Binding Terms minutes June 09
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Peter, Ben, Jim, Pascale, Judy, Susan, Ranjana, Ruth, Donghui, Petra, Harold, Alex, Rachael, Yasmin, David (til 10:30), Lakshmi, Mary, Kara, Jane, Midori, Chris, Val, Jen
Comments from Judy circulated prior to meeting
Here are some ‘go-top’ type thoughts on this, but this also incorporates the GO@MGI specific thoughts as well. I look forward to a considerate discussion.
1. support everyone who have sought to clarify the binding discussion; update documentation,
2. recognize that the binding discussion is confounded by complexity of assays and kinetics of ‘binding’ studies,
3. commit to ‘annotating to the experiment’ meaning trying to capture the specifics as much as feasible; use the binding term if the experiment shows binding, don’t use if experiment shows catalysis but not specific binding the gene product,
4. reaffirm our commitment to provide practical and useful data to enhance the work of biologists,
5. remember that ‘consistency’ is a principle, not a rule; there will be exceptions: here what is needed is a statement of standard, such as provided in ‘3’. The goal is to have ‘correct’ annotations, not that everyone should have the same annotation,
6. consider that if existing annotations (~8,000?) involving binding terms are not wrong, then we should strongly consider keeping them,
7. and, confirm that any global change will need approval by GO-top
Please feel free to add/edit these minutes as appropriate
Peter: a catalyst or transporter has to bind its substrate
Jim: if not much is known about a protein then it is good to be able to annotate to binding
Petra: For a ras exchange factor it is useful to be able to specify the specific ras protein substrate rather than create gene specific exchange factor terms.
Ben: agrees that substrate binding should be used if there is no known function.
==== EDIT:=== I agree that THIS use of substrate binding is "less worse", I do NOT agree that this is a good annotation, merely that it points out a flaw in GO that we cannot annotate a "partial understanding" of molecular function. - Ben
Peter: there is an option that the ontology could be modified so that a catalyst 'has_part' to a binding term.
Jim: During the study of thymidine biosynthesis in yeast the enzymes involved were identified due to their binding of thymidine before any catalytic activity was shown. There are likely to be many more 'binding' experiments like this, for example in chemical screening, where the binding is confirmed but the gene function is unknown.
Peter: need to consider costs involved in continuing the practice of annotating to binding terms.
Jim: this cost is unknown.
Ruth: the use of column 16 to specify specific binding targets would enable general GO terms to include more specific information about the catalytic activity of the protein. eg there are many proteins with serine-type endopeptidase activity, but only a few have proprotein convertase activity, or are coagulation factors.
Debbie: is clutter in ontology a problem?
Judy: Clutter is not a problem, we have to decide how to proceed without the concerns about finances and then decide if our proposal is financially viable, if need be.
Ranjana:are we going to create very specific substrate terms?
Alex: annotation should be to the level curator is comfortable with.
Harold: annotation describes normal function, shouldn't annotate to synthetic substrates but to the target implied by the use of the synthetic substrate.
Jim: In E.coli vast numbers of normal metabolites are being identified which are very specific targets of proteins. However, don't want to create gene specific terms.
Susan: there are some GO terms still in the ontology which are gene specific, such as bicoid localization, which do need to be removed.
General: agreement that working group should take discussion further in line with this discussion and overall recommendations by Judy (see top of page).
Action Items for working group
- Draft guidelines for use of 'binding terms' during annotation.
- Provide examples of proper use of 'binding' terms.
- Ensure that finalized document is included in the annotation document.
- Provide a report on this discussion for the GOC meeting in September.