[Ontology-editors] Precoordination of "response to" terms & drugs

[David Hill]

I think we need to re-explore the definition of the 'response to' terms. 
I would like to see them (and all other processes for that matter) 
defined with a beginning and an end, specifically with respect to 
whether we want to make them pertain to a cellular level, or an 
organismal level in multicellular organisms.  I think we need to discuss 
this at the meeting. I know that there are good arguments for annotating 
gene products that, for example change after exposure to a stimulus. I 
have seen excellent examples of why these types of annotations can be 
useful. However, Alex has valid points in his argument for not including 
these. I can present some ideas about how to handle this at the 
consortium meeting. One way would be to create 'regulation of gene 
expression in response to X' terms. These would then get the IDs of the 
responding genes as targets in column 16. This would differentiate these 
from gene products in the signaling pathways that transduce the response 
on a cellular level. The issue would then be, how to relate these gene 
expression  terms to the 'response to' terms themselves. If they become 
a part_of, then the response to terms would remain as global as they 
currently are defined.



Chris Mungall wrote:
> What's our policy here?
>
> We already have a fair number of "response to X" terms.
>
> On the surface there is a potential for explosion here. You could 
> imagine a high-throughput assay testing against a massive 
> combinatorial chemistry library and measuring gene expression levels, 
> each experiment yielding an annotation where there is upregulation or 
> downregulation of genes. And if we go beyond chemical entities, 
> there's a huge variety of behaviors an organism could potentially 
> respond to.
>
> We can restrict the number of declared GO terms by applying our rule: 
> is response to X substantially different from response to Y? Are 
> different receptors or pathways used? If not then one term will do. 
> The additional information can go in col 16. But it seems that this 
> may be hard for us to determine in many cases.
>
> Even so, I feel we should continue to pre-coordinate here. I don't 
> fear the explosion here - this part of the graph can be managed almost 
> entirely automatically, like we are beginning to do with regulation.
>
> This is related to the response to drug issue: some people don't like 
> the "response to drug" term, and we came up with a way of doing this 
> using annotation xps. But this maybe isn't necessary.
>
> CHEBI have moved from an overloaded is_a hierarchy to using has_role 
> relations between some entities and drugs. We can define "response to 
> drug" as "response to a chemical entity that is sometimes used as a 
> drug", and not worry about whether the gene product is acting in 
> response to the chemical in its drug-role or non-drug role. is_a 
> parentage under "response to drug" would be determined entirely 
> automatically based on CHEBI.
>
> Personally I don't think "response to drug" is a great scientific 
> term, but it seems it's useful for grouping and analysis purposes, it 
> doesn't really do anyone any harm. We could tag it in a slim.
>
> So I am thinking that precoordination is the way to go here.
>
> This arose from lakshmi's test GAF file with col 16 - they want to 
> annotate to "response to ryanodine". Should we just suggest that they 
> request this term? Looking at the paper it wasn't clear to me
>
> Another question: should every "X receptor activity" term be linked to 
> "response to X (stimulus)" via part_of? I don't see why not, given 
> current definitions.
>
>
>
>
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-- 
David P. Hill, Ph.D.
Bioinformatics Scientist: Ontology Development
Gene Ontology Consortium
The Jackson Laboratory
www.geneontology.org
www.informatics.jax.org
tel:207-288-6430