General Considerations

Beginning and end

Every process should have a discrete beginning and end, and these should be clearly stated in the process term definition.

Collections of processes

The biological process ontology includes terms that represent collections of processes as well as terms that represent a specific, entire process. Generally, the former will have mainly is_a children, and the latter will have part_of children that represent subprocesses. Also see "is_a or part_of" below.

is_a or part_of

To determine whether a process term should be an is_a or part_of child of its parent, ask: is an instance of the child process an instance of the entire parent process? That is, does the whole process, from start to finish, take place? If yes, the child is is_a; but if it's an instance of only a portion of the parent process, the child is part_of.

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The Cell Cycle

The representation of the cell cycle in GO is split into two sections: the physical processes that occur and the temporal stages - prophase, anaphase and so on - used to describe sets of events. This method of representation is used to prevent true path problems when organisms differ from the "canonical" (usually S. cerevisiae) cell cycle.

Terms and Structure

The cell cycle node sits under cellular physiological process ; GO:0050875 and is split into types of cell cycle (meiotic or mitotic) and stages (M phase, S phase, etc.), plus a regulation term.

Taking the example of M phase of the mitotic cell cycle, this is the structure of the child terms of M phase. Note that the terms representing temporal phases are not linked to those representing physical events.

The physical events associated with mitotis and meiosis are mainly found under the term chromosome segregation, defined as "the process by which genetic material, in the form of chromosomes [or chromatids], is organized and then physically separated and apportioned to two or more sets". The related term chromosome separation refers to the detachment of chromosomes from each other as they move towards the spindle pole.

Standard Definitions

any cell cycle phase (e.g. M phase, telophase)

Progression through [phase name], [description of phase].

any cell cycle process (e.g. mitotic chromosome condensation)

The cell cycle process whereby [description of process].

Cytokinesis

Cytokinesis is placed under cell division but not under cell cycle, something which seems counterintuitive to many. This is because bacteria, which do not have a cell cycle, undergo cytokinesis. Organisms that do have a cell cycle can use more specific terms, such as cytokinesis after meiosis I and cytokinesis after mitosis to represent cytokinesis in their organism.

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The Development Node

The set of standard terms below can be applied to each developing structure in each species covered in the ontology. However it is generally not practical to implement every term for every structure, since this would lead to a massive proliferation of terms. Where one term e.g. x development, is present, the rest of the terms for the development of x are considered to be implied, without having actually been implemented. Further terms are generally only implemented when they are required for annotation. To see an example of a more full implementation please see the children of mesoderm development, which cover the development of the mesoderm, and the axial, paraxial, and intermediate mesoderm.

This development node structure was agreed upon in 2003 and is gradually being retrofitted. Where terms appear not to conform to it, this may be because they have not yet been retrofitted, or because their development includes an exception to the normal model. Any questions about the development terms should be posted on the GO curator requests tracker [external website].

Terms and Structure

This is the structure for development terms involving tissues, organs and organisms (based on SourceForge discussion 825413 [external website] and SourceForge discussion 827566 [external website]).

This is the structure for development terms involving cells (agreed at the St. Croix consortium meeting).

Standard Definitions

On implementation, each of the standard definitions below should be followed by a brief summary of the purpose of the structure, and also, where relevant, the characteristics marking its initial formation and its arrival at the mature state. If the common usage does not conform to GO term name syntax, then it is helpful to add an exact synonym with GO syntax.

x development

The process whose specific outcome is the progression of the x over time, from its formation to the mature structure.

x morphogenesis

The process by which the anatomical structures of x are generated and organized. Morphogenesis pertains to the creation of form.

x formation

The process that gives rise to x. This process pertains to the initial formation of a structure from unspecified parts.

x structural organization

The process that contributes to creating the structural organization of x. This process pertains to the physical shaping of a rudimentary structure.

x maturation

A developmental process, independent of morphogenetic (shape) change, that is required for x to attain its fully functional state. [description of x]

[cell type] cell differentiation

The process whereby a relatively unspecialized cell acquires specialized features of a [cell type] cell. (N.B. This may be development of [cell type] cell type or a set of cells of [cell type] cell type. This will involve the change of a cell or set of cells from one cell identity to another.)

[cell type] cell fate commitment

The process whereby the developmental fate of a cell becomes restricted such that it will develop into a [cell type] cell.

[cell type] cell fate specification

The process whereby a cell becomes capable of differentiating autonomously into a [cell type] cell in an environment that is neutral with respect to the developmental pathway. Upon specification, the cell fate can be reversed.

[cell type] cell fate determination

The process whereby a cell becomes capable of differentiating autonomously into a [cell type] cell regardless of its environment; upon determination, the cell fate cannot be reversed.

[cell type] cell development

The process aimed at the progression of a [cell type] cell over time, from initial commitment of the cell to a specific fate, to the fully functional differentiated cell.

[cell type] cell morphogenesis during differentiation

The process by which the structures of a [cell type] cell are generated and organized. This process occurs while the initially relatively unspecialized cell is acquiring the specialized features of a [cell type] cell.

[cell type] cell maturation

A developmental process, independent of morphogenetic (shape) change, that is required for a [cell type] cell to attain its fully functional state. [description of [cell type]]

Note:

See Other Miscellaneous Standard Defs below for x biogenesis.

Qualifiers

The following qualifiers can be used with morphogenesis.

embryonic x morphogenesis

The process, occurring in the embryo, by which the anatomical structures of x are generated and organized. Morphogenesis pertains to the creation of form.

larval x morphogenesis

The process, occurring in the larva, by which the anatomical structures of x are generated and organized. Morphogenesis pertains to the creation of form.

post-embryonic x morphogenesis

The process, occurring after embryonic development [and prior to (e.g. larval) development], by which the anatomical structures of x are generated and organized. Morphogenesis pertains to the creation of form.

Development vs Morphogenesis

The concepts of development and morphogenesis may at first seem synonymous. On further thought however, it becomes apparent that at the level of tissues, organs and organisms, development encompasses much more than just the generation and organization of anatomical structures. In some instances it includes steps called maturation which may include a wide range of processes, one of which is described below. Development and morphogenesis are considered to be equivalent at the level of a cell.

Seed development

Seeds are complex structures whose development includes both a morphogenesis and maturation step (SourceForge discussion 916873 [external website]).

A. Seed Morphogenesis

The morphogenesis phase includes generation and organization steps, as described in Developmental Biology, 6th Edition (Scott F. Gilbert):

• To establish the basic body plan. Radial patterning produces three tissue systems, and axial patterning establishes the apical-basal (shoot-root) axis.
• To set aside meristematic tissue for postembryonic elaboration of the body structure (leaves, roots, flowers, etc.).
• To establish an accessible food reserve for the germinating embryo until it becomes autotrophic.

B. Seed Maturation

In many species the fully formed seed enters a physiological state of dormancy, and this is an example of a maturation process. At this point morphogenesis is over, but development continues with onset of dormancy phase.

Formation vs Development

Confusion often arises about the role of formation in the development process. Formation would have to do with the processes that establish a tissue. A couple of examples of these would be primary embryonic induction and epithelial to mesenchymal transition. As in other parts of the development graph, the development of a tissue would include much more than this, including morphogenic shaping of cell layers, patterning, selective apoptosis etc, depending on the tissue. Therefore formation terms are made as parts of the morphogenesis terms, and the full morphogenetic process also requires structural organization step to fully generate and organize the structure.

Structural Organization vs Morphogenesis

These are not synonymous because the structure has to be initially formed before it can increase in size and be organized. Morphogenesis covers both formation and structural development.

What is maturation?

The maturation term was instantiated for cases in which a cell is not changing morphologically (changing shape), but is still developing. The remaining development steps involve synthesis of gene products that will enable the cell or structure to become fully functional.

One example of this is the maturation of the epithelial cells of the intestinal crypts [external website]. These are born at the bottom of the crypts as columnar epithelial cells. The process making them conform to this shape is be their morphogenesis. As they mature, they don't change shape, but they move up along the villus due to the death of the cells at the tip and the birth of new cells at the bottom.

While they are moving up, they are synthesizing the gene products that make them functional absorptive cells. This is part of their maturation. Eventually they apoptose. This is also part of their maturation.

Another example would be a neuron [external website] that has already fully extended its axons and dendrites (neuron morphogenesis) and is receiving signals about what kind of receptors and neurotransmitters it is going to make. This is maturation because the process doesn't have anything to do with creating the shape of the cell but is required for attainment of full function.

To summarize, the maturation terms capture the processes that are involved in a cell becoming fully functional but that aren't directly related to the changes in shape of the cell.

Metamorphosis vs Morphogenesis

The concepts of metamorphosis and morphogenesis are closely related but have some key differences.

Metamorphosis terms refer to the radical change in shape of a whole organism, for example metamorphosis of the whole tadpole to the whole frog. Morphogenesis terms capture the process by which the shape or form of a whole organism or part of an organism is gradually formed, for example morphogenesis of a worm, a leaf, or a limb.

x metamorphosis

A change of shape or structure of the whole organism from one developmental stage to another, particularly the rapid post embryonic structural transformation from larval to adult form.

x morphogenesis

The process by which the anatomical structures of x are generated and organized. Morphogenesis pertains to the creation of form.

Note that morphogenesis terms always include the name of the mature anatomical part in the term name.

Imaginal Discs

The fly imaginal disc terms are a fusion of these two concepts as the process of fly imaginal disc morphogenesis changes the shape of a part of an organism (imaginal disc) very radically. In addition to this, the standard morphogenesis definitions will not work for imaginal disc morphogenesis as the relationship of the initial structures to the mature structures is not one-to-one. One disc can contribute to more than one mature structure, and one structure can be formed from more than one disc. For example, the Drosophila eye-antennal disc gives rise to the eye, antenna, head capsule and maxillary palps. In higher Diptera, primordia contained in different imaginal discs (labial disc, clypeolabral bud) participate in the formation of the proboscis.

Because of this, the research community investigates these processes by looking at the morphogenesis of each disc as a whole, through time, rather than looking at the formation of each individual mature structure. This means that the research results available to be annotated to the GO tend to be couched in terms of disc morphogenesis rather than in terms of morphogenesis of a single anatomical part that happens to be derived from a disc.

The standard morphogenesis terms in GO have the mature anatomical part in the term name and define the process as the steps leading to the final form of that structure. This is not possible in the case of fly imaginal discs and so a slight modification had been made to accommodate the difference in research method, but preserve the standard temporal factors in the description of the process.

Imaginal disc terms receive the name x imaginal disc morphogenesis and the exact synonym x imaginal disc metamorphosis, in which the x refers to the initial anatomical structure. Their definition is very similar to the morphogenesis standard definition but with a key difference:

x morphogenesis

The process by which the anatomical structures of x are generated and organized. Morphogenesis pertains to the creation of form.

x metamorphosis

A change of shape or structure of the whole organism from one developmental stage to another, particularly the rapid post embryonic structural transformation from larval to adult form.

x imaginal disc morphogenesis

The process by which the anatomical structures derived from the x disc are generated and organized. Morphogenesis pertains to the creation of form. This includes the transformation of a x imaginal disc from a monolayered epithelium in the larvae of holometabolous insects into the recognizable adult structures a, b, c, d and e.
exact synonym: x imaginal disc metamorphosis

The definition still captures the morphogenesis of the mature structure but the immature structure is the one explicitly named in the term name and definition, as in the biological literature. Anyone annotating to these terms should bear in mind that the imaginal disc terms are to be used for annotation of gene products involved in the processes that enable the morphogenesis of the disc (mentioned in the term name) to another anatomical part. This is different from the standard morphogenesis terms in which the term is intended to be used for annotation of gene products involved in morphogenesis bringing about the shape of the part mentioned in the term name. It is important that these differences should be borne in mind while annotating.

In summary, when using these terms, as with all GO terms, please read the definition carefully.

Differentiation vs Cell development

Q: What is the difference between 'cell differentiation' and 'cell development'?

A: Cell development should NOT include the steps involved in committing a cell to a specific fate. Differentiation includes the processes involved in commitment. Development is what the cell does once it is committed to a given fate.

To express this our standard structure is like this:

When does development start?

The situation above illustrates a central point in capturing developmental processes in an ontology. The conceptual difficulty here is deciding when the development of x begins and when it ends. For example, the embryogenesis of my mother could be considered to be part of my development, or gastrulation could be considered to be part of kidney development. Although my mother's embryogenesis led to the final state that was me, and gastrulation leads to the final state of a kidney, clearly there has to be a cut-off somewhere.

That cut off is determined by how the class development differs from the class X development. Clearly for the case of me from a biological perspective, the start can be set at the fertilised egg (although that is still argued in legal circles, and ontologists might argue that the individual is not established until the point when it is too late for the egg to divide to produce two individuals). But what about the development of a specific type of cell? It makes sense to set the start of development of a specific type of cell as occurring once the cell has been committed to its fate. Otherwise we may be considering processes that might not necessarily end in the maturation of that cell type. This is how we have expressed the situation in the process ontology.

Should we represent cell lineage in the process ontology?

One further related question that we often come up against is whether to try to represent cell lineage in the development node of the process ontology. Lineage relationships are better represented in other ontologies such as in the cell ontology or in an anatomical ontology. The sum of all processes that lead up to something can then be computed based on those relationships.

For example, you may want to know about gene products involved in neuron development and you may want to include the development of all the precursors of the neuron. To do this you can use a combination of the cell type ontology (which encodes lineage information) and the development node of the process ontology (which captures information on development).

Source: SourceForge discussion 1259770 [external website]

Q: What is the difference between 'cell differentiation' and 'cell development'?

A: Cell development should NOT include the steps involved in committing a cell to a specific fate. Differentiation includes the processes involved in commitment. Development is what the cell does once it is committed to a given fate.

Cell fate specification, determination and commitment

The differences between cell fate commitment, cell fate specification and cell fate determination are fairly subtle and so they are explained below.

Source: St. Croix Consortium Meeting minutes + subsequent changes.

cell differentiation

The process whereby relatively unspecialized cells, e.g. embryonic or regenerative cells, acquire specialized structural and/or functional features that characterize the cells, tissues, or organs of the mature organism or some other relatively stable phase of the organisms life history.

cell fate commitment

The commitment of cells to specific cell fates and their capacity to differentiate into particular kinds of cells. Positional information is established through protein signals that emanate from a localized source within a cell (the initial one-cell zygote) or within a developmental field.

cell fate specification

The process involved in the specification of cell identity. Once specification has taken place, a cell will be committed to differentiate down a specific pathway if left in its normal environment.

cell fate determination

The process involved in cell fate commitment. Once determination has taken place, a cell becomes committed to differentiate down a particular pathway regardless of its environment.

Cell maturation and differentiation of derivative cell types

What is the relationship between maturation of a cell type and differentiation of the derivative cell type in the GO process ontology?

To figure this out we have to think about how one cell type arises from another, and then consider how this information is represented in the GO process ontology and in the cell type ontology.

If we consider a cell type A, the differentation of this cell will include all the steps common to cell differentiation (standard structure and Figure 1). During the differentiation of a cell type A it is possible that some individual cells of the population of A cells will undergo a change of identity to become committed to other cell fates, B and C (Figure 1). This change in identity can occur at any time during the differentiation of a cell of type A. For example in Figure 1 the change of identity is shown as occurring at the end of an instance of cell type A's fate determination step (one A cell giving rise to an one B cell that will then develop). This change in identity is the cell fate commitment of cell type B.

Another instance of cell type A may further mature and be recommitted at another time to give rise to an instance of a cell type C. So, in this case, a cell type A can give rise to both cell type B and cell type C. The lineage information is not reflected in the biological process ontology, but is rather reflected in the cell ontology.

Figure 1: the steps in the differentiation of the three cell types A, B and C. Cell types B and C are derived from A.

The figure shows that the differentiation of a cell type begins as soon as the process of cell fate specification occurs. In the GO process ontology this would be represented as three separate cell differentiation terms (with appropriate child terms) without any lineage information as follows:

Figure 2: cell differentiation terms and child terms for cell types A, B and C. The background is highlighted in three colours to make it easier to see where the terms for the three different cell types are.

The lineage information would be captured in the cell type ontology as follows ([d] represents the relationship develops_from):

A part_of problem for cell differentiation

There is a potential problem with the use of necessarily is_part in the relationship between the differentiation terms and their parent formation terms. If cell type X cell differentiation occurs as part of the formation of two different types of tissue (e.g. anatomical structure A formation and anatomical structure B formation) then that would not work with the necessarily is_part kind of part_of relationship that is used in GO. With necessarily is_part, X cell differentiation doesn't always have to occur during B formation, but X cell differentiation must only occur as part of B formation.

This structure is incorrect.

The solution: A separate term must be made for the differentiation of the cell type in every different organ in which it is found. The standard composition of these terms can be summarized as:
[anatomical structure] + [cell type] + cell differentiation

A practical example:

History of the Development node

2002: Many of the 'development' and 'morphogenesis' terms were written before we had clearly defined the difference between these two concepts and as a consequence both their positions in the ontology and their definions were basically interchangeable. Many of the other standard terms under the development node were also defined using the names of different terms rather than a clear and correct definition.

2003: The development interest group developed standard definitions and a standard ontology structure for the terms under the development node.

2004: Implementation of the structure began as follows:

• The terms x cell fate commitment, x cell fate specification and x cell fate determination were given their standard definitions.
• x development terms were given their standard definition.
• x morphogenesis terms with definitions that did not include the word 'development' were given their standard definition.
• x cell differentiation terms were given their standard definitions.
• x structural organization generic parent was added for child terms already present.

2005: Terms covering the metamorphosis of fly imaginal discs were all converted to morphogenesis terms, with metamorphosis as synonyms. The top metamorphosis terms were retained for use in describing whole body metamorphosis.

2005-2006: Morphogenesis standard graph and definitions retrofitted.

2006: Maturation standard graph and definitions retrofitted.

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Multi-Organism Process

This term and its children were created in Jan 2005 to describe interactions that occur between organisms of different species, and to subsume the existing terms that described interactions between organisms, e.g. pathogenesis and host-pathogen interaction. These terms were felt to be too 'host-centric', due to their reference to the disease process and their non-systematic placement in the ontologies. Further terms were added after the November 2005 content meeting to flesh out the node further.

Terms and structure

Multi-organism processes are categorized according to the nature of the interaction (behavioral or physiological), and by whether they are inter- or intra-species. Interspecies interactions of an intimate or co-dependent nature fall under the term symbiosis, encompassing mutualism through parasitism, which covers all types of symbiosis between species, including mutualism (where the association is advantageous to one, or usually both, organisms) and parasitism (where the association is advantageous to one organism but detrimental to the other). All new terms that describe interactions between organisms should be placed in the interaction between organisms node under the appropriate parent(s).

The node is structured broadly like this (not all terms shown):

Symbiotic relationships may be between two organisms of similar sizes or of differing sizes, and most of the processes under symbiosis, encompassing mutualism through parasitism have child terms to specify the sizes of the organisms involved. These terms use the nomenclature host for the larger organism and symbiont for the smaller organism. For interactions where there is no clear host or symbiont, the wording other organism is used, and terms are appended with during symbiotic interaction to make it clear that they represent processes occurring during symbiosis.

Some processes may occur as part of symbiosis or outside it; the structure to represent such a process is illustrated below. Note that terms representing non-symbiotic interactions between organisms should use the wording another organism to refer to the second organism.

Standard Definitions

[process involving] other organism during symbiotic interaction

[definition of process], where the two organisms are in a symbiotic relationship.

[process involving] host

[definition of process]. The host is defined as the larger of the organisms involved in a symbiotic interaction.

[process involving] symbiont

[definition of process]. The symbiont is defined as the smaller of the organisms involved in a symbiotic interaction.

Taking the process acquisition of nutrients as an example, the terms and definitions would be as follows:

acquisition of nutrients from other organism during symbiotic interaction

The production of structures and/or molecules in an organism that are required for the acquisition and/or utilization of nutrients obtained from a second organism, where the two organisms are in a symbiotic relationship.

acquisition of nutrients from host

The production of structures and/or molecules in an organism that are required for the acquisition and/or utilization of nutrients obtained from its host. The host is defined as the larger of the organisms involved in a symbiotic interaction.

acquisition of nutrients from symbiont

The production of structures and/or molecules in an organism that are required for the acquisition and/or utilization of nutrients obtained from its symbiont. The symbiont is defined as the smaller of the organisms involved in a symbiotic interaction.

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Metabolism

Terms and structure

The process of metabolism includes both biosynthesis and catabolism. We also distinguish between metabolism that occurs at the level of a multicellular organism (organismal metabolism) and metabolism that occurs at the level of the cell (cellular metabolism). These subclasses also apply to biosynthesis and catabolism.

Metabolic processes can be described as being organismal when they occur in more than one cell type. An example of this is C4 photosynthesis, a type of carbohydrate biosynthesis achieved with the involvement of two cell types, bundle sheath cells and mesophyll cells. Metabolic processes that are restricted to a single cell or cell type are described as cellular metabolism. The vast majority of metabolic processes are cellular, so unless a corresponding organismal metabolism occurs, we do not add "cellular" to the term name.

For example, during digestion, carbohydrate catabolism occurs first in the mouth, by salivary amylase, and then in the stomach. This process would be described as organismal carbohydrate catabolism. However, carbohydrate catabolism also occurs within a single cell, e.g. glycolysis, so we also need a cellular carbohydrate catabolism term:

The general structure of metabolism terms is this:

However, remember that most types of metabolism are children of cellular metabolism (or cellular biosynthesis, cellular catabolism), and do not have the modifier 'cellular'. For example, where substrate A and substrate B metabolism are cellular processes:

Standard Definitions

substrate metabolism

The chemical reactions and pathways involving substrate, [description of substrate].

substrate biosynthesis

The chemical reactions and pathways resulting in the formation of substrate, [description of substrate].

substrate catabolism

The chemical reactions and pathways resulting in the breakdown of substrate, [description of substrate].

substrate fermentation

The enzymatic conversion of substrate to simpler components, resulting in energy in the form of adenosine triphosphate (ATP).

Qualifiers

The following qualifiers can be used with metabolism, biosynthesis and catabolism terms. The examples given use the metabolism term but the standard definitions for biosynthesis and catabolism can be substituted into the definition in its place.

cellular substrate metabolism

The chemical reactions and pathways involving substrate, as carried out by individual cells.

organismal substrate metabolism

The chemical reactions and pathways involving substrate, occurring at the tissue, organ, or organismal level of a multicellular organism.

aerobic substrate metabolism

The chemical reactions and pathways involving substrate in the presence of oxygen.

anaerobic substrate metabolism

The chemical reactions and pathways involving substrate in the absence of oxygen.

X-dependent substrate metabolism

The chemical reactions and pathways involving substrate, requiring the presence of X.

X-independent substrate metabolism

The chemical reactions and pathways involving substrate, independent of X.

More complex metabolism terms to represent specific processes can be constructed by adding one or more of the following suffixes to a term name and altering the definition as appropriate.

substrate A biosynthesis from substrate B

The chemical reactions and pathways resulting in the formation of substrate A from other compounds, including substrate B.

substrate A catabolism to substrate B

The chemical reactions and pathways resulting in the breakdown of substrate A into other compounds, including substrate B.
Can also be used with fermentation terms.

substrate A catabolism via substrate C

The chemical reactions and pathways resulting in the breakdown of substrate A into other compounds, via the intermediate substrate C.
Can also be used with biosynthesis and fermentation terms.

substrate A catabolism, using enzyme

The chemical reactions and pathways resulting in the breakdown of substrate A, catalyzed by enzyme.
Can also be used with biosynthesis and fermentation terms.

substrate A catabolism, X pathway

The chemical reactions and pathways resulting in the breakdown of substrate A, by the X pathway.
Can also be used with biosynthesis and fermentation terms.

substrate A catabolism, X cycle

The chemical reactions and pathways resulting in the breakdown of substrate A in the X cycle.
Can also be used with biosynthesis and fermentation terms.

substrate A catabolism, by biochemical process

The chemical reactions and pathways resulting in the breakdown of substrate A, by biochemical process.
Can also be used with biosynthesis and fermentation terms.

For example:

L-lysine catabolism to glutarate, by acetylation

The chemical reactions and pathways resulting in the breakdown of L-lysine into other compounds, including glutarate, by acetylation.

glucose biosynthesis from tryptophan via maltose and cystathione, using sucrose invertase

The chemical reactions and pathways resulting in the formation of glucose from other compounds, including tryptophan, via the intermediates maltose and cystathione, catalyzed by sucrose invertase.

Different pathways or processes leading to the same product

Where there are several biosynthetic pathways leading to the same product, we list each of them as a subclass of a general pathway. For example, we have:

It is straightforward to name well-known pathways (e.g. glycolysis and the pentose-phosphate pathway are two ways to accomplish glucose catabolism), but harder for nameless minor pathways. Minor pathways should be named by referring to start and end products, and intermediates if further distinguishing is required. For example:

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Regulation

Note that this structure is in the process of being implemented in the process ontology.

The regulates relationship

In GO, a regulates relationship means that the term is a process that modulates its parent process. For example, regulation of transcription regulates transcription. The regulation of a process is not a part of the process itself. For example, regulation of transcription describes the processes that affect the transcriptional machinery to modulate its activity.

Transitivity of regulates

The regulates relationship is transitive over both the is_a and part_of relationships.

is_a transitivity: If process B exists in the GO biological process ontology and it is an is_a child of process A then any process that regulates process B also regulates process A. For example:

Due to is_a transitivity, we can say that any process that regulates bipolar cell growth also regulates cell growth.

part_of transitivity: If process Y exists in the GO biological process ontology and it is a part_of child of process X then any process that regulates process Y also regulates process X.

Terms and structure

Any biological process can be regulated, and that regulation may be further classified as positive or negative. The standard structure for the regulation of a process is:

Regulation terms should also be given parentage under the most specific regulation term in the general regulation hierarchy under regulation of biological process ; GO:0050789.

Regulation can also be applied to functions, such as enzyme reactions and binding to substances. These terms would have is_a parentage under the term regulation of molecular function. There should also be a corresponding term in the molecular function ontology; in the future, inter-ontology links will be made between these terms. For example:

GO also contains regulation terms representing the regulation of a phenotype rather than a process; for example, regulation of cell size ; GO:0008361 and regulation of neuronal synaptic plasticity ; GO:0048168. These terms should have is_a parentage to the regulation of biological quality ; GO:0065008. An example of parentage is shown below:

Note that it would not make sense to have a term of the form 'regulation of protein name', e.g. regulation of actin, because a protein is neither a process nor a function, so there is no indication of what biological activity is being regulated. If terms of this sort are desired, they should be given names that represent the actual biological processes or molecular functions that they regulate.

Positive regulation can be split into three subtypes, the initiation or start up of an inactive process, the maintenance of a process already occurring, and the increase in rate of an existing process. In GO, this distinction is captured by the terms 'activation of process', to represent the start up of a process, 'maintenance of process', and 'upregulation of process', the acceleration of an existing process.

Similarly, negative regulation can be split into the cessation or halting of a process and the decrease in rate, but not stopping, of a process, and the prevention of an inactive process from becoming active. GO represents this using the terms 'downregulation of process', 'termination of process' and 'inhibition of process' respectively.

Standard definitions

regulation of process

Any process that modulates the frequency, rate or extent of process, [definition of process].

regulation of enzyme activity

Any process that modulates the frequency, rate or extent of enzyme activity, the catalysis of the reaction: [reaction].

regulation of function

Any process that modulates the frequency, rate or extent of function, [definition of function].

regulation of phenotype

Any process that modulates phenotype, [description of phenotype].

negative regulation of process

Any process that stops, prevents or reduces the frequency, rate or extent of process, [definition of process].
Can also be used with functions.

positive regulation of process

Any process that activates, maintains or increases the frequency, rate or extent of process, [definition of process].
Can also be used with functions.

activation of process

Any process that starts the inactive process process, [definition of process].
Can also be used with functions.

activation of enzyme activity

Any process that initiates the activity of the inactive enzyme enzyme name.
The initiation of the activity of the inactive enzyme enzyme name by process.

maintenance of process

Any process that maintains the frequency, rate or extent of the active process process, [definition of process].
Can also be used with functions.

maintenance of phenotype

Any process that maintains phenotype, [description of phenotype].

upregulation of process

Any process that increases the frequency, rate or extent of the active process process, [definition of process].
Can also be used with functions.

downregulation of process

Any process that reduces the frequency, rate or extent of, but does not terminate, the active process process, [definition of process].
Can also be used with functions.

inhibition of process

Any process that prevents the activation of the inactive process process, [definition of process].
Can also be used with functions.

termination of process

Any process that stops the active process process, [definition of process].
Can also be used with functions.

inactivation of enzyme activity

Any process that terminates the activity of the active enzyme enzyme name.
The termination of the activity of the active enzyme enzyme name by process.

Standard synonyms

The following synonyms can be added to terms as long as the synonym string makes sense and does not have alternative meanings.

regulation of process

narrow: process regulator

regulation of process

exact: control of process

activation of process

exact: establishment of process

exact: activation of process

exact: induction of process

activation of process by xxx

exact: xxx-induced process

inhibition of process

exact: prevention of process

downregulation of process

exact: suppression of process

termination of process

exact: inactivation of process

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Detection of and Response to Stimulus

Terms and Structure

The response of a cell or an organism to a stimulus is all the processes that occur as a result of the stimulus occurring within or outside the cell or organism. Detection of the stimulus, the process by which a stimulus is received by a cell and converted into a molecular signal, is thus a class of stimulus response. The general structure of this node is as follows:

There may be different types of response to a stimulus, such as cellular or behavioral responses. The structure for these terms would be:

Note that sensory perception is a special class of response to stimulus; please see the documentation on it below. The phrase perception of xxx should only be used in names or definitions of terms relevant to organisms capable of performing neural processing of the signal generated by the stimulus, but xxx sensing is considered by GO to be synonymous with detection of xxx.

Standard Definitions

response to stimulus type stimulus

A change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus type stimulus.

cellular response to stimulus type stimulus

A change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus type stimulus.

behavioral response to stimulus type stimulus

A change in the behavior of an organism as a result of a stimulus type stimulus.

age-dependent response to stimulus type stimulus

A change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus type stimulus, where the change varies according to the age of the cell or organism.

detection of stimulus type stimulus

The series of events in which a chemical stimulus is received and converted into a molecular signal.

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Sensory Perception

Terms and Structure

Sensory perception occurs in organisms capable of performing neurophysiological processing of the stimuli in their environment, and covers the processes commonly called "the senses": hearing, vision, taste, smell and so on. Sensory perception involves detection of the stimulus and subsequent recognition and characterization of it. There are five different stimulus types involved in sensory processing - chemical, mechanical, electrical, light and temperature.

The (known) senses are represented as processes underneath sensory perception. Most are worded sensory perception of stimulus modality, e.g. sensory perception of sound, sensory perception of touch, although some have more common names, such as visual perception or electroception.

A combination of stimuli may be used by some of the senses; for example, sensory perception of pain may come from temperature, mechanical, electrical or chemical stimuli. Similarly, stimuli of a certain type may be perceived by different senses: e.g. both sense of smell and taste use chemical stimuli. The structure is as follows:

This structure is also repeated under the response to stimulus node:

sensory perception of xxx may have the exact synonym perception of xxx.

Standard Definitions

sensory perception

The series of events required for an organism to receive a sensory stimulus, convert it to a molecular signal, and recognize and characterize the signal.

sensory perception of stimulus type stimulus

The series of events required for an organism to receive a stimulus type stimulus, convert it to a molecular signal, and recognize and characterize the signal.

detection of stimulus type stimulus during sensory perception of sensory modality

The series of events during the perception of sensory modality in which a stimulus type stimulus is received and converted to a molecular signal.

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Signaling Pathways

Standard Defs

signaling pathway

The series of molecular signals ...

downstream effect known, initiator unknown

The series of molecular signals that result in ...

events in pathway known, initiator and end targets unknown

The series of molecular signals involving ...

X receptor signaling pathway

The series of molecular signals generated as a consequence of X receptor binding to ...

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Transport and Localization

This area of the ontology covers the processes involved in positioning a substance or cellular entity and maintaining it in that location.

Terms and Structure

The processes that influence the location of a substance or entity in or outside the cell fall under the general term localization. Localization is split into two parts; there is the establishment of localization, which covers transport and/or autonomous movement of substances or cellular components, as well as orienting a protein or organelle. The maintenance of localization covers sequestering and active retrieval processes.

The structure to represent the localization of a substance or entity is shown below.

Standard Definitions

Note that not all localization terms have standard definitions at present; as a guide to term usage, x movement should be used to refer to the change in position of entities that can propel themselves, whilst x transport is intended for substances that are moved by another entity. Storage, retention or sequestration are represented by the term sequestering of x.

x localization

The processes by which x (where x is a substance or cellular entity, such as a protein complex or organelle) is transported to, and/or maintained in, a specific location.

establishment of x localization

The directed movement of x to a specific location.

maintenance of x localization

The processes by which x is maintained in a location and prevented from moving elsewhere.

x secretion

The regulated release of x from a cell or group of cells.

x transport

The directed movement of x into, out of, within or between cells.

x export

The directed movement of x out of a cell or organelle.

x import

The directed movement of x into a cell or organelle.

establishment of x orientation

The processes that set the alignment of x relative to other cellular structures.

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Transporter activity (molecular function)

Terms and Structure

Standard Definitions

Active Transporters

X transmembrane transporter activity

Catalysis of the transfer of X from one side of the membrane to the other. X is [insert description].

X uptake transmembrane transporter activity

Catalysis of the transfer of X from the outside of a cell to the inside of a cell across a membrane. X is [insert description].

X efflux transmembrane transporter activity

Catalysis of the transfer of X from the inside of a cell to the outside of the cell across a membrane. X is [insert description].

active transmembrane X transporter activity

Catalysis of the transfer of X from one side of the membrane to the other, up the solute's concentration gradient. The transporter binds the solute and undergoes a series of conformational changes. Transport works equally well in either direction. X is [insert description].

primary active transmembrane X transporter activity

Catalysis of the transport of X across a membrane, up the solute's concentration gradient, by binding the solute and undergoing a series of conformational changes. Transport works equally well in either direction and is driven by a primary energy source. Primary energy sources known to be coupled to transport are chemical, electrical and solar sources. X is [insert description].

decarboxylation-driven active transmembrane X transporter activity

Enables the transport of X across a membrane, up the solute's concentration gradient, by binding the solute and undergoing a series of conformational changes. Transport works equally well in either direction and is driven by decarboxylation of a cytoplasmic substrate. X is [insert description].

light-driven active transmembrane X transporter activity

Enables the transport of X across a membrane, up the solute's concentration gradient, by binding the solute and undergoing a series of conformational changes. Transport works equally well in either direction and is driven by light. X is [insert description].

methyl transfer-driven active transmembrane X transporter activity

Enables the transport of X across a membrane, up the solute's concentration gradient, by binding the solute and undergoing a series of conformational changes. Transport works equally well in either direction and is driven by a methyl transfer reaction. X is [insert description].

oxidoreduction-driven active transmembrane X transporter activity

Enables the transport of X across a membrane, up the solute's concentration gradient, by binding the solute and undergoing a series of conformational changes. Transport works equally well in either direction and is driven by an exothermic flow of electrons from a reduced substrate to an oxidized substrate. X is [insert description].

P-P-bond-hydrolysis-driven transmembrane X transporter activity

Enables the transport of X across a membrane, up the solute's concentration gradient, by binding the solute and undergoing a series of conformational changes. Transport works equally well in either direction and is driven by the hydrolysis of the diphosphate bond of inorganic pyrophosphate, ATP, or another nucleoside triphosphate. The transport protein may or may not be transiently phosphorylated, but the substrate is not phosphorylated. X is [insert description].

secondary active transmembrane X transporter activity

Catalysis of the transfer of X from one side of the membrane to the other, up the solute's concentration gradient. The transporter binds the solute and undergoes a series of conformational changes. Transport works equally well in either direction and is driven by a chemiosmotic source of energy. Chemiosmotic sources of energy include uniport, symport or antiport. X is [insert description].

X:solute antiporter activity

Catalysis of the transfer of X from one side of the membrane to the other, up the solute's concentration gradient. The transporter binds the solute and undergoes a series of conformational changes. Transport works equally well in either direction and is driven by a antiport mechanism whereby two or more species are transported in opposite directions in a tightly coupled process not directly linked to a form of energy other than chemiosmotic energy. X is [insert description].

X:solute symporter activity

Catalysis of the transfer of X from one side of the membrane to the other, up the solute's concentration gradient. The transporter binds the solute and undergoes a series of conformational changes. Transport works equally well in either direction and is driven by a symport mechanism whereby two or more species are transported together in the same direction in a tightly coupled process not directly linked to a form of energy other than chemiosmotic energy. X is [insert description].

X uniporter activity

Catalysis of the transfer of X from one side of the membrane to the other, up the solute's concentration gradient. The transporter binds the solute and undergoes a series of conformational changes. Transport works equally well in either direction and is driven by a uniport mechanism which is independent of the movement of any other molecular species. X is [insert description].

In secondary active transporter defs include a reaction where possible. For example:

Catalysis of the reaction: sugar(out) + H+(out) = sugar(in) + H+(in). Catalysis of the reaction: solute(out) + H+(out) = solute(in) + H+(in).

Passive Transporters

passive transmembrane X transporter activity

Catalysis of the transfer of X from one side of the membrane to the other, down the solute's concentration gradient. X is [insert description].

X channel activity

Catalysis of facilitated diffusion of X (by an energy-independent process) by passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism.

gated X channel activity

Catalysis of the transmembrane transfer of X by a channel that opens in response to a specific stimulus.

dephosphorylation-gated X channel activity

Catalysis of the transmembrane transfer of X by a channel that opens in response to dephosphorylation of one of its constituent parts.

ion-gated X channel activity

Catalysis of the transmembrane transfer of X by a channel that opens in response to a specific ion stimulus.

ligand-gated X channel activity

Catalysis of the transmembrane transfer of X by a channel that opens when a specific ligand has been bound by the channel complex or one of its constituent parts.

mechanically-gated X channel activity

Catalysis of the transmembrane transfer of X by a channel that opens in response to a mechanical stress.

phosphorylation-gated X channel activity

Catalysis of the transmembrane transfer of X by a channel that opens in response to phosphorylation of one of its constituent parts.

voltage-gated X channel activity

Catalysis of the transmembrane transfer of X by a channel whose open state is dependent on the voltage across the membrane in which it is embedded.

X channel activity

Catalysis of facilitated diffusion of X (by an energy-independent process) involving passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism.

x gated y channel activity

Catalysis of the transmembrane transfer of y by a channel that opens in response to stimulus by x. Transport by a channel involves catalysis of facilitated diffusion of a solute (by an energy-independent process) involving passage through a transmembrane aqueous pore or channel, without evidence for a carrier-mediated mechanism.

Other standard definitions

L-amino acid

L-Y is the levorotatory isomer of [insert systematic name].

D-amino acid

D-Y is the dextrorotatory isomer of [insert systematic name].

constituitive activity

This activity is constituitive and therfore always present, regardless of demand.

inducible activity

This activity is inducible and therfore only present when there is demand.

high affinity:

In high affinity transport the transporter is able to bind the solute even if it is only present at very low concentrations.

low affinity

In low affinity transport the transporter is able to bind the solute only if it is present at very high concentrations.

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Other Miscellaneous Standard Defs

membrane fusion

The joining of the lipid bilayer membrane around X to the lipid bilayer membrane around Y.

cellular component organization and biogenesis

A process that is carried out at the cellular level which results in the formation, arrangement of constituent parts, or disassembly of cellular component.

macromolecular complex assembly

The the aggregation, arrangement and bonding together of a set of components to form a complex.

xxx distribution

The processes that establish the spatial arrangement of xxx.

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