=head1 LICENSE

Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
Copyright [2016-2021] 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 <http://lists.ensembl.org/mailman/listinfo/dev>.

 Questions may also be sent to the Ensembl help desk at
 <http://www.ensembl.org/Help/Contact>.

=cut


package Bio::EnsEMBL::Variation::Utils::EnsEMBL2GFF3;

use strict;
use warnings;

# This module allows conversion of ensembl objects to GFF3 and GVF by inserting
# to_gff (and supporting _gff_hash) methods into the necessary feature classes

{
    package Bio::EnsEMBL::Slice;
   
	sub gff_version {
		return "##gff-version 3\n";
	}
	 
    sub gff_header {
        my $self = shift;
        
        my %args = @_;
        
        # build up a date string in the format specified by the GFF spec
    
        my ( $sec, $min, $hr, $mday, $mon, $year ) = localtime;
        $year += 1900;    # correct the year
        $mon++;           # correct the month
        
        my $date = sprintf "%4d-%02d-%02d", $year, $mon, $mday;
        
        my $region      = $self->seq_region_name;
        my $start       = $self->start;
        my $end         = $self->end;
        my $assembly    = $self->coord_system->version;
        
        my $mca = $self->adaptor->db->get_MetaContainerAdaptor;
        my $tax_id = $mca->get_taxonomy_id;
        
        my $hdr =
			"##file-date $date\n"
          . "##genome-build ensembl $assembly\n"
          . "##species http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=$tax_id\n";
        
        $hdr .= "##sequence-region $region $start $end\n" unless $args{no_sequence_region};
        
        return $hdr;
    }
   
	sub gvf_version {
		return "##gvf-version 1.06\n";
	}
 
    sub gvf_header {
        my $self = shift;
       
        my %args = @_;
		my $hdr = $self->gff_version;
		$hdr .= $self->gvf_version;
        $hdr .= $self->gff_header(@_);
        
        my $mca = $self->adaptor->db->get_MetaContainerAdaptor;
        my $schema_version = $mca->get_schema_version;
        my $species_name = $mca->get_scientific_name;
        $species_name =~ s/ /_/g;
        my $url = 'http://e'.$schema_version.'.ensembl.org/'.$species_name;
        
        $hdr .= "##feature-ontology http://song.cvs.sourceforge.net/viewvc/song/ontology/so.obo?revision=1.283\n";
        $hdr .= "##data-source Source=ensembl;version=$schema_version;url=$url\n";
        $hdr .= "##file-version $schema_version\n";
        
        if (my $individual = $args{individual}) {
            $hdr .= "##individual-id ".$individual->to_gvf."\n";
        }

        if (my $population = $args{population}) {
            $hdr .= "##attribute-method ".$population->to_gvf."\n";
        }

        return $hdr;
    }
}

{

    package Bio::EnsEMBL::Feature;

    sub to_gff {

        my $self = shift;
        
        my %args = @_;
        
        # This parameter is assumed to be a hashref which includes extra attributes you'd
        # like to have appended onto the gff line for the feature
        my $extra_attrs = $args{extra_attrs};

        my $gff = $self->_gff_hash(@_);

        return undef unless defined $gff;

        # default optional columns, and check that all required columns are present

        $gff->{score}  = '.' unless defined $gff->{score};
        $gff->{strand} = '.' unless defined $gff->{strand};
        $gff->{phase}  = '.' unless defined $gff->{phase};

        for my $req (qw(source type start end)) {
            die "'$req' attribute required for GFF" unless $gff->{$req};
        }

        # order as per GFF3 spec: http://www.sequenceontology.org/gff3.shtml 
 
        my $gff_str = join( "\t",
            $gff->{seqid}, $gff->{source}, $gff->{type}, $gff->{start},
            $gff->{end}, $gff->{score}, $gff->{strand}, $gff->{phase},
        );

        if ($extra_attrs) {

            # combine the extra attributes with any existing ones (duplicate keys will get squashed,
            # so attributes specified in the extra_attrs hash will override existing ones)

            $gff->{attributes} = {} unless defined $gff->{attributes};
            
            @{ $gff->{attributes} }{ keys %$extra_attrs } = values %$extra_attrs;
        }

        if ( $gff->{attributes} ) {

            my @attrs;

            for my $key (keys %{ $gff->{attributes} }) {

                my $val = $gff->{attributes}->{$key};

                if (ref $val eq 'ARRAY') {
                    push @attrs, map { $key . '='. $_ } @$val;
                }
                else {
                    push @attrs, $key . '=' . $val;
                }
            }
                
            $gff_str .= "\t" . join( ';', @attrs );
        }

        return $gff_str;
    }

    sub _gff_hash {
        my $self = shift;
        
        my %args = @_;
        
        my $rebase      = $args{rebase}; # use absolute or slice-relative coordinates
        
        my $gff_seqid   = $args{gff_seqid} || $self->slice->seq_region_name;
        my $gff_source  = $args{gff_source} || $self->_gff_source;

        my $seqid = $rebase ? $gff_seqid.'_'.$self->slice->start.'-'.$self->slice->end : $gff_seqid;
        my $start = $rebase ? $self->start : $self->seq_region_start;
        my $end = $rebase ? $self->end : $self->seq_region_end;
        
        # GFF3 does not allow start > end, and mandates that for zero-length features (e.g. insertions) 
        # start = end and the implied insertion site is to the right of the specified base, so we use the
        # smaller of the two values
        
        if ($start > $end) {
            $start = $end;
        }
        
        my $gff = {
            seqid   => $gff_seqid,
            source  => $gff_source,
            type    => $self->_gff_type,
            start   => $start,
            end     => $end,
            strand  => (
                $self->strand == 1 ? '+' : ( $self->strand == -1 ? '-' : '.' )
            )
        };

        return $gff;
    }

    sub _gff_source {
        my $self = shift;
        
        if ($self->analysis) {
            return
                $self->analysis->gff_source
                || $self->analysis->logic_name;
        }
        else {
            return ref($self);
        }
    }

    sub _gff_type {
        my $self = shift;

        return
            ( $self->analysis && $self->analysis->gff_feature )
            || 'misc_feature';
    }
}

{
    package Bio::EnsEMBL::Variation::VariationFeature;
    
    use Bio::EnsEMBL::Utils::Sequence qw(expand);

    my $REFERENCE_ALLELE_IDENTIFIER = '@';

    sub to_gvf {
        my $self = shift;
        return $self->to_gff(@_);
    }
    
    sub _gff_hash {
   
        my $self = shift;
        
        my $gff = $self->SUPER::_gff_hash(@_);
        
        my %args = @_;
        
        my $include_consequences    = $args{include_consequences};
        my $include_coding_details  = $args{include_coding_details};
        my $include_global_maf      = $args{include_global_maf};

        $gff->{source} = $self->source_name;

        $gff->{type} = $self->class_SO_term;

        my $source = $self->source_name;

        $source .= '_'.$self->source_version if defined $self->source_version;

        $gff->{attributes}->{Dbxref} = "$source:".$self->variation_name;

        $gff->{attributes}->{ID} = $self->dbID;

        # the Variant_seq attribute requires a comma separated list of alleles

        my @alleles = split '/', $self->allele_string;
        my $ref_seq = shift @alleles unless @alleles == 1; # shift off the reference allele
       
        $gff->{attributes}->{Variant_seq} = join ',', @alleles;

        my $index = 0;

        # expand tandem repeat alleles, because TranscriptVariationAlleles use the expanded sequence
        
        map { expand(\$_) } @alleles; 

        # if you expand e.g. (T)0 you get an empty string, which we treat as a deletion, so default to '-'

        my %allele_index = map { ($_ || '-') => $index++ } @alleles;

        if ($include_global_maf) {

            my $var = $self->variation;
            
            if (defined $var->minor_allele_frequency) {
                
                my $allele_idx;

                if ($var->minor_allele eq $ref_seq) {
                    $allele_idx = $REFERENCE_ALLELE_IDENTIFIER;
                }
                else {
                    $allele_idx = $allele_index{$var->minor_allele};
                }

                if (defined $allele_idx) {
                    $gff->{attributes}->{global_minor_allele_frequency} = 
                        join (' ', 
                            $allele_idx,
                            $var->minor_allele_frequency,
                            $var->minor_allele_count
                        );
                }
            }
        }
        
        # the reference sequence should be set to '~' if the sequence is longer than 50 nucleotides

        $ref_seq = '~' if (not $ref_seq) || (CORE::length($ref_seq) > 50);
        $gff->{attributes}->{Reference_seq} = $ref_seq;
        
        # Hack for HGMD mutations
       
        if ($self->allele_string eq 'HGMD_MUTATION') {
            $gff->{attributes}->{Reference_seq} = '~';
            $gff->{attributes}->{Variant_seq}   = '~';
            $allele_index{$self->allele_string} = 0;
        }
        
        if ($include_consequences || $include_coding_details) {
            
            for my $tv (@{ $self->get_all_TranscriptVariations }) {

                unless ($tv->get_all_alternate_TranscriptVariationAlleles) {
                    warn $self->variation_name." has no alternate alleles?";
                    next;
                }

                if ($include_coding_details) {
                    my $ref_tva = $tv->get_reference_TranscriptVariationAllele;

                    if (my $pep = $ref_tva->peptide) {
                        $gff->{attributes}->{reference_peptide} = $pep;
                    }
                }

                for my $tva (@{ $tv->get_all_alternate_TranscriptVariationAlleles }) {

                    my $allele_idx = $allele_index{$tva->variation_feature_seq};
                    
                    if (defined $allele_idx) {

                        if ($include_consequences) {
                            for my $oc (@{ $tva->get_all_OverlapConsequences }) {

                                push @{ $gff->{attributes}->{Variant_effect} ||= [] },
                                    join(' ',
                                        $oc->SO_term, 
                                        $allele_idx,
                                        $oc->feature_SO_term,
                                        $tv->transcript_stable_id,
                                    );
                            }
                        }
                        
                        if ($include_coding_details) {
                            if ($tva->pep_allele_string) {

                                push @{ $gff->{attributes}->{variant_peptide} ||= [] },
                                    join(' ',
                                        $allele_idx,
                                        $tva->peptide,
                                        $tv->transcript_stable_id,
                                    );

                                for my $tool (qw(sift polyphen)) {
                                    my $pred_meth = $tool.'_prediction';
                                    my $score_meth = $tool.'_score';
                                    if (my $pred = $tva->$pred_meth) {
                                        $pred =~ s/\s/_/g;
                                        push @{ $gff->{attributes}->{polyphen_prediction} ||= [] }, 
                                            join(' ', 
                                                $allele_idx, 
                                                $pred, 
                                                $tva->$score_meth,
                                                $tv->transcript_stable_id
                                            );
                                    }
                                }
                            }
                        }
                    }
                    else {
                        warn "No allele_index entry for allele: ".$tva->variation_feature_seq.
                            " of ".$self->variation_name."? Is reference " . $tva->is_reference . " ref seq " . $ref_seq . "\n";
                    }
                }
            }
        }
    
        return $gff;
    }
}

{
    package Bio::EnsEMBL::Variation::StructuralVariationFeature;
    
    sub _gff_hash {
        
        my $self = shift;
        
        my $gff = $self->SUPER::_gff_hash(@_);
        
        $gff->{attributes}->{ID} = $self->variation_name;
        
        $gff->{source} = $self->source_name;
        
        my $sv = $self->structural_variation;
        
        $gff->{attributes}->{Dbxref} = $self->source_name . ':' . $self->variation_name;
        
        $gff->{attributes}->{study_accession} = $sv->study->name if $sv->study->name;

        $gff->{type} = $self->class_SO_term;
        
        #$gff->{attributes}->{Reference_seq} = $self->end > $self->start+50 ? '~' : $self->get_reference_sequence;
     
        if ( (defined $self->inner_start) && (defined $self->outer_start) && ($self->inner_start != $self->outer_start) ) {
            $gff->{attributes}->{Start_range} = join ',', $self->outer_start, $self->inner_start;
        }

        if ( (defined $self->inner_end) && (defined $self->outer_end) && ($self->inner_end != $self->outer_end) ) {
            $gff->{attributes}->{End_range} = join ',', $self->inner_end, $self->outer_end;
        }
        
        if (my $sv = $self->structural_variation) {
            if (ref $sv eq 'Bio::EnsEMBL::Variation::SupportingStructuralVariation') {
                if (my $parents = $sv->get_all_StructuralVariations) {
                    $gff->{attributes}->{Parent} = join ',', map { $_->variation_name } @$parents;
                }
            }
        }

        return $gff;
    }
    
    sub to_gvf {
        my $self = shift;
        return $self->to_gff(@_);
    }
}

{
    package Bio::EnsEMBL::Variation::Individual;
        
    sub _gff_hash {
        
        my $self = shift;

        my $gff;

        $gff->{Gender} = $self->gender;

        $gff->{Display_name} = $self->name;

        $gff->{ensembl_description} = $self->description;

        $gff->{Type} = $self->type_description;

        $gff->{Population} = join ',', map { $_->name } @{ $self->get_all_Populations };
       
        return $gff;
    }

    sub to_gvf {
        my $self = shift;
       
        my $attrs = $self->_gff_hash(@_);

        # get rid of any empty attributes 
        map { delete $attrs->{$_} unless $attrs->{$_} } keys %$attrs;
        
        return join ';', map { $_.'='.$attrs->{$_} } keys %$attrs; 
    }
    
}

{
    package Bio::EnsEMBL::Variation::Population;
        
    sub _gff_hash {
        
        my $self = shift;

        my $gff;

        $gff->{Attribute} = 'Variant_freq';

        $gff->{population} = $self->name;
        
        $gff->{population_size} = $self->size;

        $gff->{Comment} = $self->description;
      
        return $gff;
    }

    sub to_gvf {
        my $self = shift;
       
        my $attrs = $self->_gff_hash(@_);

        # get rid of any empty attributes 
        map { delete $attrs->{$_} unless $attrs->{$_} } keys %$attrs;
        
        return join ';', map { $_.'='.$attrs->{$_} } keys %$attrs; 
    }
    
}

1;

