Rhea

Rhea provides an expert-curated, non-redundant repository of over 11,000 biochemical reactions represented using the ChEBI ontology to support enzyme annotation and integrative metabolite–proteome–transcriptome–genome analyses.

Key Features:

• Expert curation (Swiss-Prot, SIB): Rhea contains over 11,000 expert-curated biochemical reactions maintained by the Swiss-Prot group at the SIB Swiss Institute of Bioinformatics.
• ChEBI-based chemical representation: Chemical entities in reactions are represented using the ChEBI (Chemical Entities of Biological Interest) ontology to ensure standardized, non-redundant descriptions.
• Enzyme and spontaneous reaction coverage: Rhea describes enzyme-catalyzed reactions including the IUBMB Enzyme Nomenclature list and additional spontaneous reactions.
• UniProt enzyme annotation standard: Since December 2018 Rhea has been used as the standard for enzyme annotation in UniProt.
• Integration with knowledgebases: Rhea supports integration with core resources such as ChEBI, MetaboLights, and UniProt for cross-database annotation.
• RDF representation and SPARQL access: Reaction data are available in Resource Description Framework (RDF) form with a SPARQL endpoint at https://sparql.rhea-db.org/sparql for structured queries.
• Federated querying: Rhea enables federated SPARQL queries that integrate data from other SPARQL endpoints (for example UniProt) to link metabolite and protein information.

Scientific Applications:

• Enzyme annotation: Providing authoritative reaction definitions and identifiers for enzyme annotation in UniProt and related resources.
• Genome-scale metabolic modeling: Supplying curated biochemical reactions for reconstruction and curation of genome-scale metabolic models.
• Metabolite annotation and metabolomics: Supporting metabolite annotation workflows and integration with metabolomics repositories such as MetaboLights.
• Integrative omics analyses: Enabling federated queries that link the metabolome to the proteome, transcriptome, and genome for cross-omics studies.
• Linking chemistry to biology in health and disease: Associating chemical reactions with biological functions to support research into physiological and pathological processes.

Methodology:

Rhea represents chemical entities using the ChEBI ontology and exposes reaction data as RDF with a public SPARQL endpoint (https://sparql.rhea-db.org/sparql), supporting federated SPARQL queries with other endpoints such as UniProt.