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lactation IEA ensembl #2041

Closed Antonialock closed 11 months ago

Antonialock commented 6 years ago

CAV1 has a number of annotations made by BHF-UCL including

mammary gland development Source: BHF-UCL mammary gland involution Source: BHF-UCL

It also has an IEA to lactation made by ensembl.

I can't see what the IEA is based on in uniprot, how is this annotation made? Judging by the BHF annotations it looks like a phenotype (ie. if your mammary glands don't develop properly you get a problem with lactation).

Also, how do I tag ensembl?

pgaudet commented 6 years ago

@Antonialock You can see the original annotation and dispute that instead: image

In this case it come from MGI - @hdrabkin can you please have a look ?

Thanks, Pascale

Antonialock commented 6 years ago

Thanks Pascale.

Also Ezh2 https://www.uniprot.org/uniprot/Q61188 has an annotation to DNA methylation which propagates to human I'm guessing this should be histone methylation?

pgaudet commented 6 years ago

@hdrabkin can you please review the annotation ?

hdrabkin commented 6 years ago

The lactation annotation is being reviewed. However, as for DNA methlylation: i'm inclined to leave it because:

PMID:24105743 paper indicates 'increased Fas or Sfrp1 transcription following knockdown of CTCF, EZH2, BMI1, or DNMT1 in NIH 3T3/ZFP354B cells was accompanied by decreased DNA methylation (Fig. 2D; Supplemental Fig. S6D).' '

Antonialock commented 6 years ago

hmm, I guess polycomb positively regulates DNA methylation, but I don't think it is involved in DNA methylation per se? I could be wrong, but I would mainly associate it with histone methylation, chromatin remodelling and transcriptional silencing?

hdrabkin commented 6 years ago

in today's phrasing, it would be causually upstream or within.

pgaudet commented 6 years ago

Do you capture that ?

vanaukenk commented 6 years ago

@hdrabkin - it looks like MGI added an 'acts upstream of or within' qualifier for the mammary gland development and involution annotations. Is that correct? If so, this raises the issue of propagating gp2term relations when ISS annotations are made. It seems the gp2term relation should propagate, as well, but I don't think Protein2GO is set up to do that automatically.

hdrabkin commented 6 years ago

It's not in a Noctua model; it's an older annotation. But the annotator could have used (gene product acts upstream or within" mammary gland development ...
We still haven't worked out the conversion of existing IMP annotations.

hdrabkin commented 6 years ago

Sorry that wasn't clear; I added to our annotation today and will appear in our next gpad. However, these will not show up in our gaf.

pgaudet commented 5 years ago

@hdrabkin you did remove lactation ? If that the case I think this ticket can be closed, right @Antonialock ?

hdrabkin commented 5 years ago

I am away at a meeting and cannot access. I'll ask @LiNiMGI

LiNiMGI commented 5 years ago

PMID:12388746 The paper did assess the ability of Cav-1 suppress prolactin receptor signaling… We have previously demonstrated that Cav-1 expression is dramatically down-regulated during lactation; our preliminary results demonstrated that recombinant overexpression of Cav-1 in HC11 cells was sufficient to inhibit prolactin-induced activation of β-casein promoter activity and synthesis…ERK-1/2 is hyperactivated during pregnancy in Cav-1 null mammary glands compared with their wild-type counterparts. In addition, the downregulation of ERK-1/2 activation, which typically marks the onset of milk production, occurs earlier in Cav-1–deficient mice.

So I will keep the lactation annotation, and I can add "acts upstream of or within" qualifier

pgaudet commented 5 years ago

Thank @LiNiMGI @Antonialock If it's OK with you please close.

ukemi commented 5 years ago

From this paragraph and the rest of the paper, can't we make a more specific relation/qualifier than 'acts upstream of or within'?

LiNiMGI commented 5 years ago

changed to "acts upstream of negative effect" qualifier. Li

ValWood commented 5 years ago

I have a question and some comments.

Q. Why "upstream of or within" if you know it is upstream?

Comments

Note that PomBase don't want to receive ANY "causally upstream of" or "upstream or within" by annotation transfer pipelines. There are lots of reasons for this.

  1. Early in GO annotation our users dissuaded us from making indirect (here I'm using indirect to mean NOT directly involved in a process), for GO annotations.

I have tried before to indicate the effects of making casually upstream but external to a process annotations. Look at the affect on "mitotic cell cycle regulation" and "chromosome segregation" in the mock up figure https://github.com/geneontology/go-annotation/issues/1532 This type of "indirect annotation" would never be complete (and their annotation will be arbitrary). These annotations will distill the usefulness of GO for enrichment analysis and slimming of the bona fida processes.

In our experience, biologists working on a process want the genes involved directly in the process. We annotate genes affecting a process using phenotype annotations and we would like to maintain this distinction. The reasons should be obvious if you look at the cell cycle process. The numbers in my figure are only the tip of the iceberg. Probably at some level nearly everything affects the cell cycle, so such causal annotation becomes rather meaningless.

2. I know we could ignore any "causally upstream" qualifer, but we will want to use this qualifier within a process or pathway when we have not got all of the information to complete a model (i.e we don't know all of the connecting steps). I still don't know which causal relationship specifically refers to this type of "with process" causality.

  1. For example, process x is causally upstream of process y is causally upstream of process z (i.e. ribosome biognesis is upstream of translation, is upstream of splicing (for the spliced subset of genes), etc.... This could be captured in a more robust and complete way by connecting pathways, than making individual annotations that say:

gene x part_of ribosome biogenesis gene y causally_upstream_of translation

You might say "But we would not make such annotations"

I refer you back to point 1. -> Arbitrary annotation. To be useful you would need to do it for everything or not at all.

So in the example above, we know that mammary gland development is required for lacatation to occur so why report this at annotation time. It's a given?

  1. We could for example convert our PomBase 80,000 phenotype annotations which use GO logical definitions into GO with a causally upstream of qualifier to the affected downstream process. How would this be useful? All it would do is make it harder for users to interpret, consume and process GO annotation.

I think we are creating future problems unless we figure this out and be very precise about the different types, relevance and usefulness of a "Causally upstream" annotation.

@cmungall @thomaspd

ValWood commented 11 months ago

Closing. I still don't understand the deal with "causally upstream or within" but as long as they aren't used in propagation, that's fine.