Ontology meeting 2011-12-21
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- Paul Thomas
- Rebecca Foulger
- Jane Lomax
- David Hill
- Tanya Berardini
REPRESENTING REGULATION IN GO (particularly signaling)
Signaling pathways are essentially a series of regulation steps, and we need a way to better represent this in GO.
- Paul Thomas presented a preliminary proposal of representing regulatory events in GO better (with a focus on signaling pathways).
- Defining pathways as a set of MFs: need to say what the functions are regulating.
- Way of representing what a molecule DOES to another molecule (if possible, connected to the mechanism by which it does it; regulation at the molecular level).
- This brings in the idea of having 'roles' in GO, to give two branches of the function ontology. E.g:
molecular role --receptor activity --protein-specific activity regulator ----biochemical_activity_regulator -----biochemical_activity_regulator_by_protein_modification -------protein kinase activity
has Target Effect => some regulation has Target Protein => some protein
Using MAPK cascade as an example
- A MAPK cascade would consist of at least a MAP3K, a MAP2K and a MAPK.
- Class = MAPK cascade. You would have variations of class, depending on what's in the cascade, but it would have at least:
MAP4K (0 or more) | v MAP3K (at least 1) | v MAP2K (at least 1) | v MAPK (at least 1)
- MAP3K is part of the MAPK cascade, and its role in the cascade is to phosphorylate a MAP2K.
- See PMID 20811974 for a reference (The MAP Kinase Signaling Cascades: A System of Hundreds of Components)
- Some cascades will have hundreds of variations. For example PI3K activates AKT. AKT is a Ser/Thr kinase with HUGE numbers of downstream targets. Therefore, the variations on the class would be large.
- Need to capture:
- Components that signal TO PI3K (E.g IRS1)
- Components that signal FROM PI3K (E.g. TOR)
- Protein X and PI3K signal in the same pathways, but it's not known whether PI3K is upstream or downstream
How to proceed
- Keep adding in the signaling pathways VIA x cascade terms, using HAS_PART relationships.
- Connect MF and BP terms as much as possible (E.g. PI3K signaling HAS_PART PI3K activity).
- Carry on better defining the limits of the intracellular cascades
- Paul to talk to Chris M. about his proposal, and to send it round the editors list.