Searching Rhea

Content:

Introduction

There are several ways to search for data in Rhea:

  1. Text search
    Retrieve reactions with a full-text search, optionally searching in specific database fields that can be combined with logical operators.
  2. Structure search
    Retrieve reaction participants (and then reactions) by searching with a chemical structure.
  3. Retrieve/ID mapping
    Retrieve reactions by entering, or uploading, a list of identifiers from metabolic resources.
  4. SPARQL search
    Go to the Rhea SPARQL endpoint to execute semantic queries in Rhea and across the SPARQL endpoints of other resources.

Text, structure and SPARQL searches allow to search with reaction participants that are not directly used in a Rhea reaction. The next section explains how this works.

Searching via ontological relationships

Rhea uses the chemical ontology ChEBI (Chemical Entities of Biological Interest) to describe reaction participants in a computationally tractable manner. The website searches exploit some of the relationships of the ChEBI ontology, as well as the additional relationships that Rhea computes to link the different protonation states of a compound to its major microspecies at pH 7.3 that is used in Rhea reactions.

ChEBI is_a relationship

The is_a relationship classifies ChEBI concepts in a hierarchical tree. It allows to search with a general concept, e.g. a compound class like lipid (CHEBI:18059), and retrieve all reactions that use more specific forms of that concept.

Example: lipid

A text search for lipid returns reactions with at least one participant that is described using a ChEBI entity whose name or synonyms contain the query term, e.g. hepta-acyl lipid A (CHEBI:87048), or that is a more specific form of such an entity, e.g. the compound class lipid (CHEBI:18059) matches the query term, but is not itself a participant in a Rhea reaction, while its more specific forms a fatty acid (CHEBI:28868), 8(R)-HPETE (CHEBI:57447) and O-(S-fatty acylpantetheine-4'-phosphoryl)-L-serine residue (CHEBI:138651), the reactive part of a fatty acyl-[ACP] (RHEA-COMP:14125), are reaction participants and thus found by this search.

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Rhea has_major_microspecies_at_pH_7_3 relationship

The has_major_microspecies_at_pH_7_3 relationship links ChEBI entities that represent different protonation states of the same compound to to its major microspecies at pH 7.3 that is used in Rhea reactions.

Example: D-alanine

D-alanine has an amino group and a carboxylic acid group that can be (de)protonated. The different protonation states are described by 4 linked ChEBI entities:

A text search that matches any of these 4 entities will return the same result, the reactions that use the major microspecies at pH 7.3 (CHEBI:57416).

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Example: D-alpha-amino acid

D-alpha-amino acid has an amino group and a carboxylic acid group can be (de)protonated. The different protonation states are described by 3 linked ChEBI entities:

  • CHEBI:59871 - D-alpha-amino acid zwitterion (Rhea uses the synonym a D-alpha-amino acid) = major microspecies at pH 7.3
  • CHEBI:16733 - D-alpha-amino acid
  • CHEBI:60895 - D-alpha-amino acid anion

These ChEBI entities represent in fact compound classes that have subclasses, which in turn have subclasses, etc. - all linked via is_a relationships that are used by the search. A text search that matches any of these 3 entities will return the same result, the reactions that use the major microspecies at pH 7.3 (CHEBI:59871), or a more specific form like N-acyl-D-amino acid (CHEBI:59876), an N-acyl-D-glutamate (CHEBI:17503) or D-alanine (CHEBI:57416).