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Rhea - User manual1. Introduction
The ability to describe biochemical reactions precisely constitutes a very
important task as it is the foundation for accurate modelling of metabolic
networks and calculating metabolite fluxes in biological systems. Several
current efforts, such as KEGG and MetaCyc, use the Enzyme Commission (EC)
list as a basis to create enzymatically catalysed reactions, as the EC
numbering system provides both a formal description of the enzymes and a
categorisation of the enzymatic reaction taking place. Unfortunately, none
of the existing databases (the EC list included) can provide a set of
completely balanced reactions, nor do they provide a completely consistent
use of compound names. To improve the current situation we have constructed
a new reaction database (Rhea).2. Licensing
All data in Rhea is freely accessible and available for anyone to use.
All downloads are fully re-distributable.
The text on this website is available under the
Creative Commons
License.3. Scope
Rhea was initially loaded from reactions found in IntEnz and contains
mainly enzymatic reactions. All reactions were then manually annotated and
chemically balanced where possible. 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. All reactions in Rhea are
linked to their ChEBI participants which are either chemical compounds or
classes of compounds such as for example 'primary alcohol (CHEBI:15734)'.
In order for a reaction to be annotated in the Rhea database the
participants need to be appropriate ChEBI entries.4. 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 has been 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.
- Polymerization: the reaction implies the addition/removal
of monomers to/from a polymer.
- Class of reactions: at least one of the participants is
a class of compounds in ChEBI (e.g. primary alcohol,
CHEBI:15734), which means that the reaction can only occur with
concrete instances of it (e.g. ethanol, CHEBI:16236).
- Textual reaction equation (compound names)
Describes the reaction using its annotated chemical nomenclature with
each participant assigned its relevant coefficient. Note that each
unique compound in Rhea has its own unique name within Rhea, thus
ensuring 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. The chemical names can also be switched between formatted
names (the default) and ASCII names. Formatted names display the
correct formatted Unicode characters, for example
'α,α-trehalose 6-phosphate' is the formatted equivalent of the ASCII
'alpha,alpha-trehalose 6-phosphate'.
- ChEBI IDs reaction equation
Describes the reaction using ChEBI identifiers. Beside every ChEBI ID
there is an icon:
 .
Clicking on it searches Rhea for any reactions involving that very same
compound.
- Reaction equation displayed with chemical structures
The full chemical reaction is shown linked to its relevant chemical
structure. The directionalities of the reactions are indicated by the
arrows. Some reactions can be shown using Chemaxon's Marvin applet
(please refer to Marvin Quick
help for details). Others will be shown as image structures. You
can switch between representations when both are available.
- Steps/coupled reactions
If the Rhea entry being described is a decomposition of an overall
transformation into multiple elementary reactions, then these are
indicated in this field as steps or coupled reactions.
Steps are ordered in time, coupled reactions are not. They are shown
as ordered or unordered lists, respectively.
Each elementary reaction may be multiplied by its own reaction
coefficient, indicated with a numeral followed by a 'x'.
- Overall reaction
In case of decompositions (see above) the database may contain an
equivalent elementary reaction. This section will point to that entry.
- Same participants, different directions
This field lists reactions with the same sets of reactants and products,
but other directionalities. Each direction has its own unique stable
identifier. Please see Section 5.1 for more information on reaction
directions.
- Decompositions
In this section you will find any available decompositions of an
elementary reaction in steps/coupled reactions (see above).
- Decompositions this reaction is part of
If a reaction is used as part of any decompositions then these are
indicated in this field.
- Cross-references
Indicates cross-references to other related databases. Most of these
are manually annotated, but those which are automatically loaded into
the database are labelled as [AUTO].
- Literature citations
Where a reaction is described in a paper, then this may be cited by
Rhea annotators.
5. Reaction annotation policies5.1 .Directionality
Reactions may be annotated in the following directions:
- 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.
- unspecified/unknown (<?>), indicates that the direction
of this reaction is unknown.
Each direction will have its own stable independent identifier. Unless
there is evidence otherwise, it is assumed that all reaction directions
are valid and it is the user's responsibility to select the relevant
reaction. For example, in some cases the user may simply not know which
direction the reaction occurs and should in this case use the
unspecified direction.
Currently, every decomposition in Rhea is unidirectional, being the sum
of unidirectional step/coupled reactions. 5.2. Normalisation of reactions
All reactions in Rhea are normalised by using the major microspecies of
their participants at pH 7.3, in order to reduce the number of entries in
the database should they be annotated at different pH values. This is
done with ChemAxon's software MarvinBeans.
This normalisation does not affect searches: you may search for
reactions using any charged or neutral forms of compounds; the Rhea
search engine will normalise it to pH 7.3 for you.6. Searching Rhea6.1. Simple search
The first thing you see in the home page is a big text field
and a "Search" button. You can use these for simple searches.
In other pages you will also find a search box
- at the top right corner - with exactly the same functionality.
Your query can be:
- A compound name or identifier (ChEBI ID or other):
ChEBI index is used
to resolve any synonyms and cross references.
- A reaction ID (Rhea ID).
- An equation: Rhea will try to parse this and return any matching
reactions which exist within the database. If none is found,
it will look for similar reactions, i.e. with as many of the
participants in the equation as possible.
- A cross reference (ex. EC number).
- A citation (author name, title, abstract text or publication ID).
The following wildcards are allowed: ? (question mark =
one character) and * (asterisk = several characters). None of
these can be used at the beginning of a query term, though. Double
quotes are also allowed in order to search phrases (f.i. compound names
with more than one word).
When sending an equation to parse, please avoid any wildcards and use
compound names as accurate as possible. No quotes are needed in this
case for two-word compounds. 6.2. Advanced search
The advanced search page allows you to submit queries related to
the reaction itself or its participants. 6.2.1. 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 will be run against all or any one of
the following fields:
- Rhea ID
- Cross references to other reaction or pathway databases
- Bibliographic citations (author name, title, abstract
text or publication ID)
- Comments
6.2.2. 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. 6.3. 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.
At the top of the list is the simple search box, which you can use
to change your query and submit it again.7. Downloads
Rhea as a whole is available in a number of formats from the downloads page, where you will
find more detailed information about them and their usage. |