Annotation Extension: Difference between revisions

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[[Category:Annotation extension]]
==Purpose of annotation extensions==
'''Annotation Extensions''' allows GO terms in standard annotations to be further specified, using gene products, chemicals, cell types, anatomical structures. The ontology terms used to extend annotations are GO term or external ontologies. Annotation extensions allows to build a more complete model of biological systems.


==Relations valid for annotation extensions==
Relations used for GO annotation extensions are from the [https://oborel.github.io/ Relation Ontology ]
* [[has input]]
* [[has output]]
* [[occurs in]]


  Note that this documentation is being reviewed
==Dependent and independent statement in annotation extensions==
 
Protein2GO allows to make dependent (linked) and independent (separate) statements that are exported in GAF as comma and pipes, respectively. More information can be found in the [https://www.ebi.ac.uk/seqdb/confluence/display/GOAP/Protein2GO+manual#Protein2GOmanual-AnnotationExtensionfield Protein2GO documentation].


==Other pages to review==
==Other pages to review==
 
* http://wiki.geneontology.org/index.php/Annotation_Extension ''(this page)''
TO DO
* http://wiki.geneontology.org/index.php/Annotation_Extension:_Capturing_cell_and_tissue_types
Include:
* Ruth's slides
* https://github.com/geneontology/go-annotation/issues/2917#event-4918578122
* Main document: https://docs.google.com/spreadsheets/d/1vkBVTyUg1tjipUtYGan5Ob0vE14H_j6O-PuTH9619eg/edit#gid=1318491961
Spreadsheets 'P2GO - GP2Term relations' and 'P2GO - Extensions'
* http://wiki.geneontology.org/index.php/Annotation_Relations
* http://wiki.geneontology.org/index.php/Annotation_Relations
 
* http://wiki.geneontology.org/index.php/Relations
also need to clean up
* http://wiki.geneontology.org/index.php/Annotation_Extension
* http://wiki.geneontology.org/index.php/Issues_with_Annotation_Extension_relations
* http://wiki.geneontology.org/index.php/Annotation_Extension_Relation_Documentation_Jamboree
* http://wiki.geneontology.org/index.php/Guidance_for_updating_deprecated_Annotation_Extension_Relations
* http://wiki.geneontology.org/index.php/Guidance_for_updating_deprecated_Annotation_Extension_Relations
* https://github.com/geneontology/annotation_extensions (NOTE that P2GO links to this doc)
* https://github.com/geneontology/annotation_extensions (NOTE that P2GO links to this doc - ''2021-09-29 is this still the case??'') ''archived''
 
* [https://docs.google.com/presentation/d/1bsQGCTt_yDVBdBFwye2c77YSw06Oe3LBN-yLLJbi2C4/edit#slide=id.gadab9d5cef_2_75 Ruth's slides]  
==Introduction==
* Spreadsheets 'P2GO - GP2Term relations' and 'P2GO - Extensions' https://docs.google.com/spreadsheets/d/1vkBVTyUg1tjipUtYGan5Ob0vE14H_j6O-PuTH9619eg/edit#gid=1318491961
 
Each GO annotation pairs a single gene product identifier to a single term from the ontology. This format is very powerful however it can also restrict the descriptiveness of a specific instance of a functioning or subcellular location; there must be a pre-existing term in the ontology that provides full details of the specific aspects of the function.
 
It is not always possible to create individual terms that precisely describe the context of each activity (e.g. the cellular or anatomical location, the dependency on other processes, or particular, specific protein targets). 
 
It is less restrictive if the annotator is able to combine additional terms in a single annotation to provide a more detailed functional description for an individual gene product.
 
This page describes the Annotation Extension field (column 16) in the Gene Association File [http://www.geneontology.org/GO.format.gaf-2_0.shtml#annotation_ext GAF2.0 file format], which allows GO terms to be further specified, using gene product or chemical identifiers or terms from GO or external OBO ontologies.
 
When an annotator chooses to do this, they are effectively creating "on-the-fly" cross-product term. We say "on-the-fly" because the combinatorial term is not added to the ontology (although it could be at a later stage, if the ontology editors choose to create the appropriate GO term).
 
==When should a curator use the Annotation Extension field instead of requesting a new GO term?==
 
The primary way to provide more fine-grained annotations is by requesting more specific terms. For example, it is reasonable to create sub-types of the general term “apoptotic process”, for example “anoikis” (definition: 'Apoptosis triggered by inadequate or inappropriate adherence to substrate e.g. after disruption of the interactions between normal epithelial cells and the extracellular matrix').
 
Terms should be requested via the [http://sourceforge.net/tracker/?group_id=36855&atid=440764 ontology SourceForge tracker] or via [http://go.termgenie.org/ TermGenie].
However, highly detailed terms can inflate the ontology and lead to a GO term creation bottleneck. In addition it can be more efficient for an annotator to create the entire annotation statement in one step during the curation of the paper rather than in two steps that require making a term request and then going back later to include the new GO term in the annotation of the paper.
 
GO editors will regularly review the contents of the annotation extension field in submitted annotation files and create new, more specific terms if they feel enough annotations exist to warrant a pre-composed term. This effort will be assisted in future by automated methods to reason over annotations enhanced with filled annotation extension fields, to ensure the annotations are consistently grouped by an appropriate common GO term class.
 
 
'''1. GO term requests should not be made when the curator would like to describe activities or locations that are not evidently mechanistically or compositionally distinct from an existing GO term'''
 
''Example''
 
Unsuitable GO term: "regulation of Sonic hedgehog transcription from RNA polymerase II promoter"
 
There is no specific regulator for Sonic hedgehog transcription which is separable from general regulation of transcription from RNA polymerase II.
 
Curators should therefore be advised to use the existing term "regulation of transcription from RNA polymerase II promoter" (GO:0006357) and capture any further specifics (such as the Ensembl identifier for Sonic hedgehog) in the annotation_extension field.
 
'''2. Term requests should not be made for specific extensions which are outside the scope of GO.'''  
 
* Specific protein substrates or products of an enzyme
 
''Example:''
 
{| class="wikitable" border="1"
|-
! Gene Name (col 2)
! GO ID (col 5)
! Reference (col 6)
! Annotation Extension (col 16)
|-
| NEK
| GO:0004672 <span style="color:green"> protein kinase activity </span>
| PMID:10880350
| has_substrate(UniProtKB:Q9BV73 <span style="color:green"> CEP250</span>)| has_direct_input(UniProtKB:P36873 <span style="color:green"> PPP1CC</span>)
|}
 
* '''Specific chemical substrates''' for a catalytic or transporter activity are often considered trivial, therefore curators are recommended to discuss the appropriateness of a new term with the ontology editors.
 
* N.B. <span style="color:green">'''The text colored green'''</span> in the annotation examples on this page is not present in the annotation file, but is used here to improve the readers' understanding of annotation examples.
 
== The basic format ==
 
An annotated GO term can be enhanced in the annotation format by one or more 'relationship(identifier)' pairs added into the annotation extension field (column 16).
 
The aim of the information added into the annotation extension field is to refine the GO term identifier entered into the GO_ID field (Column 5) of the annotation file.
 
For example, if a gene product ''Slp1'' is localized to the plasma membrane of T-cells, the Gene Association File (GAF) would look like this (most columns omitted for brevity):
 
{| class="wikitable" border="1"
|-
! Gene Name (col 2)
! GO ID (col 5)
! Reference (col 6)
! Annotation Extension (col 16)
|-
| Slp1
| GO:0005886 <span style="color:green"> plasma membrane </span>
| PMID:1234567
| part_of(CL:0000084 <span style="color:green"> T cell</span>)
|}
 
Here CL:0000084 is the identifier for T-cell in the OBO Cell Type (CL) Ontology.
 
All relationships used in the annotation extension field should be valid relationships (i.e. not obsolete) described in the [http://viewvc.geneontology.org/viewvc/GO-SVN/trunk/ontology/extensions/gorel.obo gorel.obo file].
 
Identifiers can originate from GO or another ontology or database. All identifiers must be prefixed by the appropriate database namespace, e.g. UniProtKB:, CHEBI:, CL:, UBERON: and all database namespaces must be located in the [http://www.geneontology.org/cgi-bin/xrefs.cgi GO Database Abbreviations file].
 
'''Annotation Extension Format:'''
 
relationship_type(database namespace:identifier)
 
== Defining the appropriate relationship(identifier) pair for an annotation using Domain and Range parameters ==
 
===Relationship Domains===
 
 
The Domain tag in a relationship's stanza refers to the type of GO identifier that has been present in GO_ID field, column 5 of GAF 2.0 of an annotation. Some relationships should not be used in annotations that use a GO identifier from a particular aspect or branch of the GO.
 
For some relationships, top-level domain restrictions apply, and in these cases then top-level terms from the Basic Formal Ontology (BFO) are used:
 
'''domain: BFO:0000007 ! process'''
 
Should be interpreted as a union of the Biological Process and Molecular Function ontologies
 
'''domain: BFO:0000001 ! entity'''
 
Should be interpreted as a union of Biological Process, Molecular Function and Cellular Component ontologies (i.e. all GO identifiers can be used)
 
'''domain: BFO:0000004 ! independent continuant'''
 
Should be interpreted as the Cellular Component ontology.
 
===Relationship Ranges===
 
The Range tag  in a relationship's stanza refers to the types of database namespaces that can be appropriately used.
 
These Range values can be used as an additional check on the correctness of the relationship(identifier) pair.
 
In the Relations ontology, the range information is provided as named classes, identified by a ENTITY_UNION identifier.
 
Example:
<pre>
range: ENTITY_UNION:0000003 ! gene or gene product
</pre>
 
ENTITY_UNION identifiers are defined in separate stanzas in go_extension_rels.obo file:
 
<pre>
id: ENTITY_UNION:0000003
name: gene or gene product
def: "The union of gene, RNA and protein entities." [GOC:ecd]
union_of SO:0000704 ! gene
union_of: SO:0000673 ! transcript
union_of: PR:000000001 ! protein
</pre>
 
Specific appropriate database identifiers can be identified using the 'entity_type' tags located in the [http://www.geneontology.org/doc/GO.xrf_abbs GO References file]:
 
<pre>
abbreviation: UniProtKB
database: Universal Protein Knowledgebase
description: A central repository of protein sequence and function created by joining the information
contained in Swiss-Prot, TrEMBL, and PIR databases
entity_type: PR:000000001 ! protein
</pre>
 
===Examples of appropriate and inappropriate usage of relationship(identifier) pairs===
 
Many relationships have been restricted according to the type of term they can  appropriately  describe, and also the types of values that can be assigned.
 
'''Example from the go_annotation_extension_relations.obo file:'''
 
<pre>
[Typedef]
 
id: has_regulation_target
name: has_regulation_target
def: "Identifies a gene or gene product affected by a regulation BP." [GOC:mah]
xref: GOREL:0000015
domain: GO:0065007 ! biological regulation
range: ENTITY_UNION:0000003 ! gene or gene product
 
</pre>
 
The above extract of the go_annotation_extension_relations.obo file indicates that the ''has_regulation_target'' relationship can only correctly be applied in annotations which have used a GO term in column 5 that is a descendant of 'GO:0065007 biological regulation'.
 
In addition, only gene or gene product identifiers should be the types of values associated with this relationship, as indicated by the 'range' tag.
 
Therefore, while this annotation is correct:
 
{| class="wikitable" border="1"
|-
! Gene Name (col 2)
! GO ID (col 5)
! Reference (col 6)
! Evidence (col 7)
! Annotation Extension (col 16)
|-
| DAOA
| GO:1900758 <span style="color:green"> negative regulation of D-amino-acid oxidase activity </span>
| PMID:21679769
| IDA
| has_regulation_target(UniProtKB:P14920 <span style="color:green">D-amino-acid oxidase</span>)
|}
 
The following annotations, although containing appropriate information for the annotation extension field, inappropriately uses the has_regulation_target relationship as their use conflicts with the specified defined Range and Domain values defined in the description of the relation above.
 
{| class="wikitable" border="1"
|-
! Gene Name (col 2)
! GO ID (col 5)
! Reference (col 6)
! Evidence (col 7)
! Annotation Extension (col 16)
|-
| PEX19
| GO:0072662 <span style="color:green"> protein localization to peroxisome </span>
| PMID:18782765
| IMP
| has_regulation_target(UniProtKB:Q9Y3D6 <span style="color:green">Mitochondrial fission 1 protein</span>)
|}
 
 
The example above is not acceptable because the GO term is not a descendant of 'biological regulation'.
 
{| class="wikitable" border="1"
|-
! Gene Name (col 2)
! GO ID (col 5)
! Reference (col 6)
! Evidence (col 7)
! Annotation Extension (col 16)
|-
| C-C motif chemokine 24
| GO:0008360 <span style="color:green"> regulation of cell shape </span>
| PMID:10072545
| IDA
| has_regulation_target(CL:0000771 <span style="color:green"> eosinophil</span>)
|}
 
 
The example above is not acceptable because cell type ontology (CL) identifiers are not included within the Range scope of the has_regulation_target relation.
 
* N.B. <span style="color:green">'''The text colored green'''</span> in the annotation examples on this page is not present in the annotation file, but is used here to improve the readers' understanding of annotation examples.
 
=== Format for referencing multiple relationship(identifier) pairs ===
Only one identifier can be referenced by one relationship, therefore in order to make multiple  'relationship(identifier)' pairs in an annotation_extension field they must be separated with commas ',' or pipes '|'.
 
Very simply, the pipe can be interpreted as meaning "or" and comma meaning "and".
 
====Use of the ''Pipe'' to separate Annotation Extension values====
 
The current annotation format guidelines states that as inclusion of data in the annotation extension field is entirely optional for the correct interpretation of an annotation, two annotations should not exist that only differ by the contents of their annotation extension field.
 
Therefore where a gene product carries out its activity in different places or under different circumstances, then multiple annotation extension 'relationship(identifier)' pairs should be added into the annotation extension field of the same annotation and be separated from each other with a pipe. This format indicates to the user that the different relationship(identifier) pairs are making completely independent statements, and it would be equally correct to represent the annotation extension data in separate annotation lines.
 
''Example''
 
Where a gene product can act catalytically on any of a number of different substrates, but not all at the same instance, then the different 'relationship(identifier)' pairs should be separated using pipes:
 
{| class="wikitable" border="1"
|-
! Gene Name (col 2)
! GO ID (col 5)
! Reference (col 6)
! Evidence (col 7)
! Annotation Extension (col 16)
|-
| Nos2
| GO:0005777 <span style="color:green">peroxisome</span>
| PMID:12085352
| IDA
|
part_of(CL:0000182 <span style="color:green">hepatocyte</span>)|part_of(CL:0000091 <span style="color:green">Kupffer cell</span>)
|}
 
''Interpretation:''
 
Nos2 has been observed by direct assay to be located in the peroxisome of hepatocyte cells, and also located in the peroxisome of Kupffer cells.
 
The annotation format using multiple, pipe-separated 'relationship(identifier)' pairs supplies the equivalent information as supplying two separate annotation statement lines, each with one of the different relationship-value pairs:
 
{| class="wikitable" border="1"
|-
! Gene Name (col 2)
! GO ID (col 5)
! Reference (col 6)
! Evidence (col 7)
! Annotation Extension (col 16)
|-
| Nos2
|GO:0005777 <span style="color:green">peroxisome</span>
| PMID:15127951
| IDA
| part_of(CL:0000182 <span style="color:green">hepatocyte</span>)
|-
| Nos2
| GO:0005777 <span style="color:green">peroxisome</span>
| PMID:15127951
| IDA
| part_of(CL:0000091 <span style="color:green">Kupffer cell</span>)
 
|}
 
====Use of the ''Comma'' to separate multiple Annotation Extension values====
 
Commas enable curators to create "compound" annotation extensions. This format is applied where a combination of  'relationship(identifier)' pairs supplies a complex, detailed description of the context or specific nature of an instance of a function/location.
 
''Example:''
 
{| class="wikitable" border="1"
|-
! Gene Name (col 2)
! GO ID (col 5)
! Reference (col 6)
! Evidence (col 7)
! Annotation Extension (col 16)
|-
| TMEM115
| GO:0005634 <span style="color:green">nucleus</span>
| PMID: 17973242
| IDA
| part_of(CL:0000066 <span style="color:green">epithelial cell</span>),part_of(UBERON:0004801 <span style="color:green">cervix epithelium</span>)
|}
 
''Interpretation:''
 
TMEM115 is located in the nucleus that is part of an epithelial cell (CL:0000066) that is part of the cervix epithelium (UBERON:0004801).
 
* N.B. <span style="color:green">'''The text colored green'''</span> in the annotation examples on this page is not present in the annotation file, but is used here to improve the readers' understanding of annotation examples.
 
----
 
==Annotation Examples==
 
* [http://wiki.geneontology.org/index.php/Annotation_Extension:_Capturing_cell_and_tissue_types Annotation Extension field: Adding spatial location information to a GO annotation]
 
* [http://wiki.geneontology.org/index.php/Annotation_Extension:_Capturing_participants Annotation Extension field: Adding specific subtrates, products or targets into a GO annotation]
 
* [http://wiki.geneontology.org/index.php/Column_16:_linking_GO_functions,_processes,_and_components_in_one_annotation Annotation Extension field: Creating annotation-specific links between GO Processes and Functions]
 
* [[Annotation Extension field: Supplying temporal location information to a GO annotation]]
 
* [[Annotation usage examples for each annotation extension relation]]
 
* [http://wiki.geneontology.org/index.php/LEGO-style_annotation_ideas Data that cannot be captured by the current annotation format]
 
 
 
==Annotation Extension Meetings==


*[[Annotation Extension meeting 2014-06-16|June 16]]
[[Category:relations]]
[[Category:annotation extension]]

Latest revision as of 09:35, 9 February 2023

Purpose of annotation extensions

Annotation Extensions allows GO terms in standard annotations to be further specified, using gene products, chemicals, cell types, anatomical structures. The ontology terms used to extend annotations are GO term or external ontologies. Annotation extensions allows to build a more complete model of biological systems.

Relations valid for annotation extensions

Relations used for GO annotation extensions are from the Relation Ontology

Dependent and independent statement in annotation extensions

Protein2GO allows to make dependent (linked) and independent (separate) statements that are exported in GAF as comma and pipes, respectively. More information can be found in the Protein2GO documentation.

Other pages to review