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necessary & sufficient

Rebecca Foulger ref26 at gen.cam.ac.uk
Wed Feb 18 02:52:45 PST 2004


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


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> Subject: Re: necessary & sufficient
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> 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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