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Curator prediction of NOT kinase activity

David Hill dph at informatics.jax.org
Wed Mar 8 04:49:37 PST 2006


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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