Talk:2010 GO camp binding documentation issues

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Debby 12 Jul 2010 edits after today's binding call

Please feel free to edit what I've written and add anything that I overlooked.

Proposed Guidelines for GOC website

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, a protein with enzymatic activity MUST bind all of the substrates and products of the reaction it catalyzes. Similarly, a protein with transporter activity MUST bind the molecules it transports. The curator should try to capture the specifics as much as feasible and avoid redundant annotations. Annotate to a binding term whenever an experiment shows binding, but not catalysis/transport ; there is no need to annotate to a binding term if the experiment shows catalysis/transport. Curators should use their judgment to decide whether the interaction is physiologically relevant and capture information relevant to the in vivo situation.

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. The IPI evidence code should be used where possible for annotation of all protein-protein interactions and the precise identity of the interacting protein should be captured in the ‘with’ column (8). At present a variety of identifiers can be used in the ‘with’ column (8) or the annotation extension column (16), see GO Annotation File Format 2.0 Guide.

When a gene product is being annotated to a binding activity term, the 'with' column (8) and/or the annotation extension column (16) can be used to capture additional information about the identify of the binding partner of the gene product being annotated. To understand when to use column 8, column 16, or both, it is important to remember that entries in column 8 modify the evidence used to infer the function, while entries in column 16 modify the GO term used in the GO_ID column (5). The curator also needs to remember that the 'with' column (8) can be used with only a subset of evidence codes: IPI, IC, IEA, IGI, IMP or ISS; column 8 cannot be used with an IDA evidence code, see evidence code documentation.

Examples of using the 'with' column (8)

The annotation of Protein A to a GO binding term with evidence code IPI and Protein B in the 'with' column (8) makes the statement that Protein A has the binding activity defined by the GO term and this function was inferred from interaction with Protein B; binding to Protein B isn't necessarily the in vivo function of Protein A.

  • 1) Column 8 can be used to make annotations based on experiments where the evidence for the function of Protein A binding Protein B in species X is based on binding of protein B from species Y. For example, Human p300 was shown to bind specifically to Drosophila histone H3. This would be annotated as GO:0042393:histone binding using an IPI evidence code and putting an accession for Drosophila histone H3, UniProtKB:P02299, in the 'with' column (8). This annotation makes the statement that human p300 has the molecular function of histone binding inferred from experiments using Drosophila histone H3.
  • 2) Column 8 can be used to indicate that the evidence for binding a small molecule is based on an experiment using an analog. The annotation Protein A GO:0005524:ATP binding IPI column 8 ATP-gamma-S captures the information that ATP binding activity was inferred from binding of a non-hydrolyzable ATP analog.

Examples of using the annotation extension column (16)

The annotation of Protein A to a GO binding term with Protein B and the relationship has_participant/has_input/has_output in the annotation extension column (16) makes the statement that an in vivo molecular function of Protein A is binding to Protein B. This is equivalent to the post-compositional creation of a new child term.

  • 3) If the experiments described in example 1 above, had shown that p300 binds to human H3.1 protein, the annotation GO:0042393:histone binding with the accession for human H3, UniProtKB:P68431, in column 16 (along with a has_participant/has_input/has_output relationship) makes the statement that p300 has the molecular function of binding histone H3.1, essentially post-composing a GO term for binding to histone H3.1. In this example, since an IPI evidence code requires an entry in the 'with' column, the accession UniProtKB:P68431 would also be entered in column 8.
  • 4): The human ABCG1 protein has been annotated to GO:0034041 sterol-transporting ATPase activity with an IDA evidence code. The experiments in the paper, demonstrate that the target is 7β-hydroxycholesterol; this information can be added to the annotation by including the ChEBI ID for 7β-hydroxycholesterol, CHEBI:42989, in the annotation extension column (16): post-composing the GO term 7β-hydroxycholesterol binding.

The 'with' column (8) and 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).

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 (the GOC 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 should request new 'has_part' relationships (and terms) if these do not exist.

Quality control checks

[Ruth] ideally there will be a GOC webpage of all QCs, and therefore this information will not appear in the 'binding' guidelines.

1. No use of the 'NOT' qualifier with 'protein binding'; GO:0005515. This rule only applies to GO:0005515, children of this term can be qualified with NOT, as further information on the type of binding is then supplied in the GO Term e.g. NOT + 'GO:0051529 NFAT4 protein binding', would be fine, as the negative binding statement only applies to the NFAT4 protein.

2. Annotations to 'protein binding'; GO:0005515, should only be supplied with an evidence code where the interactor can be identified in the 'with' field. This rule only applies to GO:0005515, is not such a problem with child terms of protein binding where the type of protein is identified in the GO term name.

3. Reciprocal annotations for protein binding should be made This rule applies to GO:0005515 and it's descendants when the IPI evidence code is used

4. Annotations to 'protein binding' should not use the ISS evidence code This rule only applies to GO:0005515, is not such a problem with child terms of protein binding where the type of protein is identified in the GO term name.