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necessary & sufficient

Ranjana Kishore ranjana at its.caltech.edu
Thu Feb 19 10:25:05 PST 2004


Hello,
        I  don't like the idea of doing away with 'IMP' altogether ( I 
agree with Raymond's concern); broader is better because you know you 
are safe using that evidence code, but I don't mind that 'inferred from 
over-expression phenotype' and 'inferred from loss of function 
phenotype' exist , as sub-categories of IMP, though this would 
complicate evidence codes and lead to a multiplication of more 
codes/sub-codes that people may want.

Maybe a topic for the next GO meeting?

Ranjana Kishore
WormBase


Raymond Lee wrote:


> Hi,
>
> there are genetic mutations/molecular manipulations whose nature is 
> either not clearly known or cannot be cleanly placed into the two 
> proposed categories. thus, IMP should be kept rather than just splitted.
>
> raymond
>
>
> Rachel Drysdale (Genetics) wrote:
>
>> Hi,
>>
>> while I understand that there are good reasons for not
>> over-complicating the GO evidence codes by subdividing them further, I
>> do think that David has a strong point regarding the splitting of IMP
>> into 'inferred from over-expression phenotype' and 'inferred from loss
>> of function phenotype'.
>>
>> Were IEP to be split into 'IEP by in situ hyb' vs 'IEP by antibody
>> staining' etc IEP would still convey the meaning that the GO term was
>> conferred on the gene in question on the basis of its expression 
>> pattern.
>> Either way the gene is being expressed.  This is a good reason NOT to
>> complicate the IEP evidence code unecessarily.
>>
>> However, over-expression phenotypes and loss of function phenotypes
>> provide qualitatively different types of evidence, and there is value
>> in recording the distinction at the point of curation.  Speaking as a
>> curator, the extra curational load to be incurred by making this
>> distinction would most likely be more than offset in the value to the
>> user, who depending on the question that they are asking might choose
>> to ask for GO statements based on one kind of phenotypic evidence but 
>> not
>> the other.  (Please speak up if you disagree). This is true
>> irrespective of Stan's (erstwhile?) ambitions in trying to model
>> necessary & sufficient based on GO/evidence codes.
>>
>>
>> Rachel.
>>
>>
>>
>>
>>
>>
>>
>>  
>>
>>> Envelope-to: r.drysdale at gen.cam.ac.uk
>>> Delivery-date: Wed, 18 Feb 2004 14:54:39 +0000
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>>> Date: Wed, 18 Feb 2004 14:19:01 +0000 (GMT)
>>> From: David Sutherland <djs93 at gen.cam.ac.uk>
>>> To: Rebecca Foulger <ref26 at gen.cam.ac.uk>
>>> cc: SLetovsky at aol.com, gofriends at genome.stanford.edu
>>> Subject: Re: necessary & sufficient
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>>  
>>
>>> Hi all,
>>>
>>> The reason my attempted definitions were so genetic is that, at 
>>> least as I
>>> understand them, necessary and sufficient are fundamentally genetic
>>> concepts.  I find it particularly difficult to see what a non-genetic
>>> concept of whether a gene is necessary for some process might 
>>> consist of.
>>> (I chose to work in flies, after a PhD in Xenopus development, 
>>> precisely
>>> because I was dissatisfied with the impossibility of finding
>>> whether a gene is necessary for a process by overexpressing it.)
>>>
>>> Clearly, genetics is just one source of useful evidence for 
>>> assigning GO
>>> terms (I certainly didn't intend to imply otherwise).  Where I think 
>>> that
>>> the terms necessary or sufficient could potentially be useful is in
>>> subdividing the "inferred from mutant phenotype" evidence code. 
>>> Providing
>>> that it is possible to come up with useable (sufficiently unambiguous)
>>> rules for curators to apply these terms, they would provide an 
>>> additional
>>> tool (along with existing evidence codes) allowing users of GO data to
>>> assess confidence.  My own personal bias is that necessary alone 
>>> inspires
>>> more confidence than sufficient alone, and both together trump either
>>> seperately, but users with a different bias needn't follow this.
>>> Perhaps a less terminologically loaded way of getting the same info
>>> across would be to split IMP into 'inferred from over-expression
>>> phenotype' and 'inferred from loss of function phenotype'.  Looked 
>>> at like
>>> this, maybe the use of GO-terms at the allele level as part of a 
>>> phenotype
>>> ontology system solve this anyway (?)
>>>
>>> David
>>>
>>>
>>> On Wed, 18 Feb 2004, Rebecca Foulger wrote:
>>>
>>>   
>>>
>>>> Hi Stan,
>>>>
>>>> Just to clarify on your last point:
>>>>
>>>>
>>>>     
>>>>
>>>>> it is surprising that [snip]
>>>>> purely phenotypic criteria are used to associate a gene with a 
>>>>> biological processes.
>>>>>       
>>>>> I always thought part of the goal of GO was to move away from 
>>>>> describing
>>>>> things in terms of mutant phenos to associating genes with normal 
>>>>> biological
>>>>> processes
>>>>>       
>>>>
>>>> Curators just use a mutant phenotype to infer the 'normal' biological
>>>> process a gene product is involved in. This is only one of the 
>>>> types of
>>>> evidence that a curator may use though. Genetic interactions, direct
>>>> assays, sequence/structural homology, expression patterns etc can all
>>>> lead a curator to assign a GO term to a gene product. And curator
>>>> judgement is used to interpret the phenotype/interaction results
>>>> against the genetic background and other experimental variables in
>>>> these cases (like an un-written version of the conditions you 
>>>> propose).
>>>>
>>>>
>>>> Becky
>>>>
>>>>
>>>>     
>>>>
>>>>> Envelope-to: ref26 at gen.cam.ac.uk
>>>>> Delivery-date: Tue, 17 Feb 2004 22:14:45 +0000
>>>>> X-Authentication-Warning: fafner.Stanford.EDU: majordom set sender 
>>>>> to owner-gofriends at genome-mail.stanford.edu       
>>>>
>> using -f
>>  
>>
>>>>> From: SLetovsky at aol.com
>>>>> Date: Tue, 17 Feb 2004 15:22:38 EST
>>>>> Subject: Re: necessary & sufficient
>>>>> To: jblake at informatics.jax.org, djs93 at gen.cam.ac.uk
>>>>> CC: gofriends at genome.stanford.edu
>>>>> MIME-Version: 1.0
>>>>> X-Cam-ScannerInfo: http://www.cam.ac.uk/cs/email/scanner/
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>>>>
>> NO_REAL_NAME 0.82,  
>>
>>>> X_AUTH_WARNING -0.40)
>>>>     
>>>>
>>>>> X-Cam-SpamScore: ss
>>>>>
>>>>> In a message dated 2/16/2004 4:42:24 PM Eastern Standard Time, 
>>>>> jblake at informatics.jax.org writes:
>>>>> Hi Stan,
>>>>>
>>>>> I think David illustrates well that biological knowledge is the 
>>>>> accumulation of experimental information that allows a 'judgement' 
>>>>> ;  there is not a 'necessary and sufficient' component of a GO 
>>>>> term association that would be easy to define, I think. The 
>>>>> evidence codes provide a method of 'summary statement' of the 
>>>>> evidence used in standardized way that allows users a 'confidence' 
>>>>> assessment in a way. The citation provides the researcher access 
>>>>> to the information about the experimental procedures used, etc.
>>>>> Judy,
>>>>>
>>>>> What I was after was a general recipe for testing predicted GO 
>>>>> assignments. So the
>>>>> evidence for known GO assignments doesn't really help. David's 
>>>>> criteria are more
>>>>> on target, but they are quite complex, and fundamentally genetic. 
>>>>> They suggest (to me)
>>>>> the following N&S conditions:
>>>>>
>>>>>    gene G gets biological process term T iff
>>>>>    there exists a homo/heterozygous loss/gain-of-function mutant 
>>>>> for G,                      a genetic background
>>>>>               and an environment    that together show a perturbed 
>>>>> T which is not attributable to some other process U    which is 
>>>>> causally upstream from T but not "part-of" T,
>>>>>    and which is not evident in the same genetic background and 
>>>>> environment with    the wild-type G.
>>>>>
>>>>> (I am trying to make the definition handle lethals and pathway 
>>>>> redundancy correctly. Both cause problems -- lethals because they 
>>>>> affect everything, yet we don't say they are involved in all 
>>>>> processes, and redundant pathway steps because they may not have a 
>>>>> pheno in wild type, yet we still may say they are involved in some 
>>>>> processes. So the "which is not attributable to" is for lethals, 
>>>>> and the "in some genetic background" is for redundants.)
>>>>>
>>>>> To use this definition for experimental design would seem to require:
>>>>>
>>>>>    1. ability to generate KO / OEX constructs for any gene of 
>>>>> interest
>>>>>    2. screens/phenotypes for any process T, sensitive to "direct 
>>>>> effects" on T only
>>>>>    3. a potentially unlimited set of background genotypes (to 
>>>>> detect interactions) and      environmental conditions
>>>>>
>>>>> 1&2 is not inconceivable given high-throughput screens that have 
>>>>> been developed.
>>>>> 3 is much more problematic. Part of the beauty of the "module 
>>>>> networks" paper
>>>>> was that (2) was always microarrays, and (3) was specified by the
>>>>> automatically generated hypotheses.
>>>>> David's criteria make sense, but I am somewhat surprised at how 
>>>>> "genetic" they are --
>>>>> not that it is surprising that David would propose genetic 
>>>>> criteria, but rather that
>>>>> purely phenotypic criteria are used to associate a gene with a 
>>>>> biological processes.
>>>>> I always thought part of the goal of GO was to move away from 
>>>>> describing
>>>>> things in terms of mutant phenos to associating genes with normal 
>>>>> biological
>>>>> processes, but maybe that's just a terminological shift. Does this 
>>>>> mean that there is (in a given species) always a clear mapping 
>>>>> between phenos and BPs?
>>>>>
>>>>> Cheers, -Stan
>>>>>       
>>>>
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>>>>     
>>>
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>>
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>
>
>
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