About Rhea


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): All three types of reaction participants are linked to the ChEBI database (Chemical Entities of Biological Interest) which provides detailed information about structure, formula and charge. Rhea provides built-in validations that ensure both mass and charge balance of the reactions. We have populated the database with the reactions found in the enzyme classification (i.e. in the IntEnz and ENZYME databases), extending it with additional known reactions of biological interest. While the main focus of Rhea is enzyme-catalysed reactions, other biochemical reactions (including those that are often termed "spontaneous") also are included.

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. Availability

Rhea 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.

4. Licensing

All data in Rhea is freely accessible and available for anyone to use under the Creative Commons Attribution License. See License & Disclaimer.

5. How to cite Rhea?

Anne Morgat, Thierry Lombardot, Kristian B. Axelsen, Lucila Aimo, Anne Niknejad, Nevila Hyka-Nouspikel, Elisabeth Coudert, Monica Pozzato, Marco Pagni, Sebastien Moretti, Steven Rosanoff, Joseph Onwubiko, Lydie Bougueleret, Ioannis Xenarios, Nicole Redaschi, Alan Bridge
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. Use our SourceForge project pages for:

7. Funding

Rhea development and curation activities at the SIB are supported by the Swiss Federal Government through the State Secretariat for Education, Research and Innovation (SERI), and by the SystemsX.ch, The Swiss Initiative in Systems Biology.
Rhea curation was partially supported by MICROME (an EU Framework Programme 7 Collaborative Project. Grant Agreement Number 222886-2).

8. About the name

In 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.

User manual


1. Introduction

All 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 participants

There are three types of reaction participants (reactants and products), all of them are linked to ChEBI entries:

3. Data fields

4. Reaction annotation policies

4.1 Directionality

In Rhea, a master reaction has an unspecified/unknown (<?>) direction. Each master reaction is associated to 3 directional reactions: Each direction has its own stable independent identifier. This feature allows directional reactions from external resources to be linked to the appropriate directional reaction in Rhea.

4.2. Normalisation of reactions

Each 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 search

You can use he search box - at the top right corner - of each page to perform simple searches. Your query can be: The following wildcard characters are allowed: ? (question mark = one character) and * (asterisk = several characters). The wildcard characters cannot be used at the beginning of a query. Double quotes are also allowed in order to search for phrases (e.g. compound names consisting of more than one word).

5.2. Advanced search

The advanced search page allows you to submit queries related to the reaction itself or its participants.
5.2.1. Reaction search
In 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:
5.2.2. Chemical structure search
This 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.

5.3. Search results

The results page shows the list of matching reactions in the database, with their Rhea ID and equation, as well as the field(s) which match the query. Clicking on the Rhea ID leads to the entry page.