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necessary & sufficient

Judith Blake jblake at informatics.jax.org
Mon Feb 16 13:41:39 PST 2004


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.

At various times the GO community has discussed an 'ontology of 
evidence'.  We have not done this as a group effort since each resource 
that uses the GO incorporates experimental data to different degrees and 
such a system would not work for all of us.  In the mouse system, much raw 
data is collected and provided to users in a structured, standard way so 
that a user can, for example, look at images of hybridzations, rt-pcr gels, 
etc.  Thus a user can see that raw data and evaluated it for themselves.

One area where there has been lots of discussion is in the IEA (inferred 
from electronic annotation).  These algorithmic approaches are considered 
the weakest evidence.  Whenever I'm involved in a large, semi-automated 
genome annotation events we go through various iterations about what the 
criteria for IEA assignments might be (can we import as IEA the curated GO 
annotation to a putative homolog? of what evolutionary distance?).  The 
decisions are documented at least.

Anyway, I think it will be hard to define definitive statements of 
'necessary and sufficient' in this realm.

Judy


At 06:52 AM 2/16/2004, David Sutherland wrote:
>Hi Stan,
>
>I'm not party to any GO discussions of defintitions for these
>terms, but here's by penneth anyway:
>
>If a loss of function mutation results in a phenotype in which a structure
>or function is absent, than that gene can be considered necessary for that
>function/structure.
>- the 2 problems I can see with this are:
>1. what to do in situations when penetrance or expressivity of the
>phenotype is low (& environmental effects on these)
>2. How to account for genetic background - it is always feasible that some
>genetic background exists in which loss of function mutations of the gene
>do not cause loss of the structure/function.  Perhaps the way sround this
>is to always express necessary with a tag giving genetic background - the
>default being that mythical beast 'wild-type'.
>
>The geneticist/developmental biologist definition of sufficient, as I see
>it: If overexpression of a gene results in formation of an ectopic
>structure or function (even at low levels of penetrance or expressivity)
>then it is sufficient for formation of that structure/funtion.  Again, I
>think genetic and environmental background need to be recorded (with
>default as WT).
>
>A more ambiguous situation is in the case of overexpression of activated
>forms (e.g.- activated receptors).  Excluding these would avoid some
>difficult calls: 1.  does the activation strictly mimic activation of
>'normal' physiological function ?
>2. How do we deal with spontaneous mutations leading to activation of a
>function (not uncommon with receptors)?
>
>
>Note: There is also a competing use of the term sufficient by computer
>modellers, whose aim is often to find the minimal set of components and
>parameters "sufficient" for a system (e.g.- mechanism for patterning of
>some structure) to produce the same output as the system being studied.
>
>Hope this is useful,
>
>David
>
>
>David Sutherland
>FlyBase, Cambridge UK
>
>
>On Sat, 14 Feb 2004 SLetovsky at aol.com wrote:
>
> > Gofriends,
> >
> >     Does anyone know of any attempts to define necessary and sufficient
> > criteria
> > for GO associations? I am familiar with the attempts to provide rigorous
> > semantics
> > for ISA and partof, but I have not seen anything comparable for 
> determining
> > when it is
> > correct to say that a term does or does not apply to a gene or protein --
> > e.g. what
> > experimental result would suffice to answer the question.
> >
> > Cheers, -Stan
> >
>
>
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