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cerivs
@cerivs
Hi, I'm looking for a term to use for cellular response to RNA repeats. Transcription of genes that have over a certain number of repeats causes RNA metabolic processes to occur, often called "repeat RNA toxicity"". I'm looking at a paper that characterizes the genetic responses to a specific RNA repeat 35+ poly[GGGGCC] and can't find a GO term. @vanaukenk and @ValWood do you know where in the tree I should start looking?
Any process involved in sustaining the fidelity and copy number of rDNA repeats. PMID:14528010
I think this is probably the process you need. I would avaid "cellular response to..." as these are largely describing phenotypes and probably shouldn't be in GO...
"maintenance of rDNA"
@suzialeksander @suzialeksander
@suzialeksander We have used "has_regulation_target" for the regulatory input on process annotations when can't be sure that the input is 'direct'
Val Wood
@ValWood
Sorry everyone. I can't figure out how to reply to specific messages.
cerivs
@cerivs
This is a gene that binds transcripts that have expanded repeat sequences and then interacts with other proteins that do something, probably take the bound transcripts & target for destruction
suzialeksander
@suzialeksander
Ah no I think responding to everyone is great, lets everyone see what is decided! thanks
cerivs
@cerivs
So this protein is acting on mRNA not rDNA or rRNA. It is a normal process in response to repeat expansion in a single protein coding gene.
@ValWood
suzialeksander
@suzialeksander
Is there a “has_regulation_target” equivalent that’s available in Noctua?
cerivs
@cerivs
I can use "is acted upon" for MF for interactions between the 2 proteins. but I can't find an appropriate term for the specific RNA binding function of protein 1, nor can I find the appropriate BP term for the process so I figured others might have good suggestions since I don't annotate in this branch very often. I appreciate all the suggestions @ValWood @suzialeksander Right now I'm looking at single stranded RNA binding for the MF but that leaves out the RNA repeats part of the equation. I could request a new ChEBI term to use or maybe make a NTR for GO
cerivs
@cerivs
I found RNA surveillance which is probably ok
suzialeksander
@suzialeksander
@cerivs there are also terms around GO:1903231
mRNA binding involved in posttranscriptional gene silencing, that may be somewhere to look
Val Wood
@ValWood
RNA surveillance or a descendant sounds corrct.
@cerivs which paper is it, I'm curious..
@suzialeksander has_regulation_target might be our user facing term name... I'll check what the official name is
Val Wood
@ValWood
OK has_regulation_target is the official name.
cerivs
@cerivs
@ValWood PMID:29302778 A zebrafish model for C9orf72 ALS reveals RNA toxicity as a pathogenic mechanism
Petra Fey
@pfey03
hello glitterers
suzialeksander
@suzialeksander
Hi @pfey03!
Stacia Engel
@srengel
Petra!
sabrinatoro
@sabrinatoro
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!
goodb
@goodb
Screen Shot 2019-04-22 at 1.56.24 PM.png
Hi @sabrinatoro what do you think of modeling it like this ?
sabrinatoro
@sabrinatoro
@goodb That works for me.
@vanaukenk @ukemi : is this is the official convention?
vanaukenk
@vanaukenk
@sabrinatoro - afaik, we are still modeling this using the enabled_by relation for the MF. In that case, I would make two separate protein binding annotations with each protein as the enabler and the interacting protein as the has_input.
goodb
@goodb
@vanaukenk is there documentation on this on the wiki somewhere ?
vanaukenk
@vanaukenk
@goodb - specifically for the protein binding MF annotations, no.
goodb
@goodb
@vanaukenk seems a little wonky to use enables on this to me. Out of curiosity is that choice made because it results in gpad output? the has_input structure above won’t produce any gpad as things stand.
vanaukenk
@vanaukenk
@goodb - yes, that is currently the only way we'll get the expected GPAD output, although that's not to say we can't re-visit the rules for this.
sabrinatoro
@sabrinatoro
@vanaukenk Thank you!
vanaukenk
@vanaukenk
@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?
goodb
@goodb
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.
Petra Fey
@pfey03
Interesting discussion and thought about that a while back. Sometimes we do not have any other function (yet) but the binding. And when you say binding as evidence, can we still add the protein binding partner? Good to discuss in annotation call(s).
sabrinatoro
@sabrinatoro
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!
vanaukenk
@vanaukenk
@sabrinatoro - we could discuss this on tomorrow's GO-CAM call if you like!
sabrinatoro
@sabrinatoro
@vanaukenk : if there is time, it would be great! (we can at least start the discussion) Thanks
vanaukenk
@vanaukenk
Great; let's do it!
cerivs
@cerivs
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.
sabrinatoro
@sabrinatoro
Hello everyone!
Is there an existing GO-CAM model for ligand-receptor pathway that can be used/looked at as a reference? @vanaukenk
Jim Balhoff
@balhoff
In a GAF file, can an annotation extension contain both commas and pipes, e.g. rel(term),rel(term)|rel(term),rel(term)?
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
Petra Fey
@pfey03
In P2GO, we distinguish between AND (comma) and OR (pipe)
Jim Balhoff
@balhoff
Is it legal to have an OR of two ANDs? (a&b) or (x&y)
Petra Fey
@pfey03
Yes I think so. At least it’s possible to do in P2GO
Jim Balhoff
@balhoff
thanks
vanaukenk
@vanaukenk
@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.