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Curator prediction of NOT kinase activity
Evelyn Camon
camon at ebi.ac.uk
Wed Mar 8 04:57:11 PST 2006
sounds like that would work...
Evelyn
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
>>>>>>>
>>>>>>>
>>>>>>>
>>>>>>>
>>>>>>>
>>>>>>>
>>>>>>
>>>>>>
>>>>>>
>>>>>
>>>>>
>>>>>
>>>>
>>>>
>>>>
>>>>
>>>
>>>
>>
>>
>>
>>
>
>
--
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
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