cohesin complex update, matrix project

[ValWood]

Update on the original ticket: https://github.com/geneontology/go-annotation/issues/1396

This is how the cohesin intersections look currently:

[ValWood]

outstanding issues:

• [x] Zfin translation, I think this was reported as fixed @doughowe @zebrafishembryo
• [x] Reactome small protein conjugation or removal (becasue sumoylated) @deustp01

Issues not previously reported:

• [x] DNA replication via SGD (plus IEA's) @srengel http://amigo.geneontology.org/amigo/reference/PMID:24062159 I would call this "sister chromatid decatenation" inter-molecular strand passage of DNA to removes catenanes persisting between sister chromatids following DNA replication. This term "DNA unwinding involved in DNA replication" is describing the geometric change which occurs during replication not the topological change which occurs afterwards.

• [x] cytokinesis, reported to SGD CDC5 helpdesk

chromatin organization

• [x] TAIR SYN1 @tberardini
• [x] FlyBase Nipped B and Sce @hattrill These are both "Cohesin complex" and co-localizes with. I didn't think we used "colocalizes" in this way. I thought it was when you used colocalization with a tagged protein to infer a localization (like centromere or chromatin here), rather than a complex term Maybe we should discuss Suggest rule, do not use "colocalizes_with" with complex terms? (If it's binding, use a protein complex binterm term/extension?)

Cytoskeleton annotations remaining now the ontology issue is fixed

• [x] RGD have ISO to human, but human does not have this annotation @slaulederkind

• [x] TAIR WAPL1 and 2 (IGI to each other) (mitotic spindle organization, this looks a bit odd for cohsin) @tberardini

• [x] PomBase moa1 cohesin associated NAS (FIXED)

• [x] SGD CDC5 (already reported via e-mail for the cytokinesis intersection, this is also a "colocalizes_with cohesin" This one has been used to generate cohesin iEAs for other species which highlight a danger. https://github.com/geneontology/go-annotation/issues/1500

• [x] SMC3 human (plus ISO's and IEA's), reported to UniPROT via RT

Regulation of cell cycle phase transition

• [x] MGI mta3 query "cohesin" @ukemi
• [ ] CDC5A reported to UniPROT via RT The rest are IEAs from these 2 gene products

@vanaukenk I'll use this e.g. and a couple of others for a future annotation call.

[ValWood]

moved to

https://github.com/geneontology/go-annotation/issues/1500

[tberardini]

@ValWood : Sorry, but I missed the context. Am I supposed to be reviewing the annotations to chromatin organization and cytoskeleton? Or specific kids?

[hattrill]

Have removed co-loc with cohesin complex for Sce as paper actually does not shown this. For 2008 paper for Nipped-B removed co-loc with cohesin complex (and added some cohesin loading/unloading terms for genes in this paper as more appropriate), but for 2010 paper they show co-loc staining with cohesin complex subunits but in an IP "none of the cohesin subunit precipitations brought down detectable amounts of Nipped-B". So, I will keep this one for now for and add it to #1500 as an example.

[ValWood]

The queried annotation is "mitotic spindle organization" WAPL1 and 2. WAPL is a cohesin binding protein and cohesin release factor. I read a lot of papers on this and I'm not aware of any other role. At TAIR it has "mitotic spindle organization", the evidence is IGI to each other?

I don't think that there is a direct role in spindle organization. Phenotypes show "mitotic spindle attachment defects", this is a downstream effect because of the defect in kinetochore assembly. Historically, spindle organization was (incorrectly) a parent of "mitotic spindle attachment". This might explain the annotation.

I would not even annotate this to "mitotic spindle attachment" its too far downstream....

Of course there may be entirely another reason for this annotation that I'n unaware of!

[hattrill]

Removed the co-locs for Nipped-B and pds5. Should be public beginning of Feb.

[tberardini]

I fixed the annotation for SYN1. @lreiser will look into the WAPL1/2 annotations.

[lreiser]

Val, yes, it was based on the figure showing the mutant phenotype (a downstream effect) and I have obsoleted the annotations for WAPL1/2. Must have been those nasty "alternative facts"

MakingGOGreatAgain

irony

[ValWood]

Hello,

This is how the cohesin complex annotation intersections look today:

![cohesin complex update figure]

I'm using this intersection as an example in a paper, along with some larger studies. Also Seth Carbon will be talking about the Matrix project as ISB later this month and will use this example. This is a final call for any annotation fixes... I can remove any "pending" annotation violations from the figure. Or, if you believe them to be correct I can extend the annotation rules.

I'll summarize the outstanding issues today below.

Thanks!

Val

[ValWood]

• [ ] Zfin, intersection with translation. This was supposedly removed but it didn't disappear along with the other ones? @doughowe @zebrafishembryo

• [ ] SGD CDC5 (this is because CDC5 is annotated as "colocalizes_with" cohesin complex. I wonder if an IPI would be better here (or a MF-> substrate annotation of this is possible) There are problems associated with this type of annotation in that this is picked up and propagated without the "co localizes" qualifier. See https://github.com/geneontology/go-annotation/issues/1500 @srengel

• [ ] Human SMC1A "mitotic spindle organization" (I missed this one before so I did not query this until today raised dispute with protein to GO Dispute ID: 5913) @sylvainpoux (just spotted, also dispute Dispute ID: 4455)

And today I did the final intersection, signalling which raised the following

• [x] MGI:Mta3 Dispute ID: 5914 queried cohesin complex annotation @ukemi

• [x] SMC1A Cohesin isn't part of checkpoint signalling (here it is described as an effector) Dispute ID: 5934/5 @sylvainpoux

• [x] FB:SMC3 Dispute ID: 5935 "lateral inhibition (Helen fixed this one before I finished typing the Git Hub ticket, Thanks!) @hattrill

• [x] UniProt human SMC3 not signal transduction, its a target of a signalling pathway Dispute ID: 5933 @sylvainpoux

[ukemi]

I looked at this paper again and changed the annotations from being a part of the cohesin and NuRD complexes to 'protein complex binding' with those complexes as inputs. Although it is a fine line about when something is part of a complex and when it binds the complex, in this case, I think the authors intent is to say that the protein interacts with the core complexes.

[ValWood]

Although it is a fine line about when something is part of a complex and when it binds the complex, in this case, I think the authors intent is to say that the protein interacts with the core complexes.

I agree, its sometimes tricky. In this case cohesin is a well defined complex but it has some transient interactors. Complex binding with extension works better (especially since these have been picked up by PAINt and Ensembl piplines and propagated)

[ValWood]

More outstanding

• [x] FB:san Q9NHD5 via UniPRot Outstanding dispute Dispute ID: 4458)

[srengel]

reading David's comment above, i will change this colocalizes_with to 'protein complex binding' with a col-16 entry. it seems that would be better.

[ValWood]

I think these are all done, but I noticed a new one

cohesion complex FB:FBgn0024188 san (N-acetyltransferase) cohesin complex (it acetylates a cohesion subunit but isn’t part of the complex per se (binding maybe) @hattrill could you take a look

Then I'll close this.

[hattrill]

• [x] Hi @ValWood FBgn0024188 Q9NHD5 is a UniProt annotation. I've raised a dispute via Protein2GO.

[pgarmiri]

• [x] Hi @ValWood, I have now deleted the misleading annotation for Q9NHD5. Thanks @hattrill for the notification. Thanks, Penelope

[ValWood]

closing. Cohesin complex now looks cleaned up. I opened tickets for a couple of remaining issues