RHEA and EC mappings

Cross-references for enzyme reactions

GO uses Rhea for the definitions of reactions. At some point in the future, we will use the Rhea xrefs to automatically populate definitions and to classify reactions based on participation. In addition, we will use Rhea as the source of information for EC xrefs when the Rhea xref is available.

Note that those cross-references should only be applied to MF terms.

Other mappings for Molecular Functions

Database cross-references used in GO

Ontology	Database	Sample dbxref
Function	Enzyme Commission	EC:3.5.1.6
	Transport Protein Database	TC:2.A.29.10.1
	University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD)	UM-BBD_enzymeID:e0310
	MetaCyc metabolic pathway database	MetaCyc:XXXX-RXN
Process	MetaCyc metabolic pathway database	MetaCyc:2ASDEG-PWY
	University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD)	UM-BBD_pathwayID:dcb
Component	None

Plan of Action (2012/2013)

Plan for setting up a pipeline for automatically incorporating curated catalytic reactions from Rhea into GO MF. 1 and 2 can happen simultaneously.

1. Map existing GO catalytic activity terms to Rhea. Will require some text-ming/matching etc. and lots of manual review. Add Rhea xrefs to GO. Submit missing reactions to Rhea.

   Considerations:

   • grouping classes won't go into Rhea - will need be handled separately. How do we make axioms for these?
   • do Rhea want to incorporate our reactions?
   • intern to do this?

   Inputs

   • http://www.ebi.ac.uk/rhea/download.xhtml
2. Design pattern for catalytic reaction xps. Create xps, review and add to GO.

   Considerations:

   • bi-directionality of the reactions won't work in OWL. Did we have a solution to this?
3. add missing reactions from Rhea to GO. Not sure if we'll want to add all, but certainly everything with an EC. Rhea is available as BioPax, so we will need to convert to OWL and add reactions names, figure out where they fit in the hierarchy.

   Considerations:

   • on what basis we will auto-classify - use EC mechanism as a grouping?
   • naming classes from Rhea - use KEGG?
4. Set up a pipeline for importing new reactions from Rhea to GO (upon Rhea release?):
   • pull out new reactions from Rhea
   • convert BioPax to OWL
   • use reasoner to place new classes in GO MF
   • manual check
   • add to live GO

   Considerations:

   • interval between imports
   • do we recommend people submit new reactions via Rhea rather than GO?
   • do we also have a TG template for new catalytic reactions?

Background on Rhea

In the Rhea project the curators from the SIB are currently working on several aspects, including improving the coverage of known reactions, as well as improving the handling and representation of reactions including polymers and macromolecules, in collaboration with colleagues from ChEBI. The main focus at the current time is really improving the coverage of Rhea (chemically balanced reactions), with a view to promoting its use as a resource for metabolic network reconstruction (e.g. Microme, MetaNetX projects) and as a source of reaction descriptions for UniProt.

Rhea can be used as a source for automation of some of the GO--ChEBI cross-products. It confers the benefit of a more sophisticated representation of chemical roles in reactions than just "input" and "output".

However, it might be more efficient if GO just outsources the whole reaction hierarchy to Rhea, and gets everything from Rhea - text definitions, logical definitions, synonyms etc. The GO editors would give Rhea a block of GO IDs and new reaction term requests would go via Rhea. Either way, we would get the ec2go links via go2rhea and rhea2ec

Current SOPs for handling enzyme updates and new terms

Amelia's Guidelines for New Enzyme Requests

http://wiki.geneontology.org/index.php/Curator_Guide:_Enzymes_and_Reactions

S.O.P for multi-step enzyme reactions

E.g. EC:1.14.13.78

See Amelia's notes

Links to enzyme resources

• Rhea: Expert-curated knowledgebase of chemical and transport reactions of biological interest - and the standard for enzyme and transporter annotation in UniProtKB.
• Intenz IntEnz (Integrated relational Enzyme database) is a freely available resource focused on enzyme nomenclature. IntEnz is created in collaboration with the Swiss Institute of Bioinformatics (SIB). This collaboration is responsible for the production of the ENZYME resource.
• Enzyme Commission - IUBMB
• EC enzyme nomenclature
• KEGG reactions
• MetaCyc