[go] contributes_to question

Valerie Wood val at sanger.ac.uk
Thu Aug 16 06:10:52 PDT 2007


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>
>>>>>
>>>>>   
>>>>>
>>>>>          
>>>>>
>>>> 
>>>>
>>>>        
>>>>
>>
>>    
>>
>
>
>  
>



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