Talk:2010 GO camp binding documentation issues

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Siegele 00:30, 1 July 2010 (UTC)

As many terms in the Molecular Function ontology implicitly or explicitly imply the binding of a chemical or protein, it is unnecessary to co-annotate a gene product to a term from the binding node of GO to describe the binding of substrates or products that are already adequately captured in the definition of the Molecular Function term. For instance, an enzyme MUST bind all of the substrates and products of the reaction it catalyzes. Similarly, a transporter MUST bind the molecules it transports. Therefore, as binding is implied, curators should avoid making redundant annotations.

There will be some cases, however, where it is appropriate to annotate a binding relationship. For example, published experiments may show that a gene product binds a non-hydrolyzable ATP analog, without demonstrating that it has ATPase activity. In such a case, it would be appropriate to annotate to GO:0005524 ATP binding using an IDA evidence code.

The GO is committed to ‘annotating to the experiment’. Therefore the curator should try to capture the specifics as much as feasible: use the binding term if the experiment shows binding, but not catalysis/transport; don’t use the binding term if the experiment does show catalysis/transport.

The curator may come across Molecular Function terms where the definition doesn't adequately describe the specific substrate/target being bound, and where the request of a more specific Molecular Function would be considered inappropriate. In such cases, the identity of the substrate/target being bound can be captured in the [‘with’ column (8) or] annotation extension column (16) using identifiers from other ontologies or databases. Small molecule substrate/targets should be identified with accessions from ChEBI, and protein substrate/targets can be identified with accessions from UniProtKB (others?). Substrate/target information should be entered in [column 8 or] column 16 in the form CheBI:xxxx or UniProtKB:xxxxx. Multiple entries should be separated by pipes (add example). Keep in bind that [column 8 or] the annotation extension column (16) should be used only for direct interactions and only when the binding relationship is not already included in the GO term and/or definition.

Annotations to protein binding terms should be maximally informative. Child terms that describe a particular class of protein binding (e.g. GO:0030971 ‘receptor tyrosine kinase binding’) should be used in preference to the parent term 'protein binding'; GO:0005515. Where possible the precise identity of the interacting protein should be captured in [the ‘with’ field or] the annotation extension column (16) of an annotation. The IPI evidence code should be used for annotation of ‘’’all’’’ protein-protein interactions rather than IDA.

Future ontology development efforts should be relied upon to improve the searching capability of any user who is specifically interested in gene products carrying out a certain type of substrate/product binding. Ongoing relevant ontology development of 'has_part' relationships will provide links to implied substrate binding (Chris and Jane are developing 'has_part' relationships to implying substrate binding). [something missing here] existing GO to follow this new format eg Transcription factor activity has_part DNA binding. Curators can request new 'has_part' relationships (and terms) if these do not exist.


  • Not sure where the following statement belongs:

Curators should use their judgment to decide whether the interaction is physiologically relevant and capture information relevant to the in vivo situation, not artificial substrates.

  • Not sure whether I captured what was meant by the following statement:

The annotation extension (column 16) should only be used for direct (target of catalytic activity (using relationship ontology).

Usage of the With/From Column for IPI

We strongly recommend making an entry in the with/from column when using this evidence code to include an identifier for the other protein or other macromolecule or other chemical involved in the interaction. When multiple entries are placed in the with/from field, they are separated by pipes. Consider using IDA when no identifier can be entered in the with/from column.

Ruth edits 1 July 2010

changes highlighted in red

As many terms in the Molecular Function ontology implicitly or explicitly imply the binding of a chemical or protein, it is unnecessary to co-annotate a gene product to a term from the binding node of GO to describe the binding of substrates or products that are already adequately captured in the definition of the Molecular Function term. For instance, an enzyme MUST bind all of the substrates and products of the reaction it catalyzes. Similarly, a transporter MUST bind the molecules it transports. Therefore, as binding is implied, curators should avoid making redundant annotations.

There will be some cases, however, where it is appropriate to annotate a binding relationship. For example, published experiments may show that a gene product binds a non-hydrolyzable ATP analog, without demonstrating that it has ATPase activity. In such a case, it would be appropriate to annotate to GO:0005524 ATP binding using an IDA evidence code.

The GO is committed to ‘annotating to the experiment’. Therefore the curator should try to capture the specifics as much as feasible: use the binding term if the experiment shows binding, but not catalysis/transport; don’t use the binding term if the experiment does show catalysis/transport. (added this orphan sentence:)Curators should use their judgment to decide whether the interaction is physiologically relevant and capture information relevant to the in vivo situation, not artificial substrates.

The curator may come across Molecular Function terms where the definition doesn't adequately describe the specific substrate/target being bound, and where the request of a more specific Molecular Function would be considered inappropriate. In such cases, the identity of the substrate/target being bound can be captured in the ‘with’ column (8) or annotation extension column (16) using identifiers from other ontologies or databases. Small molecule substrate/targets should be identified with accessions from ChEBI, and protein substrate/targets can be identified with accessions from UniProtKB (others?). (deleted sentence) Multiple entries should be separated by pipes (add example). (deleted keep in mind) The 'with column (8) or the annotation extension column (16) should be used only for direct interactions and only when the binding relationship is not already included in the GO term and/or definition. See column16 documentation for relationship types to use when adding IDs in the annotation extension column (16).

Annotations to protein binding terms should be maximally informative. Child terms that describe a particular class of protein binding (e.g. GO:0030971 receptor tyrosine kinase binding) should be used in preference to the parent term GO:0005515 protein binding. Where possible the precise identity of the interacting protein should be captured in the ‘with’ column (8) or the annotation extension column (16) of an annotation. The IPI evidence code should be used in preference to IDA for annotation of all protein-protein interactions.

Future ontology development efforts should be relied upon to improve the searching capability of any user who is specifically interested in gene products carrying out a certain type of substrate/product binding. Ongoing relevant ontology development of 'has_part' relationships will provide links to implied substrate binding (Chris and Jane are developing 'has_part' relationships to implying substrate binding). The existing GO will follow this new format e.g. Transcription factor activity will have a 'has_part' relationship to DNA binding rather than an 'is_a' relationship. Curators can request new 'has_part' relationships (and terms) if these do not exist.

Other comments

Pascale: "The GO is committed to ‘annotating to the experiment’." I just worry that this misleads curators into doing 'text mining' rather than interpreting experiments.

One example that comes to mind (which is unrelated to protein binding) is the mouse gene Hnf1a (MGI:98504), a homeobox protein annotated to 'insulin secretion' based on the observation that a mouse lacking that gene has impaired insulin secretion following certain stimulation (PMID: 9733737). In this case, I agree that the experiment was annotated; however the authors seems to suggest a role in beta-cell glycolytic signaling rather than in insulin secretion. I am not sure what would be an experiment that directly tests signaling.

Serenella: it is worthwhile to be more precise: For instance, a catalytic subunit of an enzyme MUST bind all of the substrates and products of the reaction it catalyzes. instead of For instance, an enzyme MUST bind all of the substrates and products of the reaction it catalyzes.?

Ruth: this may be particularly relevant when annotating transporters, which is an issue Emily raised previously.

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