Closed cthoyt closed 1 year ago
Would this also set precedence for adding other, more specific mechanism properties? e.g. mechanisms in biolink
I think it would be totally fantastic to have biolink-like properties standardized in RO as well!
+1 to standardizing Biolink predicates/properties in RO 🚀
Notes for RO meeting:
@cthoyt maybe we could create some test GO-CAMs and then decide which nodes you would like these relations to go between. It also might help us to define any additional rules that would be useful.
@wdduncan in the last few commits, I moved these relations under the directly negatively regulates activity of and directly positively regulates activity of, which have clear domain and range annotations both being material entities. The description of these properties directly addresses the comments made by @addiehl to better notate that the existence of a relation mibolerone (CHEBI:34849) is agonist of androgen receptor (PR:P10275)
implies that there is some activity of PR:P10275
that is getting modulated.
I found the example usage
annotation and added some explicit examples for each both in the PR description and in the ontology.
I added seeAlso links to related Wikidata properties.
I improved the descriptions for each as well.
@balhoff here's a first stab at the relations that might be in a GO CAM
subject name | subject curie | relation name | relation curie | object name | object curie |
---|---|---|---|---|---|
tretinoin | CHEBI:15367 | is antagonist of | RO:0018029 | Nuclear receptor ROR-beta | PR:Q92753 |
Nuclear receptor ROR-beta | PR:Q92753 | enables | RO:0002327 | activity nuclear receptor activity | GO:0004879 |
tretinoin | CHEBI:15367 | is small molecule inhibitor of | RO:0012006 | activity nuclear receptor activity | GO:0004879 |
(updated based on comments from Jim)
Thanks @cthoyt ! This area is out of my domain of expertise. So, I am going to defer to those more knowledge than me about whether this PR is read to be merged :)
@balhoff here's a first stab at the relations that might be in a GO CAM
@cthoyt great, thanks! For your 'has activity' cell, you would use enables. Should there be a way to infer 'is antagonist of'? For example:
'is small molecule inhibitor of' o 'enabled by' -> 'is antagonist of'
Or is there not enough information there to distinguish 'is antagonist of' from 'is inverse agonist of'?
Similar question for is small molecule activator of and 'is agonist of'.
@balhoff thank you for the feedback! I don't think we can make this super general as the difference between antagonism and inverse agonism is based on the way that the chemical binds to the receptor. Also, not all 'is small molecule inhibitor of' o 'enabled by'
should be 'is antagonist of'
. This should only be true if only if we restrict the range of the enabled by
to be receptor activity (GO:0004872) and we say something specific about the mechanism of bindin (seems a bit complicated for this first pass)
In Biolink we define antagonism
as "A causal mechanism in which the effector binds to a receptor and prevents activation by an agonist through competing for the binding site."
And inverse agonism
in Biolink is "A causal mechanism in which the effector binds to the same receptor-binding site as an agonist and antagonizes its effects, often exerting the opposite effect of the agonist by suppressing spontaneous receptor signaling."
Do these definitions reflect your understanding of the difference @cthoyt?
Yeah that’s basically what I wrote, but we can also update the definitions if you think that would be more clear
@balhoff @sierra-moxon @addiehl
Am I correct in assuming that you all have approved this PR, and it is ready to be merged?
Closes #371
Motivation
For ChIRO and the Chemical Roles Graph (https://github.com/chemical-roles/chemical-roles), we need more detailed relationships to describe causal interactions between chemicals (material entities) and receptors (material entity).
Existing relationships (i.e., directly negatively regulates activity of and directly positively regulates activity of) are not detailed enough.
See similar issue about drug-target relationships in https://github.com/oborel/obo-relations/issues/144.
What this PR does
This PR creates 3 new properties:
Big thanks to Jie, Alexander, Darren, Bill, and everyone else at the 2022-11-01 RO meeting who gave feedback and helped improve this PR.