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Curator prediction of NOT kinase activity

Pascale Gaudet pgaudet at northwestern.edu
Wed Mar 8 05:04:14 PST 2006


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





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