Working with Biolink Model

The model and how to curate the model has been addressed in other sections. But how to make use of the Biolink Model in practical terms? How to use the classes and slots defined in the model for representing nodes and edges in a graph?

We can consider a small example and see how it can be represented using the Biolink Model.

Example:

protein1 protein2
9606.ENSP00000000233 9606.ENSP00000272298
9606.ENSP00000000233 9606.ENSP00000253401
9606.ENSP00000000233 9606.ENSP00000401445

The above lines are from STRING DB.

The information can be represented using Biolink Model as follows: - use Biolink entity class protein for protein entities - use Biolink entity class gene for gene entities - use Biolink predicate slot interacts with as the relationship or predicate for representing an edge between interacting partners - use Biolink association class gene to gene association to type the edge

One modeling consideration we are going to make here is that we will be projecting the interaction between proteins to interaction between genes.

Annotating nodes

Each individual protein and gene can be treated as nodes in a graph.

Each protein node has protein as its category.

Each gene node has gene as its category.

As per the model, protein nodes should have identifiers from UniProtKB and gene nodes should have identifiers NCBIGene.

One can further type the protein and gene entities using the Biolink slot type (which corresponds to rdf:type).

In KGX serialization format the nodes can be represented as follows:

id  name    category    provided_by xref    type    in_taxon
UniProtKB:P84085    ARF5    biolink:Protein STRING  ENSEMBL:ENSP00000000233     NCBITaxon:9606
UniProtKB:P0DP24    CALM2   biolink:Protein STRING  ENSEMBL:ENSP00000272298     NCBITaxon:9606
UniProtKB:O43307    ARHGEF9 biolink:Protein STRING  ENSEMBL:ENSP00000253401     NCBITaxon:9606
UniProtKB:O75460    ERN1    biolink:Protein STRING  ENSEMBL:ENSP00000401445     NCBITaxon:9606
NCBIGene:381    ARF5    biolink:Gene    STRING  ENSEMBL:ENSG00000004059 SO:0001217  NCBITaxon:9606
NCBIGene:805    CALM2   biolink:Gene    STRING  ENSEMBL:ENSG00000143933 SO:0001217  NCBITaxon:9606
NCBIGene:23229  ARHGEF9 biolink:Gene    STRING  ENSEMBL:ENSG00000131089 SO:0001217  NCBITaxon:9606
NCBIGene:2081   ERN1    biolink:Gene    STRING  ENSEMBL:ENSG00000178607 SO:0001217  NCBITaxon:9606

Note: While the entity classes are defined as gene and protein in the model, when using them the reference to the class should always be in their CURIE form which includes the biolink prefix.

Node semantics

There are three ways of attaching semantics to a node: - using Biolink slot category - the value of the category must be from the named thing hierarchy - using Biolink slot type - can have a value from any external ontology, controlled vocabulary, thesauri, or taxonomy - using Biolink predicate slot subclass_of (or rdfs:subClassOf) - can have a value from any external ontology, controlled vocabulary, thesauri, or taxonomy

Annotating edges

Each individual interaction between genes can be treated as an edge with, - interacts with as its predicate - gene to gene association as its category

And we have additional edges that go from gene to protein to signify that a gene encodes for a protein via the Biolink predicate slot has gene product.

In KGX serialization format the edges can be represented as follows:

id  subject predicate   object    provided_by category
985eb9e6-e0bf-4cef-be0a-3d8ea12d228b    NCBIGene:381    biolink:interacts_with  NCBIGene:805    STRING  biolink:GeneToGeneAssociation
5550b653-69ff-48cc-a1ef-638ecdc50ea3    NCBIGene:381    biolink:interacts_with  NCBIGene:23229  STRING  biolink:GeneToGeneAssociation
8bff8da0-6da2-4154-b507-a8e9f75c55f8    NCBIGene:381    biolink:interacts_with  NCBIGene:2081   STRING  biolink:GeneToGeneAssociation
36e2edf0-d490-4417-9407-7070f4320083    NCBIGene:381    biolink:has_gene_product    UniProtKB:P84085    STRING  
0dd21d53-4985-467c-8e6d-0a79c0410016    NCBIGene:805    biolink:has_gene_product    UniProtKB:P0DP24    STRING  
fe5f9383-c5f6-4eba-9dc4-185e6d331459    NCBIGene:23229  biolink:has_gene_product    UniProtKB:O43307    STRING  
8c60c2b2-ff6c-45d5-a18f-e927ab1dec35    NCBIGene:2081   biolink:has_gene_product    UniProtKB:O75460    STRING

Note: While association class is defined as gene to gene association and predicate slots are defined as interacts with and has gene product in the model, when using them the reference to the class should always be in their CURIE form which includes the biolink prefix.

Edge semantics

There are 3 ways of attaching the semantics to an edge: - using the Biolink association slot predicate - must have a value from the related to hierarchy - using the Biolink slot category - must have a value from the association hierarchy - using Biolink slot type - can have a value from any external ontology, controlled vocabulary, thesauri, or taxonomy

Biolink Model representation in Neo4j

The model itself is very close to labelled property graphs.

The previous example can be easily converted to a Neo4j compatible TSV using KGX.

nodes.tsv:

id:ID   name    category:LABEL  xref    provided_by:string[]    in_taxon    type
UniProtKB:P84085    ARF5    biolink:Protein ENSEMBL:ENSP00000000233 STRING  NCBITaxon:9606  
UniProtKB:P0DP24    CALM2   biolink:Protein ENSEMBL:ENSP00000272298 STRING  NCBITaxon:9606  
UniProtKB:O43307    ARHGEF9 biolink:Protein ENSEMBL:ENSP00000253401 STRING  NCBITaxon:9606  
UniProtKB:O75460    ERN1    biolink:Protein ENSEMBL:ENSP00000401445 STRING  NCBITaxon:9606  
NCBIGene:381    ARF5    biolink:Gene    ENSEMBL:ENSG00000004059 STRING  NCBITaxon:9606  SO:0001217
NCBIGene:805    CALM2   biolink:Gene    ENSEMBL:ENSG00000143933 STRING  NCBITaxon:9606  SO:0001217
NCBIGene:23229  ARHGEF9 biolink:Gene    ENSEMBL:ENSG00000131089 STRING  NCBITaxon:9606  SO:0001217
NCBIGene:2081   ERN1    biolink:Gene    ENSEMBL:ENSG00000178607 STRING  NCBITaxon:9606  SO:0001217

edges.tsv:

id  subject:START_ID    predicate:TYPE  object:END_ID   provided_by:string[]    category:string[]
985eb9e6-e0bf-4cef-be0a-3d8ea12d228b    NCBIGene:381    biolink:interacts_with  NCBIGene:805    STRING  biolink:GeneToGeneAssociation
5550b653-69ff-48cc-a1ef-638ecdc50ea3    NCBIGene:381    biolink:interacts_with  NCBIGene:23229  STRING  biolink:GeneToGeneAssociation
8bff8da0-6da2-4154-b507-a8e9f75c55f8    NCBIGene:381    biolink:interacts_with  NCBIGene:2081   STRING  biolink:GeneToGeneAssociation
36e2edf0-d490-4417-9407-7070f4320083    NCBIGene:381    biolink:has_gene_product    UniProtKB:P84085    STRING  
0dd21d53-4985-467c-8e6d-0a79c0410016    NCBIGene:805    biolink:has_gene_product    UniProtKB:P0DP24    STRING  
fe5f9383-c5f6-4eba-9dc4-185e6d331459    NCBIGene:23229  biolink:has_gene_product    UniProtKB:O43307    STRING  
8c60c2b2-ff6c-45d5-a18f-e927ab1dec35    NCBIGene:2081   biolink:has_gene_product    UniProtKB:O75460    STRING

Biolink Model representation in RDF

Since RDF graphs do not allow for properties on edges, the most practical alternative is to use reification where an edge is transformed into a node of type biolink:Association (or its descendants) and any edge properties then becomes properties of this reified node.

Using reification, the previous example can be easily converted to RDF using KGX,

@prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#> .
@prefix xsd: <http://www.w3.org/2001/XMLSchema#> .
@prefix biolink: <https://w3id.org/biolink/vocab/> .
@prefix rdf: <http://www.w3.org/1999/02/22-rdf-syntax-ns#> .

<http://identifiers.org/uniprot/P84085>
  rdfs:label "ARF5"^^xsd:string ;
  biolink:category biolink:Protein ;
  biolink:provided_by "STRING" ;
  biolink:xref <http://identifiers.org/ensembl/ENSP00000000233> ;
  biolink:in_taxon <http://purl.obolibrary.org/obo/NCBITaxon_9606> .

<http://identifiers.org/uniprot/P0DP24>
  rdfs:label "CALM2"^^xsd:string ;
  biolink:category biolink:Protein ;
  biolink:provided_by "STRING" ;
  biolink:xref <http://identifiers.org/ensembl/ENSP00000272298> ;
  biolink:in_taxon <http://purl.obolibrary.org/obo/NCBITaxon_9606> .

<http://identifiers.org/uniprot/O43307>
  rdfs:label "ARHGEF9"^^xsd:string ;
  biolink:category biolink:Protein ;
  biolink:provided_by "STRING" ;
  biolink:xref <http://identifiers.org/ensembl/ENSP00000253401> ;
  biolink:in_taxon <http://purl.obolibrary.org/obo/NCBITaxon_9606> .

<http://identifiers.org/uniprot/O75460>
  rdfs:label "ERN1"^^xsd:string ;
  biolink:category biolink:Protein ;
  biolink:provided_by "STRING" ;
  biolink:xref <http://identifiers.org/ensembl/ENSP00000401445> ;
  biolink:in_taxon <http://purl.obolibrary.org/obo/NCBITaxon_9606> .

<http://www.ncbi.nlm.nih.gov/gene/381>
  rdfs:label "ARF5"^^xsd:string ;
  biolink:category biolink:Gene ;
  biolink:provided_by "STRING" ;
  biolink:xref <http://identifiers.org/ensembl/ENSG00000004059> ;
  a <http://purl.obolibrary.org/obo/SO_0001217> ;
  biolink:in_taxon <http://purl.obolibrary.org/obo/NCBITaxon_9606> ;
  biolink:has_gene_product <http://identifiers.org/uniprot/P84085> .

<http://www.ncbi.nlm.nih.gov/gene/805>
  rdfs:label "CALM2"^^xsd:string ;
  biolink:category biolink:Gene ;
  biolink:provided_by "STRING" ;
  biolink:xref <http://identifiers.org/ensembl/ENSG00000143933> ;
  a <http://purl.obolibrary.org/obo/SO_0001217> ;
  biolink:in_taxon <http://purl.obolibrary.org/obo/NCBITaxon_9606> ;
  biolink:has_gene_product <http://identifiers.org/uniprot/P0DP24> .

<http://www.ncbi.nlm.nih.gov/gene/23229>
  rdfs:label "ARHGEF9"^^xsd:string ;
  biolink:category biolink:Gene ;
  biolink:provided_by "STRING" ;
  biolink:xref <http://identifiers.org/ensembl/ENSG00000131089> ;
  a <http://purl.obolibrary.org/obo/SO_0001217> ;
  biolink:in_taxon <http://purl.obolibrary.org/obo/NCBITaxon_9606> ;
  biolink:has_gene_product <http://identifiers.org/uniprot/O43307> .

<http://www.ncbi.nlm.nih.gov/gene/2081>
  rdfs:label "ERN1"^^xsd:string ;
  biolink:category biolink:Gene ;
  biolink:provided_by "STRING" ;
  biolink:xref <http://identifiers.org/ensembl/ENSG00000178607> ;
  a <http://purl.obolibrary.org/obo/SO_0001217> ;
  biolink:in_taxon <http://purl.obolibrary.org/obo/NCBITaxon_9606> ;
  biolink:has_gene_product <http://identifiers.org/uniprot/O75460> .

<https://www.example.org/UNKNOWN/985eb9e6-e0bf-4cef-be0a-3d8ea12d228b>
  rdf:subject <http://www.ncbi.nlm.nih.gov/gene/381> ;
  rdf:predicate biolink:interacts_with ;
  rdf:object <http://www.ncbi.nlm.nih.gov/gene/805> ;
  biolink:provided_by "STRING" ;
  biolink:category biolink:GeneToGeneAssociation .

<https://www.example.org/UNKNOWN/5550b653-69ff-48cc-a1ef-638ecdc50ea3>
  rdf:subject <http://www.ncbi.nlm.nih.gov/gene/381> ;
  rdf:predicate biolink:interacts_with ;
  rdf:object <http://www.ncbi.nlm.nih.gov/gene/23229> ;
  biolink:provided_by "STRING" ;
  biolink:category biolink:GeneToGeneAssociation .

<https://www.example.org/UNKNOWN/8bff8da0-6da2-4154-b507-a8e9f75c55f8>
  rdf:subject <http://www.ncbi.nlm.nih.gov/gene/381> ;
  rdf:predicate biolink:interacts_with ;
  rdf:object <http://www.ncbi.nlm.nih.gov/gene/2081> ;
  biolink:provided_by "STRING" ;
  biolink:category biolink:GeneToGeneAssociation .