[Annotation] Process annotation for ribosomal proteins

Rama Balakrishnan rama at genome.stanford.edu
Fri Aug 29 14:11:27 PDT 2008


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?

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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