1. Genomes to Biological SystemKEGG is a database resource for understanding high-level functions and utilities of the biological system, such as the cell, the organism and the ecosystem, from genomic and molecular-level information. It is a computer representation of the biological system, consisting of molecular building blocks of genes and proteins (genomic information) and chemical substances (chemical information) that are integrated with the knowledge on molecular wiring diagrams of interaction, reaction and relation networks (systems information). It also contains disease and drug information (health information) as perturbations to the biological system.
The KEGG database has been in development by Kanehisa Laboratories since 1995, and is now a prominent reference knowledge base for integration and interpretation of large-scale molecular data sets generated by genome sequencing and other high-throughput experimental technologies.
2. The KEGG DatabaseKEGG is an integrated database resource consisting of sixteen databases shown below. They are broadly categorized into systems information, genomic information, chemical information and health information, which are distinguished by color coding of web pages.
|KEGG PATHWAY||KEGG pathway maps|
|KEGG BRITE||BRITE hierarchies and tables|
|KEGG MODULE||KEGG modules and reaction modules|
|KEGG ORTHOLOGY (KO)||Functional orthologs|
|KEGG GENES||Genes and proteins|
|KEGG GENOME||KEGG organisms and viruses|
|KEGG COMPOUND||Metabolites and other chemical substances|
|KEGG ENZYME||Enzyme nomenclature|
|KEGG NETWORK||Disease-related network variations|
|KEGG VARIANT||Human gene variants|
|KEGG DISEASE||Human diseases|
These databases contain various data objects for computer representation of the biological systems. Thus, the database entry of each database is called the KEGG object, which is identified by the KEGG object identifier consisting of a database-dependent prefix and a five-digit number (see: KEGG objects).
|1995||KEGG PATHWAY||map number|
|KEGG GENES||locus_tag / GeneID|
|KEGG ENZYME||EC number|
|KEGG COMPOUND||C number|
|1998||KEGG REACTION||R number|
|2000||KEGG GENOME||organism code / T number|
|2002||KEGG ORTHOLOGY||K number||Ortholog IDs in 2000|
|2003||KEGG GLYCAN||G number|
|2004||KEGG RPAIR||RP number||Discontinued in 2016|
|2005||KEGG BRITE||br number|
|KEGG DRUG||D number|
|2006||KEGG MODULE||M number|
|2008||KEGG DISEASE||H number|
|2010||KEGG RCLASS||RC number|
|KEGG EDRUG||E number||Renamed to ENVIRON|
|2011||KEGG ENVIRON||E number||Discontinued in 2021|
|2014||KEGG DGROUP||DG number|
|2017||KEGG NETWORK||N number / nt number|
|KEGG VARIANT||GeneID+variant number|
3. KEGG Molecular NetworksThe most unique data object in KEGG is the molecular networks -- molecular interaction, reaction and relation networks representing systemic functions of the cell and the organism. Experimental knowledge on such systemic functions is captured from literature and organized in the following forms:
- Pathway map - in KEGG PATHWAY (see: Pathway maps)
- Brite hierarchy and table - in KEGG BRITE (see: Brite hierarchies)
- Membership (logical expression) - in KEGG MODULE
- Membership (simple list) - in KEGG DISEASE
In 1995 the concept of mapping was first introduced in KEGG for linking genomes to metabolic pathways (metabolic reconstruction) using the EC number. Once the EC numbers were assigned to enzyme genes in the genome, organism-specific pathways could be generated automatically by matching against the enzyme (EC number) networks of the KEGG reference metabolic pathways. The EC number is no longer used as an identifier in KEGG. The KEGG Orthology (KO) system is the basis for genome annotation and KEGG mapping.
|1995-1999||EC number||Metabolic pathways||Domain based|
|2000-2002||Ortholog ID||Metabolic and regulatory pathways||Domain based|
|2003-||KO||Pathways and BRITE hierarchies||Gene based|
From a different perspective, individual instances of genes are grouped into KO entries representing functional orthologs in the molecular networks. There are two more types of such generalization in KEGG as shown below.
|All types||KO (gene ortholog)||Genes in KEGG GENES|
|Biochemical reaction||RC (reaction class)||Reactions in KEGG REACTION|
|Drug interaction||DG (drug group)||Drugs in KEGG DRUG|
4. Network VariantsThe KEGG database has been developed by focusing on conservation and variation of genes and genomes among different organisms. The reference datasets of KEGG pathway maps, BRITE hierarchies and KEGG modules have been developed with the concept of functional orthologs (KOs), so that KEGG pathway mapping and other procedures can be applied to any cellular organism.
However, this generic approach is inadequate for understanding more detailed features caused by variations of genes and genomes within a species, especially for understanding disease related variations of human genes and genomes. KEGG NETWORK represents a renewed attempt by KEGG to capture knowledge on diseases and drugs in terms of network variants caused by not only gene variants, but also viruses and other factors.
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- Kanehisa, M., Goto, S., Sato, Y., Kawashima, M., Furumichi, M., and Tanabe, M.; Data, information, knowledge and principle: back to metabolism in KEGG. Nucleic Acids Res. 42, D199–D205 (2014). [pubmed] [doi]
- Kanehisa, M., Sato, Y., Kawashima, M., Furumichi, M., and Tanabe, M.; KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res. 44, D457-D462 (2016). [pubmed] [doi]
- Kanehisa, Furumichi, M., Tanabe, M., Sato, Y., and Morishima, K.; KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 45, D353-D361 (2017). [pubmed] [doi]
- Kanehisa, M., Sato, Y., Furumichi, M., Morishima, K., and Tanabe, M.; New approach for understanding genome variations in KEGG. Nucleic Acids Res. 47, D590-D595 (2019). [pubmed] [doi]
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- Kanehisa, M., Furumichi, M., Sato, Y., Ishiguro-Watanabe, M., and Tanabe, M.; KEGG: integrating viruses and cellular organisms. Nucleic Acids Res. 49, D545-D551 (2021). [pubmed] [doi]
Last updated: August 10, 2021