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Curator prediction of NOT kinase activity

Sandra Orchard orchard at ebi.ac.uk
Wed Mar 8 05:59:43 PST 2006


The main problem with that from a GO point of view is that you already 
have the kinase annotation by IEA. Without the NOT annotation, that will 
remain and be incorrect.

Sandra

Alexander D. Diehl wrote:

> Hi,
>
> Sorry to be so late on this discussion, but I would like suggest that 
> perhaps the annotation is inappropriate on the grounds that NOT 
> annotations in general are very tricky assertions, and are best based 
> on actual experimental evidence, which itself is very dependent on the 
> experimental conditions used.  There's a universe of proteins that I 
> could provide NOT kinase activity for, but of course most people would 
> not confuse them with kinases.  The question here is more whether the 
> original algorithms for predicting kinase activity need to be refined 
> so that proteins lacking the correct residues in the active site are 
> not flagged as kinases in the first place.  Such refinement, of 
> course, ought best to be based on experimental evidence (wet science) 
> that feeds the computational algorithm development, and that's where 
> expert input is needed.
>
> I thus vote against any annotation at all in this case.
>
> -- Alex
>
>
> Evelyn Camon wrote:
>
>>> what were the objections to a GO_REF, this would be unambiguous 
>>
>>
>> Hi,
>>
>> The issue of using the GO_REF vs extension of the evidence codes is on
>> the GO Consortium meeting agenda.
>>
>> Arguments against GO_REF include:
>>
>> I don't think the users will read about GO_REF (is that our problem?)
>> I don't think the users will even see GO_REF in most tools, 
>> microarray, we are also limited in UniProt ffl to 4 fields of GO 
>> information
>> Users can filter on GO_REF plus evidence code but are we simply 
>> avoiding extending the number of useful GO evidence codes, for manual 
>> codes I can see that extending the codes might slow down curation but 
>> for more granular IEA codes, they are created electronically so no 
>> extra effort from curator required.
>> Biology is complex. Although I don't like to see information lost I 
>> think we further complicate what was a simple annotation process and 
>> output.
>>
>> Arguments in favour GO_REF include:
>>
>> many different techniques not practical (or is it) to create ne 
>> evidence codes, helps to disambiguate annotations
>>
>> I am really not wishing to start a new thread here...can we leave 
>> GO_REF and codes to Consortium meeting, I am still collecting 
>> ideas..you could reply to me directly if you wish me to collect 
>> further 'for' and 'aganist' examples for discussion.
>>
>> cheers
>> Evelyn
>>
>>
>>>
>>>
>>> So all annotations which use
>>>
>>> NOT with the ISS evidence code and GO_REF:xxx and a dbxref to an
>>> alignment
>>> mean that:
>>>
>>> The curator or an expert have looked at  the alignment of this sequence
>>> to the associated database entry, protein family or hmm, and on the
>>> basis of the absence of critical residues have inferred that this 
>>> family
>>> member is unlikely possess the associated activity.
>>>
>>> Or words to that effect.
>>>
>>>
>>>
>>> David Hill wrote:
>>>
>>>> I can see your point, but that would mean that every database should
>>>> have an internal ISS reference. We have one, but it is only for
>>>> orthology and subsequent inheritence of GO terms. Our's doesn't 
>>>> address
>>>> this issue of a NOT. I think in either case, a User might be confused.
>>>> If I were a naive User and I saw the annotation as you describe, I 
>>>> might
>>>> think the NOT was a mistake becasue the proteins were so similar. 
>>>> If the
>>>> protein in the with field is taken from the paper that discusses the
>>>> critical residues, then maybe it would be less confusing. I'm not 
>>>> sure.
>>>> I think we could generate confusion both ways.
>>>>
>>>> David
>>>>
>>>> Pascale Gaudet wrote:
>>>>
>>>>
>>>>> Hi,
>>>>>
>>>>> Is this allowed? I thought that the reference had to directly relate
>>>>> to the annotation. In this case I would have used our standard
>>>>> 'dictybase curators ISS' reference, because that's how the annotation
>>>>> was made.
>>>>>
>>>>> If I was to see the annotation as you describe it, I might be tempted
>>>>> to go and look at the reference, and I would be very confused because
>>>>> it doesn't talk about the protein at all.
>>>>>
>>>>> Pascale
>>>>>
>>>>>
>>>>> At 07:49 AM 3/8/2006 -0500, David Hill wrote:
>>>>>
>>>>>
>>>>>> This is a bit out of the ordinary, but what about an ISS evidence
>>>>>> code with an active kinase and then a reference to a paper that
>>>>>> identifies the critical residues for kinase activity?
>>>>>>
>>>>>> David
>>>>>>
>>>>>> Midori Harris wrote:
>>>>>>
>>>>>>
>>>>>>> Seems to me it would be a valuable part of the story, but not
>>>>>>> necessarily the whole thing. It would tell you what the important
>>>>>>> residues are, but would miss out the part about observing that 
>>>>>>> those
>>>>>>> residues are altered/absent in this particular protein. Also, 
>>>>>>> citing
>>>>>>> only the important-residue reference could give the impression that
>>>>>>> that paper (or whatever it is) actually states that protein XYZ
>>>>>>> doesn't have the activity -- which I assume is not the case.
>>>>>>>
>>>>>>> m
>>>>>>>
>>>>>>> On Wed, 8 Mar 2006, jyoti khadake wrote:
>>>>>>>
>>>>>>>
>>>>>>>
>>>>>>>
>>>>>>>> Hi,
>>>>>>>>
>>>>>>>> In this particular instance would the reference which identifies
>>>>>>>> residues important for the kinase activity in members of the 
>>>>>>>> family
>>>>>>>> be the appropriate reference?
>>>>>>>>
>>>>>>>> JK
>>>>>>>>
>>>>>>>> Midori Harris wrote:
>>>>>>>>
>>>>>>>>
>>>>>>>>
>>>>>>>>
>>>>>>>>> The reference has to identify the source of the information. In
>>>>>>>>> this case,
>>>>>>>>> it comes from what the curator knows, and from the work she did
>>>>>>>>> examining
>>>>>>>>> the protein sequence. So I don't think the protein ID would 
>>>>>>>>> suffice,
>>>>>>>>> because it would capture nothing of the curator's involvement. 
>>>>>>>>> The
>>>>>>>>> advantage of a GO_REF is that we could include everything the
>>>>>>>>> curator did,
>>>>>>>>> and make it unambiguous ... but it's not for me to decide whether
>>>>>>>>> that
>>>>>>>>> advantage outweighs the problems (btw, what are the arguments
>>>>>>>>> against a
>>>>>>>>> GO_REF?)
>>>>>>>>>
>>>>>>>>> m
>>>>>>>>>
>>>>>>>>> On Wed, 8 Mar 2006, Emily Dimmer wrote:
>>>>>>>>>
>>>>>>>>>
>>>>>>>>>
>>>>>>>>>
>>>>>>>>>
>>>>>>>>>> So if using the ISS code with these kinds of annotations, what
>>>>>>>>>> reference information should be provided? Should the reference
>>>>>>>>>> field refer back to the protein's identifier? Or to a specific
>>>>>>>>>> GO_REF (which isn't ideal)
>>>>>>>>>> e.g.
>>>>>>>>>> UniProt     P12345      GO:0004672      UniProt:P12345     
>>>>>>>>>> ISS   F
>>>>>>>>>> protein    taxon:9606 20060308       UniProt
>>>>>>>>>>
>>>>>>>>>> Midori Harris wrote:
>>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>>> The documentation for ISS says that it can be used for 
>>>>>>>>>>> predicted
>>>>>>>>>>> or observed sequence features, and that in such cases the 
>>>>>>>>>>> 'with'
>>>>>>>>>>> field can be left blank. If we choose to regard altered 
>>>>>>>>>>> 'active'
>>>>>>>>>>> site residues as features -- which seems reasonable -- ISS will
>>>>>>>>>>> work.
>>>>>>>>>>>
>>>>>>>>>>> Also, using IC would not solve the reference problem, so you
>>>>>>>>>>> would still have to either (a) make a GO_REF entry or (b) think
>>>>>>>>>>> of something else to use as the reference.
>>>>>>>>>>>
>>>>>>>>>>> m
>>>>>>>>>>>
>>>>>>>>>>> On Wed, 8 Mar 2006, Evelyn Camon wrote:
>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>>> ok..so sequence similar to what?? the sequence/domain for the
>>>>>>>>>>>> active kinase??? or could we have Inferred by Curator from
>>>>>>>>>>>> Sequence (ICS??)..hmmm
>>>>>>>>>>>>
>>>>>>>>>>>> Ev
>>>>>>>>>>>>
>>>>>>>>>>>> Valerie Wood wrote:
>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>>> I think I prefer ISS, because this is essentially a judgement
>>>>>>>>>>>>> which has
>>>>>>>>>>>>> been made by assessing the sequence.....
>>>>>>>>>>>>>
>>>>>>>>>>>>> Evelyn Camon wrote:
>>>>>>>>>>>>>
>>>>>>>>>>>>>
>>>>>>>>>>>>>
>>>>>>>>>>>>>
>>>>>>>>>>>>>
>>>>>>>>>>>>>
>>>>>>>>>>>>>
>>>>>>>>>>>>>
>>>>>>>>>>>>>> Hi,
>>>>>>>>>>>>>>
>>>>>>>>>>>>>> I'm not keen on the GO_REF idea I'm afraid...could we 
>>>>>>>>>>>>>> propose
>>>>>>>>>>>>>> that IC
>>>>>>>>>>>>>> could be used without GO ID on these odd occasions...not 
>>>>>>>>>>>>>> sure
>>>>>>>>>>>>>> what
>>>>>>>>>>>>>> publication you would use though...
>>>>>>>>>>>>>>
>>>>>>>>>>>>>> Ev
>>>>>>>>>>>>>>
>>>>>>>>>>>>>> Sandra Orchard wrote:
>>>>>>>>>>>>>>
>>>>>>>>>>>>>>
>>>>>>>>>>>>>>
>>>>>>>>>>>>>>
>>>>>>>>>>>>>>
>>>>>>>>>>>>>>
>>>>>>>>>>>>>>
>>>>>>>>>>>>>>
>>>>>>>>>>>>>>> Most kinase recognition patterns are HMMs which can only
>>>>>>>>>>>>>>> predict a
>>>>>>>>>>>>>>> domain but will not tell you if it is active or not. The
>>>>>>>>>>>>>>> kinases in
>>>>>>>>>>>>>>> these examples were hit by the HMMs. The only method which
>>>>>>>>>>>>>>> will give any
>>>>>>>>>>>>>>> indication of activity are ProSite patterns which
>>>>>>>>>>>>>>> specifically say a
>>>>>>>>>>>>>>> particular residue needs to be in a particulr position. The
>>>>>>>>>>>>>>> HMMs are
>>>>>>>>>>>>>>> correct in that these are part of the kinase family, but 
>>>>>>>>>>>>>>> are
>>>>>>>>>>>>>>> inactive
>>>>>>>>>>>>>>> members of it, they are not false positives in that sense.
>>>>>>>>>>>>>>> This is true
>>>>>>>>>>>>>>> for many different classes of enzyme.
>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>> And I do not remove enzyme InterPro2GO annotation just
>>>>>>>>>>>>>>> because a family
>>>>>>>>>>>>>>> contains a few inactive members - all the big enzyme
>>>>>>>>>>>>>>> families do and
>>>>>>>>>>>>>>> they can only really be recognised by manual annotation.
>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>> Sandra
>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>> Valerie Wood wrote:
>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>> Hi Emily,
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>> A few comments which may be relevant:
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>> Out of interest, which protein kinase family is this (i.e.
>>>>>>>>>>>>>>>> which
>>>>>>>>>>>>>>>> Interpro domain). Is it a family where some (but not all)
>>>>>>>>>>>>>>>> members are
>>>>>>>>>>>>>>>> protein kinases, in
>>>>>>>>>>>>>>>> which case the mapping should be removed?
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>> Alternatively, if this appears to be a spurious hit,
>>>>>>>>>>>>>>>> instead of adding a
>>>>>>>>>>>>>>>> NOT annotation, you can get spurious matches suppressed by
>>>>>>>>>>>>>>>> Interpro as
>>>>>>>>>>>>>>>> false positives (I often do this for S. pombe).
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>> Or, could it be a sequencing or gene predicition error?
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>> Val
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>> Midori Harris wrote:
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>> Hi,
>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>> I think there's no doubt whatsoever that this information
>>>>>>>>>>>>>>>>> should be
>>>>>>>>>>>>>>>>> captured. The question is what to put for reference and
>>>>>>>>>>>>>>>>> evidence. The
>>>>>>>>>>>>>>>>> best
>>>>>>>>>>>>>>>>> evidence code is probably TAS, although one could 
>>>>>>>>>>>>>>>>> possibly
>>>>>>>>>>>>>>>>> also make a
>>>>>>>>>>>>>>>>> case for ISS (note that IC is restricted to inferences
>>>>>>>>>>>>>>>>> from other GO
>>>>>>>>>>>>>>>>> annotations, so isn't suitable).
>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>> For a reference, one possibility is to add an item to the
>>>>>>>>>>>>>>>>> GO_REF
>>>>>>>>>>>>>>>>> collection; then there would be an ID to plug into the 
>>>>>>>>>>>>>>>>> file.
>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>> m
>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>> On Wed, 8 Mar 2006, Emily Dimmer wrote:
>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>> Hi,
>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>> One of our annotators, who is an expert on protein
>>>>>>>>>>>>>>>>>> kinases, has looked
>>>>>>>>>>>>>>>>>> at the sequence of a putative protein kinase and from
>>>>>>>>>>>>>>>>>> noticing a couple
>>>>>>>>>>>>>>>>>> of amino acids changes at its active site, has predicted
>>>>>>>>>>>>>>>>>> that it does
>>>>>>>>>>>>>>>>>> not possess any kinase activity - she did not use any
>>>>>>>>>>>>>>>>>> software and
>>>>>>>>>>>>>>>>>> there
>>>>>>>>>>>>>>>>>> is no published work on this protein.
>>>>>>>>>>>>>>>>>> Do you think this type of annotation should be
>>>>>>>>>>>>>>>>>> represented in GO (we
>>>>>>>>>>>>>>>>>> feel this annotation is of high quality and adds 
>>>>>>>>>>>>>>>>>> valuable
>>>>>>>>>>>>>>>>>> information to
>>>>>>>>>>>>>>>>>> a protein which has not yet been characterized), and if
>>>>>>>>>>>>>>>>>> so how should
>>>>>>>>>>>>>>>>>> this annotation be shown?
>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>> Thanks,
>>>>>>>>>>>>>>>>>> Emily
>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>>>>
>>>>>>>>>>>>>> -- 
>>>>>>>>>>>>>> Evelyn Camon
>>>>>>>>>>>>>> GOA Coordinator
>>>>>>>>>>>>>> Senior Scientific Curator
>>>>>>>>>>>>>> European Bioinformatics Institute
>>>>>>>>>>>>>> Tel:01223-494465
>>>>>>>>>>>>>> Fax:01223-494468
>>>>>>>>>>>>>> E-mail: camon at ebi.ac.uk
>>>>>>>>>>>>>> URL: http://www.ebi.ac.uk/goa
>>>>>>>>>>>>>>
>>>>>>>>>>>>>>
>>>>>>>>>>>>>>
>>>>>>>>>>>>>>
>>>>>>>>>>>>>>
>>>>>>>>>>>>>
>>>>>>>>>>>>>
>>>>>>>>>>>>>
>>>>>>>>>>>>>
>>>>>>>>>>>>>
>>>>>>>>>>>> -- Evelyn Camon
>>>>>>>>>>>> GOA Coordinator
>>>>>>>>>>>> Senior Scientific Curator
>>>>>>>>>>>> European Bioinformatics Institute
>>>>>>>>>>>> Tel:01223-494465
>>>>>>>>>>>> Fax:01223-494468
>>>>>>>>>>>> E-mail: camon at ebi.ac.uk
>>>>>>>>>>>> URL: http://www.ebi.ac.uk/goa
>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>>
>>>>>>>>>
>>>>>>>
>>>>>>
>>>>>> -- 
>>>>>> David P. Hill, Ph.D.
>>>>>> Senior Scientific Curator
>>>>>> Mouse Genome Informatics
>>>>>> Gene Ontology Consortium
>>>>>> The Jackson Laboratory
>>>>>> 600 Main Street
>>>>>> Bar Harbor, ME 04609-1500
>>>>>> tel:207-288-6430
>>>>>> htpp://www.informatics.jax.org
>>>>>> http://www.geneontology.org
>>>>>
>>>>>
>>>>>
>>>>>
>>>> -- 
>>>> David P. Hill, Ph.D.
>>>> Senior Scientific Curator
>>>> Mouse Genome Informatics
>>>> Gene Ontology Consortium
>>>> The Jackson Laboratory
>>>> 600 Main Street
>>>> Bar Harbor, ME 04609-1500
>>>> tel:207-288-6430
>>>> htpp://www.informatics.jax.org
>>>> http://www.geneontology.org
>>>
>>>
>>>
>>
>>
>
>

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