The Gene Ontology is a controlled vocabulary, a set of standard terms—words and phrases—used for indexing and retrieving information. In addition to defining terms, GO also defines the relationships between the terms, making it a structured vocabulary.
GO as a Graph
The structure of GO can be described in terms of a graph, where each GO term is a node, and the relationships between the terms are arcs between the nodes. The relationships used in GO are directed—for example, a mitochondrion is an organelle, but an organelle is not a mitochondrion—and the graph is acyclic, meaning that cycles are not allowed in the graph. The ontologies resemble a hierarchy, as child terms are more specialized and parent terms are less specialized, but unlike a hierarchy, a term may have more than one parent term. For example, the biological process term hexose biosynthetic process has two parents, hexose metabolic process and monosaccharide biosynthetic process. This is because biosynthetic process is a type of metabolic process and a hexose is a type of monosaccharide.
The following diagram is a screenshot from the ontology editing software OBO-Edit, showing a small set of terms from the ontology.
In the diagram, relations between the terms are represented by the colored arrows; the letter in the box midway along each arrow is the relationship type. Note that the terms get more specialized going down the graph, with the most general terms—the root nodes, cellular component, biological process and molecular function—at the top of the graph. Terms may have more than one parent, and they may be connected to parent terms via different relations. The GO relations documentation describes these relations in greater detail.
One Ontology... or Three?
As the diagram above suggests, the three GO domains (cellular component, biological process, and molecular function) are each represented by an ontology term. All terms in a domain can trace their parentage to the root term, although there may be numerous different paths via varying numbers of intermediary terms to the ontology root. The three root nodes are unrelated and do not have a common parent node, and hence GO is referred to both as three ontologies (as in "the GO ontologies") and as a single ontology consisting of three sub-ontologies. Some graph-based software may require a single root node; in these cases, a "fake" term can be added as a parent of the three existing root nodes.
Occasionally, a term is found that is outside the scope of GO, is misleadingly named or defined, or describes a concept that would be better represented in another way. Rather than delete the term, it is deprecated or made obsolete. The term and ID still exist in the GO database, but the term is tagged as obsolete, and all relationships to other terms are removed. A comment is added to the term, detailing the reason for the obsoletion and suggesting alternative(s) if appropriate.
Unique identifier and term name
Every term has a term name—e.g. mitochondrion, glucose transport, amino acid binding—and a unique zero-padded seven digit identifier (often called the term accession or term accession number) prefixed by GO:, e.g. GO:0005125 or GO:0060092. The numerical portion of the ID has no inherent meaning or relation to the position of the term in the ontologies. Ranges of GO IDs are assigned to individual ontology editors or editing groups, and can thus be used to trace who added the term.
A textual description of what the term represents, plus reference(s) to the source of the information. All new terms added to the ontology must have a definition; there remains a very small set of terms from the original ontology that lack definitions, but the vast majority of terms are defined.
Relationships to other terms
One or more links that capture how the term relates to other terms in the ontology. All terms (other than the root terms representing each namespace, above) have an is a sub-class relationship to another term; for example, GO:0015758 : glucose transport is a GO:0015749 : monosaccharide transport. The Gene Ontology employs a number of other relations, including part of (e.g. GO:0031966 : mitochondrial membrane part of GO:0005740 : mitochondrial envelope) and regulates (e.g. GO:0006916 : anti-apoptosis regulates GO:0012501 : programmed cell death). The relations documentation has more information on the relations used in the ontology.
Alternate IDs that refer to a term. Secondary IDs come about when two or more terms are identical in meaning, and are merged into a single term. All terms IDs are preserved so that no information (for example, annotations to the merged IDs) is lost.
Alternative words or phrases closely related in meaning to the term name, with indication of the relationship between the name and synonym given by the synonym scope. The scopes for GO synonyms are:
- an exact equivalent; interchangeable with the term name
- e.g. ornithine cycle is an exact synonym of urea cycle
- the synonym is broader than the term name
- e.g. cell division is a broad synonym of cytokinesis
- the synonym is narrower or more precise than the term name
- e.g. pyrimidine-dimer repair by photolyase is a narrow synonym of photoreactive repair
- the terms are related in some way not covered above
e.g. cytochrome bc1 complex is a related synonym of ubiquinol-cytochrome-c reductase activity
virulence is a related synonym of pathogenesis
Custom synonym types are also used in the ontology. For example, a number of synonyms are designated as systematic synonyms; synonyms of this type are exact synonyms of the term name.
Database cross-references, or dbxrefs, refer to identical or very similar objects in other databases. For instance, the molecular function term retinal isomerase activity is cross-referenced with the Enzyme Commission entry EC:188.8.131.52; the biological process term sulfate assimilation has the cross-reference MetaCyc:PWY-781.
Any extra information about the term and its usage.
Indicates that the term belongs to a designated subset of terms, e.g. one of the GO slims.
Indicates that the term has been deprecated and should not be used.
Sample GO Term
The following is a GO term taken from the OBO format file.
name: cell growth
def: "The process in which a cell irreversibly increases in size over time by accretion and biosynthetic production of matter similar to that already present." [GOC:ai]
synonym: "cell expansion" RELATED 
synonym: "cellular growth" EXACT 
synonym: "growth of cell" EXACT 
is_a: GO:0009987 ! cellular process
is_a: GO:0040007 ! growth
relationship: part_of GO:0008361 ! regulation of cell size
Cross-Products and Logical Definitions
To be maximally useful, the Gene Ontology should be accessible to computers as well as to human users, enabling tools to access the data and perform tasks and analyses that would be time-consuming and work intensive for humans. One aspect that can aid automated access to the ontology is creating computable logical definitions to complement the existing text definitions. These logical definitions are in the genus-differentia form: the definition consists of the genus, the broader class to which the term belongs, and the differentia, the properties that distinguish the term from other members of the class. For example:
mitochondrial DNA replication is DNA replication that occurs in a mitochondrion
DNA replication is the genus and the differentia is occurs in a mitochondrion.
lysosomal membrane is the membrane that surrounds a lysosome
membrane is the genus and the differentia is surrounds a lysosome.
If we use ontology terms in the genus and the differentia, we can see that these logical definitions take the general form
term = term that relation term
mitochondrial DNA replication is DNA replication that occurs in a mitochondrion
lysosomal membrane is a membrane that surrounds a lysosome
These definitions of terms created by combining other terms with relations are called cross-products in GO parlance. In the OBO 1.2 format file, the human-readable text definition is held in the def line, and the cross-product definition in the intersection_of lines of a stanza. The cross-products above would be represented as follows:
name: mitochondrial DNA replication
def: "The process whereby new strands of DNA are synthesized in the mitochondrion." [source: GOC:ai]
intersection_of: GO:0006260 ! DNA replication
intersection_of: OBO_REL:occurs_in GO:0005739 ! mitochondrion
name: lysosomal membrane
def: "The lipid bilayer surrounding the lysosome and separating its contents from the cell cytoplasm." [source: GOC:ai]
intersection_of: GO:0016020 ! membrane
intersection_of: part_of GO:0005764 ! lysosome
Cross-Products with external ontologies
Cross-products need not be restricted to terms within GO; cross-products can also be created by combining GO terms with those from other ontologies. For example, by using the Cell Ontology, we can easily extract cell type information from GO terms. For example:
megasporocyte nucleus (GO:0043076) is a nucleus (GO:0005634) that is part of a megasporocyte (CL:0000320)
name: megasporocyte nucleus
def: "The nucleus of a megasporocyte, a diploid cell that undergoes meiosis to produce four megaspores, and its descendents." [source: GOC:jl, ISBN:0618254153]
intersection_of: GO:0005634 ! nucleus
intersection_of: part_of CL:0000320 ! megasporocyte
osteoblast development (GO:0002076) is cell development (GO:0048468) that results in the complete development of an osteoblast (CL:0000062)
name: osteoblast development
def: "The process whose specific outcome is the progression of an osteoblast over time, from its formation to the mature structure. Osteoblast development does not include the steps involved in committing a cranial neural crest cell or an osteoprogenitor cell to an osteoblast fate. An osteoblast is a cell that gives rise to bone." [source: GOC:dph]
intersection_of: GO:0048468 ! cell development
intersection_of: OBO_REL:results_in_complete_development_of CL:0000062 ! osteoblast
Cross-products are currently being retrofitted to existing ontology terms and added to new terms. Eventually, the hope is that cross-products could be dynamically generated, rather than having be added manually each time a new term is required. This would obviate the need for some of highly specific terms in GO—for example, many of the terms referring to organism anatomy or chemical entities—and simplify ontology searches and browsing.
More information on the ongoing work on cross-products can be found in the cross-products category on the GO wiki.