Christopher Fields > BioPerl-Network > Bio::Network::ProteinNet

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NAME ^

Bio::Network::ProteinNet - a representation of a protein interaction graph.

SYNOPSIS ^

  # Read in from file
  my $graphio = Bio::Network::IO->new(-file   => 'human.xml',
                                      -format => 'psi25');
  my $graph = $graphio->next_network();

  my @edges = $gr->edges;

  for my $edge (@edges) {
    for my $node ($edge->[0],$edge->[1]) {
      my @proteins = $node->proteins;
      for my $protein (@proteins) {
        print $protein->display_id," ";
      }
    }
  }

Perl Graph module ^

The bioperl-network package uses the Perl Graph module, use version .86 or greater.

Working with Nodes

A Node object represents either a protein or a protein complex. Nodes can be retrieved through their identifiers:

  # Get a node (represented by a sequence object) from the graph.
  my $node = $graph->get_nodes_by_id('UniProt:P12345');

  # A node that's a protein can be treated just like a Sequence object
  print $node->seq;

  # Remove a node by specifying its identifier
  $graph->remove_nodes($graph->get_nodes_by_id('UniProt:P12345'));

  # How many nodes are there?
  my $ncount = $graph->nodes();

  # Get interactors of your favourite protein
  my $node = $graph->get_nodes_by_id('RefSeq:NP_023232');
  my @neighbors = $graph->neighbors($node); 
  print "      NP_023232 interacts with ";
  print join " ,", map{$_->primary_id()} @neighbors;
  print "\n";

  # Annotate your sequences with interaction info
  my @seq_objects = ($seq1, $seq2, $seq3);
  for my $seq (@seq_objects) {
    if ( $graph->get_nodes_by_id($seq->accession_number) ) {
       my $node = $graph->get_nodes_by_id( $seq->accession_number);
       my @neighbors = $graph->neighbors($node);
       for my $n (@neighbors) {
          my $ft = Bio::SeqFeature::Generic->new(
                    -primary_tag => 'Interactor',
                    -tag         => { id => $n->accession_number }
                   );
          $seq->add_SeqFeature($ft);
        }
     }
  }

  # Get proteins with > 10 interactors
  my @nodes = $graph->nodes();
  my @hubs;
  for my $node (@nodes) {
    if ($graph->neighbors($node) > 10) {
       push @hubs, $node;
    }
  }
  print "the following proteins have > 10 interactors:\n";
  print join "\n", map {$_->primary_id()} @hubs;

  # Get clustering coefficient of a given node.
  my $id = "RefSeq:NP_023232";
  my $cc = $graph->clustering_coefficient($graph->get_nodes_by_id($id));
  if ($cc != -1) {  ## result is -1 if cannot be calculated
    print "CC for $id is $cc";
  }

Working with Edges

  # How many edges are there?
  my $ecount = $graph->edges;

  # Get all the paired nodes, or edges, in the graph as an array
  my @edges = $graph->edges

Working with Interactions

  # How many interactions are there?
  my $icount = $graph->interactions;

  # Retrieve all interactions
  my @interx = $graph->interactions;

  # Get interactions above a threshold confidence score
  for my $interx (@interx) {
         if ($interx->weight > 0.6) {
                 print $interx->primary_id, "\t", $interx->weight, "\n";
         }
  }

Working with Graphs

  # Get graph density
  my $density = $graph->density();

  # Get connected sub-graphs
  my @graphs = $graph->connected_components();

  # Copy interactions from one graph to another
  $graph1->add_interactions_from($graph2);

Creating networks from your own data

If you have interaction data in your own format, e.g.

  <interaction id>  <protein id 1>  <protein id 2>  <score>

A simple approach would look something like this:

  my $io = Bio::Root::IO->new(-file => 'mydata');
  my $graph = Bio::Network::ProteinNet->new(refvertexed => 1);

  while (my $l = $io->_readline() ) {
     my ($id, $nid1, $nid2, $sc) = split /\s+/, $l;

     my $prot1 = Bio::Seq->new(-accession_number => $nid1);
     my $prot2 = Bio::Seq->new(-accession_number => $nid2);

     # create new Interaction object based on an id and weight
     my $interaction = Bio::Network::Interaction->new(-id   => $id,
                                                    -weight => $sc );
     $graph->add_interaction(-nodes => [($prot1,$prot2)]),
                             -interaction => $interaction );
  }

DESCRIPTION ^

A ProteinNet is a representation of a protein interaction network. Its functionality comes from the Graph module of Perl and from BioPerl, the nodes or vertices in the network are Sequence objects.

Nodes

A node is one or more BioPerl sequence objects, a Bio::Seq or Bio::Seq::RichSeq object. Essentially the graph can use any objects that implement Bio::AnnotatableI and Bio::IdentifiableI interfaces since these objects hold useful identifiers. This is relevant since the identity of nodes is determined by their identifiers.

Interactions and Edges

Since bioperl-network is built on top of the Graph and Graph::Undirected modules of Perl it uses its formal model as well. An Edge corresponds to a pair of nodes, and there is only one Edge per pair. An Interaction is an attribute of an Edge, and there can be 1 or more Interactions per Edge. So

  $ecount = $network->edges

Tells you how many paired nodes there are and

  $icount = $network->interactions

Tells you how many node-node interactions there are. An Interaction is equivalent to one experiment or one experimental observation.

FOR DEVELOPERS ^

In this module, the nodes or vertexes are represented by Bio::Seq objects containing database identifiers but usually without sequence, since the data is parsed from protein-protein interaction data.

Interactions should be Bio::Network::Interaction objects, which are Bio::IdentifiableI implementing objects. At present Interactions only have an identifier and a weight() method, to hold confidence data.

A ProteinNet object has the following internal data, aside from the data structures of Graph itself:

_id_map

Look-up hash ('_id_map') for finding a node using any of its ids. The keys are standard identifiers (e.g. "GenBank:A12345") and the values are memory addresses used by Graph (e.g. "Bio::Network::Node=HASH(0x1bc53e4)").

_interx_id_map

Look-up hash for Interactions ('_interx_id_map'),used for retrieving an Interaction object using an identifier. The keys are primary ids of the Interaction (e.g. "DIP:2341E") and the values are addresses of Interactions (e.g. "Bio::Network::Interaction=HASH(0x1bc46f2)").

The function of these hashes is either to facilitate fast lookups or to cache data.

API CHANGES ^

These modules were first released as part of the core BioPerl package and were called Bio::Graph. Bio::Graph was copied to a separate package, bioperl-network, and renamed Bio::Network. All of the modules were revised and a new module, Interaction.pm, was added. The functionality of the PSI MI parser, IO/psi.pm, was significantly enhanced.

Graph manipulation in Bio::Graph was based on the Bio::Graph::SimpleGraph module by Nat Goodman. The first release as a separate package, bioperl-network, replaced SimpleGraph with the Perl Graph package. Other API changes were also made, partly to keep nomenclature consistent with BioPerl, partly to use the terms used by the interaction databases, and partly to accomodate the differences between Graph and Bio::Graph::SimpleGraph.

The advantages to using Graph are that Bioperl developers are not responsible for maintaining the code that actually handles graph manipulation and there is more functionality in Graph than in SimpleGraph.

Bio::Graph::Edge

Bio::Graph::Edge has been replaced by Bio::Network::Interaction and Bio::Network::Edge

next_graph()

This method has been replaced by next_network().

union()

The union() method has been removed since it was not performing a true union. It has been replaced by add_interaction_from

remove_nodes()

remove_nodes() is now an alias to Graph::delete_vertices

_get_ids_by_db()

_get_ids_by_db() has been renamed get_ids_by_node

add_node()

add_node() is now an alias to Graph::add_vertex

components()

components() is now an alias to Graph::connected_components

edge_count()

edge_count() is now an alias to Graph::edges

node_count()

node_count() is now an alias to Graph::vertices

nodes_by_id()

nodes_by_id() is now an alias to get_nodes_by_id

edge_by_id()

This method has been removed since edges no longer have identifiers, Interactions do. Use get_interaction_by_id

unconnected_nodes()

unconnected_nodes() is now an alias to Graph::isolated_vertices

object_id()

object_id() is now an alias to Interaction::primary_id()

REQUIREMENTS ^

To use this module you need Graph.pm, version .80 or greater. To read XML data (e.g. PSI XML) you will need XML::Twig.

SEE ALSO ^

Bio::Network::IO Bio::Network::Edge Bio::Network::Node Bio::Network::Interaction Bio::Network::IO::dip Bio::Network::IO::psi

FEEDBACK ^

Mailing Lists

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

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

Support

Please direct usage questions or support issues to the mailing list:

bioperl-l@bioperl.org

rather than to the module maintainer directly. Many experienced and reponsive experts will be able look at the problem and quickly address it. Please include a thorough description of the problem with code and data examples if at all possible.

Reporting Bugs

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

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

AUTHORS ^

Brian Osborne bosborne at alum.mit.edu Richard Adams richard.adams@ed.ac.uk

Maintained by Brian Osborne

The first version of this package was based on the Bio::Graph::SimpleGraph module written by Nat Goodman.

get_interaction_by_id

 Name      : get_interaction_by_id
 Purpose   : Get an interaction using an id
 Usage     : $interx = $g->get_interaction_by_id($id)
 Returns   : One or more Interactions
 Arguments : One or more Interaction identifiers, the primary id

get_nodes_by_id

 Name      : get_nodes_by_id
 Purpose   : Get node using an id
 Usage     : $node = $g->get_nodes_by_id($id)
 Returns   : One node
 Arguments : One or more protein identifiers

get_interactions

  Name      : get_interactions
  Purpose   : Get 1 or more Interaction objects given a pair of nodes 
  Usage     : @interx = $g->get_interactions($n1,$n2)
  Returns   : A hash of Interaction objects where the key is the primary
              id of the Interaction and the value is the Interaction
  Arguments : 2 nodes
  Notes     : 

add_id_to_interaction

 Name      : add_id_to_interaction
 Purpose   : Store identifiers in an internal hash that is used to look
             up interactions by id - this does not add ids to Interaction 
             objects. 
 Usage     : $g->add_id_to_interaction($id,$interaction)
 Arguments : Identifier and Interaction object.
 Returns   : 
 Notes     : The identifier should be concatenated
             with a database or namespace name in order to make
             accurate comparisons when you are merging data from different 
             formats. Examples: DIP:3455E.
             Use _get_standard_name() to find a standardized name.

See _get_standard_name

add_id_to_node

 Name      : add_id_to_node
 Purpose   : Store identifiers in an internal hash that is used to look
             up nodes by id - this does not add ids to Node objects
             or their associated Annotation objects. 
 Usage     : $g->add_id_to_node($id,$node)   or
             $g->add_id_to_node(\@ids,$node)
 Arguments : Identifier (or reference to an array of identifiers), node.
 Returns   : 
 Notes     : The identifier should be concatenated
             with a database or namespace name in order to make
             accurate comparisons when you are merging data from different 
             formats. Examples: DIP:3455N, UniProt:Q45772, GenBank:7733911.
             Use _get_standard_name() to find a standardized name.

See _get_standard_name

add_interactions_from

 Name        : add_interactions_from
 Purpose     : To copy interactions from one graph to another
 Usage       : $graph1->add_interactions_from($graph2)
 Returns     : void
 Arguments   : A Graph object of the same class as the calling object. 
 Description : This method copies interactions from the graph passed as the 
               argument to the calling graph. To take account of 
               differing IDs identifying the same protein, all ids are
               compared. The following rules are used:

         1. If a pair of nodes exist in both graphs then:
            a. No Interactions with the same primary id will be copied
               from $graph2 to $graph1.
            b. All other Interactions from $graph2 will be copied
               to $graph1, even if these nodes do not interact in $graph1.

         2. Nodes are never copied from $graph2 to $graph1. This is rather 
            conservative but prevents the problem of having duplicated,
            identical nodes in $graph1 due to the same protein being identified 
            by different ids in the 2 graphs.

         So, for example 

              Interaction   N1    N2   Comment

    Graph 1:  E1            P1    P2
              E2            P3    P4
              E3            P1    P4

    Graph 2:  E1            P1    P2   E1 will not be copied to Graph1
              X2            P1    P3   X2 will be copied to Graph 1
              X3            P1    P4   X3 will be copied to Graph 1
              X4            Z4    Z5   Nothing copied to Graph1

         There are measures one could take to allow copying nodes from $graph2
         to $graph1, currently unimplemented:

         1. Use sequence, if available, and some threshold measure of similarity,
            or length, to prove that proteins are not identical and can be copied.

         2. Use species information. For example, if $graph1 is entirely composed
            of human proteins then any non-human proteins could be copied to
            $graph1 without risk (and cross-species interactions are fairly common
            due the nature of interaction experiments).

         3. Use namespace or dataspace when assessing identity. For example, assume
            that all nodes in $graph1 are identified by Swissprot ids. Assume a 
            protein in $graph2 is also identified by a Swissprot id, not found in
            $graph1. This could be reasonable grounds for allowing the protein in
            $graph2 to be copied to $graph1.

          4. Some combination of the above.

subgraph

 Name      : subgraph
 Purpose   : Construct a subgraph of nodes from another network, including
             all Interactions.
 Usage     : my $subgraph = $graph->subgraph(@nodes).
 Returns   : A subgraph composed of nodes, edges, and Interactions from the 
             original graph.
 Arguments : A list of nodes.

get_ids_by_node

 Name     : get_ids_by_node
 Purpose  : Gets all ids for a node
 Arguments: A Bio::SeqI object
 Returns  : A hash: Keys are db ids, values are identifiers
 Usage    : my %ids = $gr->get_ids_by_node($seqobj);

add_interaction

 Name        : add_interaction
 Purpose     : Adds an Interaction to a graph.
 Usage       : $gr->add_interaction(-interaction => $interx
                                    -nodes => \@nodes );
 Arguments   : An Interaction object and a reference to an array holding 
               a pair of nodes
 Returns     :
 Description : This is the method to use to add an interaction to a graph.

add_edge

 Name        : add_edge
 Purpose     : 
 Usage       : $gr->add_edge(@nodes)
 Arguments   : A pair of nodes
 Returns     :
 Description : 

add_vertex

 Name        : add_vertex
 Purpose     : Adds a node to a graph.
 Usage       : $gr->add_vertex($n)
 Arguments   : A Bio::Network::Node object
 Returns     :
 Description : 

add_node

 Name        : add_node
 Purpose     : Alias to add_vertex
 Usage       : $gr->add_node($node)
 Arguments   : A Bio::Network::Node object
 Returns     : 
 Description : 

clustering_coefficient

 Name      : clustering_coefficient
 Purpose   : Determines the clustering coefficient of a node, a number 
             in range 0-1 indicating the extent to which the neighbors of
             a node are interconnnected.
 Arguments : A Node or a text identifier
 Returns   : The clustering coefficient. 0 is a valid result.
             If the CC is not calculable ( if the node has <2 neighbors),
                returns -1.
 Usage     : my $node = $gr->get_nodes_by_id('P12345');
             my $cc   = $gr->clustering_coefficient($node);

remove_nodes

 Name      : remove_nodes
 Purpose   : Alias to Graph::delete_vertices
 Usage     : $graph2 = $graph1->remove_nodes($node);
 Arguments : A single Node object or a list of Node objects
 Returns   : A Graph with the given nodes deleted
 Notes     :

get_random_edge

 Name      : get_random_edge
 Purpose   : Alias to Graph::random_edge
 Usage     : $edge = $graph1->get_random_edge;
 Arguments : 
 Returns   : An Edge object
 Notes     :

get_random_node

 Name      : get_random_node
 Purpose   : Alias to Graph::random_vertex
 Usage     : $node = $graph1->get_random_node;
 Arguments : 
 Returns   : A Node object
 Notes     :

is_forest

 Name      : is_forest
 Purpose   : Determine if a graph is a forest (2 or more trees)
 Usage     : if ($gr->is_forest){ ..... }
 Arguments : none
 Returns   : 1 or ""

is_tree

 Name      : is_tree
 Purpose   : Determine if the graph is a tree
 Usage     : if ($gr->is_tree){ ..... }
 Arguments : None
 Returns   : 1 or ""

is_empty

 Name      : is_empty
 Purpose   : Determine if graph has no nodes
 Usage     : if ($gr->is_empty){ ..... }
 Arguments : None
 Returns   : 1 or ""

articulation_points

 Name      : articulation_points
 Purpose   : Find nodes in a graph that if removed will fragment
             the graph into sub-graphs.
 Usage     : my @nodes = $gr->articulation_points
                            or
             my $count = $gr->articulation_points
 Arguments : None
 Returns   : An array or a count of the array of nodes that will fragment 
             the graph if deleted. 
 Notes     : This method is currently broken due to bugs in Graph v. .69
             and later

is_articulation_point

 Name      : is_articulation_point
 Purpose   : Determine if a given node is an articulation point or not. 
 Usage     : if ($gr->is_articulation_point($node)) {....}
 Arguments : A node (Sequence object)
 Returns   : 1 if node is an articulation point, 0 if it is not 
 Notes     : This method is currently broken due to bugs in Graph v. .69

nodes

 Name     : nodes
 Purpose  : Alias to Graph::vertices()
 Arguments: 
 Returns  : An integer
 Usage    : my $count = $graph->nodes;

has_node

 Name     : has_node
 Purpose  : Alias to Graph::has_vertex
 Arguments: 
 Returns  : True if the node exists
 Usage    : if ( $graph->has_node($node) ){ ... }

interactions

 Name     : interactions
 Purpose  : Count the total number of Interactions in the network (an Edge can 
            have one or more Interactions) or retrieve all the Interactions in 
            the network as an array
 Usage    : my $count = $gr->interactions or
            my @interx = $gr->interactions
 Arguments:
 Returns  : A number or an array of Interactions
 Notes    :

nodes_by_id

  Name      : nodes_by_id
  Purpose   : Alias to get_nodes_by_id
  Notes     : Deprecated

edge_count

 Name     : edge_count
 Purpose  : Alias to edges()
 Notes    : Deprecated, use edges()

neighbor_count

 Name      : neighbor_count
 Purpose   : Alias to Graph::neighbors
 Usage     : my $count = $gr->neighbor_count($node)
 Arguments : A node
 Returns   : An integer
 Notes     : Deprecated

node_count

 Name     : node_count
 Purpose  : Alias to Graph::vertices()
 Notes    : Deprecated, use nodes()

components

 Name      : components
 Purpose   : Alias to Graph::connected_components
 Usage     : my @components = $gr->components
 Arguments :
 Returns   : 
 Notes     : Deprecated

unconnected_nodes

 Name      : unconnected_nodes
 Purpose   : Alias to Graph::isolated_vertices
 Arguments : None
 Returns   : An array of unconnected nodes
 Notes     : Deprecated

_all_pairs

 Name      : _all_pairs
 Purpose   : Find unique set of all pairwise combinations
 Usage     : my @pairs = $self->_all_pairs(@arr)
 Arguments : An array
 Returns   : An array of array references, each array in the 2nd dimension
             is a 2-element array

_ids

 Name      : _ids
 Purpose   : 
 Usage     : 
 Arguments : 
 Returns   : 

next_interaction

 Name      : next_interaction
 Purpose   : Retrieve Interactions using an edge
 Usage     : while (my $interx = $edge->next_interaction){ ... }
 Returns   : Interactions, one by one.
 Arguments :

next_edge

 Name      : next_edge
 Purpose   : Retrieve all edges
 Usage     : while (my $edge = $graph->next_edge){ ... }
 Returns   : Edges, one by one.
 Arguments :

next_node

 Name      : next_node
 Purpose   : Retrieve all nodes
 Usage     : while (my $node = $graph->next_node){ ... }
 Returns   : Nodes, one by one.
 Arguments :
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