[go] contributes_to question

Valerie Wood val at sanger.ac.uk
Thu Aug 16 07:36:08 PDT 2007


Hi,

Thanks Julie, I think we do need to clarify when it should and shouldn't 
be used.
At this point I'm not sure. The reasoning here sound like this one is OK.
I'm not so sure about the chromatin remodelling complex subunit type 
annotations made by IPI, but maybe these are OK too. Its not clear to me 
though if this is a correct use or not.

The ISS's made from these contributes_to are a seperate issue and depend 
on the outcome of when contributes_to should be used (but should keep 
contributes_to).

Cheers

Val





Julie Park wrote:

> Hi Val,
>
> I'm sure that there are other examples of confusing contributes_to  
> annotations, but I recently made the addition of "contributes_to" to  
> the FET3/iron transporter annotation that Val brought up (so Susan,  
> the qualifier wasn't dropped on your end, but added on our end not  
> too long ago) and wanted to give the reason that I made it.
>
> In this case, the transporter protein Ftr1p only transports iron if  
> it has been reduced by Fet3p--the equivalent oxidized iron ion added  
> exogenously is not a substrate for this transporter. In other words,  
> iron transport activity does not occur without Fet3p and so I felt  
> that it does directly contribute_to this function and that the  
> annotation was appropriate and provided useful information.
>
> However, if it turns out that this is not a good way to use the  
> qualifier, I have no problem with reannotating this gene.  It seems  
> that discussion, clarification and standardization of the use of this  
> qualifier would be good.
>
> -Julie
>
> On Aug 16, 2007, at 7:10 AM, Valerie Wood wrote:
>
>> Hi Susan,
>>
>> I'm asking why we make these annotations in the first place (and  
>> using these annotations as an example why the original annotations  
>> are misleading).
>>
>> I can't see why process annotations  are not adequate (with  function 
>> unknown, or the known function of the gene product).
>>
>> If we do this, then presumably every subunit of a complex should be  
>> annotated to every activity within a complex? (this would be a huge  
>> amount of additioanl annotation)
>>
>> In the case of this oxidase, it doesn't directly contribute_to the  
>> transporter activity. It reduces the iron so that it can be  
>> transported.
>>
>> These were just used as examples of the confusion that  
>> contributes_to can cause with its 'looser' meaning.
>>
>> Val
>>
>>
>>
>>
>> Susan Tweedie wrote:
>>
>>> Hi Val
>>>
>>> On Thu, 2007-08-16 at 13:19 +0100, Valerie Wood wrote:
>>>
>>>> It seems we have all used it slightly differently anyway.
>>>> 2.
>>>> FET3/YMR058W
>>>> is a copper oxidate involved in iron assimilation by reduction  and 
>>>> transport. it isn't a transporter but it is part of the  
>>>> transporter complex.
>>>> This has an iron transporter activity (with contributes to) in  
>>>> SGD, and has been ISS's to this activity (without contributes_to)  
>>>> by two drosophila genes (FBgn0032116 and FBgn0039387)
>>>>
>>> Thanks for pointing these out. I'll review these old ISS  
>>> annotations for
>>> FBgn0032116 and FBgn0039387. In general, we shouldn't drop the
>>> 'contributes_to' when making an ISS.
>>> I'll also have a look at our 'contributes_to' annotations to see how
>>> consistent we have been. I've used it fairly sparingly for essential
>>> subunits of an activity.
>>>
>>> Susan
>>>
>>>
>>>> I see man many examples of this (too many to give feedback on)
>>>>
>>>> Can this go on the agenda for September meeting?
>>>>
>>>> Val
>>>>
>>>>
>>>>
>>>>
>>>>
>>>> Pascale Gaudet wrote:
>>>>
>>>>
>>>>> I did mean unessential role; ie, the complex might have the  
>>>>> activity without the protein you're annotating, but adding it  
>>>>> enhances the activity (but not a regulator-- that would be  
>>>>> 'positive regulation of...'). But if adding it does nothing, I  
>>>>> would annotate to unknown.
>>>>>
>>>>> Pascale
>>>>>
>>>>> Valerie Wood wrote:
>>>>>
>>>>>
>>>>>> It seems so to me too, these are equivalent to process annotations
>>>>>> But did you mean essential role in the activity ? This is how I  
>>>>>> would use it.
>>>>>>
>>>>>> VAl
>>>>>>
>>>>>>
>>>>>> Pascale Gaudet <pgaudet at northwestern.edu> wrote:
>>>>>>
>>>>>>> <!DOCTYPE html PUBLIC "-//W3C//DTD HTML 4.01 Transitional//EN">
>>>>>>> <html>
>>>>>>> <head>
>>>>>>> <meta content="text/html;charset=ISO-8859-1" http- 
>>>>>>> equiv="Content-Type">
>>>>>>> <title></title>
>>>>>>> </head>
>>>>>>> <body bgcolor="#ffffff" text="#000000">
>>>>>>> Val, <br>
>>>>>>> My understanding was that the subunit had to have at least an
>>>>>>> unessential role in the activity, although the documentation  is 
>>>>>>> very
>>>>>>> ambiguous. But what you are describing is really capturing  
>>>>>>> component
>>>>>>> information with a function annotation. That seems wrong. <br>
>>>>>>> <br>
>>>>>>> Pascale<br>
>>>>>>> <br>
>>>>>>> <br>
>>>>>>> Valerie Wood wrote:
>>>>>>> <blockquote cite="mid:E1ILDTY-0006f2- 
>>>>>>> Vx at web-2-10.internal.sanger.ac.uk"
>>>>>>> type="cite">
>>>>>>> <pre wrap="">I'm really asking the question why arbitrarily  add 
>>>>>>> these function annotations to the 'unknown' subunits
>>>>>>> of complexes in the first place, when they are clearly not the  
>>>>>>> subunit that posseses the catalytic activity, or when they  
>>>>>>> clearly have another activity.
>>>>>>>
>>>>>>> Some of these complexes have
>>>>>>> ATPase activity,
>>>>>>> ubiquitin ligase activity
>>>>>>> acetyltransferase activity
>>>>>>> etc.
>>>>>>>
>>>>>>> so if this type of annotation was valid (or useful)  then we  
>>>>>>> would (presumably) add all these annotations to all subunits  
>>>>>>> for completion?
>>>>>>>
>>>>>>> Wouldn't users rather see  which subunits had known function  
>>>>>>> and which had 'unknown function'.
>>>>>>> It just seems that the qualifier is being used much more  
>>>>>>> liberally than was originally intended (i.e as a filler to  
>>>>>>> avoid adding an 'unknown' annotation)
>>>>>>>
>>>>>>> and it skews functional predictions/genome comparisons.
>>>>>>>
>>>>>>>
>>>>>>> val
>>>>>>>
>>>>>>>
>>>>>>>
>>>>>>>
>>>>>>> Chris Mungall <a class="moz-txt-link-rfc2396E"  
>>>>>>> href="mailto:cjm at fruitfly.org">&lt;cjm at fruitfly.org&gt;</a>  
>>>>>>> wrote: </pre>
>>>>>>> <blockquote type="cite">
>>>>>>>   <pre wrap="">..which like many such recommendations will be  
>>>>>>> ignored by the  majority of implementations (in this case it  is 
>>>>>>> forgivable if we  issue the recommendation at this late  stage..)
>>>>>>>
>>>>>>> Perhaps any association qualified in any way should be omitted  
>>>>>>> from  the default annotations we provide. We would of course  
>>>>>>> also provide  the full annotation set but it would be made  
>>>>>>> obvious that this  'advanced' set came with certain caveats
>>>>>>>
>>>>>>> On Aug 14, 2007, at 8:00 AM, Midori Harris wrote:
>>>>>>>
>>>>>>>   </pre>
>>>>>>>   <blockquote type="cite">
>>>>>>>     <pre wrap="">Whatever we decide, I would recommend that  
>>>>>>> computational analyses  omit 'contributes_to' annotations.
>>>>>>>
>>>>>>> m
>>>>>>>
>>>>>>> On Mon, 13 Aug 2007, Valerie Wood wrote:
>>>>>>>
>>>>>>>     </pre>
>>>>>>>     <blockquote type="cite">
>>>>>>>       <pre wrap="">Recently I'm wondering recently why we have  
>>>>>>> 2 meanings for  contributes_to:
>>>>>>>
>>>>>>> When the qualifier was initially implemented, it was so  
>>>>>>> function  terms could be added to complexes like DNA  polymerase 
>>>>>>> and the F1  Fo ATPase where the function cannot be  attributed 
>>>>>>> to a single  subunit. This seems fine.
>>>>>>>
>>>>>>> Increasingly I see annotations to complexes which are  described 
>>>>>>> as  (for example) a histone acetyltransferase  complex, and all 
>>>>>>> of the  subunits are given histone de/ acetlytransferase or  
>>>>>>> methyltransferase activity with  contributes_to, even thought 
>>>>>>> the  other subunits clearly have  other functions (I see 
>>>>>>> ATPases,  ubiquitin ligases actin-like  proteins etc, which are 
>>>>>>> commonly  associated with histone  acetyltransferases and 
>>>>>>> methyltransferases).
>>>>>>>
>>>>>>> This seems odd, for a number of reasons.
>>>>>>> Often these subunits are not required for the activity, but  
>>>>>>> their  deletion (sometimes, but not always) affects the rate   
>>>>>>> the activity
>>>>>>>
>>>>>>> Primarily I don't understand what this type of  
>>>>>>> 'contributes_to'  annotation provides  to GO users above a  
>>>>>>> process annotation to the  histone acetylation (if this has  
>>>>>>> been shown), a complex  annotation, and a function term to  
>>>>>>> unknown/root node.  Isn't it  more useful to know that there  is 
>>>>>>> some information about the  process, but the molecular  function 
>>>>>>> is not known?
>>>>>>>
>>>>>>> 1) Another problem is that these particular chromatin  
>>>>>>> associated  complexes often have shared subunits so the  
>>>>>>> function annotations  aren't so clear-cut (i.e some of these  
>>>>>>> subunits may be members of  other complexes which do not have  
>>>>>>> this activity)
>>>>>>>
>>>>>>> 2) Also computational analysis using RCA which infer these   
>>>>>>> 'functions' to similar proteins which, from their domain   
>>>>>>> composition it is unlikely possess this activity. 3) It makes   
>>>>>>> cross species comparisons difficult because you get different   
>>>>>>> numbers of functions to what you would  expect when comparing   
>>>>>>> annotations between species. For example it is known how many   
>>>>>>> histone acetyltransferases /methytrasferases etc. pombe has,   
>>>>>>> compered to S. cerevisiae, but when I compare the 2 the  
>>>>>>> numbers  are skewed.
>>>>>>>
>>>>>>> The documentation clearly allows this (although there is not  
>>>>>>> an  example of this type of annotation in the documentation,  so 
>>>>>>> I  wonder if this is what we meant?):
>>>>>>>
>>>>>>>       </pre>
>>>>>>>       <blockquote type="cite">
>>>>>>>         <pre wrap="">From the documentation:
>>>>>>>         </pre>
>>>>>>>       </blockquote>
>>>>>>>       <pre wrap="">
>>>>>>> Annotating individual gene products according to attributes of  
>>>>>>> a  complex is especially useful for molecular function  
>>>>>>> annotations in  cases where a complex has an activity, but not  
>>>>>>> all of the  individual subunits do. (For example, there may be  
>>>>>>> a known  catalytic subunit and one or more additional  subunits, 
>>>>>>> or the  activity may only be present when the  complex is 
>>>>>>> assembled.)  Molecular function annotations of  complex subunits 
>>>>>>> that are not  known to possess the activity  of the complex must 
>>>>>>> include the  entry contributes_to in the  Qualifier column.
>>>>>>>
>>>>>>> Note that contributes_to is not needed to annotate a  catalytic  
>>>>>>> subunit. Furthermore, contributes_to may be used  for any non- 
>>>>>>> catalytic subunit, whether the subunit is  essential for the  
>>>>>>> activity of the complex or not.
>>>>>>>
>>>>>>>
>>>>>>>
>>>>>>>       </pre>
>>>>>>>     </blockquote>
>>>>>>>   </blockquote>
>>>>>>> </blockquote>
>>>>>>> <pre wrap=""><!---->
>>>>>>> </pre>
>>>>>>> </blockquote>
>>>>>>> </body>
>>>>>>> </html>
>>>>>>>
>>>>>>>
>>>>>>>
>>>>>>
>>>>>>
>>>>
>>>>
>>>
>>>
>>>
>>
>>
>>
>> -- 
>> The Wellcome Trust Sanger Institute is operated by Genome Research  
>> Limited, a charity registered in England with number 1021457 and a  
>> company registered in England with number 2742969, whose registered  
>> office is 215 Euston Road, London, NW1 2BE.
>
>
>



-- 
The Wellcome Trust Sanger Institute is operated by Genome Research 
Limited, a charity registered in England with number 1021457 and a 
company registered in England with number 2742969, whose registered 
office is 215 Euston Road, London, NW1 2BE.



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