Annotation Relations: Difference between revisions

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= Gene Product to GO Term Relations =
== Biological Process ==
[[acts upstream of or within]]
[[acts upstream of or within, positive effect]]
[[acts upstream of or within, negative effect]]
[[acts upstream of]]
[[acts upstream of, positive effect]]
[[acts upstream of, negative effect]]
[[involved in]]
== Molecular Function ==
[[enables]]
[[contributes to]]
== Cellular Component ==
[[part of (GP2Term)]]
[[is active in]]
[[colocalizes with]]
= GO-CAM Relations =
= GO-CAM Relations =
== Molecular Function to Gene Product ==
[[enabled by]]
== Molecular Function to Cellular Component ==
[[occurs in]]
== Molecular Function to Molecular Function ==
[[directly provides input for]]
[[directly positively regulates]]
[[directly negatively regulates]]
== Molecular Function to Biological Process  ==
[[part of]]
[[causally upstream of or within, positive effect]]
[[causally upstream of or within, negative effect]]
[[causally upstream of, positive effect]]
[[causally upstream of negative effect]]
== Molecular Function to Inputs and Outputs ==
[[has input]]
[[has output]]
== Molecular Function to Temporal Phase ==
[[happens during]]
== Biological Process to Molecular Function ==
[[causally upstream of, positive effect]]
[[causally upstream of negative effect]]
[[positively regulates]]
[[negatively regulates]]
== Biological Process to Cellular Component ==
[[occurs in]]
== Biological Process to Cell or Anatomy Term ==
[[occurs in]]
== Biological Process to Temporal Phase ==
[[happens during]]
== Biological Process to Inputs and Outputs ==


[[has input]]
GO-CAM models use contextual (e.g. occurs in) and causal (e.g. directly positively regulates) relations. For more details and specific examples of usage, click on the link to the specific relation page below.


[[has output]]
== GO-CAM: Contextual Relations  ==
 
Contextual relations are used to provide information that qualifies where, e.g. cellular components, anatomical entities, and when, e.g. biological phases, activities and processes occur.  Contextual relations can also provide information on specific targets of activities or processes, e.g. small molecules and gene products.
== Biological Process to Biological Process ==
 
= Annotation Extension Relations =
*[http://wiki.geneontology.org/index.php/Annotation_usage_examples_for_each_annotation_extension_relation Annotation Extension Relations]
 
= Relations Tables (works in progress) =


{| class="wikitable"
{| class="wikitable"
!colspan="2" |Gene Product-to-GO Term Relations
!Ontology Terms to Link
! Relation
!Usage
|-
|-
|rowspan="2"|Molecular Function
|rowspan="1"|Molecular Function to Gene Product
|[[enables]]
|[[enabled by]]
|Links a Molecular Function to the gene, gene product, or protein-containing complex that executes the activity.
|-
|-
|[[contributes to]] (as complex member)
|rowspan="1"|Molecular Function to Biological Process
|[https://wiki.geneontology.org/Part_of_relation part of]
|Links a Molecular Function to a Biological Process when the Molecular Function is an integral part of the Biological Process.
|-
|-
|rowspan="7"|Biological Process
|rowspan="1"|Molecular Function to Anatomical Entity
|[[involved in]]
|[[occurs in]]
|Links a Molecular Function to the anatomical entity, e.g. a GO cellular component or a cell or tissue type, where it occurs. 
|-
|-
|[[acts upstream of or within]]
|rowspan="2"|Molecular Function to Inputs and Outputs
|[[has input]]
|Links a Molecular Function to a specific molecular target acted upon.
|-
|-
|[[acts upstream of or within, positive effect]]
|[[has output]]
|Links a Molecular Function to the specific molecular output produced by the reaction or process.
|-
|-
|[[acts upstream of or within, negative effect]]
|rowspan="1"|Molecular Function to Temporal Phase
|-
|[[happens during]]
|[[acts upstream of]]
|Links a Molecular Function to a biological phase or stage, e.g. [http://amigo.geneontology.org/amigo/term/GO:0000279 M phase] or [https://ontobee.org/ontology/WBls?iri=http://purl.obolibrary.org/obo/WBls_0000106 L1 larval stage] ''when'' it occurs.
|-
|[[acts upstream of, positive effect]]
|-
|[[acts upstream of, negative effect]]
|-
|rowspan="4"|Cellular Component
|[[is active in]]
|-
|-
|rowspan="1"|Biological Process to Biological Process
|[[part of]]
|[[part of]]
|Links a Biological Process to another Biological Process, e.g. MAPK cascade part of a receptor signaling pathway or a receptor signaling pathway part of a development process, of which it is an integral part. 
|-
|-
|[[located in]]
|rowspan="1"|Biological Process to Anatomical Entity
|-
|[[colocalizes with]]
|}
 
 
{| class="wikitable"
!colspan="3" | GO-CAM Relations
|-
!colspan="3"| Molecular Function
|-
|rowspan="1"| Molecular Function - Gene Product
|[[enabled by]]
|protein kinase activity ''enabled by'' PLK1
|-
|rowspan="1"| Molecular Function - Location
|[[occurs in]]
|[[occurs in]]
|protein kinase activity ''occurs in'' cytosol
|Links a Biological Process to the anatomical entity, e.g. a GO cellular component or a cell or tissue type, where it occurs
|-
|-
|rowspan="1"| Molecular Function - Input
|rowspan="2"|Biological Process to Inputs and Outputs
|[[has input]]
|[[has input]]
|protein kinase activity ''has input'' MCM3
|Links a Biological Process to a specific molecular target acted upon.
|-
|-
|rowspan="1"| Molecular Function - Output
|[[has output]]
|[[has output]]
|protein kinase activity ''has output'' MCM3-2P
|Links a Biological Process to the specific molecular output produced by the reaction or process.
|-
|-
|rowspan="1"| Molecular Function - Temporal Phase
|rowspan="1"|Biological Process to Temporal Phase
|[[happens during]]
|[[happens during]]
|protein kinase activity ''happens during'' G1 phase
|Links a Biological Process to a biological phase or stage, e.g. [http://amigo.geneontology.org/amigo/term/GO:0000279 M phase] or [https://ontobee.org/ontology/WBls?iri=http://purl.obolibrary.org/obo/WBls_0000106 L1 larval stage] ''when'' it occurs.
|-
|-
|rowspan="1"| Molecular Function - Molecular Function
|rowspan="1"|Anatomical Entity to Anatomical Entity
|[[directly positively regulates]]
|[https://wiki.geneontology.org/Part_of_relation part of]
|protein kinase activity ''directly positively regulates'' ion transmembrane transporter activity
|Links anatomical entities to one another to refine the location of the entity, e.g. a [http://amigo.geneontology.org/amigo/term/GO:0005634 nucleus] may be part of an [https://ontobee.org/ontology/UBERON?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FCL_0002563 intestinal epithelial cell].
|-
|-
|rowspan="1"| Molecular Function - Molecular Function
|rowspan="1"|Protein Containing Complex to Gene Product
|[[directly negatively regulates]]
|has part
|protein kinase activity ''directly negatively regulates'' peroxidase activity
|Links protein containing complexes to the genes or gene products that are members of that complex.
|-
|-
|rowspan="1"| Molecular Function - Molecular Function
|[[directly provides input for]]
|peptidase activity ''directly provides input for'' receptor activity
|}
|}


----
== GO-CAM: Causal Relations ==
 
Causal relations are used to link activities to one another, and small molecules to activities, to indicate how an upstream activity or small molecule affects execution of a downstream activity.  Curators should strive to use causal relations that indicate the mechanism by which activities influence one another; if the mechanism is not known, a 'causally upstream of' relation may be used until a more informative causal relation can be included in the model. 
= Relations Tables (Pascale - work in progress) =
 


{| class="wikitable"
{| class="wikitable"
!colspan="7"| Molecular Function
!Ontology Pair
! Relation
!Usage
|-
|-
!rowspan="2"| Linked entities
|rowspan="9"|Molecular Function to Molecular Function
!rowspan="2"| Usage
|[[causally upstream of, negative effect]]
!rowspan="2"| Types of objects (range)
|Links two activities when the upstream activity has a negative causal effect (decreasing or inhibiting) on the downstream activity but the mechanism is not known.
!colspan="2"| GO-CAM
!colspan="2"| Corresponding Gene Product to GO Term relation in GPAD output
|-
|-
!rowspan="1"| GO-CAM relation
|[[causally upstream of, positive effect]]
!rowspan="1"| GO-CAM Example
|Links two activities when the upstream activity has a positive causal effect (increasing or activating) on the downstream activity but the mechanism is not known.
!rowspan="1"| GPAD relation
!rowspan="1"| GPAD example
|-
|-
|'''Molecular Function''' to '''Gene Product'''
|[[provides input for]] 
|Indicate that the molecular activity described by the GO term is executed by the gene or gene product.
|Links two successive activities when the product (output) of the upstream activity is the substrate (input) for the downstream activity, and the product is a macromolecule (i.e. DNA, RNA, protein).
| ChEBI information biomacromolecule  (genes and gene products)
|[[enabled by]]
|protein kinase activity ''[[enabled by]]'' PLK1
|[[enables]]
| PLK1 ''[[enables]]'' protein kinase activity
|-
|-
| '''Molecular Function''' to '''Cellular Component'''
|[[removes input for]]
|Identify the cell, tissue, cellular component or anatomical entity in which the molecular function (or biological process) takes place.
|Links two activities when the upstream activity has a negative causal effect (decreasing or inhibiting) on the downstream activity and the two activities act on or modify the same molecular target at the same site(s).
| GO cellular_component
|[[occurs in]]
|protein kinase activity ''[[enabled by]]'' PLK1 ''[[occurs in]]'' cytosol
|[[is active in]]
| (1) PLK1 ''[[is active in]]'' cytosol and (2) PLK1 ''[[enables]]'' protein kinase activity AE: ''[[occurs in]]'' cytosol <span style="color:red">if the evidence for the activity and the location is the same</span>
|-
|-
|'''Molecular Function ''' to '''Input'''
|[[constitutively upstream of]]
|Identify an entity affected <span style="color:red">targeted?</span> (bound, transported, modified, consumed or destroyed) by the gene product's participation in a molecular function (or biological process).
|Links two activities when the upstream activity is required for the downstream activity, but does not regulate the downstream activity.
| ChEBI molecule (includes information biomacromolecule)
|[[has input]]
|protein kinase activity ''[[has input]]'' MCM3
|AE: [[has input]]
| PLK1 ''[[enables]]'' protein kinase activity AE:''[[has input]]'' MCM3
|-
|-
|'''Molecular Function''' to '''Temporal Phase'''
|[[directly negatively regulates]]
|Identify the temporal phase during which a Molecular Function is executed or developmental stages in life stage ontologies
|Links two activities when the upstream activity has a negative causal effect (decreasing or inhibiting) on an immediately downstream activity. Immediately means there is no intervening activity. The mechanism by which the upstream activity controls the downstream activity must be known.
| GO:0044848 biological phase and children or terms from developmental stages in life stage ontologies.  
|[[happens during]]
|protein kinase activity ''[[happens during]]'' G1 phase
|AE: [[happens during]]
| PLK1 ''[[enables]]'' protein kinase activity AE: ''[[happens during]]'' G1 phase
|-
|-
| '''Molecular Function''' activating a '''Molecular Function'''
| Indicate two consecutive GO Molecular Functions, in which the first Molecular Function has a '''positive effect''' on the second one.
|GO Molecular Function
|[[directly positively regulates]]
|[[directly positively regulates]]
|protein kinase activity ''[[directly positively regulates]]'' ion transmembrane transporter activity
|Links two activities when the upstream activity has a positive causal effect (increasing or activating) on an immediately downstream activity. Immediately means there is no intervening activity. The mechanism by which the upstream activity controls the downstream activity must be known.
|AE: [[directly positively regulates]]
|PLK1 ''[[enables]]'' protein kinase activity AE: ''[[directly positively regulates]]'' ion transmembrane transporter activity
|-
|-
| '''Molecular Function''' inhibiting a '''Molecular Function'''
|[[indirectly negatively regulates]]
| Indicate two consecutive GO Molecular Functions, in which the first Molecular Function has a '''negative effect''' on the second one.
|Links two activities when the upstream activity has a negative regulatory effect (decreasing or inhibiting) on the downstream activity via a larger process (e.g. proteasome-mediated protein degradation) that is reused in many contexts and the curator does not want to reproduce that process in the GO-CAM. The mechanism by which the upstream activity controls the downstream activity must be known.
|GO Molecular Function
|-
|[[directly negatively regulates]]
|[[indirectly positively regulates]]
|protein kinase activity ''[[directly negatively regulates]]'' peroxidase activity
|Links two activities when the upstream activity has a positive regulatory effect (increasing or activating) on the downstream activity via a larger process (e.g. transcription) that is reused in many contexts and the curator does not want to reproduce that process in the GO-CAM. The mechanism by which the upstream activity controls the downstream activity must be known.
|AE: [[directly negatively regulates]]  
|-
| PLK1 ''[[enables]]'' protein kinase activity AE: ''[[directly negatively regulates]]'' peroxidase activity
|rowspan="2"| Molecular Function to Small Molecule
|[[Has small molecular activator |has small molecular activator]]
| Links a small molecule (ChEBI) to a Molecular Function or Biological Process the small molecule activates.
|-
|[[Has small molecular inhibitor |has small molecular inhibitor]]
| Links a small molecule (ChEBI) to a Molecular Function or Biological Process small molecule inhibits.
|-
|rowspan="2"| Small Molecule to Molecular Function
|[[is small molecule activator of]]
|Links a small molecule and an activity, when the small molecule activates the activity.
|-
|[[is small molecule inhibitor of]]
|Links a small molecule and an activity, when the small molecule inhibits the activity.
|-
|-
| '''Molecular Function''' to '''Molecular Function'''
| Relate two GO Molecular Functions that succeed one another directly, and the first provides an input for the Molecular Function of the second. Main use is to connect consecutive metabolic reactions.
|GO Molecular Function
|[[directly provides input for]]
|peptidase activity ''[[directly provides input for]]'' receptor activity <span style="color:red">Example wrong - provide metabolic example</span>
|AE: [[directly provides input for]]
|
|}
|}


= Standard Annotation Relations =
Standard GO annotations link gene products to GO terms.  A different set of RO relations, sometimes referred to as 'gp2term' relations, is used for standard annotations.  Standard GO annotation relations may be: 1) asserted manually, 2) asserted as part of a computational annotation pipeline, or 3) derived from a GO-CAM model.  Standard annotation relations are included in the GAF and GPAD annotation file formats.


== Standard Annotation: Gene Product to Term (gp2term) Relations ==
For each GO aspect there exists a default (i.e. least specific) gp2term relation that can be correctly [https://github.com/geneontology/go-site/blob/master/metadata/rules/gorule-0000061.md applied] to standard annotations if no gp2term relation is asserted. The default relation for each aspect is indicated below in '''bold'''.


{| class="wikitable"
{| class="wikitable"
!colspan="5"| Biological Process
!GO Aspect
!Gene Product-to-GO Term Relation
!Usage
|-
|rowspan="2"|Molecular Function
|'''[[enables]]'''
|Links a gene product to a Molecular Function it executes.
|-
|-
!rowspan="2"| Linked entities
|[[contributes to]]
!rowspan="2"| Usage
|Links a gene product to a Molecular Function executed by a macromolecular complex, in which the Molecular Function cannot be ascribed to an individual subunit of that complex. Only the complex subunits required for the Molecular Function are annotated to the Molecular Function term with 'contributes to'.
!rowspan="2"| Types of objects (range)
!colspan="2"| GO-CAM
!colspan="2"| Corresponding Gene Product to GO Term relation in GPAD output
|-
|-
| '''Biological Process''' to '''Gene Product'''
|rowspan="7"|Biological Process
|
|[[involved in]]
| ChEBI information biomacromolecule  (genes and gene products)
|Links a gene product and a Biological Process in which the gene product's Molecular Function plays an integral role, i.e. is 'part of' the process.
|[[part of]] <span style="color:red">was missing from other table</span>
|[[part of]]
|-
|-
| '''Biological Process''' to '''Gene Product'''
|'''[[acts upstream of or within | <span style="color:grey">acts upstream of or within</span>]]'''
|<span style="color:grey">Links a gene product and a Biological Process when the mechanism relating the gene product's activity to the Biological Process is not known. This is the most general gene product to GO term relation for Biological Process.  ''Curators should always strive to use one of the more specific child relations that capture the directionality of the effect, either positive or negative. /span>''
| ChEBI information biomacromolecule  (genes and gene products)
|[[acts upstream of or within]]
|[[acts upstream of or within]]
|-
|-
| '''Biological Process''' to '''Gene Product'''
|[[acts upstream of or within, positive effect]]
|
| ChEBI information biomacromolecule  (genes and gene products)
|[[acts upstream of or within, positive effect]]
|[[acts upstream of or within, positive effect]]
|Links a gene product and a Biological Process when the mechanism relating the gene product's activity to the Biological Process is not known, but the activity of the gene product has a positive effect on the process.
|-
|-
| '''Biological Process''' to '''Gene Product'''
|[[acts upstream of or within, negative effect]]
|
| ChEBI information biomacromolecule  (genes and gene products)
|[[acts upstream of or within, negative effect]]
|[[acts upstream of or within, negative effect]]
|Links a gene product and a Biological Process when the mechanism relating the gene product's activity to the Biological Process is not known, but the activity of the gene product has a negative effect on the process.
|-
|-
| '''Biological Process''' to '''Gene Product'''
|[[acts upstream of | <span style="color:grey">acts upstream of </span>]]
|[[acts upstream of]]  
|<span style="color:grey">Links a gene product and a Biological Process when the mechanism relating a gene product's activity to a Biological Process is known and the activity occurs before the Biological Process but does not regulate it. ''Curators should always strive to use one of the more specific child relations that capture the directionality of the effect, either positive or negative. </span>''
|  
| ChEBI information biomacromolecule  (genes and gene products)
|[[acts upstream of]]
|-
|-
| '''Biological Process''' to '''Gene Product'''
|[[acts upstream of, positive effect]]
|
| ChEBI information biomacromolecule  (genes and gene products)
|[[acts upstream of, positive effect]]
|[[acts upstream of, positive effect]]
|Links a gene product and a Biological Process when the mechanism relating a gene product's activity to a Biological Process is known and the activity occurs before the Biological Process, is required for the process to occur, but does not regulate it.
|-
|-
| '''Biological Process''' to '''Gene Product'''
|[[acts upstream of, negative effect]]
|
| ChEBI information biomacromolecule  (genes and gene products)
|[[acts upstream of, negative effect]]
|[[acts upstream of, negative effect]]
|Links a gene product and a Biological Process when the mechanism relating a gene product's activity to a Biological Process is known and the activity occurs before the Biological Process, prevents or reduces the process, but does not regulate the process.
|-
|rowspan="4"|Cellular Component
|[[is active in]]
|Links a gene product and a Cellular Component, specifically a [http://amigo.geneontology.org/amigo/term/GO:0110165 cellular anatomical anatomy] or [http://amigo.geneontology.org/amigo/term/GO:0044423 virion component], in which it enables its Molecular Function. Note that 'located in' is not used for relating gene products to a [http://amigo.geneontology.org/amigo/term/GO:0032991 protein-containing complex]; those associations use 'part of'.
|-
|'''[[located in]]'''
|Links a gene product and the Cellular Component, specifically a [http://amigo.geneontology.org/amigo/term/GO:0110165 cellular anatomical anatomy] or [http://amigo.geneontology.org/amigo/term/GO:0044423 virion component], in which a gene product has been detected.  Note that 'is active in' is not used for relating gene products to a [http://amigo.geneontology.org/amigo/term/GO:0032991 protein-containing complex]; those associations use 'part of'.
|-
|'''[https://wiki.geneontology.org/Part_of_relation#Relating_Gene_Products_to_Protein-containing_Complexes part of]'''
|Links a gene product and a [http://amigo.geneontology.org/amigo/term/GO:0032991 protein-containing complex].
|-
|[[colocalizes with]]
|Being deprecated. Was used for transient or dynamic localizations.
|}


|}
== Standard Annotation: Annotation Extension Relations ==
* Annotation extensions provide context for standard annotations to MF, BP, and CC terms.
 
* Note that currently this table only lists MF to BP annotation extension relations; additional annotation extension relations will be added soon
Molecular Function to Biological Process relations can also be used in standard annotations to relate activities to processes using one of the relations below.


{| class="wikitable"
{| class="wikitable"
!colspan="4"| Cellular component
!Ontology Pair
!Allowed Relation
!Usage
|-
|rowspan="8"|Molecular Function to Biological Process
|[https://wiki.geneontology.org/Part_of_relation part of]
|Links a Molecular Function to a Biological Process when the Molecular Function is an integral part of the Biological Process.
|-
|[[causally upstream of or within |<span style="color:grey">causally upstream of or within</span>]]
|<span style="color:grey">Links an activity and a Biological Process when the mechanism relating the activity to the Biological Process is not known. This is the most general Molecular Function to Biological Process relations.  ''Although this relation is used in the MOD imports into Noctua for new annotation, curators should always strive to use one of the more specific child relations that capture the directionality of the effect, either positive or negative.''</span>
|-
|-
!colspan="1" | GO-CAM relations
|[[causally upstream of or within, negative effect]]
!colspan="1" | Usage
|Links an activity and a Biological Process when the mechanism relating the activity to the Biological Process is not known, but the activity has a positive effect on the process.
!colspan="1" | Example
!colspan="1" | Corresponding Gene Product to GO Term relation in GPAD output
|-
|-
|[[is active in]]
|[[causally upstream of or within, positive effect]]
|The Cellular Component in which the gene or gene product enables its Molecular Function.
|Links an activity and a Biological Process when the mechanism relating the activity to the Biological Process is not known, but the activity has a negative effect on the process.
|PLK1 ''is active'' in nucleus
|-
|[[is active in]]
|[[causally upstream of |<span style="color:grey">causally upstream of</span>]]
|<span style="color:grey">Links an activity and a Biological Process when the mechanism relating the activity to the Biological Process is known and the activity occurs before the Biological Process, but does not regulate it.  ''Curators should always strive to use one of the more specific child relations that capture the directionality of the effect, either positive or negative.''</span>
|-
|[[causally upstream of, negative effect]]
|Links an activity and a Biological Process when the mechanism relating an activity to a Biological Process is known and the activity occurs before the Biological Process, reduces or prevents the process from occurring, but does not regulate it.
|-
|-
|[[part of]]
|[[causally upstream of, positive effect]]
|(a) Relates a cellular component to some cellular component, cell or anatomical structure that it is part of. (b) It may also be used to relate a molecular function or biological process to a biological process or developmental stage of which it is a part.
|Links an activity and a Biological Process when the mechanism relating an activity to a Biological Process is known and the activity occurs before the Biological Process, is required for the process to occur, but does not regulate it.
|Represented as an AE: TLR4 ''[[is active]]'' perinuclear region of cytoplasm ''[[part of]]'' CL:0000451 (dendritic cell)
|Annotation Extension:[[part of]]
|-
|-
|[[located in]]
|[[happens during]]
|Gene product detected in a cellular location, but not shown to be active there.
|Links an activity and a biological phase, such as a cell cycle phase or a developmental stage, when the activity is executed during that phase.
|PLK1 ''[[located in]]'' in nucleus
|[[located in]]
|-
|-
|[[colocalizes with]]
| Represents transient or peripheral associations. 
|PLK1 ''[[colocalizes with]]'' in nucleus
|[[colocalizes with]]
|}
|}
= Review Status =
Last reviewed: September 5th, 2023
Reviewed by: Pascale Gaudet, Kimberly Van Auken


[[Category: Relations]]
[[Category: Relations]]

Latest revision as of 08:59, 13 March 2024

GO-CAM Relations

GO-CAM models use contextual (e.g. occurs in) and causal (e.g. directly positively regulates) relations. For more details and specific examples of usage, click on the link to the specific relation page below.

GO-CAM: Contextual Relations

Contextual relations are used to provide information that qualifies where, e.g. cellular components, anatomical entities, and when, e.g. biological phases, activities and processes occur. Contextual relations can also provide information on specific targets of activities or processes, e.g. small molecules and gene products.

Ontology Terms to Link Relation Usage
Molecular Function to Gene Product enabled by Links a Molecular Function to the gene, gene product, or protein-containing complex that executes the activity.
Molecular Function to Biological Process part of Links a Molecular Function to a Biological Process when the Molecular Function is an integral part of the Biological Process.
Molecular Function to Anatomical Entity occurs in Links a Molecular Function to the anatomical entity, e.g. a GO cellular component or a cell or tissue type, where it occurs.
Molecular Function to Inputs and Outputs has input Links a Molecular Function to a specific molecular target acted upon.
has output Links a Molecular Function to the specific molecular output produced by the reaction or process.
Molecular Function to Temporal Phase happens during Links a Molecular Function to a biological phase or stage, e.g. M phase or L1 larval stage when it occurs.
Biological Process to Biological Process part of Links a Biological Process to another Biological Process, e.g. MAPK cascade part of a receptor signaling pathway or a receptor signaling pathway part of a development process, of which it is an integral part.
Biological Process to Anatomical Entity occurs in Links a Biological Process to the anatomical entity, e.g. a GO cellular component or a cell or tissue type, where it occurs.
Biological Process to Inputs and Outputs has input Links a Biological Process to a specific molecular target acted upon.
has output Links a Biological Process to the specific molecular output produced by the reaction or process.
Biological Process to Temporal Phase happens during Links a Biological Process to a biological phase or stage, e.g. M phase or L1 larval stage when it occurs.
Anatomical Entity to Anatomical Entity part of Links anatomical entities to one another to refine the location of the entity, e.g. a nucleus may be part of an intestinal epithelial cell.
Protein Containing Complex to Gene Product has part Links protein containing complexes to the genes or gene products that are members of that complex.

GO-CAM: Causal Relations

Causal relations are used to link activities to one another, and small molecules to activities, to indicate how an upstream activity or small molecule affects execution of a downstream activity. Curators should strive to use causal relations that indicate the mechanism by which activities influence one another; if the mechanism is not known, a 'causally upstream of' relation may be used until a more informative causal relation can be included in the model.

Ontology Pair Relation Usage
Molecular Function to Molecular Function causally upstream of, negative effect Links two activities when the upstream activity has a negative causal effect (decreasing or inhibiting) on the downstream activity but the mechanism is not known.
causally upstream of, positive effect Links two activities when the upstream activity has a positive causal effect (increasing or activating) on the downstream activity but the mechanism is not known.
provides input for Links two successive activities when the product (output) of the upstream activity is the substrate (input) for the downstream activity, and the product is a macromolecule (i.e. DNA, RNA, protein).
removes input for Links two activities when the upstream activity has a negative causal effect (decreasing or inhibiting) on the downstream activity and the two activities act on or modify the same molecular target at the same site(s).
constitutively upstream of Links two activities when the upstream activity is required for the downstream activity, but does not regulate the downstream activity.
directly negatively regulates Links two activities when the upstream activity has a negative causal effect (decreasing or inhibiting) on an immediately downstream activity. Immediately means there is no intervening activity. The mechanism by which the upstream activity controls the downstream activity must be known.
directly positively regulates Links two activities when the upstream activity has a positive causal effect (increasing or activating) on an immediately downstream activity. Immediately means there is no intervening activity. The mechanism by which the upstream activity controls the downstream activity must be known.
indirectly negatively regulates Links two activities when the upstream activity has a negative regulatory effect (decreasing or inhibiting) on the downstream activity via a larger process (e.g. proteasome-mediated protein degradation) that is reused in many contexts and the curator does not want to reproduce that process in the GO-CAM. The mechanism by which the upstream activity controls the downstream activity must be known.
indirectly positively regulates Links two activities when the upstream activity has a positive regulatory effect (increasing or activating) on the downstream activity via a larger process (e.g. transcription) that is reused in many contexts and the curator does not want to reproduce that process in the GO-CAM. The mechanism by which the upstream activity controls the downstream activity must be known.
Molecular Function to Small Molecule has small molecular activator  Links a small molecule (ChEBI) to a Molecular Function or Biological Process the small molecule activates.
has small molecular inhibitor  Links a small molecule (ChEBI) to a Molecular Function or Biological Process small molecule inhibits.
Small Molecule to Molecular Function is small molecule activator of Links a small molecule and an activity, when the small molecule activates the activity.
is small molecule inhibitor of Links a small molecule and an activity, when the small molecule inhibits the activity.

Standard Annotation Relations

Standard GO annotations link gene products to GO terms. A different set of RO relations, sometimes referred to as 'gp2term' relations, is used for standard annotations. Standard GO annotation relations may be: 1) asserted manually, 2) asserted as part of a computational annotation pipeline, or 3) derived from a GO-CAM model. Standard annotation relations are included in the GAF and GPAD annotation file formats.

Standard Annotation: Gene Product to Term (gp2term) Relations

For each GO aspect there exists a default (i.e. least specific) gp2term relation that can be correctly applied to standard annotations if no gp2term relation is asserted. The default relation for each aspect is indicated below in bold.

GO Aspect Gene Product-to-GO Term Relation Usage
Molecular Function enables Links a gene product to a Molecular Function it executes.
contributes to Links a gene product to a Molecular Function executed by a macromolecular complex, in which the Molecular Function cannot be ascribed to an individual subunit of that complex. Only the complex subunits required for the Molecular Function are annotated to the Molecular Function term with 'contributes to'.
Biological Process involved in Links a gene product and a Biological Process in which the gene product's Molecular Function plays an integral role, i.e. is 'part of' the process.
acts upstream of or within Links a gene product and a Biological Process when the mechanism relating the gene product's activity to the Biological Process is not known. This is the most general gene product to GO term relation for Biological Process. Curators should always strive to use one of the more specific child relations that capture the directionality of the effect, either positive or negative. /span>
acts upstream of or within, positive effect Links a gene product and a Biological Process when the mechanism relating the gene product's activity to the Biological Process is not known, but the activity of the gene product has a positive effect on the process.
acts upstream of or within, negative effect Links a gene product and a Biological Process when the mechanism relating the gene product's activity to the Biological Process is not known, but the activity of the gene product has a negative effect on the process.
acts upstream of Links a gene product and a Biological Process when the mechanism relating a gene product's activity to a Biological Process is known and the activity occurs before the Biological Process but does not regulate it. Curators should always strive to use one of the more specific child relations that capture the directionality of the effect, either positive or negative.
acts upstream of, positive effect Links a gene product and a Biological Process when the mechanism relating a gene product's activity to a Biological Process is known and the activity occurs before the Biological Process, is required for the process to occur, but does not regulate it.
acts upstream of, negative effect Links a gene product and a Biological Process when the mechanism relating a gene product's activity to a Biological Process is known and the activity occurs before the Biological Process, prevents or reduces the process, but does not regulate the process.
Cellular Component is active in Links a gene product and a Cellular Component, specifically a cellular anatomical anatomy or virion component, in which it enables its Molecular Function. Note that 'located in' is not used for relating gene products to a protein-containing complex; those associations use 'part of'.
located in Links a gene product and the Cellular Component, specifically a cellular anatomical anatomy or virion component, in which a gene product has been detected. Note that 'is active in' is not used for relating gene products to a protein-containing complex; those associations use 'part of'.
part of Links a gene product and a protein-containing complex.
colocalizes with Being deprecated. Was used for transient or dynamic localizations.

Standard Annotation: Annotation Extension Relations

  • Annotation extensions provide context for standard annotations to MF, BP, and CC terms.
  • Note that currently this table only lists MF to BP annotation extension relations; additional annotation extension relations will be added soon

Molecular Function to Biological Process relations can also be used in standard annotations to relate activities to processes using one of the relations below.

Ontology Pair Allowed Relation Usage
Molecular Function to Biological Process part of Links a Molecular Function to a Biological Process when the Molecular Function is an integral part of the Biological Process.
causally upstream of or within Links an activity and a Biological Process when the mechanism relating the activity to the Biological Process is not known. This is the most general Molecular Function to Biological Process relations. Although this relation is used in the MOD imports into Noctua for new annotation, curators should always strive to use one of the more specific child relations that capture the directionality of the effect, either positive or negative.
causally upstream of or within, negative effect Links an activity and a Biological Process when the mechanism relating the activity to the Biological Process is not known, but the activity has a positive effect on the process.
causally upstream of or within, positive effect Links an activity and a Biological Process when the mechanism relating the activity to the Biological Process is not known, but the activity has a negative effect on the process.
causally upstream of Links an activity and a Biological Process when the mechanism relating the activity to the Biological Process is known and the activity occurs before the Biological Process, but does not regulate it. Curators should always strive to use one of the more specific child relations that capture the directionality of the effect, either positive or negative.
causally upstream of, negative effect Links an activity and a Biological Process when the mechanism relating an activity to a Biological Process is known and the activity occurs before the Biological Process, reduces or prevents the process from occurring, but does not regulate it.
causally upstream of, positive effect Links an activity and a Biological Process when the mechanism relating an activity to a Biological Process is known and the activity occurs before the Biological Process, is required for the process to occur, but does not regulate it.
happens during Links an activity and a biological phase, such as a cell cycle phase or a developmental stage, when the activity is executed during that phase.

Review Status

Last reviewed: September 5th, 2023

Reviewed by: Pascale Gaudet, Kimberly Van Auken