[go] contributes_to question

Valerie Wood val at sanger.ac.uk
Thu Aug 16 05:19:22 PDT 2007


It seems we have all used it slightly differently anyway.

But here are two 2 examples why it is bad.

1.
I had annotated the ortholog of  S. cerevisiae SIF2 (histone deacetylase 
complex subunit) to
histone deacetylase activity, contributes_to ISS.
It is a WD repeat protein  (which doesn't have HD activity, so it seems 
odd to attribute this function) the original SGD annotation is IPI.
I am now removing the pombe  annotation.

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)

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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