=head1 LICENSE

Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
Copyright [2016-2020] EMBL-European Bioinformatics Institute

Licensed under the Apache License, Version 2.0 (the "License");
you may not use this file except in compliance with the License.
You may obtain a copy of the License at

     http://www.apache.org/licenses/LICENSE-2.0

Unless required by applicable law or agreed to in writing, software
distributed under the License is distributed on an "AS IS" BASIS,
WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
See the License for the specific language governing permissions and
limitations under the License.

=cut


=head1 CONTACT

 Please email comments or questions to the public Ensembl
 developers list at <dev@ensembl.org>.

 Questions may also be sent to the Ensembl help desk at
 <helpdesk@ensembl.org>.

=cut

#
# Ensembl module for Bio::EnsEMBL::Variation::DBSQL::ReadCoverageAdaptor
#
#

=head1 NAME

Bio::EnsEMBL::Variation::DBSQL::ReadCoverageAdaptor

=head1 SYNOPSIS
  $reg = 'Bio::EnsEMBL::Registry';
  
  $reg->load_registry_from_db(-host => 'ensembldb.ensembl.org', -user => 'anonymous');
  
  $rca = $reg->get_adaptor('human', 'variation', 'readcoverage');
  $sa = $reg->get_adaptor('human', 'core', 'slice);
  $sa = $reg->get_adaptor('human', 'variation', 'sample');

  # get read coverage in a region for a certain population in in a certain level
  $slice = $sa->fetch_by_region('chromosome', 'X', 1e6, 2e6);

  $sample = $sa->fetch_by_name("UNKNOWN");
  $level = 1;

  foreach $rc (@{$vfa->fetch_all_by_Slice_Sample_depth($slice, $sample, $level)}) {
    print $rc->start(), '-', $rc->end(), "\n";
  }


=head1 DESCRIPTION

This adaptor provides database connectivity for ReadCoverage objects.
Coverage information for reads can be obtained from the database using this
adaptor.  See the base class BaseFeatureAdaptor for more information.

=head1 METHODS

=cut

use strict;
use warnings;

package Bio::EnsEMBL::Variation::DBSQL::ReadCoverageAdaptor;

use Bio::EnsEMBL::Variation::ReadCoverage;
use Bio::EnsEMBL::Mapper::RangeRegistry;
use Bio::EnsEMBL::DBSQL::BaseFeatureAdaptor;
use Bio::EnsEMBL::Utils::Exception qw(throw warning);

our @ISA = ('Bio::EnsEMBL::DBSQL::BaseFeatureAdaptor');

=head2 fetch_all_by_Slice_Sample_depth

    Arg[0]      : Bio::EnsEMBL::Slice $slice
    Arg[1]      : (optional) Bio::EnsEMBL::Variation::Sample $sample
    Arg[2]      : (optional) int $level
    Example     : my $features = $rca->fetch_all_by_Slice_Sample_depth($slice, $sample, $level); or
                  my $features = $rca->fetch_all_by_Slice_Sample_depth($slice, $sample); or
                  my $features = $rca->fetch_all_by_Slice_Sample_depth($slice, $level); or
                  my $features = $rca->fetch_all_by_Slice_Sample_depth($slice); 
    Description : Gets all the read coverage features for a given sample (or strain) in a certain level
                  in the provided slice
    ReturnType  : reference to list of Bio::EnsEMBL::Variation::ReadCoverage
    Exceptions  : thrown on bad arguments
    Caller      : general
    Status      : Stable

=cut

sub fetch_all_by_Slice_Sample_depth {
  my $self = shift;
  my $slice = shift;
  my @args = @_; #can contain sample and/or level
  my $rcs;

  if(!ref($slice) || !$slice->isa('Bio::EnsEMBL::Slice')) {
    throw('Bio::EnsEMBL::Slice arg expected');
  }
  
  if (defined $args[0]) { #contains, at least, 1 parameter, either a Individual or the level
    my $constraint;
    my $levels = $self->get_coverage_levels();
    
    if (defined $args[1]) { #contains both parameters, first the Individual and second the level
      if(!ref($args[0]) || !$args[0]->isa('Bio::EnsEMBL::Variation::Sample')) {
        throw('Bio::EnsEMBL::Variation::Sample arg expected');
      }
      if(!defined($args[0]->dbID())) {
        throw("Sample arg must have defined dbID");
      }
      if ((grep {$args[1] == $_} @{$levels}) > 0) {
        $constraint = "rc.sample_id = " . $args[0]->dbID . " AND rc.level = " . $args[1];
        # $constraint = "rc.sample_id = ? AND rc.level = ?";
        # $self->bind_param_generic_fetch($args[0]->dbID,SQL_INTEGER);
        # $self->bind_param_generic_fetch($args[1],SQL_INTEGER);
      }
      else {
        warning("Level must be a number of: " . join(",", @{$levels}));
        return [];
      }
    }
    else { #there is just 1 argument, can either be the Individual or the level
      if (!ref($args[0])) {
        #it should just contain the level
        if ((grep {$args[0] == $_} @{$levels}) > 0) {
          $constraint = "rc.level = " . $args[0];
          #$constraint = "rc.level = ? ";
          #$self->bind_param_generic_fetch($args[0],SQL_INTEGER);
        }
        else {
          warning("Level must be a number of: " . join(",", @{$levels}));
          return [];
        }									   
      }
      else {
        #it should contain the Sample
        if (!$args[0]->isa('Bio::EnsEMBL::Variation::Sample')) {
          throw('Bio::EnsEMBL::Variation::Sample arg expected');
        }
        $constraint = "rc.sample_id = " . $args[0]->dbID;
      }
    }
    $rcs = $self->fetch_all_by_Slice_constraint($slice, $constraint);    
    return $rcs;
  }
  
  #call the method fetch_all_by_Slice
  $rcs = $self->fetch_all_by_Slice($slice);    
  return $rcs;
}

#returns a list of regions that are covered by all the samples given
sub fetch_all_regions_covered {
  my $self = shift;
  my $slice = shift;
  my $samples = shift;  #listref of sample names to get the coverage from

  my $sample_adaptor = $self->db->get_SampleAdaptor;
  my $range_registry = [];
  my $max_level = scalar(@{$samples});
  _initialize_range_registry($range_registry,$max_level);
  
  foreach my $sample_name (@{$samples}){
    my $sample = shift @{$sample_adaptor->fetch_all_by_name($sample_name)};
    my $coverage = $self->fetch_all_by_Slice_Sample_depth($slice, $sample); #get coverage information
    foreach my $cv_feature (@{$coverage}){
      my $range = [$cv_feature->seq_region_start, $cv_feature->seq_region_end]; #store toplevel coordinates
      _register_range_level($range_registry, $range, 1, $max_level);	   
    }
  }
  return $range_registry->[$max_level]->get_ranges(1);
}

=head2 get_coverage_levels

    Args        : none
    Example     : my @coverage_levels = @{$rca->fetch_coverage_levels()};
    Description : Gets the read coverage depths calculated in the database
    ReturnType  : reference to list of int
    Exceptions  : none
    Caller      : general
    Status      : At Risk

=cut

sub get_coverage_levels {
  my $self = shift;
  my @levels;
  my $level_coverage;
  my $sth = $self->prepare(qq{SELECT meta_value from meta where meta_key = 'read_coverage.coverage_level'});
  $sth->execute();
  $sth->bind_columns(\$level_coverage);
  while ($sth->fetch()){
    push @levels, $level_coverage;
  }
  $sth->finish();
    
  # HACK
  @levels = (1, 2) unless scalar @levels;

  return \@levels;
}

sub _initialize_range_registry {
  my $range_registry = shift;
  my $max_level = shift;

  foreach my $level (1..$max_level){
    $range_registry->[$level] = Bio::EnsEMBL::Mapper::RangeRegistry->new();
  }

  return;
}


sub _register_range_level {
  my $range_registry = shift;
  my $range = shift;
  my $level = shift;
  my $max_level = shift;
    
  return if ($level > $max_level);
  my $rr = $range_registry->[$level];
  my $pair = $rr->check_and_register(1,$range->[0],$range->[1]);
  my $pair_inverted = _invert_pair($range,$pair);
  return if (!defined $pair_inverted);
  foreach my $inverted_range (@{$pair_inverted}){
    _register_range_level($range_registry, $inverted_range, $level+1, $max_level);
  }
}

#for a given range and the one covered, returns the inverted
sub _invert_pair {
  my $range = shift; #initial range of the array
  my $pairs = shift; #listref with the pairs that have been added to the range

  my @inverted_pairs;
  my $inverted;

  my $rr = Bio::EnsEMBL::Mapper::RangeRegistry->new();

  foreach my $pair (@{$pairs}) {
    $rr->check_and_register(1, $pair->[0], $pair->[1]);
  }
  return $rr->check_and_register(1, $range->[0], $range->[1]); #register again the range
}

sub _tables { return (['read_coverage','rc'] )}


sub _columns {
  return qw (rc.seq_region_id rc.seq_region_start rc.seq_region_end rc.level rc.sample_id);
}


sub _objs_from_sth{
  my ($self, $sth, $mapper, $dest_slice) = @_;
  
  my $sa = $self->db()->dnadb()->get_SliceAdaptor();

  #
  # This code is ugly because an attempt has been made to remove as many
  # function calls as possible for speed purposes.  Thus many caches and
  # a fair bit of gymnastics is used.
  #

  my ($seq_region_id, $seq_region_start, $seq_region_end, $level, $sample_id);
  my $seq_region_strand = 1; #assume all reads are in the + strand

  $sth->bind_columns(\$seq_region_id, \$seq_region_start, \$seq_region_end, \$level, \$sample_id);
  my @features;
  my %seen_samples;
  my %slice_hash;
  my %sr_name_hash;
  my %sr_cs_hash;
  my $asm_cs;
  my $cmp_cs;
  my $asm_cs_vers;
  my $asm_cs_name;
  my $cmp_cs_vers;
  my $cmp_cs_name;

  if($mapper) {
    $asm_cs = $mapper->assembled_CoordSystem();
    $cmp_cs = $mapper->component_CoordSystem();
    $asm_cs_name = $asm_cs->name();
    $asm_cs_vers = $asm_cs->version();
    $cmp_cs_name = $cmp_cs->name();
    $cmp_cs_vers = $cmp_cs->version();
  }
  
  my $dest_slice_start;
  my $dest_slice_end;
  my $dest_slice_strand;
  my $dest_slice_length;

  if($dest_slice) {
    $dest_slice_start  = $dest_slice->start();
    $dest_slice_end    = $dest_slice->end();
    $dest_slice_strand = $dest_slice->strand();
    $dest_slice_length = $dest_slice->length();
  }

  my $read_coverage;
  FEATURE: while ($sth->fetch()){

    #get the population_adaptor object
    my $ia = $self->db()->get_SampleAdaptor();
    #get the slice object
    my $slice = $slice_hash{"ID:".$seq_region_id};
    if(!$slice) {
      $slice = $sa->fetch_by_seq_region_id($seq_region_id);
      $slice_hash{"ID:".$seq_region_id} = $slice;
      $sr_name_hash{$seq_region_id} = $slice->seq_region_name();
      $sr_cs_hash{$seq_region_id} = $slice->coord_system();
    }
    #
    # remap the feature coordinates to another coord system
    # if a mapper was provided
    #
    if($mapper) {
      my $sr_name = $sr_name_hash{$seq_region_id};
      my $sr_cs   = $sr_cs_hash{$seq_region_id};
	  
      ($sr_name,$seq_region_start,$seq_region_end,$seq_region_strand) =
      $mapper->fastmap($sr_name, $seq_region_start, $seq_region_end,
      $seq_region_strand, $sr_cs);
	  
      #skip features that map to gaps or coord system boundaries
      next FEATURE if(!defined($sr_name));
	  
      #get a slice in the coord system we just mapped to
      if($asm_cs == $sr_cs || ($cmp_cs != $sr_cs && $asm_cs->equals($sr_cs))) {
        $slice = $slice_hash{"NAME:$sr_name:$cmp_cs_name:$cmp_cs_vers"} ||=
        $sa->fetch_by_region($cmp_cs_name, $sr_name,undef, undef, undef,
        $cmp_cs_vers);
      } else {
        $slice = $slice_hash{"NAME:$sr_name:$asm_cs_name:$asm_cs_vers"} ||=
        $sa->fetch_by_region($asm_cs_name, $sr_name, undef, undef, undef,
        $asm_cs_vers);
      }
    }
      
    #
    # If a destination slice was provided convert the coords
    # If the dest_slice starts at 1 and is foward strand, nothing needs doing
    #
    if($dest_slice) {
      if($dest_slice_start != 1 || $dest_slice_strand != 1) {
        if($dest_slice_strand == 1) {
          $seq_region_start = $seq_region_start - $dest_slice_start + 1;
          $seq_region_end   = $seq_region_end   - $dest_slice_start + 1;
        } else {
          my $tmp_seq_region_start = $seq_region_start;
          $seq_region_start = $dest_slice_end - $seq_region_end + 1;
          $seq_region_end   = $dest_slice_end - $tmp_seq_region_start + 1;
          $seq_region_strand *= -1;
        }
	      
        #throw away features off the end of the requested slice
        if($seq_region_end < 1 || $seq_region_start > $dest_slice_length) {
          next FEATURE;
        }
      }
      $slice = $dest_slice;
    }

    my $sample;
    if($sample_id){
      $sample = $seen_samples{$sample_id} ||= $ia->fetch_by_dbID($sample_id);
    }
    $read_coverage = Bio::EnsEMBL::Variation::ReadCoverage->new(
      -start => $seq_region_start,
      -end   => $seq_region_end,
      -slice => $slice,
      -adaptor  => $self,
      -level => $level,
      -sample => $sample,
      -strand => 1,
    );
    push @features, $read_coverage;
  }
  
  $sth->finish();
  return \@features;
}

1;
