Annotation Relations

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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

A specific set of term from the Relations Ontology (RO), sometimes referred to as 'gp2term' relations, is used to link gene products to GO terms in 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.
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