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

[Chris Mungall]

I think putting this on the agenda is a good idea

On Mar 12, 2009, at 2:49 PM, David Hill wrote:

> 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
>
>