Epistemic formalism (was Re: [Phenoscape] Re: [go] evidence code ontology)

[David Hill]

Tanya Berardini wrote:
>> But even then there may be key contexts that we are not testing for
>> in experiments.
>>     
>
> Yes, but this is the nature of research in biology.  You test as many
> of the contexts that you can think of are relevant but how do you know
> which are relevant?  It's the old 'unknown unknown' question.  So, we
> are stuck with capturing what has been tested and published.
>   
I agree.Even in the lab, it is often a challenge to make all the right 
controls, conditions etc while you are designing your experiments.
>   
>>> Another simple case of context is is two authors measuring the
>>> expression of a gene at the RNA level. If one author measures by
>>> Northern Blot, they may conclude the gene is not expressed. If
>>> another author uses a very sensitive assay such as RT-PCR they may
>>> detect expression of the gene. Would you consider this
>>> contradictory? I'd conclude that you can't detect it by Northern,
>>> but you can by RT-PCR. I'd also conclude that it is expressed. So
>>> in a way the conclusion made by the first author is incorrect, but
>>> it is consistent with the context in which he did the experiment.
>>>       
>> Out of interest, when annotating an experiment as this, would a
>> curator make a NOT annotation? To what extent does this depend on the
>> certainty of the author, and to what on the curators judgement
>> (including knowledge of the sensitivity of various techniques?)
>>     
>
> I think this is a great example of curation as an art opposed to a
> science.  It's easy to make hard and fast rules that are just waiting
> to be broken:  "If you don't see it in a Northern, it's not there."
> vs. "If you don't see it in a Northern, it could be there but you need
> more tissue/more mRNA/longer exposure/more sensitive probe...."
> Personally, I annotate the positives in Northerns and tend to stay
> away from the negatives (don't make the NOT annoation) because, you
> never know.   On the other hand, if the transcript isn't detected by
> Q- or SQ-RT-PCR, I would make that NOT annotation.
> Others may differ in that practice.
>   

I think Tanya really hits the nail on the head here. I don't think any 
of us exhaustively annotate NOT. If the author seems to feel that it's 
an important conclusion (maybe it was totally unexpected) then we 
annotate with a NOT annotation. The idea behind it in it's original 
context was to give people a 'heads up' that on the surface we may have 
a gene product where it seems like it should be given a GO annotation, 
but in fact it has been shown that this is not the case. If my memory 
serves me correctly the original discussion of NOT was for something 
like a peptidase that had great sequence similarity to other known 
peptidases, but was shown to lack a key residue and was therefore 
catalytically inactive.
>