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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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