1. What is Rhea?Rhea is a freely available and comprehensive resource of expert-curated biochemical reactions. It has been designed to provide a non-redundant set of chemical transformations for applications such as the functional annotation of enzymes, pathway inference and metabolic network reconstruction. There are three types of reaction participants (reactants and products):
- Small molecules
- Rhea polymers
- Generic compounds
2. Who is involved?Rhea is a collaborative effort between the Swiss-Prot Group at the SIB Swiss Institute of Bioinformatics and the EMBL-EBI.
3. AvailabilityRhea is available via this public web interface. Rhea as a whole is available in a number of formats from the Download page, where more detailed information about the formats and their usage is provided. Rhea is also available via web services and a SPARQL endpoint.
4. LicensingAll data in Rhea is freely accessible and available for anyone to use under the Creative Commons Attribution License. See License & Disclaimer.
Updates in Rhea - an expert curated resource of biochemical reactions
Nucleic Acids Research (2017) 45:D415–D418; doi: 10.1093/nar/gkw990
6. How to contact Rhea?Send your comments to the Rhea team using the feedback form.
7. FundingRhea development and curation activities at the SIB are supported by the Swiss Federal Government through the State Secretariat for Education, Research and Innovation (SERI).
Rhea curation was previously supported by SystemsX.ch and by MICROME (an EU Framework Programme 7 Collaborative Project. Grant Agreement Number 222886-2).
8. About the nameIn classical Greek mythology, Rhea (greek Ρέα; /ˈriːə/) was the daughter of Uranus and Gaia, and was known as the mother of gods. Her name is often linked to the Greek word ρείν ("flow") but has no relation to the word "reaction". Rhea is the name of a genus of flightless birds, also known as ñandú. Rhea is also the name of the second-largest moon of Saturn.
1. IntroductionAll reactions in Rhea are manually annotated and chemically balanced where possible (some reactions with status preliminary may not be balanced due to a limited knowledge of the reaction mechanism).
Reactions in Rhea are independent of their spatial location (subcellular, tissue, organ, species) and their catalyst. Hence Rhea may also contain non-enzymatic reactions, for example, what are often termed 'spontaneous' reactions.
2. Reaction participantsThere are three types of reaction participants (reactants and products), all of them are linked to ChEBI entries:
- Small molecule
- Rhea polymer
- Rhea generic
- A small molecule is linked to one ChEBI compound. Its accession is the ChEBI accession.
Example: CHEBI:57844 in Rhea reaction RHEA:10048.
- A Rhea polymer is linked to one ChEBI compound (the underlying polymer), it has an accession of the form POLYMER:xxxxx or RHEA-COMP:xxxxx (with xxxxx being a numeric identifier).
A Rhea polymer can exist with several different polymerization indexes.
Example: POLYMER:9584 (RHEA-COMP:9584) [(1->4)-alpha-D-glucosyl]n, POLYMER:9587 (RHEA-COMP:9587) [(1->4)-alpha-D-glucosyl]n+1 and POLYMER:9586 (RHEA-COMP:9586) [(1->4)-alpha-D-glucosyl]n-1) which is different from a ChEBI polymer which always exists with polymerization index n
Example of Rhea reaction involving Rhea polymers: RHEA:24572.
- A Rhea generic is a molecule that is not represented as is in ChEBI, it has an accession of the form GENERIC:xxxxx or RHEA-COMP:xxxxx (with xxxxx a numeric identifier).
Rhea generics are proteins, nucleic acids or polysaccharides acting as reactants or products in a Rhea reaction.
Such molecules are modeled with the residues and/or functional groups that are directly involved in the chemical transformations. The residues and/or functional groups are linked to ChEBI compounds.
Examples: GENERIC:9685 (RHEA-COMP:9685) (holo-[ACP]) or GENERIC:9621 (RHEA-COMP:9621) (acetyl-[ACP]) in RHEA:41788
It is possible to find several generic compounds with the same functional group (e.g. GENERIC:9669 (RHEA-COMP:9669) tRNA(Ser) and GENERIC:9657 (RHEA-COMP:9657) tRNA(Ala)).
3. Data fields
- Rhea Identifier
The Rhea identifier is a randomly chosen numeric identifier used solely for the purpose of identifying the reaction. The Rhea identifier is stable and will not be removed from any future versions of Rhea. If an error is found in the data then the Rhea reactions may be deprecated but then this will be clearly indicated when searching for the identifier.
- Last modification date
Indicates the last time this reaction was modified.
- Qualifiers (if any)
- Chemically balanced: the stoichiometry has been checked as valid according to formulae retrieved from ChEBI.
- Transport: a participant appearing on both sides of the reaction traverses some biological membrane.
- Class of reactions: at least one of the participants is a class of compounds in ChEBI (e.g. primary alcohol, CHEBI:15734), which means the reaction cover several reactions with similar compounds (e.g. ethanol, CHEBI:16236, propan-1-ol, CHEBI:28831).
- Textual reaction equation (compound names)
Describes the reaction using the annotated names of the participants with each participant assigned its relevant coefficient.
Note that each unique compound in Rhea has its own unique name within Rhea. This constitutes a controlled vocabulary.
The chemical names are selected to be unambiguous wherever possible, with the controlled vocabulary of chemical nomenclature being stored and maintained within the ChEBI database.
- Reaction equation displayed with chemical structures
The full chemical reaction is shown linked to its chemical structure.
The directionalities of the reactions are indicated by the arrows.
- Same participants, different directions
This field lists reactions with the same sets of reactants and products, but with different directionalities.
Each direction has its own unique stable identifier. Please see Section 4.1 for more information on reaction directions.
Indicates cross-references to other related databases.
- Manually annotated cross-references
- Automatically generated cross-references
- MACiE (Mechanism, Annotation and Classification in Enzymes)
- UniProt protein entries
UniProt cross-references are inferred from cross-references to EC numbers.
- Reaction relationships
Relations between two Rhea reactions, sorted by "outgoing" and "incoming". E.g.: reactionA can have an outgoing relationship "reactionA is a reactionB" or an incoming relationship "reactionB is a reactionA". See e.g. RHEA:18596.
When a reaction is described in the literature, the original citation is added.
4. Reaction annotation policies
4.1 DirectionalityIn Rhea, a master reaction has an unspecified/unknown (=) direction. Each master reaction is associated to 3 directional reactions:
- left to right (=>), indicates the direction flows from left to right.
- right to left (<=), indicates the direction flows in the reverse direction.
- bidirectional (<=>), indicates the direction occurs in both directions.
4.2. Normalisation of reactionsEach master reaction is uniquely represented at an arbitrarily chosen pH of 7.3.
Rhea uses the Marvin pKa calculator from ChemAxon to select the major microspecies found at pH 7.3 and at a temperature of 298K.
This guarantees data consistency, since the same protonation state will be used in all reactions.
This convention is in accord with that adopted by some existing resources, such as MetaCyc, but contrasts with that adopted by others, such as KEGG.
This feature does not affect searches: you may search for reactions using any charged or neutral form of compounds; the Rhea search engine will calculate the correct form from the query.
5. Searching Rhea
5.1. Simple searchYou can use the search box at the top of each page to perform simple searches. Your query can be:
- A compound name or a compound identifier (ChEBI ID, Rhea polymer ID or Rhea generic ID): the ChEBI index is used to resolve any synonyms or cross references.
- A reaction ID (Rhea ID).
- A cross reference (e.g. an EC number).
- A citation (author name, title, abstract text or publication ID).
5.2. Advanced searchThe advanced search page allows you to submit queries related to the reaction itself or its participants.
5.2.1. Reaction searchIn this section you can perform a text search, choosing to match any of the search terms (logical operator OR), all of them (logical operator AND) or the exact phrase.
An additional text field allows you to exclude results with a given word.
The search is performed in all or any one of the following fields:
- Rhea ID
- Reaction participants
- Cross references to other reaction or pathway databases
- Bibliographic citations (author name, title, abstract text or publication ID)
5.2.2. Chemical structure searchThis section is powered by ChEBI's search engine, including its powerful structure search feature. Please refer to ChEBI's User Manual for details.
Following submission of the query to ChEBI, a table will be displayed showing matching compounds. Clicking on one of the "Rhea reactions" links will send you to the results page relevant to a given compound.