File Coverage

blib/lib/OBO/Util/Ontolome.pm

Criterion	Covered	Total	%
statement	472	578	81.6
branch	109	156	69.8
condition	22	57	38.6
subroutine	7	7	100.0
pod	4	4	100.0
total	614	802	76.5

# $Id: Ontolome.pm 2014-10-22 erick.antezana $
#
# Module  : Ontolome.pm
# Purpose : Management of a set of ontologies.
# License : Copyright (c) 2006-2015 by Erick Antezana. All rights reserved.
#           This program is free software; you can redistribute it and/or
#           modify it under the same terms as Perl itself.
# Contact : Erick Antezana
#
package OBO::Util::Ontolome;

our @ISA = qw(OBO::Util::ObjectSet);
use OBO::Util::ObjectSet;

use strict;
use warnings;

=head2 union

  Usage    - $ome->union($o1, $o2, ...)
  Returns  - an ontology (OBO::Core::Ontology) being the union of the parameters (ontologies)
  Args     - the ontologies (OBO::Core::Ontology) to be united
  Function - creates an ontology having the union of terms and relationships from the given ontologies
  Remark 1 - the IDspace's are collected and added to the result ontology
  Remark 2 - the union is made on the basis of the IDs
  Remark 3 - the default namespace is taken from the last ontology argument
  Remark 4 - the merging order is important while merging definitions: the one from the last ontology will be taken

=cut

sub union () {
	my ($self, @ontos) = @_;
	my $result         = OBO::Core::Ontology->new();

	$result->saved_by('ONTO-perl');
	$result->remarks('Union of ontologies');

	my $default_namespace;
	my $default_relationship_id_prefix;

	foreach my $ontology (@ontos) {
		$result->remarks($ontology->remarks()->get_set());    # add all the remark's of the ontologies
		$result->treat_xrefs_as_equivalent($ontology->treat_xrefs_as_equivalent->get_set()); # treat-xrefs-as-equivalent
		$result->treat_xrefs_as_is_a($ontology->treat_xrefs_as_is_a->get_set()); # treat_xrefs_as_is_a
		$result->idspaces($ontology->idspaces()->get_set());  # assuming the same idspace
		$result->subset_def_map($ontology->subset_def_map()); # add all subset_def_map's by default
		$result->synonym_type_def_set($ontology->synonym_type_def_set()->get_set()); # add all synonym_type_def_set by default
		$default_namespace = $ontology->default_namespace();  # keep the namespace of the last ontology argument
		$default_relationship_id_prefix = $ontology->default_relationship_id_prefix();  # keep the default relationship ID prefix of the last ontology argument

		my @terms = @{$ontology->get_terms()};
		foreach my $term (@terms){
			my $term_id      = $term->id();
			my $current_term = $result->get_term_by_id($term_id); # N.B. it could also be $result->get_term_by_name_or_synonym()
			if ($current_term) { # TODO && $current_term is in $term->namespace()  i.e. check if they belong to an identical namespace
				$current_term->is_anonymous($term->is_anonymous());
				foreach ($term->alt_id()->get_set()) {
					$current_term->alt_id($_);
				}
				$current_term->def($term->def()) if (!defined $current_term->def()->text() && $term->def()->text()); # TODO implement the case where the def xref's are not balanced!
				foreach ($term->namespace()) {
					$current_term->namespace($_);
				}
				$current_term->comment($term->comment()) if (!defined $current_term->comment() && $term->comment());
				foreach ($term->subset()) {
					$current_term->subset($_);
				}
				foreach ($term->synonym_set()) {
					# Special case: the synonym is identical and the scope is not...
					# Solution    : take the one from the last ontology and avoid an entry with something like:
					#   synonym: "lateral root-cap-epidermal stem cell" EXACT []
					#   synonym: "lateral root-cap-epidermal stem cell" RELATED []
					$current_term->synonym_set($_);
				}
				foreach ($term->xref_set()->get_set()) {
					$current_term->xref_set()->add($_);
				}
				foreach ($term->intersection_of()) {
					$current_term->intersection_of($_);
				}
				foreach ($term->union_of()) {
					$current_term->union_of($_);
				}
				foreach ($term->disjoint_from()) {
					$current_term->disjoint_from($_);
				}
				$current_term->created_by($term->created_by());
				$current_term->creation_date($term->creation_date());
				$current_term->is_obsolete($term->is_obsolete());
				foreach ($term->replaced_by()->get_set()) {
					$current_term->replaced_by($_);
				}
				foreach ($term->consider()->get_set()) {
					$current_term->consider($_);
				}
				$current_term->builtin($term->builtin());

				# fix the rel's
				my @rels = @{$ontology->get_relationships_by_target_term($term)};
				foreach my $r (@rels) {
					my $cola    = $r->tail();
					my $tail_id = $cola->id();

					#croak 'There is no ID for the tail term linked to: ', $term->id() if (!$tail_id);

					my $tail = $result->get_term_by_id($tail_id); # Is $cola already present in the growing ontology?
					if (!defined $tail) {
						my $new_term = OBO::Core::Term->new();
						$new_term->id($tail_id);
						$new_term->name($cola->name());
						$result->add_term($new_term);			  # add $cola if it is not present yet!
						$tail = $result->get_term_by_id($tail_id);
					}
					my $r_type   = $r->type(); # e.g. is_a
					my $rel_type = $ontology->get_relationship_type_by_id($r_type);
					$result->has_relationship_type($rel_type) || $result->add_relationship_type_as_string($rel_type->id(), $r_type);

					$result->create_rel($tail, $r_type, $current_term);
				}
			} else {
				my $new_term = OBO::Core::Term->new();
				$new_term->id($term_id);
				$new_term->name($term->name());
				$result->add_term($new_term);
				push @terms, $term; # trick to visit again the just added term which wasn't treated yet
			}
		}

		#
		# Add relationships
		#
		my @relationships = @{$ontology->get_relationships()};
		foreach my $rela (@relationships){
			my $rel_type_id    = $rela->type();
			my $onto_rela_type = $ontology->get_relationship_type_by_id($rel_type_id);
			my $rel_type       = $result->get_relationship_type_by_id($rel_type_id);

			if (!defined $rel_type) {
				my $rt_name       = $onto_rela_type->name();
				my $rel_type_name = (defined $rt_name)?$rt_name:$rel_type_id;
				$result->add_relationship_type_as_string($rel_type_id, $rel_type_id);
				$rel_type = $result->get_relationship_type_by_id($rel_type_id);
			} elsif (!$result->has_relationship_type($rel_type)) {
				$result->add_relationship_type($rel_type); # add rel types between rel's (typical is_a, part_of)
				$rel_type = $result->get_relationship_type_by_id($rel_type_id);
			}

			if ($onto_rela_type) {
				$rel_type->is_anonymous($onto_rela_type->is_anonymous());

				foreach ($onto_rela_type->alt_id()->get_set()) {
					$rel_type->alt_id($_);
				}

				$rel_type->builtin($onto_rela_type->builtin());

				$rel_type->def($onto_rela_type->def()) if (!defined $rel_type->def()->text() && $onto_rela_type->def()->text()); # TODO implement the case where the def xref's are not balanced!

				foreach ($onto_rela_type->namespace()) {
					$rel_type->namespace($_);
				}

				$rel_type->comment($onto_rela_type->comment()) if (!defined $rel_type->comment() && $onto_rela_type->comment());

				foreach ($onto_rela_type->subset()) {
					$rel_type->subset($_);
				}
				foreach ($onto_rela_type->synonym_set()) {
					$rel_type->synonym_set($_);
				}
				foreach ($onto_rela_type->xref_set()->get_set()) {
					$rel_type->xref_set()->add($_);
				}
				foreach my $domain ($onto_rela_type->domain()->get_set()) {
					$rel_type->xref_set()->add($domain);
				}
				foreach my $range ($onto_rela_type->range()->get_set()) {
					$rel_type->xref_set()->add($range);
				}
				$rel_type->is_anti_symmetric($onto_rela_type->is_anti_symmetric());
				$rel_type->is_cyclic($onto_rela_type->is_cyclic());
				$rel_type->is_reflexive($onto_rela_type->is_reflexive());
				$rel_type->is_symmetric($onto_rela_type->is_symmetric());
				$rel_type->is_transitive($onto_rela_type->is_transitive());

				my $ir = $onto_rela_type->inverse_of();
				$rel_type->inverse_of($ir) if (defined $ir);

				$rel_type->transitive_over($onto_rela_type->transitive_over()->get_set());

				foreach my $holds_over_chain ($onto_rela_type->holds_over_chain()) {
					$rel_type->holds_over_chain(@{$holds_over_chain}[0], @{$holds_over_chain}[1]);
				}

				$rel_type->is_functional($onto_rela_type->is_functional());
				$rel_type->is_inverse_functional($onto_rela_type->is_inverse_functional());

				$rel_type->created_by($onto_rela_type->created_by());
				$rel_type->creation_date($onto_rela_type->creation_date());

				$rel_type->modified_by($onto_rela_type->modified_by());
				$rel_type->modification_date($onto_rela_type->modification_date());

				$rel_type->is_obsolete($onto_rela_type->is_obsolete());

				foreach ($onto_rela_type->replaced_by()->get_set()) {
					$rel_type->replaced_by($_);
				}

				foreach ($onto_rela_type->consider()->get_set()) {
					$rel_type->consider($_);
				}

				$rel_type->is_metadata_tag($onto_rela_type->is_metadata_tag());

				$rel_type->is_class_level($onto_rela_type->is_class_level());

			} else {
				# TODO Why do we have this case?
			}

			#
			# link the rels:
			#
			my $rel_id = $rela->id();
			if (! $result->has_relationship_id($rel_id)) {
				$result->add_relationship($rela); # add rel's between rel's
			}
		}

		#
		# Add relationship types
		#
		my @relationship_types = @{$ontology->get_relationship_types()};
		foreach my $relationship_type (@relationship_types){
			my $relationship_type_id      = $relationship_type->id();
			my $current_relationship_type = $result->get_relationship_type_by_id($relationship_type_id); # N.B. it could also be $result->get_relationship_type_by_name_or_synonym()
			if ($current_relationship_type) { # TODO && $current_relationship_type is in $relationship_type->namespace()  i.e. check if they belong to an identical namespace
				$current_relationship_type->is_anonymous($relationship_type->is_anonymous());
				foreach ($relationship_type->namespace()) {
					$current_relationship_type->namespace($_);
				}
				foreach ($relationship_type->alt_id()->get_set()) {
					$current_relationship_type->alt_id($_);
				}
				$current_relationship_type->builtin($relationship_type->builtin());
				$current_relationship_type->def($relationship_type->def()) if (!defined $current_relationship_type->def()->text() && $relationship_type->def()->text()); # TODO implement the case where the def xref's are not balanced!
				$current_relationship_type->comment($relationship_type->comment()) if (!defined $current_relationship_type->comment() && $relationship_type->comment());
				foreach ($relationship_type->subset()) {
					$current_relationship_type->subset($_);
				}
				foreach ($relationship_type->synonym_set()) {
					$current_relationship_type->synonym_set($_);
				}
				foreach ($relationship_type->xref_set()->get_set()) {
					$current_relationship_type->xref_set()->add($_);
				}
				foreach ($relationship_type->domain()->get_set()) {
					$current_relationship_type->domain($_);
				}
				foreach ($relationship_type->range()->get_set()) {
					$current_relationship_type->range($_);
				}
				$current_relationship_type->is_anti_symmetric($relationship_type->is_anti_symmetric());
				$current_relationship_type->is_cyclic($relationship_type->is_cyclic());
				$current_relationship_type->is_reflexive($relationship_type->is_reflexive());
				$current_relationship_type->is_symmetric($relationship_type->is_symmetric());
				$current_relationship_type->is_transitive($relationship_type->is_transitive());

				$current_relationship_type->inverse_of($relationship_type->inverse_of());

				foreach ($relationship_type->transitive_over()->get_set()) {
					$current_relationship_type->transitive_over($_);
				}
				foreach ($relationship_type->holds_over_chain()) {
					$current_relationship_type->holds_over_chain(@{$_}[0], @{$_}[1]);
				}
				$current_relationship_type->is_functional($relationship_type->is_functional());
				$current_relationship_type->is_inverse_functional($relationship_type->is_inverse_functional());
				foreach ($relationship_type->intersection_of()) {
					$current_relationship_type->intersection_of($_);
				}
				foreach ($relationship_type->union_of()) {
					$current_relationship_type->union_of($_);
				}
				foreach ($relationship_type->disjoint_from()) {
					$current_relationship_type->disjoint_from($_);
				}
				$current_relationship_type->created_by($relationship_type->created_by());
				$current_relationship_type->creation_date($relationship_type->creation_date());
				$current_relationship_type->modified_by($relationship_type->modified_by());
				$current_relationship_type->modification_date($relationship_type->modification_date());
				$current_relationship_type->is_obsolete($relationship_type->is_obsolete());
				foreach ($relationship_type->replaced_by()->get_set()) {
					$current_relationship_type->replaced_by($_);
				}
				foreach ($relationship_type->consider()->get_set()) {
					$current_relationship_type->consider($_);
				}
				$current_relationship_type->is_metadata_tag($relationship_type->is_metadata_tag());
				$current_relationship_type->is_class_level($relationship_type->is_class_level());
			} else {
				my $new_relationship_type = OBO::Core::RelationshipType->new();
				$new_relationship_type->id($relationship_type_id);
				$new_relationship_type->name($relationship_type->name());
				$result->add_relationship_type($new_relationship_type);
				push @relationship_types, $relationship_type; # trick to visit again the just added relationship_type which wasn't treated yet
			}
		}

		#
		# Add instances
		#
		my @instances = @{$ontology->get_instances()};
		foreach my $term (@instances){
		#TODO
		}
	}
	$result->default_relationship_id_prefix($default_relationship_id_prefix) if (defined $default_relationship_id_prefix);
	$result->default_namespace($default_namespace) if (defined $default_namespace);

	return $result;
}

=head2 intersection

  Usage    - $ome->intersection($o1, $o2)
  Return   - an ontology (OBO::Core::Ontology) holding the 'intersection' of $o1 and $o2
  Args     - the two ontologies (OBO::Core::Ontology) to be intersected
  Function - finds the intersection ontology from $o1 and $o2. All the common terms by ID
             are added to the resulting ontology. This method provides a way of comparing two
             ontologies. The resulting ontology gives hints about the missing and identical
             terms (comparison done by term ID). A closer analysis should be done to identify
             the differences
  Remark   - Performance issues with huge ontologies

=cut

sub intersection () {
	my ($self, $onto1, $onto2) = @_;
	my $result = OBO::Core::Ontology->new();
	$result->saved_by('ONTO-perl');
	$result->default_relationship_id_prefix($onto1->default_relationship_id_prefix()); # use the default_relationship_id_prefix of the first argument
	$result->default_namespace($onto1->default_namespace());                           # use the default_namespace of the first argument
	$result->remarks('Intersection of ontologies');

	#
	# treat_xrefs_as_equivalent
	#
	my @txae1 = $onto1->treat_xrefs_as_equivalent->get_set();
	my @txae2 = $onto2->treat_xrefs_as_equivalent->get_set();
	if ($#txae1 > 0 && $#txae2 > 0) {
		my %inter = ();
		foreach my $ids_xref (@txae1, @txae2) {
			$inter{$ids_xref}++;
		}
		$result->treat_xrefs_as_equivalent(sort keys %inter);
	}

	#
	# treat_xrefs_as_is_a
	#
	my @txaia1 = $onto1->treat_xrefs_as_is_a->get_set();
	my @txaia2 = $onto2->treat_xrefs_as_is_a->get_set();
	if ($#txaia1 > 0 && $#txaia2 > 0) {
		my %inter = ();
		foreach my $ids_xref (@txaia1, @txaia2) {
			$inter{$ids_xref}++;
		}
		$result->treat_xrefs_as_is_a(sort keys %inter);
	}

	# the IDspace's of both ontologies are added to the intersection ontology
	$result->idspaces($onto1->idspaces()->get_set());
	$result->idspaces($onto2->idspaces()->get_set());

	$result->subset_def_map($onto1->subset_def_map()); # add all subset_def_map's by default

	foreach my $term (@{$onto1->get_terms()}){
		my $current_term = $onto2->get_term_by_id($term->id()); ### could also be $result->get_term_by_name_or_synonym()
		if (defined $current_term) {  # term intersection
			$result->add_term($term); # added the term from onto2
			foreach my $ins ($term->class_of()->get_set()) {
				$result->add_instance($ins); # add its instances
			}
		}
	}
	my $onto1_number_relationships  = $onto1->get_number_of_relationships();
	my $onto2_number_relationships  = $onto2->get_number_of_relationships();
	my $min_number_rels_onto1_onto2 = ($onto1_number_relationships < $onto2_number_relationships)?$onto1_number_relationships:$onto2_number_relationships;

	my @terms = @{$result->get_terms()};

	my $stop  = OBO::Util::Set->new();
	map {$stop->add($_->id())} @terms;

	# path of references
	my @pr1;
	my @pr2;

	# link the common terms
	foreach my $term (@terms) {
		my $term_id = $term->id();

		#
		# path of references: onto1 and onto2
		#

		# onto1
		my @pref1 = $onto1->get_paths_term_terms($term_id, $stop);
		push @pr1, [@pref1];

		# onto2
		my @pref2 = $onto2->get_paths_term_terms($term_id, $stop);
		push @pr2, [@pref2];
	}

	# pr1
	my %cand;
	foreach my $pref (@pr1) {
		foreach my $ref (@$pref) {
			my $type = @$ref[0]->type(); # first type
			my $invalid = 0;
			my $r_type;
			foreach my $tt (@$ref) {
				$r_type = $tt->type();
				if ($type ne $r_type) {
					$invalid = 1;
					last; # no more walking
				}
			}
			if (!$invalid) {
				my $f = @$ref[0]->tail()->id();
				my $l = @$ref[$#$ref]->head()->id();
				$cand{$f.'->'.$r_type.'->'.$l} = 1; # there could be more than 1 path
				$invalid = 0;
			}
		}
	}

	# pr2
	my %r_cand;
	foreach my $pref (@pr2) {
		foreach my $ref (@$pref) {
			my $type = @$ref[0]->type(); # first type
			my $invalid = 0;
			my $r_type;
			foreach my $tt (@$ref) {
				$r_type = $tt->type();
				if ($type ne $r_type) { # ONLY identical rel types in the path are admitted!!!
					#warn 'INVALID REL: ', $tt->id();
					$invalid = 1;
					last; # no more walking
				}
			}
			if (!$invalid) {
				my $f = @$ref[0]->tail()->id();
				my $l = @$ref[$#$ref]->head()->id();
				$cand{$f.'->'.$r_type.'->'.$l}++;
				$r_cand{$f.'->'.$l} = $r_type;
				$invalid = 0;
			}
		}
	}

	# cleaning candidates
	foreach (sort keys (%cand)) {
		delete $cand{$_} if ($cand{$_} < 2);
	}

	# candidates simplified
	my %cola;
	foreach (keys (%cand)) {
		my $f = $1, my $r = $2, my $l = $3 if ($_ =~ /(.*)->(.*)->(.*)/);
		$cola{$f} .= $l.' ';  # hold the candidates
	}

	# transitive reduction
	while ( my ($k, $v) = each(%cola)) {
		my $V = OBO::Util::Set->new();
		$V->add($v);

		my @T      = split (' ', $v);
		my %target = ();
		my $r_type = $r_cand{$k.'->'.$T[$#T]}; # check

		while ($#T > -1) {
			my $n = pop @T;
			$target{$r_type.'->'.$n}++;
			if (!$V->contains($n)) {
				$V->add($n);
				push @T, split(' ', $cola{$n}) if ($cola{$n});
			}
		}

		while (my ($t, $veces) = each(%target)) {
			if ($veces > 1) { # if so, the delete $k->$t
				delete $cand{$k.'->'.$t};
			}
		}
	}

	# after 'transitive reduction' we have
	while (my ($k, $v) = each(%cand)) {
		my $s = $1, my $r_type = $2, my $t = $3 if ($k =~ /(.*)->(.*)->(.*)/);
		my $source    = $result->get_term_by_id($s);
		my $target    = $result->get_term_by_id($t);

		if (!($result->has_relationship_type_id($r_type))) {
			$result->add_relationship_type_as_string($r_type, $r_type); # ID = NAME
		}
		$result->create_rel($source, $r_type, $target);
	}
	return $result;
}

=head2 transitive_closure

  Usage    - $ome->transitive_closure($o, @transitive_relationship_types)
  Return   - an ontology (OBO::Core::Ontology) with the transitive closure
  Args     - the ontology (OBO::Core::Ontology) to be expanded and
  			 optionally an array with the transitive relationship
  			 types (by default: 'is_a' and 'part_of') to be considered
  Function - expands all the transitive relationships (e.g. is_a, part_of) along the
  			 hierarchy and generates a new ontology holding all possible paths
  Remark   - Performance issues with huge ontologies.
           - an experimental code is enabled (flag: $composition) based on http://www.geneontology.org/GO.ontology.relations.shtml

=cut

sub transitive_closure () {
	my ($self, $ontology, @trans_rts, $composition) = @_;

	my @default_trans_rts = ('is_a', 'part_of');
	if (scalar @trans_rts > 0) {
		@default_trans_rts = @trans_rts;
	}

	my $result = OBO::Core::Ontology->new();
	$result->saved_by('ONTO-perl');
	$result->idspaces($ontology->idspaces()->get_set());
	$result->default_relationship_id_prefix($ontology->default_relationship_id_prefix());
	$result->default_namespace($ontology->default_namespace());
	$result->remarks('Ontology with transitive closures');
	$result->treat_xrefs_as_equivalent($ontology->treat_xrefs_as_equivalent->get_set()); # treat-xrefs-as-equivalent
	$result->treat_xrefs_as_is_a($ontology->treat_xrefs_as_is_a->get_set());             # treat_xrefs_as_is_a
	$result->subset_def_map($ontology->subset_def_map());                                # add all subset_def_map's by default
	$result->synonym_type_def_set($ontology->synonym_type_def_set()->get_set());         # add all synonym_type_def_set by default

	my @terms = @{$ontology->get_terms()};
	foreach my $term (@terms) {
		my $current_term =  $result->get_term_by_id($term->id());
		if (defined $current_term) { # TODO && $current_term is in $term->namespace()  i.e. check if they belong to an identical namespace
			$current_term->is_anonymous(1) if (!defined $current_term->is_anonymous() && $term->is_anonymous());
			foreach ($term->alt_id()->get_set()) {
				$current_term->alt_id($_);
			}
			$current_term->def($term->def()) if (!defined $current_term->def()->text() && $term->def()->text()); # TODO implement the case where the def xref's are not balanced!
			foreach ($term->namespace()) {
				$current_term->namespace($_);
			}
			$current_term->comment($term->comment()) if (!defined $current_term->comment() && $term->comment());
			foreach ($term->subset()) {
				$current_term->subset($_);
			}
			foreach ($term->synonym_set()) {
				$current_term->synonym_set($_);
			}
			foreach ($term->xref_set()->get_set()) {
				$current_term->xref_set()->add($_);
			}
			foreach ($term->intersection_of()) {
				$current_term->intersection_of($_);
			}
			foreach ($term->union_of()) {
				$current_term->union_of($_);
			}
			foreach ($term->disjoint_from()) {
				$current_term->disjoint_from($_);
			}
			$current_term->is_obsolete(1) if (!defined $current_term->is_obsolete() && $term->is_obsolete());
			foreach ($term->replaced_by()->get_set()) {
				$current_term->replaced_by($_);
			}
			foreach ($term->consider()->get_set()) {
				$current_term->consider($_);
			}
			$current_term->builtin(1) if (!defined $current_term->builtin() && $term->builtin());

			# fix the rel's
			my @rels = @{$ontology->get_relationships_by_target_term($term)};
			foreach my $r (@rels) {
				my $cola    = $r->tail();
				my $cola_id = $cola->id();

				#croak 'There is no ID for the tail term linked to: ', $term->id() if (!$tail_id);

				my $tail = $result->get_term_by_id($cola_id); # Is $cola already present in the growing ontology?
				if (!defined $tail) {
					$result->add_term($cola);            # add $cola if it is not present!
					foreach my $ins ($cola->class_of()->get_set()) {
						$result->add_instance($ins); # add its instances
					}
					$tail = $result->get_term_by_id($cola_id);

					my @more_rels = @{$ontology->get_relationships_by_target_term($cola)};
					@rels = (@rels, @more_rels); # trick to 'recursively' visit the just added rel
				}
				my $r_type = $r->type();

				#
				# relationship type
				#
				my $rel_type = $ontology->get_relationship_type_by_id($r_type);
				$result->has_relationship_type($rel_type) || $result->add_relationship_type($rel_type);

				$r->id($cola_id.'_'.$r_type.'_'.$current_term->id());
				$r->link($tail, $current_term);

				# add the relationship after adding its type
				$result->add_relationship($r);
			}
		} else {
			$result->add_term($term);
			foreach my $ins ($term->class_of()->get_set()) {
				$result->add_instance($ins); # add its instances
			}
			push @terms, $term; # trick to 'recursively' visit the just added term
		}
	}
	foreach my $rel (@{$ontology->get_relationships()}) {
		if (! $result->has_relationship_id($rel->id())) {
			my $rel_type = $ontology->get_relationship_type_by_id($rel->type());
			$result->has_relationship_type($rel_type) || $result->add_relationship_type($rel_type);

			# add the relationship after adding its type
			$result->add_relationship($rel);
		}
	}
	@terms = @{$result->get_terms()}; # set 'terms' (avoding the pushed ones)

	my $stop = OBO::Util::Set->new();
	map { $stop->add($_->id()) } @terms;

#print STDERR "\nNUMBER OF RELS BEFORE = ", $result->get_number_of_relationships();

	# link the common terms
	foreach my $term (@terms) {
		my $term_id = $term->id();
		# path of references:
		foreach my $type_of_rel (@default_trans_rts) {
			#$result->create_rel($term, $type_of_rel, $term); # reflexive one (not working line since ONTO-PERL does not allow more that one reflexive relationship)

			# take the paths from the original ontology
			my @ref_paths = $ontology->get_paths_term_terms_same_rel($term_id, $stop, $type_of_rel);

			foreach my $ref_path (@ref_paths) {
				#next if !defined @$ref_path[0]; # reflexive relationships (e.g. GO:0000011_is_a_GO:0000011) are problematic...
				my $f = @$ref_path[0]->tail();
				my $l = @$ref_path[$#$ref_path]->head();
				$result->create_rel($f, $type_of_rel, $l); # add the transitive closure relationship!

				my $new_rel_id = $f->id().'_'.$type_of_rel.'_'.$l->id();
				#print STDERR "NEW_transitive_closure_relationship1: ".$new_rel_id."\n";
			}
		}
	}

	#
	# compositions: isa*partof=>partof and partof*isa=>partof
	#
	$composition = 1;   # experimental code: ENABLED !!!!!!!!!!!!!!!!!!!!

	if ($composition) { # http://wiki.geneontology.org/index.php/Relation_composition

	#
	#
	#
#print STDERR "\n\nNUMBER OF RELS AFTER 1 = ", $result->get_number_of_relationships();

	#@terms = @{$result->get_terms()}; # set 'terms' (avoding the pushed ones)
	#my $stop = OBO::Util::Set->new();
	#map {$stop->add($_->id())} @terms;

		foreach my $term (@terms) {
			my $term1_id = $term->id();

			foreach my $term2_id ($stop->get_set()) {

				next if ($term1_id eq $term2_id); # reflexive relationships are skipped

				my @ref_paths = $result->get_paths_term1_term2($term1_id, $term2_id);

				#print STDERR "\n\tNUMBER_OF_PATHS: ", scalar @ref_paths;
				foreach my $ref_path (@ref_paths) {

					next if !defined @$ref_path[0];
					next if !defined @$ref_path[1]; # two elements (at least) are needed to make the composition

					my $left_entry  = @$ref_path[0]->tail();
					my $left_type   = @$ref_path[0]->type();
					my $right_entry = @$ref_path[1]->head();
					my $right_type  = @$ref_path[1]->type();

					if ($left_type eq $right_type) {

						my $new_rel_id = $left_entry->id().'_'.$left_type.'_'.$right_entry->id();
						if (!$result->has_relationship_id($new_rel_id)) {
							$result->create_rel($left_entry, $left_type, $right_entry); # add a missed transitivity relationship!
							#print STDERR "\nNEW_TRANSITIVITY: ".$new_rel_id;
						}
					} else {
						my $new_rel_id = $left_entry->id()."_part_of_".$right_entry->id();

						if (!$result->has_relationship_id($new_rel_id)) {
							$result->create_rel($left_entry, 'part_of', $right_entry); # add the composed relationship!
							#print STDERR "\tNEW_COMPOSITION: ".$new_rel_id."\n";
						}
					}
				}
			}
		}

#print STDERR "\n\nNUMBER OF RELS AFTER 2 = ", $result->get_number_of_relationships();


		#
		# second transitivity pass on the NEW ontology so far!
		#
		{
			@terms = @{$result->get_terms()}; # set 'terms' (avoding the pushed ones)

			my $stop = OBO::Util::Set->new();
			map {$stop->add($_->id())} @terms;

			# link the common terms
			foreach my $term (@terms) {
				my $term_id = $term->id();
				# path of references:
				foreach my $type_of_rel (@default_trans_rts) {
					#$result->create_rel($term, $type_of_rel, $term); # reflexive one (not working line since ONTO-PERL does not allow more that one reflexive relationship)

					# take the paths from the original ontology
					my @ref_paths = $result->get_paths_term_terms_same_rel($term_id, $stop, $type_of_rel);

					foreach my $ref_path (@ref_paths) {
						next if !defined @$ref_path[0]; # reflexive relationships (e.g. GO:0000011_is_a_GO:0000011) are problematic...
						my $f = @$ref_path[0]->tail();
						my $l = @$ref_path[$#$ref_path]->head();
						my $new_rel_id = $f->id().'_'.$type_of_rel.'_'.$l->id();

						if (!$result->has_relationship_id($new_rel_id)) {
							$result->create_rel($f, $type_of_rel, $l); # add the transitive closure relationship!
							#print STDERR "\nNEW_transitive_closure_relationship2: ".$new_rel_id;
						}
					}
				}
			}
		}

#print STDERR "\n\nNUMBER OF RELS AFTER 3 = ", $result->get_number_of_relationships();

		#
		# second composition pass: needed?
		#
		if (1) {
			@terms = @{$result->get_terms()}; # set 'terms' (avoding the pushed ones)

			my $stop = OBO::Util::Set->new();
			map {$stop->add($_->id())} @terms;

			foreach my $term (@terms) {
				my $term1_id = $term->id();

				foreach my $term2_id ($stop->get_set()) {

					next if ($term1_id eq $term2_id); # reflexive relationships are skipped

					my @ref_paths = $result->get_paths_term1_term2($term1_id, $term2_id);

					foreach my $ref_path (@ref_paths) {

						next if !defined @$ref_path[0];
						next if !defined @$ref_path[1]; # two elements (at least) are needed to make the composition

						my $left_entry  = @$ref_path[0]->tail();
						my $left_type   = @$ref_path[0]->type();
						my $right_entry = @$ref_path[1]->head();
						my $right_type  = @$ref_path[1]->type();

						#next if ($left_type eq $right_type); # done above already
						if ($left_type eq $right_type) {

							my $new_rel_id = $left_entry->id().'_'.$left_type.'_'.$right_entry->id();
							if (!$result->has_relationship_id($new_rel_id)) {
								$result->create_rel($left_entry, $left_type, $right_entry); # add a missed transitivity relationship!
								print STDERR "\nNEW_TRANSITIVITY: ".$new_rel_id;
							}
						} else {
							my $new_rel_id = $left_entry->id()."_part_of_".$right_entry->id();

							if (!$result->has_relationship_id($new_rel_id)) {
								$result->create_rel($left_entry, 'part_of', $right_entry); # add the composed relationship!
								print STDERR "\tNEW_COMPOSITION: ".$new_rel_id."\n";
							}
						}
					}
				}
			}
#print STDERR "\n\nNUMBER OF RELS AFTER 4 = ", $result->get_number_of_relationships();
		}
	}
#print STDERR "\n\nNUMBER OF RELS AFTER 5 = ", $result->get_number_of_relationships();

	return $result;
}

=head2 transitive_reduction

  Usage    - $ome->transitive_reduction($o, @transitive_relationship_types)
  Return   - an ontology (OBO::Core::Ontology) ensuring transitive reduction
  Args     - an ontology (OBO::Core::Ontology) on which the transitive reduction algorithm will be applied
  			 and optionally an array with the transitive relationship types (by default: 'is_a' and 'part_of') to be considered
  Function - reduces all the transitive relationships (e.g. is_a, part_of) along the
  			 hierarchy and generates a new ontology holding the minimal paths (relationships)
  Remark   - Performance issues with huge ontologies.

=cut

sub transitive_reduction () {
	my ($self, $ontology, @trans_rts) = @_;
	my @default_trans_rts = ('is_a', 'part_of', 'located_in');
	if (scalar @trans_rts > 0) {
		@default_trans_rts = @trans_rts;
	}

	my $result = OBO::Core::Ontology->new();
	$result->saved_by('ONTO-perl');
	$result->idspaces($ontology->idspaces()->get_set());
	$result->default_relationship_id_prefix($ontology->default_relationship_id_prefix());
	$result->default_namespace($ontology->default_namespace());
	$result->remarks('Ontology with transitive reduction');
	$result->treat_xrefs_as_equivalent($ontology->treat_xrefs_as_equivalent->get_set()); # treat-xrefs-as-equivalent
	$result->treat_xrefs_as_is_a($ontology->treat_xrefs_as_is_a->get_set());             # treat_xrefs_as_is_a
	$result->subset_def_map($ontology->subset_def_map());                                # add all subset_def_map's by default
	$result->synonym_type_def_set($ontology->synonym_type_def_set()->get_set());         # add all synonym_type_def_set by default

	my @terms = @{$ontology->get_terms()};
	foreach my $term (@terms) {
		my $current_term =  $result->get_term_by_id($term->id());
		if (defined $current_term) { # TODO && $current_term is in $term->namespace()  i.e. check if they belong to an identical namespace
			$current_term->is_anonymous(1) if (!defined $current_term->is_anonymous() && $term->is_anonymous());
			foreach ($term->alt_id()->get_set()) {
				$current_term->alt_id($_);
			}
			$current_term->def($term->def()) if (!defined $current_term->def()->text() && $term->def()->text()); # TODO implement the case where the def xref's are not balanced!
			foreach ($term->namespace()) {
				$current_term->namespace($_);
			}
			$current_term->comment($term->comment()) if (!defined $current_term->comment() && $term->comment());
			foreach ($term->subset()) {
				$current_term->subset($_);
			}
			foreach ($term->synonym_set()) {
				$current_term->synonym_set($_);
			}
			foreach ($term->xref_set()->get_set()) {
				$current_term->xref_set()->add($_);
			}
			foreach ($term->intersection_of()) {
				$current_term->intersection_of($_);
			}
			foreach ($term->union_of()) {
				$current_term->union_of($_);
			}
			foreach ($term->disjoint_from()) {
				$current_term->disjoint_from($_);
			}
			$current_term->is_obsolete(1) if (!defined $current_term->is_obsolete() && $term->is_obsolete());
			foreach ($term->replaced_by()->get_set()) {
				$current_term->replaced_by($_);
			}
			foreach ($term->consider()->get_set()) {
				$current_term->consider($_);
			}
			$current_term->builtin(1) if (!defined $current_term->builtin() && $term->builtin());

			# fix the rel's
			my @rels = @{$ontology->get_relationships_by_target_term($term)};
			foreach my $r (@rels) {
				my $cola    = $r->tail();
				my $cola_id = $cola->id();

				#croak 'There is no ID for the tail term linked to: ', $term->id() if (!$tail_id);

				my $tail = $result->get_term_by_id($cola_id); # Is $cola already present in the growing ontology?
				if (!defined $tail) {
					$result->add_term($cola);                 # add $cola if it is not present!
					foreach my $ins ($cola->class_of()->get_set()) {
						$result->add_instance($ins);          # add its instances
					}
					$tail = $result->get_term_by_id($cola_id);

					my @more_rels = @{$ontology->get_relationships_by_target_term($cola)};
					@rels = (@rels, @more_rels); # trick to 'recursively' visit the just added rel
				}

				my $r_type = $r->type();

				#
				# relationship type
				#
				my $rel_type = $ontology->get_relationship_type_by_id($r_type);
				$result->has_relationship_type($rel_type) || $result->add_relationship_type($rel_type);

				# add the relationship after adding its type
				$r->id($cola_id.'_'.$r_type.'_'.$current_term->id());
				$r->link($tail, $current_term);
				$result->add_relationship($r);
			}
		} else {
			$result->add_term($term);
			foreach my $ins ($term->class_of()->get_set()) {
				$result->add_instance($ins); # add its instances
			}
			push @terms, $term; # trick to 'recursively' visit the just added term
		}
	}

	#
	# In this loop, relationships of the Typedefs are added
	#
	foreach my $rel (@{$ontology->get_relationships()}) {
		if (!$result->has_relationship_id($rel->id())) {
			my $rel_type = $ontology->get_relationship_type_by_id($rel->type());
			$result->has_relationship_type($rel_type) || $result->add_relationship_type($rel_type);

			# add the relationship after adding its type
			$result->add_relationship($rel);
		}
	}

	#
	# Add NON-USED relationship types
	#
	foreach my $rel_type ( @{$ontology->get_relationship_types_sorted_by_id()} ) {
			$result->has_relationship_type($rel_type) || $result->add_relationship_type($rel_type);
	}

	@terms = @{$result->get_terms()}; # set 'terms' (avoding the pushed ones)

	my $stop = OBO::Util::Set->new();
	map {$stop->add($_->id())} @terms;

	# delete implicit rel's
	foreach my $term (@terms) {
		my $term_id = $term->id();
		# path of references:
		foreach my $type_of_rel (@default_trans_rts) {
			#$result->create_rel($term, $type_of_rel, $term); # reflexive one (not working line since ONTO-PERL does not allow more that one reflexive relationship)

			# take the paths from the original ontology
			my @ref_paths = $result->get_paths_term_terms_same_rel($term_id, $stop, $type_of_rel);

			foreach my $ref_path (@ref_paths) {
				next if !defined @$ref_path[0];
				my $i = $#$ref_path;
				my $f = @$ref_path[0]->tail();
				my $l = @$ref_path[$i]->head();
				my $v = $result->get_relationship_by_id($f->id().'_'.$type_of_rel.'_'.$l->id());

				if ($v && ($i > 0)) {
					$result->delete_relationship($v);
				}
			}
		}
	}

	# delete compositon of rel's
	foreach my $term (@terms) {
		my $term_id = $term->id();
		foreach my $term2_id ($stop->get_set()) {
			next if ($term_id eq $term2_id); # reflexive
			my @ref_paths = $result->get_paths_term1_term2($term_id, $term2_id);

			my $rel_id = $term_id."_part_of_".$term2_id; # deleting the "part of" relationships added by following the simplest rule: isa*partof=>partof and partof*isa=>partof

			next if (!$result->has_relationship_id($rel_id));

			foreach my $ref_path (@ref_paths) {
				next if !defined @$ref_path[0]; # reflexive relationships (e.g. GO:0000011_is_a_GO:0000011) are problematic...
				next if !defined @$ref_path[1]; # two elements (at least) are needed to make the composition

				my $left_entry  = @$ref_path[0]->tail();
				my $left_type   = @$ref_path[0]->type();
				my $i           = $#$ref_path;
				my $right_entry = @$ref_path[$i]->head();
				my $right_type  = @$ref_path[$i]->type();

				#next if ($left_type eq $right_type);

				my $new_rel_id = $left_entry->id()."_part_of_".$right_entry->id(); # deleting the "part of" relationships added by following the simplest rule: isa*partof=>partof and partof*isa=>partof

				if ($result->has_relationship_id($new_rel_id)) {
					my $v = $result->get_relationship_by_id($new_rel_id);
					$result->delete_relationship($v); # delete the composed relationship!
				}
			}
		}
	}

	return $result;
}

1;

__END__