name
               The name of the coordinate system of the slice to be created
               This may be a name of an acutal coordinate system or an alias
               to a coordinate system.  Valid aliases are 'seqlevel' or
               'toplevel'.
  Arg [2]    : string $seq_region_name
               The name of the sequence region that the slice will be
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               created on.                
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  Arg [3]    : int $start (optional, default = 1)
               The start of the slice on the sequence region
  Arg [4]    : int $end (optional, default = seq_region length)
               The end of the slice on the sequence region
  Arg [5]    : int $strand (optional, default = 1)
               The orientation of the slice on the sequence region
  Arg [6]    : string $version (optional, default = default version)
               The version of the coordinate system to use (e.g. NCBI33)
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  Example    : $slice = $slice_adaptor->fetch_by_region('chromosome', 'X');
               $slice = $slice_adaptor->fetch_by_region('clone', 'AC008066.4');
  Description: Retrieves a slice on the requested region.  At a minimum the
               name of the coordinate system and the name of the seq_region to
               fetch must be provided.

               Some fuzzy matching is performed if no exact match for
               the provided name is found.  This allows clones to be
               fetched even when their version is not known.  For
               example fetch_by_region('clone', 'AC008066') will
               retrieve the sequence_region with name 'AC008066.4'.

               If the requested seq_region is not found in the database undef
               is returned.

  Returntype : Bio::EnsEMBL::Slice or undef
  Exceptions : throw if no seq_region_name is provided
               throw if invalid coord_system_name is provided
               throw if start > end is provided
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  Caller     : general
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=cut

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sub fetch_by_region {
  my ($self, $coord_system_name, $seq_region_name,
      $start, $end, $strand, $version) = @_;

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  $start  = 1 if(!defined($start));
  $strand = 1 if(!defined($strand));

  throw('seq_region_name argument is required') if(!defined($seq_region_name));
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  my $csa = $self->db()->get_CoordSystemAdaptor();
  my $coord_system = $csa->fetch_by_name($coord_system_name,$version);

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  if(!$coord_system) {
    throw("Unknown coordinate system:\n name='$coord_system_name' " .
          "version='$version'\n");
  }
  if($coord_system->is_top_level()) {
    throw("Cannot fetch_by_region using the 'toplevel' pseudo coordinate " .
          "system.\n");
  }

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  #check the cache so we only go to the db if necessary
  my $name_cache = $self->{'_name_cache'};
  my $key = lc(join(':',$seq_region_name,
                    $coord_system->name(),
                    $coord_system->version));

  my $length;

  if(exists($name_cache->{$key})) {
    $length = $name_cache->{$key}->[1];
  } else {
    my $sth = $self->prepare("SELECT seq_region_id, length " .
                             "FROM seq_region " .
                             "WHERE name = ? AND coord_system_id = ?");
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    #force seq_region_name cast to string so mysql cannot treat as int
    $sth->execute("$seq_region_name", $coord_system->dbID());

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    if($sth->rows() == 0) {
      $sth->finish();
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      #do fuzzy matching, assuming that we are just missing a version on 
      #the end of the seq_region name
   
      $sth = $self->prepare("SELECT name, seq_region_id, length " .
                            "FROM   seq_region " .
                            "WHERE  name LIKE ?" .
                            "AND    coord_system_id = ?");

      $sth->execute("$seq_region_name.%", $coord_system->dbID());

      my $prefix_len = length($seq_region_name) + 1;
      my $highest_version = undef;

      # find the fuzzy-matched seq_region with the highest postfix (which ought
      # to be a version)

      my ($tmp_name, $id, $tmp_length);

      while(($tmp_name, $id, $tmp_length) = $sth->fetchrow_array()) {
        $key = lc(join(':',$tmp_name,
                       $coord_system->name(),
                       $coord_system->version));
        $name_cache->{$key}         = [$id,$tmp_length];
        $self->{'_id_cache'}->{$id} = [$tmp_name,$tmp_length,$coord_system];
        
        my $version = substr($tmp_name, $prefix_len);

        #skip versions which are non-numeric and apparently not versions
        next if($version !~ /^\d+$/);

        if(!defined($highest_version) || ($version <=> $highest_version) > 0) {
          $seq_region_name = $tmp_name;
          $length          = $tmp_length;
          $highest_version = $version;
        } 
      } 
      $sth->finish();

      #return if we did not find any appropriate match:
      return undef if(!defined($highest_version));
    } else {

      my $id;
      ($id, $length) = $sth->fetchrow_array();
      $sth->finish();

      #cache results to speed up future queries
      $name_cache->{$key}         = [$id,$length];
      $self->{'_id_cache'}->{$id} = [$seq_region_name, $length, $coord_system];
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    }
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  }
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  $end = $length if(!defined($end));
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  if($end < $start) {
    throw('start [$start] must be less than or equal to end [$end]');
  }

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  return Bio::EnsEMBL::Slice->new(-COORD_SYSTEM      => $coord_system,
                                  -SEQ_REGION_NAME   => $seq_region_name,
                                  -SEQ_REGION_LENGTH => $length,
                                  -START             => $start,
                                  -END               => $end,
                                  -STRAND            => $strand,
                                  -ADAPTOR           => $self);
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}



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=head2 fetch_by_name
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  Arg [1]    : string $name
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  Example    : $name  = 'chromosome:NCBI34:X:1000000:2000000:1';
               $slice = $slice_adaptor->fetch_by_name($name);
               $slice2 = $slice_adaptor->fetch_by_name($slice3->name());
  Description: Fetches a slice using a slice name (i.e. the value returned by
               the Slice::name method).  This is useful if you wish to 
               store a unique identifier for a slice in a file or database or
               pass a slice over a network.
               Slice::name allows you to serialise/marshall a slice and this
               method allows you to deserialise/unmarshal it.
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               Returns undef if no seq_region with the provided name exists in
               the database.

  Returntype : Bio::EnsEMBL::Slice or undef
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  Exceptions : throw if incorrent arg provided
  Caller     : Pipeline
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=cut

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sub fetch_by_name {
  my $self = shift;
  my $name = shift;
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  if(!$name) {
    throw("name argument is required");
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  }
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  my @array = split(/:/,$name);

  if(@array != 6) {
    throw("Malformed slice name [$name].  Format is " .
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        "coord_system:version:name:start:end:strand");
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  }

  my ($cs_name, $cs_version, $seq_region, $start, $end, $strand) = @array;

  return $self->fetch_by_region($cs_name,$seq_region, $start,
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                                $end, $strand, $cs_version);
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}
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=head2 fetch_by_seq_region_id

  Arg [1]    : string $seq_region_id
               The internal identifier of the seq_region to create this slice
               on
  Example    : $slice = $slice_adaptor->fetch_by_seq_region_id(34413);
  Description: Creates a slice object of an entire seq_region using the
               seq_region internal identifier to resolve the seq_region.
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               Returns undef if no such slice exists.
  Returntype : Bio::EnsEMBL::Slice or undef
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  Exceptions : none
  Caller     : general
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=cut

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sub fetch_by_seq_region_id {
  my ($self, $seq_region_id) = @_;

  my $id_cache = $self->{'_id_cache'};

  my ($name, $length, $cs);

  if(exists $id_cache->{$seq_region_id}) {
    ($name, $length, $cs) = @{$id_cache->{$seq_region_id}};
  } else {
    my $sth = $self->prepare("SELECT name, length, coord_system_id " .
                             "FROM seq_region " .
                             "WHERE seq_region_id = ?");

    $sth->execute($seq_region_id);

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    return undef if($sth->rows() == 0);
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    my $cs_id;
    ($name, $length, $cs_id) = $sth->fetchrow_array();
    $sth->finish();

    $cs = $self->db->get_CoordSystemAdaptor->fetch_by_dbID($cs_id);

    #cache results to speed up repeated queries
    $id_cache->{$seq_region_id} = [$name, $length, $cs];
    my $key = lc(join(':', $name, $cs->name, $cs->version));
    $self->{'_name_cache'}->{$key} = [$seq_region_id, $length];
  }

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  return Bio::EnsEMBL::Slice->new(-COORD_SYSTEM      => $cs,
                                  -SEQ_REGION_NAME   => $name,
                                  -SEQ_REGION_LENGTH => $length,
                                  -START             => 1,
                                  -END               => $length,
                                  -STRAND            => 1,
                                  -ADAPTOR           => $self);
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}

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=head2 get_seq_region_id
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  Arg [1]    : Bio::EnsEMBL::Slice $slice
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               The slice to fetch a seq_region_id for
  Example    : $srid = $slice_adaptor->get_seq_region_id($slice);
  Description: Retrieves the seq_region id (in this database) given a slice
               Seq region ids are not stored on the slices themselves
               because they are intended to be somewhat database independant
               and seq_region_ids vary accross databases.
  Returntype : int
  Exceptions : throw if the seq_region of the slice is not in the db
               throw if incorrect arg provided
  Caller     : BaseFeatureAdaptor
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=cut
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sub get_seq_region_id {
  my $self = shift;
  my $slice = shift;
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  if(!$slice || !ref($slice) || !$slice->isa('Bio::EnsEMBL::Slice')) {
    throw('Slice argument is required');
  }

  my $cs_name = $slice->coord_system->name();
  my $cs_version = $slice->coord_system->version();
  my $seq_region_name = $slice->seq_region_name();

  my $key = lc(join(':', $seq_region_name,$cs_name,$cs_version));
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  my $name_cache = $self->{'_name_cache'};

  if(exists($name_cache->{$key})) {
    return $name_cache->{$key}->[0];
  }

  my $csa = $self->db()->get_CoordSystemAdaptor();
  my $coord_system = $csa->fetch_by_name($cs_name,$cs_version);

  my $sth = $self->prepare("SELECT seq_region_id, length " .
                           "FROM seq_region " .
                           "WHERE name = ? AND coord_system_id = ?");

  #force seq_region_name cast to string so mysql cannot treat as int
  $sth->execute("$seq_region_name", $coord_system->dbID());

  if($sth->rows() != 1) {
    throw("Non existant or ambigous seq_region:\n" .
          "  coord_system=[$cs_name],\n" .
          "  name=[$seq_region_name],\n" .
          "  version=[$cs_version]");
  }

  my($seq_region_id, $length) = $sth->fetchrow_array();
  $sth->finish();

  #cache information for future requests
  $name_cache->{$key} = [$seq_region_id, $length];
  $self->{'_id_cache'}->{$seq_region_id} =
    [$seq_region_name, $length, $coord_system];

  return $seq_region_id;
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}
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=head2 get_seq_region_attribs
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  Arg [1]    : Bio::EnsEMBL::Slice $slice
               The slice to fetch attributes for
  Example    : %attribs = %{$slice_adaptor->get_seq_region_attribs($slice)};
               ($htg_phase) = @{$attribs->{'htg_phase'} || []};
               @synonyms    = @{$attribs->{'synonym'} || []};
  Description: Retrieves a reference to a hash containing attrib code values
               and listref value keys.
  Returntype : hashref
  Exceptions : throw if the seq_region of the slice is not in the db
               throw if incorrect arg provided
  Caller     : Bio::EnsEMBL::Slice

=cut

sub get_seq_region_attribs {
  my $self = shift;
  my $slice = shift;

  if(!ref($slice) || !$slice->isa('Bio::EnsEMBL::Slice')) {
    throw('Slice argument is required');
  }

  my $srid = $self->get_seq_region_id($slice);
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  if(!$srid) {
    throw('Slice is not on a seq_region stored in this database.');
  }

  $self->{'_attribs_cache'} ||= {};
  if($self->{'_attribs_cache'}->{$srid}) {
    return $self->{'_attribs_cache'}->{$srid};
  }

  my $sth = $self->prepare('SELECT at.code, sra.value ' .
                           'FROM   seq_region_attrib sra, attrib_type at ' .
                           'WHERE  sra.seq_region_id = ? ' .
                           'AND    at.attrib_type_id = sra.attrib_type_id');

  $sth->execute($srid);

  my($code, $attrib);
  $sth->bind_columns(\$code, \$attrib);

  my %attrib_hash;
  while($sth->fetch()) {
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    $attrib_hash{uc($code)} ||= [];
    push @{$attrib_hash{uc($code)}}, $attrib;
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  }

  $sth->finish();
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  $self->{'_attribs_cache'}->{$srid} = \%attrib_hash;
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  return \%attrib_hash;
}


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=head2 set_seq_region_attrib

  Arg [1]    : Bio::EnsEMBL::Slice $slice
               The seq_region of the slice is the one which gets this attribute set
  Arg [2]    : string $code
               code in attrib_type table. This method can not set name or description in
               that table.
  Arg [3]    : string $value
               An attribute value for the given code and seq_region
  Example    : $slice_adaptor->set_seq_region_attrib
                                 ( $chromosome_slice, "GeneCount", 23332 )
  Description: Set an attribute for given slices seq_region.
  Returntype : none
  Exceptions : none
  Caller     : general

=cut

sub set_seq_region_attrib {
  my $self = shift;
  my $slice = shift;
  my $code = shift;
  my $value = shift;

  my $sth = $self->prepare
    ("INSERT IGNORE INTO attrib_type set code = ?");
  $sth->execute($code);

  my $atid = $sth->{'mysql_insertid'};

  $sth->finish();

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  if( $self->db->db_handle->{'mysql_info'} == 0 ){
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    # the insert failed because the code is already stored
    $sth = $self->prepare
      ("SELECT attrib_type_id FROM attrib_type " .
       "WHERE code = ?");
    $sth->execute($code);
    ($atid) = $sth->fetchrow_array();

    $sth->finish();

    if(!$atid) {
      throw("Could not store or fetch attrib_type code [$code]\n" .
	    "Wrong permissions?");
    }
  }

  my $srid = $self->get_seq_region_id($slice);

  $sth = $self->prepare
    ("INSERT INTO seq_region_attrib " .
     "SET seq_region_id=?, value=?, attrib_type_id=?" );
  $sth->execute( $srid, $value, $atid );

  $sth->finish();

  #update the cache if it exists already
  if(exists $self->{'_attribs_cache'} &&
     exists $self->{'_attribs_cache'}->{$srid}) {
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    $self->{'_attribs_cache'}->{$srid}->{uc($code)} ||= [];
    push(@{$self->{'_attribs_cache'}->{$srid}->{uc($code)}}, $value);
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  }

  return;
}


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=head2 fetch_all

  Arg [1]    : string $coord_system_name
               The name of the coordinate system to retrieve slices of.
               This may be a name of an acutal coordinate system or an alias
               to a coordinate system.  Valid aliases are 'seqlevel' or
               'toplevel'.
  Arg [2]    : string $coord_system_version (optional)
               The version of the coordinate system to retrieve slices of
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  Arg [3]    : bool $include_non_reference (optional)
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               If this argument is not provided then only reference slices
               will be returned. If set, both reference and non refeference
               slices will be rerurned.
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  Arg [4]    : int $no_duplicates (optional)
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               If set no duplicate entries will be returned.
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  Example    : @chromos = @{$slice_adaptor->fetch_all('chromosome','NCBI33')};
               @contigs = @{$slice_adaptor->fetch_all('contig')};


  Description: Retrieves slices of all seq_regions for a given coordinate
               system.  This is analagous to the methods fetch_all which were
               formerly on the ChromosomeAdaptor, RawContigAdaptor and
               CloneAdaptor classes.  Slices fetched span the entire
               seq_regions and are on the forward strand.
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               If the coordinate system with the provided name and version
               does not exist an empty list is returned.
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               If the coordinate system name provided is 'toplevel', all
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               non-redundant toplevel slices are returned.
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               Retrieved slices can be broken into smaller slices using the
               Bio::EnsEMBL::Utils::Slice module.

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  Returntype : listref of Bio::EnsEMBL::Slices
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  Exceptions : none
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  Caller     : general
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=cut

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sub fetch_all {
  my $self = shift;
  my $cs_name = shift;
  my $cs_version = shift || '';

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  my ($include_non_reference, $include_duplicates) = @_;
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  #
  # verify existance of requested coord system and get its id
  #
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  my $csa       = $self->db->get_CoordSystemAdaptor();
  my $orig_cs   = $csa->fetch_by_name($cs_name, $cs_version);

  return [] if(!$orig_cs);

  my $sth;
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  my %bad_vals=();
  #
  # Get a hash of non reference seq regions
  #
  if(!$include_non_reference){
    my $sth2 = $self->prepare(
			      "SELECT sr.seq_region_id ".
			      "FROM seq_region sr, seq_region_attrib sra, attrib_type at ".
			      " WHERE at.code='non_ref'".
			      "  AND sra.seq_region_id=sr.seq_region_id ".
			      "  AND at.attrib_type_id=sra.attrib_type_id " );
    $sth2->execute();
    my ($seq_region_id);
    $sth2->bind_columns(\$seq_region_id);
    while($sth2->fetch()) {
      $bad_vals{$seq_region_id} = 1;
    }
    $sth2->finish();
  }
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  #
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  # Retrieve the seq_regions from the database
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  #
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  if($orig_cs->is_top_level()) {
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   $sth =
       $self->prepare("SELECT sr.seq_region_id, sr.name, sr.length, " .
                      "       sr.coord_system_id " .
                      "FROM seq_region sr, " .
                      "     seq_region_attrib sra, attrib_type at " .
                      "WHERE at.code='toplevel' " .
                      "AND   at.attrib_type_id=sra.attrib_type_id " .
                      "AND   sra.seq_region_id=sr.seq_region_id");
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    $sth->execute();
  } else {
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     $sth =
       $self->prepare('SELECT seq_region_id, name, length, coord_system_id ' .
                      'FROM   seq_region ' .
                      'WHERE  coord_system_id =?');
     $sth->execute($orig_cs->dbID);
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  }
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  my ($seq_region_id, $name, $length, $cs_id);
  $sth->bind_columns(\$seq_region_id, \$name, \$length, \$cs_id);
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  my $name_cache = $self->{'_name_cache'};
  my $id_cache   = $self->{'_id_cache'};
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  my $cache_count = 0;
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  my @out;
  while($sth->fetch()) {
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    if(!defined($bad_vals{$seq_region_id})){
      my $cs = $csa->fetch_by_dbID($cs_id);
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      if(!$cs) {
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        throw("seq_region $name references non-existent coord_system $cs_id.");
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      }
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      my $cs_key = lc($cs->name().':'.$cs_version);
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      #cache values for future reference, but stop adding to the cache once we
      #we know we have filled it up
      if($cache_count < $SEQ_REGION_CACHE_SIZE) {
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        my $key = lc($name) . ':'. $cs_key;
        $name_cache->{$key} = [$seq_region_id, $length];
        $id_cache->{$seq_region_id} = [$name, $length, $cs];
        $cache_count++;
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      }
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      my $slice = Bio::EnsEMBL::Slice->new
        (-START             => 1,
         -END               => $length,
         -STRAND            => 1,
         -SEQ_REGION_NAME   => $name,
         -SEQ_REGION_LENGTH => $length,
         -COORD_SYSTEM      => $cs,
         -ADAPTOR           => $self);

      if(!defined($include_duplicates) or !$include_duplicates){
        #do not include duplicates
        my @dup = @{$self->fetch_normalized_slice_projection($slice)};
        foreach my $dup_test( @dup){
          if($dup_test->[2]->get_seq_region_id == $slice->get_seq_region_id){
            push @out, $dup_test->[2];
          }
        }
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      }
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      else {
        push @out, $slice;
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      }
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    }
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  }
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  $sth->finish();
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  return \@out;
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}


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sub deleteObj {
  my $self = shift;

  $self->SUPER::deleteObj;
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  $self->{'_id_cache'} = {};
  $self->{'_name_cache'} = {};
  $self->{'_exc_cache'} = {};
}



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=head2 fetch_by_band

 Title   : fetch_by_band
 Usage   :
 Function: create a Slice representing a series of bands
 Example :
 Returns :
 Args    : the band name

=cut

sub fetch_by_band {
  my ($self,$band) = @_;

  my $sth = $self->db->prepare
        ("select s.name,max(k.seq_region_id)-min(k.seq_region_id, min(k.seq_region_start), max(k.seq_region_id) " .
         "from karyotype as k " .
         "where k.band like ? and k.seq_region_id = s.seq_region_id");

  $sth->execute( "$band%" );
  my ( $seq_region_name, $discrepancy, $seq_region_start, $seq_region_end) = $sth->fetchrow_array;

  if($seq_region_name && $discrepancy>0) {
    throw("Band maps to multiple seq_regions");
  } else {
    return $self->fetch_by_region('toplevel',$seq_region_name,$seq_region_start,$seq_region_end);
  }
  throw("Band not recognised in database");
}

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=head2 fetch_by_chr_band

 Title   : fetch_by_chr_band
 Usage   :
 Function: create a Slice representing a series of bands
 Example :
 Returns :
 Args    : the band name

=cut

sub fetch_by_chr_band {
  my ($self,$chr,$band) = @_;

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  my $chr_slice = $self->fetch_by_region('toplevel', $chr);
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  my $seq_region_id = $self->get_seq_region_id($chr_slice);

  my $sth = $self->db->prepare
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        ("select min(k.seq_region_start), max(k.seq_region_end) " .
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         "from karyotype as k " .
         "where k.seq_region_id = ? and k.band like ?");

  $sth->execute( $seq_region_id, "$band%" );
  my ( $slice_start, $slice_end) = $sth->fetchrow_array;

  if(defined $slice_start) {
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    return $self->fetch_by_region('toplevel',$chr,$slice_start,$slice_end);
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  }

  throw("Band not recognised in database");
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}



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=head2 fetch_by_exon_stable_id

  Arg [1]    : string $exonid
               The stable id of the exon around which the slice is 
               desired
  Arg [2]    : (optional) int $size
               The length of the flanking regions the slice should encompass 
               on either side of the exon (0 by default)
  Example    : $slc = $sa->fetch_by_exon_stable_id('ENSE00000302930',10);
  Description: Creates a slice around the region of the specified exon. 
               If a context size is given, the slice is extended by that 
               number of basepairs on either side of the
               transcript.
  Returntype : Bio::EnsEMBL::Slice
  Exceptions : Thrown if the exon is not in the database.
  Caller     : general

=cut

sub fetch_by_exon_stable_id{
  my ($self,$exonid,$size) = @_;

  throw('Exon argument is required.') if(!$exonid);

  my $ea = $self->db->get_ExonAdaptor;
  my $exon = $ea->fetch_by_stable_id($exonid);

  throw("Exon [$exonid] does not exist in DB.") if(!$exon);

  return $self->fetch_by_Feature($exon, $size);
}

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=head2 fetch_by_transcript_stable_id
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  Arg [1]    : string $transcriptid
               The stable id of the transcript around which the slice is 
               desired
  Arg [2]    : (optional) int $size
               The length of the flanking regions the slice should encompass 
               on either side of the transcript (0 by default)
  Example    : $slc = $sa->fetch_by_transcript_stable_id('ENST00000302930',10);
  Description: Creates a slice around the region of the specified transcript. 
               If a context size is given, the slice is extended by that 
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               number of basepairs on either side of the
               transcript.
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  Returntype : Bio::EnsEMBL::Slice
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  Exceptions : Thrown if the transcript is not in the database.
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  Caller     : general
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=cut

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sub fetch_by_transcript_stable_id{
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  my ($self,$transcriptid,$size) = @_;

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  throw('Transcript argument is required.') if(!$transcriptid);

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  my $ta = $self->db->get_TranscriptAdaptor;
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  my $transcript = $ta->fetch_by_stable_id($transcriptid);
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  throw("Transcript [$transcriptid] does not exist in DB.") if(!$transcript);

  return $self->fetch_by_Feature($transcript, $size);
}
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=head2 fetch_by_transcript_id

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  Arg [1]    : int $transcriptid
               The unique database identifier of the transcript around which 
               the slice is desired
  Arg [2]    : (optional) int $size
               The length of the flanking regions the slice should encompass 
               on either side of the transcript (0 by default)
  Example    : $slc = $sa->fetch_by_transcript_id(24, 1000);
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  Description: Creates a slice around the region of the specified transcript.
               If a context size is given, the slice is extended by that
               number of basepairs on either side of the
               transcript.
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  Returntype : Bio::EnsEMBL::Slice
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  Exceptions : throw on incorrect args
               throw if transcript is not in database
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  Caller     : general
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=cut

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sub fetch_by_transcript_id {
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  my ($self,$transcriptid,$size) = @_;
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  throw('Transcript id argument is required.') if(!$transcriptid);
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  my $transcript_adaptor = $self->db()->get_TranscriptAdaptor();
  my $transcript = $transcript_adaptor->fetch_by_dbID($transcriptid);

  throw("Transcript [$transcriptid] does not exist in DB.") if(!$transcript);

  return $self->fetch_by_Feature($transcript, $size);
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}

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=head2 fetch_by_gene_stable_id
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  Arg [1]    : string $geneid
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               The stable id of the gene around which the slice is
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               desired
  Arg [2]    : (optional) int $size
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               The length of the flanking regions the slice should encompass
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               on either side of the gene (0 by default)
  Example    : $slc = $sa->fetch_by_transcript_stable_id('ENSG00000012123',10);
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  Description: Creates a slice around the region of the specified gene.
               If a context size is given, the slice is extended by that
               number of basepairs on either side of the gene.
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               The slice will be created in the genes native coordinate system.
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  Returntype : Bio::EnsEMBL::Slice
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  Exceptions : throw on incorrect args
               throw if transcript does not exist
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  Caller     : general
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=cut

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sub fetch_by_gene_stable_id {
  my ($self,$geneid,$size) = @_;
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  throw('Gene argument is required.') if(!$geneid);
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  my $gene_adaptor = $self->db->get_GeneAdaptor();
  my $gene = $gene_adaptor->fetch_by_stable_id($geneid);
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  throw("Gene [$geneid] does not exist in DB.") if(!$gene);
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  return $self->fetch_by_Feature($gene, $size);
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}


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=head2 fetch_by_Feature
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  Arg [1]    : Bio::EnsEMBL::Feature $feat
               The feature to fetch the slice around
  Arg [2]    : int size (optional)
               The desired number of flanking basepairs around the feature.
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               The size may also be provided as a percentage of the feature 
               size such as 200% or 80.5%.
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  Example    : $slice = $slice_adaptor->fetch_by_Feature($feat, 100);
  Description: Retrieves a slice around a specific feature.  All this really
               does is return a resized version of the slice that the feature
               is already on. Note that slices returned from this method
               are always on the forward strand of the seq_region regardless of
               the strandedness of the feature passed in.
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  Returntype : Bio::EnsEMBL::Slice
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  Exceptions : throw if the feature does not have an attached slice
               throw if feature argument is not provided
  Caller     : fetch_by_gene_stable_id, fetch_by_transcript_stable_id,
               fetch_by_gene_id, fetch_by_transcript_id
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=cut

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sub fetch_by_Feature{
  my ($self, $feature, $size) = @_;
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  $size ||= 0;

  if(!ref($feature) || !$feature->isa('Bio::EnsEMBL::Feature')) {
    throw('Feature argument expected.');
  }

  my $slice = $feature->slice();
  if(!$slice || !$slice->isa('Bio::EnsEMBL::Slice')) {
    throw('Feature must be attached to a valid slice.');
  }

  my $fstart = $feature->start();
  my $fend   = $feature->end();
  if(!defined($fstart) || !defined($fend)) {
    throw('Feature must have defined start and end.');
  }

  #convert the feature slice coordinates to seq_region coordinates
  my $slice_start  = $slice->start();
  my $slice_end    = $slice->end();
  my $slice_strand = $slice->strand();
  if($slice_start != 1 || $slice_strand != 1) {
    if($slice_strand == 1) {
      $fstart = $fstart + $slice_start - 1;
      $fend   = $fend   + $slice_start - 1;
    } else {
      my $tmp_start = $fstart;
      $fstart = $slice_end - $fend      + 1;
      $fend   = $slice_end - $tmp_start + 1;
    }
  }

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  ## Size may be stored as a %age of the length of the feature
  ## Size = 100% gives no context
  ## Size = 200% gives context - 50% the size of the feature either side of 
  ## feature
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  $size = int( ($1-100)/200 * ($fend-$fstart+1) ) if( $size =~/([\d+\.]+)%/ );

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  #return a new slice covering the region of the feature
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  return Bio::EnsEMBL::Slice->new
    (-seq_region_name   => $slice->seq_region_name,
     -seq_region_length => $slice->seq_region_length,
     -coord_system      => $slice->coord_system,
     -start             => $fstart - $size,
     -end               => $fend + $size,
     -strand            => 1,
     -adaptor           => $self);
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}



=head2 fetch_by_misc_feature_attribute

  Arg [1]    : string $attribute_type
               The code of the attribute type
  Arg [2]    : (optional) string $attribute_value
               The value of the attribute to fetch by
  Arg [3]    : (optional) int $size
               The amount of flanking region around the misc feature desired.
  Example    : $slice = $sa->fetch_by_misc_feature_attribute('superctg',
                                                             'NT_030871');
               $slice = $sa->fetch_by_misc_feature_attribute('synonym',
                                                             'AL00012311',
                                                             $flanking);
  Description: Fetches a slice around a MiscFeature with a particular
               attribute type and value. If no value is specified then
               the feature with the particular attribute is used.
               If no size is specified then 0 is used.
  Returntype : Bio::EnsEMBL::Slice
  Exceptions : Throw if no feature with the specified attribute type and value
               exists in the database
               Warning if multiple features with the specified attribute type
               and value exist in the database.
  Caller     : webcode

=cut

sub fetch_by_misc_feature_attribute {
  my ($self, $attrib_type_code, $attrib_value, $size) = @_;
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  my $mfa = $self->db()->get_MiscFeatureAdaptor();
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  my $feats = $mfa->fetch_all_by_attribute_type_value($attrib_type_code,
                                                   $attrib_value);
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  if(@$feats == 0) {
    throw("MiscFeature with $attrib_type_code=$attrib_value does " .
          "not exist in DB.");
  }
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  if(@$feats > 1) {
    warning("MiscFeature with $attrib_type_code=$attrib_value is " .
            "ambiguous - using first one found.");
  }
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  my ($feat) = @$feats;
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  return $self->fetch_by_Feature($feat, $size);
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}

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=head2 fetch_normalized_slice_projection
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  Arg [1]    : Bio::EnsEMBL::Slice $slice
  Example    :  ( optional )
  Description: gives back a project style result. The returned slices 
               represent the areas to which there are symlinks for the 
               given slice. start, end show which area on given slice is 
               symlinked
  Returntype : [[start,end,$slice][]]
  Exceptions : none
  Caller     : BaseFeatureAdaptor

=cut


sub fetch_normalized_slice_projection {
  my $self = shift;
  my $slice = shift;

  my $slice_seq_region_id = $self->get_seq_region_id( $slice );

  my $result = $self->{'asm_exc_cache'}->{$slice_seq_region_id};

  if(!defined($result)) {
    my $sql = "
      SELECT seq_region_id, seq_region_start, seq_region_end,
             exc_type, exc_seq_region_id, exc_seq_region_start,
             exc_seq_region_end
        FROM assembly_exception
       WHERE seq_region_id = ?";

    my $sth = $self->prepare( $sql );
    $sth->execute( $slice_seq_region_id );
    $result = $sth->fetchall_arrayref();
    $self->{'asm_exc_cache'}->{$slice_seq_region_id} = $result;
  }

  my (@haps, @pars);

  foreach my $row (@$result) {
    my ( $seq_region_id, $seq_region_start, $seq_region_end,
         $exc_type, $exc_seq_region_id, $exc_seq_region_start,
         $exc_seq_region_end ) = @$row;

    # need overlapping PAR and all HAPs if any
    if( $exc_type eq "PAR" ) {
      if( $seq_region_start <= $slice->end() && 
          $seq_region_end >= $slice->start() ) {
        push( @pars, [ $seq_region_start, $seq_region_end, $exc_seq_region_id,
                       $exc_seq_region_start, $exc_seq_region_end ] );
      }
    } else {
      push( @haps, [ $seq_region_start, $seq_region_end, $exc_seq_region_id,
                     $exc_seq_region_start, $exc_seq_region_end ] );
    }
  }

  if(!@pars && !@haps) {
    #just return this slice, there were no haps or pars
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    return  [bless ( [1,$slice->length, $slice], "Bio::EnsEMBL::ProjectionSegment")];
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  }

  my @syms;
  if( @haps > 1 ) {
    my @sort_haps = sort { $a->[1] <=> $b->[1] } @haps;
    throw( "More than one HAP region not supported yet" );
  } elsif( @haps == 1 ) {
    my $hap = $haps[0];

    my $seq_reg_slice = $self->fetch_by_seq_region_id($slice_seq_region_id);
    my $exc_slice = $self->fetch_by_seq_region_id( $hap->[2] );

    #
    # lengths of haplotype and reference in db may be different
    # we want to use the maximum possible length for the mapping
    # between the two systems
    #
    my $len1 = $seq_reg_slice->length();
    my $len2 = $exc_slice->length();
    my $max_len = ($len1 > $len2) ? $len1 : $len2;

    #the inserted region can differ in length, but mapped sections
    #need to be same lengths
    my $diff = $hap->[4] - $hap->[1];

    # we want the region of the haplotype INVERTED
    push( @syms, [ 1, $hap->[0]-1, $hap->[2], 1, $hap->[3] - 1 ] );
    push( @syms, [ $hap->[1]+1, $max_len - $diff, 
                   $hap->[2], $hap->[4] + 1, $max_len ] );   
  }

  # for now haps and pars should not be both there, but in theory we 
  # could handle it here by cleverly merging the pars into the existing syms,
  # for now just:
  push( @syms, @pars );

  my $mapper = Bio::EnsEMBL::Mapper->new( "sym", "org" );
  for my $sym ( @syms ) {
    $mapper->add_map_coordinates( $slice_seq_region_id, $sym->[0], $sym->[1],
                                  1, $sym->[2], $sym->[3], $sym->[4] );
  }
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  my @linked = $mapper->map_coordinates( $slice_seq_region_id,
                                         $slice->start(), $slice->end(),
                                         $slice->strand(), "sym" );
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  # gaps are regions where there is no mapping to another region
  my $rel_start = 1;

  #if there was only one coord and it is a gap, we know it is just the
  #same slice with no overlapping symlinks
  if(@linked == 1 && $linked[0]->isa('Bio::EnsEMBL::Mapper::Gap')) {
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    return [bless( [1,$slice->length, $slice], "Bio::EnsEMBL::ProjectionSegment" )];
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  }

  my @out;
  for my $coord ( @linked ) {
    if( $coord->isa( "Bio::EnsEMBL::Mapper::Gap" )) {
      my $exc_slice = Bio::EnsEMBL::Slice->new
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        (-START             => $coord->start(),
         -END               => $coord->end(),
         -STRAND            => $slice->strand(),
         -COORD_SYSTEM      => $slice->coord_system(),
         -ADAPTOR           => $self,
         -SEQ_REGION_NAME   => $slice->seq_region_name(),
         -SEQ_REGION_LENGTH => $slice->seq_region_length());
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      push( @out, bless ( [ $rel_start, $coord->length()+$rel_start-1,
                        $exc_slice ], "Bio::EnsEMBL::ProjectionSegment") );
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    } else {
      my $exc_slice = $self->fetch_by_seq_region_id( $coord->id() );
      my $exc2_slice = Bio::EnsEMBL::Slice->new
        (
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         -START             => $coord->start(),
         -END               => $coord->end(),
         -STRAND            => $coord->strand(),
         -SEQ_REGION_NAME   => $exc_slice->seq_region_name(),
         -SEQ_REGION_LENGTH => $exc_slice->seq_region_length(),
         -COORD_SYSTEM      => $exc_slice->coord_system(),
         -ADAPTOR           => $self
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        );
	
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      push( @out, bless( [ $rel_start, $coord->length() + $rel_start - 1,
                    $exc2_slice ], "Bio::EnsEMBL::ProjectionSegment") );
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    }
    $rel_start += $coord->length();
  }

  return \@out;
}




=head2 store

  Arg [1]    : Bio::EnsEMBL::Slice $slice
  Arg [2]    : (optional) $seqref reference to a string
               The sequence associated with the slice to be stored.
  Example    : $slice = Bio::EnsEMBL::Slice->new(...);
               $seq_region_id = $slice_adaptor->store($slice, \$sequence);
  Description: This stores a slice as a sequence region in the database
               and returns the seq region id. The passed in slice must
               start at 1, and must have a valid seq_region name and coordinate
               system. The attached coordinate system must already be stored in
               the database.  The sequence region is assumed to start at 1 and
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               to have a length equalling the length of the slice.  The end of
               the slice must equal the seq_region_length.
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               If the slice coordinate system is the sequence level coordinate
               system then the seqref argument must also be passed.  If the
               slice coordinate system is NOT a sequence level coordinate
               system then the sequence argument cannot be passed.
  Returntype : int 
  Exceptions : throw if slice has no coord system.
               throw if slice coord system is not already stored.
               throw if slice coord system is seqlevel and no sequence is 
                     provided.
               throw if slice coord system is not seqlevel and sequence is
                     provided.
               throw if slice does not start at 1
               throw if sequence is provided and the sequence length does not
                     match the slice length.
               throw if the SQL insert fails (e.g. on duplicate seq region)
               throw if slice argument is not passed
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               throw if the slice end is not equal to seq_region_length
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  Caller     : database loading scripts

=cut



sub store {
  my $self = shift;
  my $slice = shift;
  my $seqref = shift;

  #
  # Get all of the sanity checks out of the way before storing anything
  #

  if(!ref($slice) || !$slice->isa('Bio::EnsEMBL::Slice')) {
    throw('Slice argument is required');
  }

  my $cs = $slice->coord_system();
  throw("Slice must have attached CoordSystem.") if(!$cs);

  my $db = $self->db();
  if(!$cs->is_stored($db)) {
    throw("Slice CoordSystem must already be stored in DB.") 
  }

  if($slice->start != 1 || $slice->strand != 1) {
    throw("Slice must have start==1 and strand==1.");
  }

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  if($slice->end() != $slice->seq_region_length()) {
    throw("Slice must have end==seq_region_length");
  }

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  my $sr_len = $slice->length();
  my $sr_name  = $slice->seq_region_name();

  if(!$sr_name) {
    throw("Slice must have valid seq region name.");
  }

  if($cs->is_sequence_level()) {
    if(!$seqref) {
      throw("Must provide sequence for sequence level coord system.");
    }
    if(ref($seqref) ne 'SCALAR') {
      throw("Sequence must be a scalar reference.");
    }
    my $seq_len = length($$seqref);

    if($seq_len != $sr_len) {
      throw("Sequence length ($seq_len) must match slice length ($sr_len).");
    }
  } else {
    if($seqref) {
      throw("Cannot provide sequence for non-sequence level seq regions.");
    }
  }

  #store the seq_region

  my $sth = $db->prepare("INSERT INTO seq_region " .
                         "SET    name = ?, " .
                         "       length = ?, " .
                         "       coord_system_id = ?" );

  $sth->execute($sr_name, $sr_len, $cs->dbID());

  my $seq_region_id = $sth->{'mysql_insertid'};

  if(!$seq_region_id) {
    throw("Database seq_region insertion failed.");
  }

  if($cs->is_sequence_level()) {
    #store sequence if it was provided
    my $seq_adaptor = $db->get_SequenceAdaptor();
    $seq_adaptor->store($seq_region_id, $$seqref);
  }

  return $seq_region_id;
}


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=head2 prepare

  Arg [1]    : String $sql
  Example    :  ( optional )
  Description: overrides the default adaptor prepare method.
               All slice sql will usually use the dna_db.
  Returntype : DBD::sth 
  Exceptions : none
  Caller     : internal, convenience method

=cut



sub prepare {
  my $self = shift;
  my $sql = shift;

  return $self->db()->dnadb()->prepare( $sql );
}


  


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#####################################
# sub DEPRECATED METHODs
#####################################

=head2 fetch_by_mapfrag

 Function: DEPRECATED use fetch_by_misc_feature_attribute('synonym',$mapfrag)
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=cut

sub fetch_by_mapfrag{
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   my ($self,$mymapfrag,$flag,$size) = @_;
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   deprecate('Use fetch_by_misc_feature_attribute instead');
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   $flag ||= 'fixed-width'; # alt.. 'context'
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   $size ||= $flag eq 'fixed-width' ? 100000 : 0;
   return $self->fetch_by_misc_feature_attribute('synonym',$mymapfrag,$size);
}
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=head2 fetch_by_chr_start_end

  Description: DEPRECATED use fetch_by_region instead

=cut

sub fetch_by_chr_start_end {
  my ($self,$chr,$start,$end) = @_;
  deprecate('Use fetch_by_region() instead');

  #assume that by chromosome the user actually meant top-level coord
  #system since this is the old behaviour of this deprecated method
  my $csa = $self->db->get_CoordSystemAdaptor();
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  my ($cs) = @{$csa->fetch_all()}; # get the highest coord system
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  return $self->fetch_by_region($cs->name,$chr,$start,$end,1,$cs->version);
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}



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=head2 fetch_by_contig_name
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  Description: Deprecated. Use fetch_by_region(), Slice::project(),
               Slice::expand() instead
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=cut
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sub fetch_by_contig_name {
  my ($self, $name, $size) = @_;

  deprecate('Use fetch_by_region(), Slice::project() and Slice::expand().');

  #previously wanted chromosomal slice on a given contig.  Assume this means
  #a top-level slice on a given seq_region in the seq_level coord system
  my $csa = $self->db()->get_CoordSystemAdaptor();
  my $seq_level = $csa->fetch_sequence_level();

  my $seq_lvl_slice = $self->fetch_by_region($seq_level->name(), $name);

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  if(!$seq_lvl_slice) {
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    return undef;
  }

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  my @projection = @{$seq_lvl_slice->project('toplevel')};

  if(@projection != 1) {
    warning("$name is mapped to multiple toplevel locations.");
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  }

  return $projection[0]->[2]->expand($size, $size);
}


=head2 fetch_by_clone_accession

  Description: DEPRECATED.  Use fetch_by_region, Slice::project, Slice::expand
               instead.
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=cut

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sub fetch_by_clone_accession{
  my ($self,$name,$size) = @_;
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