Searching Rhea

Content:

Introduction

There are several ways to search for data in Rhea:

  1. Text search (simple and advanced)
    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 other resources.
  4. SPARQL search
    Go to the Rhea SPARQL endpoint to execute semantic queries in Rhea and across the SPARQL endpoints of other resources.

All searches allow to search with reaction participants that are not directly used in a Rhea reaction by exploiting ontological relationships. 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. Furthermore, Rhea reactions are linked to the Gene Ontology (GO) and the EC number classification of the NC-IUBMB. When your query matches a concept from one of these ontologies, the result will include Rhea reactions that are directly related to the matching concept, as well as Rhea reactions that are related to concepts that are themselves related to the matching concept via certain ontological relationships.

The next subsections describe some of the relationships that are used by the searches. If you are not familiar with ontologies and/or ChEBI, you may also want to read the document Which ChEBIs are used in Rhea? for more details on ontological relationships.

Searching with different compound protonation states (has_major_microspecies_at_pH_7_3 relationship)

The ChEBI ontology describes each protonation state of a given compound (neutral, protonated, zwitterionic, tautomeric) with a separate class and links related classes by specific relationships (is conjugate acid of, is conjugate base of, is tautomer of). Rhea uses only those ChEBI entities that describe the form that is the major microspecies at pH 7.3 and it links this entity via has_major_microspecies_at_pH_7_3 relationships to the other forms.

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).

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A structure similarity search with D-alpha-amino acid anion (CHEBI:60895) retrieves the major microspecies at pH 7.3 (CHEBI:59871).

Searching with a compound class (is_a relationship)

The ChEBI 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. For instance, 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.