GO should not allow gene product names inside GO terms. It is still useful, however, to be able to annotate to this level of granularity; for instance to able to state that a gene product IL18_HUMAN is involved in 'interleukin-13 biosynthesis'. Cross products between orthogonal concepts are currently hard to maintain using available tools.
Some GO terms could have 'slots', which would be filled in the gene_associations file. For instance, 'biosynthesis' would have a 'slot' named 'synthesizes'. In this case the GO term 'interleukin-13 biosynthesis' would not exist. Instead, the annotation for IL18_HUMAN would include an entry to GO term 'cytokine biosynthesis ; GO:0042089' or just plain 'biosynthesis ; GO:0009058'; this entry/line would also have a column for 'slot', which would read "synthesises(interleukin-13)". Interleukin-13 could be replaced with an identifier from a product/family/physical-entity ontology.
Enzymes in the molecular function ontology carry a cross-reference to an EC number from the enzyme nomenclature database http://www.Chem.Qmw.Ac.Uk/iubmb/enzyme/ This allows automated cross-referencing by other databases and in the past was used for automatic transfer of definitions from the enzyme nomenclature database to the gene ontology. The EC numbers are not entered into the cellular component ontology.
Incomplete EC numbers:
The EC numbers all follow the pattern EC n.N.N.N, for example EC 18.104.22.168
In some cases the function of an enzyme has not been completely characterized and so the EC number will also be incomplete and would take the format EC n.N.-.-. Incomplete EC entries have all been removed from the molecular function ontology, but they have been retained in the EC to GO flatfile. In the future we will work through these numbers to distinguish between the EC numbers corresponding to uncharacterized enzymes and those that simply correspond to enzymes whose functions require less than four digits for a full definition.
Some similar enzymes are found to act at different pHs. In this case a separate entry will be made only if the two enzymes carry different EC numbers.
Coupled and uncoupled enzymatic reactions: ATPase
EC 3.6.3.N. And EC 3.6.4.N all correspond to ATPases. EC 22.214.171.124 Is the number for the enzyme that can hydrolyse ATP without being coupled to any other reaction, whilst all other ATPases have another reaction coupled to their activity, as in the case of EC 126.96.36.199, Which is the Ca2+-transporting ATPase. For the purposes of GO, the enzymes are categoriesed according to whether they perform coupled and uncoupled reactions.
These two concepts are very different because one is derived from a type of experimental data (cellular fractionation by centrifugation) and the other corresponds to a cellular component (the membrane):
1) Membrane term GO:0016020: Double layer of lipid molecules that encloses all cells, and, in eukaryotes, many organelles; may be a single or double lipid bilayer, also includes associated proteins.
2) Membrane fraction term GO:0005624: That fraction of cells, prepared by disruptive biochemical methods, that includes the plasma and other membranes.
The experiments that give rise to membrane fraction data involve the complete disruption of cellular structure followed by the mixing of cellular components and their division into soluble and insoluble fractions by centrifugation. There are various other fraction term names to encompass data from similar kinds of experiment which distinguish between substances with different solubilities. It is clear, that the xxx fraction term is not synonymous with a part of child of xxx.
The experiments that give rise to xxx fraction data involve the complete disruption of cellular structure followed by the mixing of cellular components and their division into soluble and insoluble fractions by centrifugation. Therefore, whilst we can derive information about the solubility of components from the result, we cannot draw any conclusions about their original cellular location. For this reason, the xxx fraction term is retained only as a repository for experimental data, and no interpretation of the data is carried over to the children of the xxx term.
Where more than one expression can be used to refer to the same concept, a single term will be created and the other names will be entered as synonyms. This may also include expressions that are in common usage, and that are likely to be used by scientists searching for the particular term that pertains to their work. It may also include concepts that are a more general or more specific version of an existing term. In this case it is likely that the synonym will eventually be added as a term in it's own right, and that the addition of the synonym is simply a temporary measure. In order to distinguish these different types of synonyms, a set of symbols was created to show the different relationships of synonyms to their respective terms:
Synonym types = the term is an exact synonym ~ the terms are related (eg. XXX complex and XXX) < the synonym is broader than the term name > the synonym is more precise than the term name != the term is not the same as the synonym (no precise relationship assigned)
For more information about synonyms and their documentation and use please read the Guide to Synonyms.
Sensu MagnoliophytaA problem was discovered with the sensu Magnoliophyta terms. Many of these temrs seem misleading because they actually refer to phenonmena that also occur more broadly outside Magnoliophyta. However it was pointed out that that 'sensu Magnoliophyta' just means 'in the sense of Magnoliophyta' and so does not exclude annotation of non-flowering plant gene products to such a term.
To get rid of the Magnoliophyta term and add a sensu term covering all groups that could actually by annotated to a term would be quite time consuming because we would have to check in the case of each term, whether it applied to all plants and whether all green algae were included etc.
At the moment there are no non-flowering plant species being annotated and so there is not an urgent need for terms to be created for the annotation of non-flowering plants.
With these points in mind it was decided that we should concentrate on making the flowering plant terms exhaustive and stick to sensu Magnoliophyta and then we can do the rest once we have non-flowering plants being annotated.
This illustrates some of the forces governing the level of granularity of the GO. For plant annotation, it is currently appropriate to make terms to this level of granularity, but this will change in the future when other plant species are being annotated to the GO. Therefore, the granularity of the GO may be assumed to be constantly changing in response to the various forces at work.
Sensu termsVery often, similar processes operate in markedly different ways between organisms. The sensu terms were created to address this problem.
An example of the use of 'sensu':
In addition, the creation of sensu terms was restricted to those with class-level distinctions. For instance, mouse will represent the class Mammalia; Drosophila will represent the class Insecta.
In spite of the creation of these rules to minimise the number of sensu terms, the word 'sensu' has found it's place as one of the most frequently used words in the ontologies, alongside 'of' and 'and'.
BehaviourShould GO include behavior terms or are there too few that are proven to be directly affected by gene activity? Peter Midford in Arizona, already is working on behaviour ontologies for loggerhead turtles, jumping spiders and we feel this level of detail seems to be beyond the scope of GO. However, there still needs to be some descriptive capability for behaviour within GO, both for Drosophila and maybe for mouse, to be able to annotate certain genes since both species have genes known to directly affect behavior. The essential questions relate to what should be included in Process. It is clear in Drosophila that one can pin certain genes to behaviours like walking or circadian rhythms because these are hard-wired. Conversely, there is need for an auxiliary ontology developed specifically to deal with behaviors in mouse since much knowledge in this area is not tied directly to specific gene activity
Conclusion - we do want behaviour in GO, but there may be other ontologies, for groups like mouse, that will extend these. In these cases we'll recommend that these auxiliary ontologies be consistent with GO and include any necessary cross-references to GO terms. To support this the GO terms should be at a level that can be used for many organisms for behaviours that have a genetically defined component.
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