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Hi everyone! I have a question about protein binding curation using Noctua.
What we want to curate is that protein A binds to protein B. There is no evidence of these proteins function together as a complex. Can we (should we) curate this using Noctua? If so how? Should we say "protein A - protein binding" with proteinB in the "with" field? (consistent with conventional annoations?) or should we say "protein A-protein binding-has input proteinB"? Or create a macromolecular complex with both protein (and link it to nothing since we don't know the function of the complex)
If this is a larger discussion, we can talk about it at one of our call.
Thanks!
What we want to curate is that protein A binds to protein B. There is no evidence of these proteins function together as a complex. Can we (should we) curate this using Noctua? If so how? Should we say "protein A - protein binding" with proteinB in the "with" field? (consistent with conventional annoations?) or should we say "protein A-protein binding-has input proteinB"? Or create a macromolecular complex with both protein (and link it to nothing since we don't know the function of the complex)
If this is a larger discussion, we can talk about it at one of our call.
Thanks!
Hi @sabrinatoro what do you think of modeling it like this ?
@goodb - I do think a broader discussion of how 'protein binding' annotations fit into GO-CAM models is warranted. One issue I'd like to sort out is: when is protein binding really the main MF of a gene product vs when is protein binding just supportive evidence for a direct regulatory relationship between two activities? If only the latter, could the binding be used as evidence for the relation, but then could we still get the conventional binding annotations back out in the GPAD?
Hi @vanaukenk agree that this ought to be nailed down. Perhaps a subject of your annotation call to resolve the question? My take based on how we are approaching the reactome information and my understanding of the go-cam model would be (1) to model the case @sabrinatoro brought up as I proposed because there is no evidence of signaling or that the “function” of either protein is really to bind. Its just a starting point for building up a more complete model (and/or its a pattern for the GO to record PPIs which aren’t really “functional” but are useful information). If we need to make tabular output to link these proteins to “protein binding” then I think that is a rule we can add to the exporter. As I understand things, we should only be using ‘enables’ when linking a gene product to what is understood as its purposeful function. (2) After spending a few hours in the room with Paul, I don’t think the function of many proteins is “to bind”. That is just something they do along the way to achieving their actual purpose. So i’d suggest focusing on the structuring of the regulatory relationships as the main priority. In that case, IMO I don’t like mixing up the biological model with the evidence model. Would rather not use binding as evidence unless that was explicity pulled out of the go-cam and into ECO. Probably easier if we had a white board or shared some screentime.
I am having some difficulties creating a model for the following statement.
"caspy2 binds directly to lipopolysaccharide, resulting in caspy2 oligomerization, which is critical for pyroptosis" (PMID:30076291)
I started a GOCAM model, but I am not sure it is correct: gomodel:5c4605cc00004193
Could someone review this model, please?
Also, I can imagine this might require more discussions,... maybe at one of the GOCAM calls?
Thank you!
"caspy2 binds directly to lipopolysaccharide, resulting in caspy2 oligomerization, which is critical for pyroptosis" (PMID:30076291)
I started a GOCAM model, but I am not sure it is correct: gomodel:5c4605cc00004193
Could someone review this model, please?
Also, I can imagine this might require more discussions,... maybe at one of the GOCAM calls?
Thank you!
Another question about binding and modeling protein interactions. Gene is asah1b Drer (ZFIN:ZDB-GENE-040426-1512)
"The difference between masses on size-exclusion chromatography, SDS-PAGE suggested that zebrafish AC exists as a homodimer of heterodimer (α+β) having two α-subunit and two β-subunits. Our findings resemble previous findings of the human AC as homotrimers of heterodimer in urine"
The homodimers form from the same polypeptide " Majority of the purifiedenzyme was obtained in the unprocessed form; however, small amounts of α-and β-subunits were also obtained".
Right now I just say protein herodimerization in my model since they showed that 2 ways. I'm not sure how much detail is helpful for users.
"The difference between masses on size-exclusion chromatography, SDS-PAGE suggested that zebrafish AC exists as a homodimer of heterodimer (α+β) having two α-subunit and two β-subunits. Our findings resemble previous findings of the human AC as homotrimers of heterodimer in urine"
The homodimers form from the same polypeptide " Majority of the purifiedenzyme was obtained in the unprocessed form; however, small amounts of α-and β-subunits were also obtained".
Right now I just say protein herodimerization in my model since they showed that 2 ways. I'm not sure how much detail is helpful for users.
I looked here (http://geneontology.org/docs/go-annotation-file-gaf-format-2.1/#annotation-extension-column-16) but it doesn’t really have a precise grammar
@balhoff Yes, it is possible to have both commas and pipes in the annotation extensions. The pipes are meant to signify independent extensions, while the commas indicate extensions that, together, provide context for the GO term. I'll double-check our GPX2.0 specs to make sure we're clear on this, but let me know if you want any clarification.
@vanaukenk I need to parse these in a tool so I’m trying to make sure I know exactly what can be there. If both are used in one extension, do commas take precedence over pipes? Is it possible to group using parentheses? I thought I had seen a more explicit grammar doc at one point but I can’t find it since the website overhaul. This page (http://geneontology.org/docs/go-annotation-file-gaf-format-2.1/) isn’t explicit enough.
At the bottom of the gpad table is the current explanation of annotation extensions format, but we can make this clearer, if needed: https://github.com/geneontology/go-annotation/blob/master/specs/gpad-gpi-2-0.md
Annotation_Extensions ::= [Extension_Conj] ('|' Extension_Conj)*
I think that’s what the spec is saying
@pfey03 With my interaction head on, if the expt shows physical binding it's IPI... and you need the partner in the WITH field for those who parse the data out. Identical protein binding is very common, hence why I keep saying we need to capture homomeric complexes :) It would be different if it was self-interaction of the same molecule, then you can't have a GP in WITH but I don't know if GO captures that. It would require an exception rule. We do :) (and we may export this data to GO...)
@pfey03 We are recommending that 'identical protein binding' be annotated with IPI and the ID of the same annotated entity be included in the With field for exactly the reasons Birgit states. We need to be consistent in how we capture physical interactions as much as possible, even if the binding is to the same protein. I know in some cases we have said that when we can't assign a specific ID to an interactor, e.g. actin, it is okay to annotate to a term like 'actin binding' using IDA, but I think it'd be good to enumerate these specific cases so there is no confusion about why we think these IDA annotations are okay.
We have a discussion here in the office : in 21844191, Fig 7 shows that reelin binding its receptor (binding shown in F6) indirectly activates Dab1 phosphorylation (which is much much weaker if reelin is mutated). I annotated it to GO:0038026 reelin-mediated signaling pathway as IDA (maybe it should be IMP - different discussion!) but Livia questions if we can say this is a direct evidence for reelin's involvement in the pathway. Discuss!
http://www.jbc.org/content/286/40/35247.long
http://www.jbc.org/content/286/40/35247.long
I am creating a model which requires a lot of adding individuals and making relationship. Every time I add an individual or creating a new relationship, the view of the whole model changes, and everything is sent WAY far right to the right, making it extremely difficult (and frustrating).
Is there any way around this? Is there a way to stop the "boxes" to change location everytime I do something? Thanks!
Is there any way around this? Is there a way to stop the "boxes" to change location everytime I do something? Thanks!
@sabrinatoro This is an outstanding issue that we still need to get to: geneontology/noctua#173
In the meantime, there are workbenches that can help rally and control the node layout ("Cytoscape layout tool"). Of things should more-or-less fit on the screen, you can also use "Compact layout" under "Tools".
In the meantime, there are workbenches that can help rally and control the node layout ("Cytoscape layout tool"). Of things should more-or-less fit on the screen, you can also use "Compact layout" under "Tools".
Hello! In GORULE:0000015, we check that when a GAF has two taxon IDs, that they are formed correctly. I had a couple questions to clarify what the intention is. Here's the link to the rule: https://github.com/geneontology/go-site/blob/master/metadata/rules/gorule-0000015.md
Is this rule saying that 1) the first taxon should be attached to the gp, and 2) the second should be the interacting species (is that just what it means, or is there a way to verify this?) 3) the 2 allowed terms that can be used with dual taxons ('GO:0044419 : interspecies interaction between organisms', and 'GO:0044215 : other organism'), is that to mean only those terms are allowed? Or are children terms also allowed?
@dougli1sqrd - As I understand the rule, the first of the pipe-separated taxon IDs should correspond to the taxon of the annotated gp, and the second taxon to that of the other species involved in the process. Children of the two GO terms listed in the description are also allowed for annotation. The statement about ancestor is the relevant part for this: "These annotations should be used only in conjunction with terms that have the biological process term 'GO:0044419 : interspecies interaction between organisms' or the cellular component term 'GO:0044215 : other organism' as an ancestor." Let me know if you want to touch base to discuss further. Thx.
