[Annotation] annotating ribosomal proteins

Karen Christie kchris at genome.stanford.edu
Fri Jun 27 13:42:39 PDT 2008


Hi Judy,

comments inserted inline

On Fri, 27 Jun 2008, Judith Blake wrote:

> Karen,
>
>
> Karen Christie wrote:
>> Hi Judy,
>> 
>> I really don't think we should use the 'co-localizes' qualifier in this 
>> way. Currently, when the 'co-localizes' qualifier is used (only allowed for 
>> component annotations), it means that the annotated gene product 
>> co-localized with the object indicated by the GO term to which it was 
>> annotated, e.g. ESF2 colocalizes with the 90S preribosome, where the ESF2 
>> gene is annotated to the GO term "90S preribosome".
>
> yes that's what I mean.  ESF2 colocalizes with the 90S preribosome where the 
> ESF2 is annotated to the GO term 90S preribosome.

Actually, for the annotation of ESF2 to the complex term "90S preribosome, 
the evidence is IDA. Since deciding that IPI had to be direct, we can't 
use IPI since you don't know that ESF2 is interacting with the protein 
that contains the tag. I should add, I don't have a problem with using IDA 
for the complex annotation, there is a direct assay for all the components 
being members of the same complex, so IDA seems fine here.

> Now.
>
> the evidence for that might be an IPI, yes?
>
> IPI with what?
>
> with the 902 preribosome.  This 90S preribosome is  a 'complex'.   I think in 
> following through on this, the complexes would need to be distinguishable 
> from other CC terms.

I'm not following what you mean here.

> The above would distinguish gp involved in complexes from a gp associated 
> with  another gp by IPI and a gpID in the with field.
>
> That's all from me on this.  Maybe I'm missing something fundamental.   I was 
> trying to think about distinctions.  I'll talk with Harold :)

We don't have a problem with the complex annotation. It's fine to say that 
protein/gene X is in a complex by IDA.

Our issue is with the process annotations for things where the only thing 
you know is that it is part of a complex, e.g. RPS25A is part of the 
ribosome, or UTP21 is part of the 90S preribosome. For both of these 
proteins, the sum total of the available experimental evidence is that 
they are part of the specified complex. There is no individual biochemical 
or genetic characterization. Nevertheless, the researchers who work on 
these complexes feel that being part of a big complex, whose function is 
known, e.g. translation for the ribosome and ribosome biogenesis and 
assembly for the 90S preribosome, is good evidence that a given gene 
product participates in that process.

Before the 2006 Annotation Camp decision that IPI could only be used when 
you know it is direct, we used to use IPI for the process annotations. 
Now, I'm not really sure what evidence code to use in order to be able to 
annotate UTP21 to the process of "ribosome biogenesis and assembly". Since 
I can't put anything specific in the with field because I only know that 
UTP21 is part of the complex, but not whether it interacted specifically 
with any of the tagged proteins used to pull it down, we don't use IPI 
anymore. The experiment showed that UTP21 came down in the 90S preribosome 
complex, but while this is IDA for the component annotation, is it IDA for 
the process annotation?

It has also been suggested to use IC from the GOID from the component 
term. However, this hides the fact that there is an experimental basis to 
believe that protein X is involved in a process Y. We're really not keen 
on this idea.

To me, it seems that IPI is really the best explanation of the type of 
evidence for the process annotation, i.e. we know that protein X 
physically interacts with these other gene products as part of complex Z. 
I think we should either go back to the pre-2006 Annot Camp guidelines for 
IPI, which did NOT require direct interaction, or allow some form of 
complex ID in the with field to cover these situations.

-Karen


> Judy
>> 
>> To use the 'co-localizes' qualifier to qualify the identifier in the 
>> with/from column, which is basically supporting information for the 
>> evidence code, would be a very different use of the qualifier. We have 
>> previously decided that we did not want to mix and match what these 
>> qualifiers meant because it would be confusing.
>> 
>> Considering that the ID put in the with column is supporting evidence, I 
>> think that it would be OK to allow IPI with "GOID for a complex" to include 
>> both where the annotated gene product is part of the complex and where the 
>> annotated gene product interacts with the complex. In the specific example 
>> brought up, we are talking about making a process annotation, and I think 
>> that it would be valid to make process annotations based either on a given 
>> gene product being in a complex or interacting with it.
>> 
>> -Karen
>> 
>> 
>> 
>> On Fri, 27 Jun 2008, Judith Blake wrote:
>> 
>>> Here's what I was thinking.
>>> 
>>> IPI for the binding
>>> with the GO:complexID in the "with" field
>>> 
>>> and the 'co-localizes' as the qualifier.
>>> 
>>> Thus, the gene product 'colocalizes' with 'complexID' by evidence code 
>>> 'IPI'
>>> 
>>> which is different than
>>> 
>>> 
>>> Rama Balakrishnan wrote:
>>>> Hi Judy,
>>>> 
>>>> Comment below.
>>>> 
>>>> On Jun 25, 2008, at 4:51 AM, Judith Blake wrote:
>>>> 
>>>>> Rama,
>>>>> 
>>>>> I agree that the solution needs to go beyond ReactomeIDs.  However, 
>>>>> there are many other complex resources, and my summer intern is in the 
>>>>> process of collecting a more global (one would hope comprehensive) list 
>>>>> of complexes with IDs from these other resources.  So putting a complex 
>>>>> ID in the 'with' field seems correct.  And allowing the GO:ID seems 
>>>>> correct too
>>>>> 
>>>>> I think distinguishing between 'member of complex' and 'interacts with 
>>>>> complex' is very important.    The CC assignment places a gp in a 
>>>>> complex. I think using the IPI code here, while technically defensible, 
>>>>> might result in the confusion.  Would this be a place that IPI with 
>>>>> 'co-localizes' would clarify the distinction?
>>>> 
>>>> Hmm...I don't think I follow your last sentence completely.
>>>> So far, we have used Qualifiers to qualify the GO term and not the 
>>>> evidence. And we don't use qualifiers for Process terms. Contributes_to 
>>>> is specifically meant for Function, and co_localizes is meant for CC.
>>>> 
>>>> Thanks,
>>>> 
>>>> Rama
>>>> 
>>>> 
>>>> 
>>>>> 
>>>>> 
>>>>> judy
>>>>> 
>>>>> Rama Balakrishnan wrote:
>>>>>> Hi all,
>>>>>> 
>>>>>> I am sure all the other groups annotating ribosomal genes are facing 
>>>>>> the same issue. I would like to hear from you about the new proposal 
>>>>>> for IPI or if you have other suggestions.
>>>>>> 
>>>>>> Thanks,
>>>>>> 
>>>>>> Rama
>>>>>> 
>>>>>> On Jun 18, 2008, at 2:53 PM, Rama Balakrishnan wrote:
>>>>>> 
>>>>>>> Hi,
>>>>>>> 
>>>>>>> 1) Although there is a REACTOME ID for the yeast ribosome complex, I 
>>>>>>> think a better solution would be to allow the GOID for the complex in 
>>>>>>> the 'with' column for IPI. This is because, Reactome has IDs only for 
>>>>>>> human and yeast, and this solution won't scale for other organisms.
>>>>>>> 
>>>>>>> 2) If we move towards the idea of using IPI in this fashion, we also 
>>>>>>> need to update the documentation for IPI because by saying that the 
>>>>>>> subunit interacts physically with the complex, one could infer that 
>>>>>>> the subunit peripherally interacts with the complex as oppose to 
>>>>>>> inferring that the subunit is part of the complex.
>>>>>>> 
>>>>>>> Thanks,
>>>>>>> 
>>>>>>> Rama
>>>>>>> 
>>>>>>> 
>>>>>>> On Jun 18, 2008, at 9:25 AM, D'Eustachio, Peter wrote:
>>>>>>> 
>>>>>>>> 
>>>>>>>> Hi, Midori,
>>>>>>>> 
>>>>>>>> We do have such identifiers (though in general - this case is an 
>>>>>>>> exception - only for human proteins and complexes) and this sounds 
>>>>>>>> like a legitimate use of them, but it also seems like a kind of hack 
>>>>>>>> around the basic problem. Earlier in this thread, someone pointed to 
>>>>>>>> one paper that supports the assertion "ribosomes are required for 
>>>>>>>> translation to occur", and another that supports the assertion 
>>>>>>>> "subunit X is required for the assembly of a complete ribosome", but 
>>>>>>>> no single paper that asserts "the ribosomes that actually participate 
>>>>>>>> in translation have been shown to contain subunit X", and so we are 
>>>>>>>> left to draw this conclusion by inference, reading the two papers in 
>>>>>>>> succession. I guess all of this violates the principle that there 
>>>>>>>> should be a 1:1:1 mapping of protein : GO term : publication and 
>>>>>>>> evidence code. Here, Reactome has silently done the inference so 
>>>>>>>> formally you can make a 1:1:1 relationship, but there's still a 
>>>>>>>> hidden multi-step inference in there.
>>>>>>>> 
>>>>>>>> That said, we live by that hack - our unit of curation is the 
>>>>>>>> reaction, and I have yet to find the reaction all of whose attributes 
>>>>>>>> can be annotated without combining evidence assertions inferentially 
>>>>>>>> from multiple papers.
>>>>>>>> 
>>>>>>>> Peter
>>>>>>>> 
>>>>>>>> 
>>>>>>>> -----Original Message-----
>>>>>>>> From: annotation-bounces at genome.stanford.edu on behalf of Midori 
>>>>>>>> Harris
>>>>>>>> Sent: Wed 6/18/2008 5:02 AM
>>>>>>>> To: Karen Christie
>>>>>>>> Cc: GO Annotation list
>>>>>>>> Subject: Re: [Annotation] annotating ribosomal proteins
>>>>>>>> 
>>>>>>>> Reactome has identifiers for complexes ... could you use IPI with the
>>>>>>>> Reactome ID for the ribosome? (E.g. S. cerevisiae ribosome is
>>>>>>>> Reactome:141693; H. sapiens is 72500.)
>>>>>>>> 
>>>>>>>> If this is a stupid idea, I'll bow out quietly ... it's been a long, 
>>>>>>>> long
>>>>>>>> time since I did annotation.
>>>>>>>> 
>>>>>>>> m
>>>>>>>> 
>>>>>>>> On Tue, 17 Jun 2008, Karen Christie wrote:
>>>>>>>> 
>>>>>>>>> As of the 2006 Annotation camp, we agreed that IPI could only be 
>>>>>>>>> used when
>>>>>>>>> you know it is a direct interaction and that you should fill the 
>>>>>>>>> with column
>>>>>>>>> with the directly interacting gene products.
>>>>>>>>> 
>>>>>>>>> Prior to that, I often used to use IPI for the proteins that came 
>>>>>>>>> down in a
>>>>>>>>> complex, and for 'modern' purifications where one protein was 
>>>>>>>>> tagged, I'd put
>>>>>>>>> that one in the with column. But we agreed that it isn't known that 
>>>>>>>>> this is
>>>>>>>>> direct, so we quit doing it. I've been having the same problem with
>>>>>>>>> spliceosomal complexes and have become rather unkeen on the decision 
>>>>>>>>> that IPI
>>>>>>>>> could only be used for known direct interactions. It seems that this
>>>>>>>>> requirement got added by the people who want to use the IPI with 
>>>>>>>>> field as a
>>>>>>>>> protein-protein interaction database.
>>>>>>>>> 
>>>>>>>>> Anyway, I thought that IPI with the tagged protein seemed like a 
>>>>>>>>> much better
>>>>>>>>> representation of the evidence for the process than IDA. Coming down 
>>>>>>>>> as part
>>>>>>>>> of a complex doesn't seem like a direct assay for process. IPI with 
>>>>>>>>> one of
>>>>>>>>> the proteins in the complex seems like a better representation of 
>>>>>>>>> what was
>>>>>>>>> actually done, but we can't do now that because of the direct 
>>>>>>>>> interaction
>>>>>>>>> requirement.
>>>>>>>>> 
>>>>>>>>> IC also seems a little unsatisfying, since it's not experimental. I 
>>>>>>>>> don't
>>>>>>>>> know, maybe for complexes as well characterized as the ribosome, or 
>>>>>>>>> the
>>>>>>>>> spliceosome, just being in the complex is direct evidence that it's 
>>>>>>>>> part of
>>>>>>>>> the process that the complex is experimentally characterized to be 
>>>>>>>>> part of...
>>>>>>>>> 
>>>>>>>>> I've been a bit muddled about how best to deal with these ever since 
>>>>>>>>> the 2006
>>>>>>>>> Annotation camp. I liked using IPI better than IDA...
>>>>>>>>> 
>>>>>>>>> -Karen
>>>>>>>>> 
>>>>>>>>> 
>>>>>>>>> On Tue, 17 Jun 2008, Pascale Gaudet wrote:
>>>>>>>>> 
>>>>>>>>>> Can you then IPI the process?
>>>>>>>>>> 
>>>>>>>>>> Doug howe wrote:
>>>>>>>>>>    I think:
>>>>>>>>>>    "the IDA is just for the annotation to the complex term and then 
>>>>>>>>>> use
>>>>>>>>>> IC from the
>>>>>>>>>>    complex term for the Process annotation"
>>>>>>>>>>    is the way to go.
>>>>>>>>>>
>>>>>>>>>>    Doug
>>>>>>>>>>
>>>>>>>>>>    Karen Christie wrote:
>>>>>>>>>>          Hi Pascale,
>>>>>>>>>>
>>>>>>>>>>          Rama is looking at the original papers, and ribosomes and 
>>>>>>>>>> the
>>>>>>>>>> processes
>>>>>>>>>>          of ribosome assembly are probably better characterized in
>>>>>>>>>> cerevisiae
>>>>>>>>>>          than in any other eukaryote.
>>>>>>>>>>
>>>>>>>>>>          The real issue here is that what has been shown is that 
>>>>>>>>>> protein
>>>>>>>>>> X is
>>>>>>>>>>          part of a big complex, e.g. the ribosome, for which the
>>>>>>>>>> function is
>>>>>>>>>>          known. The sum total of the experimental evidence 
>>>>>>>>>> available for
>>>>>>>>>> a
>>>>>>>>>>          significant number of ribosomal proteins is that they are
>>>>>>>>>> purified as
>>>>>>>>>>          part of the ribosome complex. So, for component, it's 
>>>>>>>>>> easy.
>>>>>>>>>> This is IDA
>>>>>>>>>>          evidence that protein X is in the ribosome, or in the 
>>>>>>>>>> Small
>>>>>>>>>> SubUnit
>>>>>>>>>>          (SSU) or in the Large SubUnit (LSU), or whatever complex 
>>>>>>>>>> is
>>>>>>>>>>          characterized.
>>>>>>>>>>
>>>>>>>>>>          But is being in the ribosome considered to be IDA evidence 
>>>>>>>>>> for
>>>>>>>>>> a process
>>>>>>>>>>          annotation to translation? In one way of looking at it, 
>>>>>>>>>> the
>>>>>>>>>> direct assay
>>>>>>>>>>          is that it's part of a complex and then you're assuming 
>>>>>>>>>> that
>>>>>>>>>> the
>>>>>>>>>>          individual protein is involved in translation because it's 
>>>>>>>>>> in
>>>>>>>>>> that
>>>>>>>>>>          complex. Is this a direct assay for being involved in
>>>>>>>>>> translation? Can
>>>>>>>>>>          we use IDA for a process annotation? or is it a more 
>>>>>>>>>> accurate
>>>>>>>>>> statement
>>>>>>>>>>          to say that the IDA is just for the annotation to the 
>>>>>>>>>> complex
>>>>>>>>>> term and
>>>>>>>>>>          then use IC from the complex term for the Process 
>>>>>>>>>> annotation?
>>>>>>>>>>
>>>>>>>>>>          -Karen
>>>>>>>>>> 
>>>>>>>>>> 
>>>>>>>>>>
>>>>>>>>>>          On Tue, 17 Jun 2008, Pascale Gaudet wrote:
>>>>>>>>>>
>>>>>>>>>>                Hi Rama,
>>>>>>>>>>
>>>>>>>>>>                I think this is a perfect case where one of us 
>>>>>>>>>> should go
>>>>>>>>>>                back to the original papers and find
>>>>>>>>>>                what we all need to ISS to (in which organism the 
>>>>>>>>>> funtion
>>>>>>>>>>                and process were shown).
>>>>>>>>>>
>>>>>>>>>>                Pascale
>>>>>>>>>>
>>>>>>>>>>                Rama Balakrishnan wrote:
>>>>>>>>>>                      Hi,
>>>>>>>>>>
>>>>>>>>>>                      I have couple of ribosomal proteins to 
>>>>>>>>>> annotate as
>>>>>>>>>>                part of the ref-genome curation
>>>>>>>>>>                      project. Turns out that there is no direct
>>>>>>>>>>                experimental evidence showing that these
>>>>>>>>>>                      proteins are involved in translation. Almost 
>>>>>>>>>> all
>>>>>>>>>> the
>>>>>>>>>>                studies purify the ribosome
>>>>>>>>>>                      from yeast and identify the subunits by one or 
>>>>>>>>>> more
>>>>>>>>
>>>>>>>>>>                techniques.
>>>>>>>>>>
>>>>>>>>>>                      I can do IDA for CC annotation, that is
>>>>>>>>>>                straightforward. Is IDA for function
>>>>>>>>>>                      annotation- structural constituent of 
>>>>>>>>>> ribsomome
>>>>>>>>>> okay?
>>>>>>>>>>                What about BP? I can do IC
>>>>>>>>>>                      from the CC term, but that is not direct
>>>>>>>>>> experimental
>>>>>>>>>>                evidence. What do you all
>>>>>>>>>>                      think?
>>>>>>>>>>
>>>>>>>>>>                      Thanks for your time,
>>>>>>>>>>
>>>>>>>>>>                      Rama
>>>>>>>>>>
>>>>>>>>>>                      _______________________________________________
>>>>>>>>>>                      Annotation mailing list
>>>>>>>>>>                      Annotation at geneontology.org
>>>>>>>>>>                      http://fafner.stanford.edu/mailman/listinfo/annotation
>>>>>>>>>> 
>>>>>>>>>> 
>>>>>>>>>> 
>>>>>>>>>>
>>>>>>>>>>          _______________________________________________
>>>>>>>>>>          Annotation mailing list
>>>>>>>>>>          Annotation at geneontology.org
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>>>>>>>>>> 
>>>>>>>>>> 
>>>>>>>>>> 
>>>>>>>>>> 
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