Relations in the Gene Ontology
Overview
The ontologies of GO are structured as a graph, withterms asnodes in the graph and therelations (also known asobject properties) between the terms asedges (more ontology information atGene Ontology Overview). Just as each GO term is defined, the relations between GO terms are also categorized and defined. This document provides a description of some of the commonly used relationships in GO:is a (is a subtype of);part of; has part;regulates,negatively regulates andpositively regulates.
All terms (except from the root terms representing each aspect) have anis a sub-class relationship to another term; for example,
GO:1904659:glucose transportis aGO:0015749:monosaccharide transport.
The Gene Ontology employs a number of other relations, includingpart of, e.g.
GO:0031966:mitochondrial membrane ispart ofGO:0005740:mitochondrial envelope
andregulates, e.g:
GO:0098689:latency-replication decisionregulatesGO:0019046:release from viral latency
This set is not exhaustive and includes only a subset of relations used in the GO ontologies, logical definitions and annotations. For more technical information about relations and their properties used in GO and other ontologies see theOBO Relations Ontology (RO).
Using relations to group related annotations
Relations are widely used by GO browsing tools such asAmiGO andQuickGO and in over-representation analysis to group related GO annotations. For example, the annotations on theAmiGO page for kinase activity include annotations made to ‘fucokinase activity’, ‘protein kinase activity’ etc. Note that not all relations can be safely used to group annotations via the GO graph. Please see below for notes and examples illustrating when and why grouping of annotations via relationships can be done safely.
Conventions used to describe relations
There are a number of ways of referring to and representing logical relations. The GO relations documentation uses the following conventions (in keeping with the graph-based terminology):
- Anode refers to a GO term
- Aparent refers to the node closer to the root(s) of the graph, and achild to that closer to the leaf nodes; for the relationsis_a andpart_of, the parent would be a broader GO term, and the child would be a more specific term
- Thearrowhead indicates the direction of the relationship
- Dotted lines represent an inferred relationship, i.e. one that has not been expressly stated in the ontology.
This diagram would be interpreted as follows:
- Ais a B
- B ispart of C
- we can infer that A ispart of C
The formal mathematical / logical representation of the inference made in the graph above is:is a ∘part of →part of
GO basics
Nodes in the GO graph can have any number and type of relationships to other nodes. Like hierarchies—for example, a family tree or a taxonomy of species—a node may have connections to more than one child (more specific) node, but unlike them, it can also have more than one parent (broader) node, and different relations to its different parents; for example, a node may have a part of relationship to one node, and an is a relationship to another. The following diagram illustrates this point:
- mitochondrion has two parents: itis an organelle and it ispart of the cytoplasm;
Main relations used in GO
| Relation | Description | Use for grouping annotations | |
|---|---|---|---|
| is a | The is a relation forms the basic structure of GO. If we say Ais a B, we mean that node A is a subtype of node B. For example, mitotic cell cycleis a cell cycle, or lyase activityis a catalytic activity. | It is safe to useis a to group annotations. For example if a gene product X is annotated as having tyrosine kinase activity and the ontology records that tyrosine kinase activityis a (type of) kinase activity, then we can safely conclude that gene product X has kinase activity. | |
| part of | Thepart of relation is used to represent part-whole relationships.part of has a specific meaning in GO, and apart of relation would only be added between A and B if B isnecessarilypart of A: wherever B exists, it is aspart of A, and the presence of the B implies the presence of A. However, given the occurrence of A, we cannot say for certain that B exists. | It is safe to use part of to group annotations. For example if a gene product X is annotated as located in the inner mitochondrial membrane and the ontology records apart of relation between inner mitochondrial membrane and mitochondrion, we can safely conclude that X is located in a mitochondrion. | |
| has part | The logical complement to thepart of relation ishas part, which represents a part-whole relationship from the perspective of the parent. As withpart of, the GO relationhas part is only used in cases where A always has B as a part, i.e. where A necessarilyhas part B. If A exists, B will always exist; however, if B exists, we cannot say for certain that A exists. i.e. all A have part B; some B part of A. | It is NOT correct to usehas part for grouping annotations. For example, we might assert in the ontology that a receptor tyrosine kinase activityhas part ATP hydrolysis activity. However it would not then be correct to group all annotations to kinase activity under ATPase activity. | |
| regulates | A relation that describes case in which one process directly affects the manifestation of another process or quality, i.e. the formerregulates the latter. The target of the regulation may be another process, for e.g., regulation of a pathway or an enzymatic reaction, or it may be a quality, such as cell size or pH. Analogously topart of, this relation is used specifically to meannecessarilyregulates: if both A and B are present, B alwaysregulates A, but A may not always be regulated by B., i.e. all Bregulate A; some A areregulated by B. | Unlikeis a andpart of, grouping annotations to gene products grouped viaregulates changes the relationship between the GO term and the gene product over theis a andpart of relations. If gene product X is annotated as involved in a process thatregulates glycolysis, it would not be correct to conclude that X participates in glycolysis. Nevertheless, some tools useregulates relations to group annotations. This can be useful for gene-set enrichment. The resulting gene sets include genes that are involved in processes that are causally related to the grouping term. |