[Annotation] [Refgenome] Process annotation for ribosomal proteins

Chris Mungall cjm at berkeleybop.org
Sat Aug 30 11:23:31 PDT 2008


There should be a link in the ontology, ribosome functions_in protein  
biosynthesis. Then the IC becomes redundant.

On Aug 29, 2008, at 10:31 PM, Harold Drabkin wrote:

> Rama Balakrishnan wrote:
>> Considering that ribosomal genes are the Ref.Genome targets for  
>> Aug, I would like to revive this discussion.
>>
>> There was no clear answer on what evidence code is best for PROCESS  
>> annotation in a situation where all you know is that the protein is  
>> a subunit of a larger well established complex?
>
> If for example, there is a good experimental to a complex like a  
> ribosome,  one could use an IC to translation based on the GO id for  
> the ribosome and it's reference.,  I would think. Unfortunately for  
> mouse, the ribosomal protein genes don't even have a real experiment  
> to show they are in the ribosome 8-( Most cloned via sequence  
> similarity etc. etc.
>
> hjd
>
>>
>> Here is Karen's summary of the whole issue.
>>>
>>> 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
>>
>> I would greatly appreciate your feedback.
>>
>> Thanks,
>>
>> Rama
>>
>>
>>
>>
>>
>>
>>
>>
>>
>>
>>
>>>
>>>> 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
>>>>>>>>>>>>>
>>>>>>>>>>>>>                     
>>>>>>>>>>>>> _______________________________________________
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