Reactome is a free online database of
biological pathways.
There are several Reactomes that concentrate on specific organisms, the largest of these is focused on
human biology
Human biology is an interdisciplinary area of academic study that examines humans through the influences and interplay of many diverse fields such as genetics, evolution, physiology, anatomy, epidemiology, anthropology, human ecology, ecology, hum ...
, the following description concentrates on the human Reactome. It is authored by biologists, in collaboration with Reactome editorial staff. The content is cross-referenced to many bioinformatics databases. The rationale behind Reactome is to visually represent biological pathways in full mechanistic detail, while making the source data available in a computationally accessible format.
The website can be used to browse pathways and submit data to a suite of data analysis tools. The underlying data is fully downloadable in a number of standard formats including
PDF
Portable Document Format (PDF), standardized as ISO 32000, is a file format developed by Adobe in 1992 to present documents, including text formatting and images, in a manner independent of application software, hardware, and operating systems. ...
,
SBML
The Systems Biology Markup Language (SBML) is a representation format, based on XML, for communicating and storing computational models of biological processes. It is a free and open standard with widespread software support and a community of use ...
and
BioPAX. Pathway diagrams use a Systems Biology Graphical Notation (
SBGN
The Systems Biology Graphical Notation (SBGN) is a standard graphical representation intended to foster the efficient storage, exchange and reuse of information about signaling pathways, metabolic networks, and gene regulatory networks amongst com ...
)-based style.
The core unit of the Reactome data model is the reaction. Entities (nucleic acids, proteins, complexes and small molecules) participating in reactions form a network of biological interactions and are grouped into pathways. Examples of biological pathways in Reactome include signaling, innate and acquired immune function, transcriptional regulation, translation, apoptosis and classical intermediary metabolism.
The pathways represented in Reactome are species-specific, with each pathway step supported by literature citations that contain an experimental verification of the process represented. If no experimental verification using human reagents exists, pathways may contain steps manually inferred from non-human experimental details, but only if an expert biologist, named as Author of the pathway, and a second biologist, names as reviewer, agree that this is a valid inference to make. The human pathways are used to computationally generate by an orthology-based process derived pathways in other organisms.
Database organization
In Reactome, human biological processes are annotated by breaking them down into series of molecular events. Like classical chemistry reactions each Reactome event has input physical entities (substrates) which interact, possibly facilitated by enzymes or other molecular catalysts, to generate output physical entities (products).
Reactions include the classical chemical interconversions of intermediary metabolism, binding events, complex formation, transport events that direct molecules between cellular compartments, and events such as the activation of a protein by cleavage of one or more of its peptide bonds. Individual events can be grouped together into pathways.
Physical entities can be small molecules like glucose or ATP, or large molecules like DNA, RNA, and proteins, encoded directly or indirectly in the human genome. Physical entities are cross-referenced to relevant external databases, such as
UniProt
UniProt is a freely accessible database of protein sequence and functional information, many entries being derived from genome sequencing projects. It contains a large amount of information about the biological function of proteins derived from ...
for proteins and
ChEBI
Chemical Entities of Biological Interest, also known as ChEBI, is a chemical database and ontology of molecular entities focused on 'small' chemical compounds, that is part of the Open Biomedical Ontologies (OBO) effort at the European Bioinf ...
for small molecules. Localization of molecules to subcellular compartments is a key feature of the regulation of human biological processes, so molecules in the Reactome database are associated with specific locations. Thus in Reactome instances of the same chemical entity in different locations (e.g., extracellular glucose and cytosolic glucose) are treated as distinct chemical entities.
The
Gene Ontology
The Gene Ontology (GO) is a major bioinformatics initiative to unify the representation of gene and gene product attributes across all species. More specifically, the project aims to: 1) maintain and develop its controlled vocabulary of gene and g ...
controlled vocabularies are used to describe the subcellular locations of molecules and reactions, molecular functions, and the larger biological processes that a specific reaction is part of.
Database content
The database contains curated annotations that cover a diverse set of topics in
molecular and
cellular biology
Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and ...
. Details of current and future annotation projects can be found in th
calendar of annotation projects
Topics of annotation include;
*
cell cycle
The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...
*
metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
*
signaling
In signal processing, a signal is a function that conveys information about a phenomenon. Any quantity that can vary over space or time can be used as a signal to share messages between observers. The ''IEEE Transactions on Signal Processing'' ...
*
transport
Transport (in British English), or transportation (in American English), is the intentional movement of humans, animals, and goods from one location to another. Modes of transport include air, land (rail and road), water, cable, pipeline, an ...
*
cell motility
*
immune function
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
*
host-virus interaction
*
neural function
In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...
Tools
There are tools on the website for viewing an interactive pathway diagram, performing pathway mapping and pathway over-representation analysis and for overlaying expression data onto Reactome pathways. The pathway mapping and over-representation tools take a single column of protein/compound identifiers, Uniprot and ChEBI accessions are preferred but the interface will accept and interpret many other identifiers or symbols. Mixed identifiers can be used. Over-representation results are presented as a list of statistically over-represented pathways.
Expression data is submitted in a multi-column format, the first column identifying the protein, additional columns are expected to be numeric expression values, they can in fact be any numeric value, e.g. differential expression, quantitative proteomics, GWAS scores. The expression data is represented as colouring of the corresponding proteins in pathway diagrams, using the colours of the visible spectrum so 'hot' red colours represent high values. If multiple columns of numeric data are submitted the overlay tool can display them as separate 'experiments', e.g. timepoints or a disease progression.
The database can be browsed and searched as an on-line textbook. An on-line users' guide is available. Users can also download the current data set or individual pathways and reactions in a variety of formats including PDF,
BioPAX, and
SBML
The Systems Biology Markup Language (SBML) is a representation format, based on XML, for communicating and storing computational models of biological processes. It is a free and open standard with widespread software support and a community of use ...
Links to Reactome
*
Reactome Quick Tour on EBI Train OnLine
See also
*
KEGG
KEGG (Kyoto Encyclopedia of Genes and Genomes) is a collection of databases dealing with genomes, biological pathways, diseases, drugs, and chemical substances. KEGG is utilized for bioinformatics research and education, including data analysis i ...
(The Kyoto Encyclopedia of Genes and Genomes)
*
BioCyc database collection
The BioCyc database collection is an assortment of organism specific Pathway/Genome Databases (PGDBs) that provide reference to genome and metabolic pathway information for thousands of organisms. As of June 2021, there were over 17,800 databases w ...
*
BRENDA
Brenda is a feminine given name in the English language.
Origin
The overall accepted origin for the female name Brenda is the Old Nordic male name ''Brandr'' meaning both ''torch'' and ''sword'': evidently the male name Brandr took root in areas ...
(The BRaunschweig ENzyme DAtabase)
*
WikiPathways
WikiPathways is a community resource for contributing and maintaining content dedicated to biological pathways. Any registered WikiPathways user can contribute, and anybody can become a registered user. Contributions are monitored by a group of ad ...
(which exposes Reactome pathways
)
*
Comparative Toxicogenomics Database
The Comparative Toxicogenomics Database (CTD) is a public website and research tool launched in November 2004 that curates scientific data describing relationships between chemicals/drugs, genes/proteins, diseases, taxa, phenotypes, GO annotations ...
References
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Related resources
Other molecular pathway databases
GeneNetworkPanther Pathways*
Pathway Commons
Biological databases