KEGG: new perspectives on genomes, pathways, diseases and drugs

Abstract

KEGG (http://www.kegg.jp/ or http://www.genome.jp/kegg/) is an encyclopedia of genes and genomes. Assigning functional meanings to genes and genomes both at the molecular and higher levels is the primary objective of the KEGG database project. Molecular-level functions are stored in the KO (KEGG Orthology) database, where each KO is defined as a functional ortholog of genes and proteins. Higher-level functions are represented by networks of molecular interactions, reactions and relations in the forms of KEGG pathway maps, BRITE hierarchies and KEGG modules. In the past the KO database was developed for the purpose of defining nodes of molecular networks, but now the content has been expanded and the quality improved irrespective of whether or not the KOs appear in the three molecular network databases. The newly introduced addendum category of the GENES database is a collection of individual proteins whose functions are experimentally characterized and from which an increasing number of KOs are defined. Furthermore, the DISEASE and DRUG databases have been improved by systematic analysis of drug labels for better integration of diseases and drugs with the KEGG molecular networks. KEGG is moving towards becoming a comprehensive knowledge base for both functional interpretation and practical application of genomic information.

Figure 1.

Definition and KO fields of GENES entries. (A) GenBank derived entry nca:Noca_0613 and (B) manually created entry ag:CAD47941 in the addendum category.

Figure 2.

KO entry K19188 defined from an experimentally characterized protein sequence, ag:CAD47941 for EC:3.7.1.19.

Figure 3.

(A) A portion of the KEGG pathway map of nicotinate and nicotinamide metabolism (map00760) for Nocardioides sp. JS614 (nca), where Noca_0613 for EC:3.7.1.19 is marked red. (B) Ortholog table for the KEGG module of nicotine degradation pyridine pathway (M00810), where coloring of positional correlation indicates that Noca_0613 for EC:3.7.1.19 is adjacent to Noca_0612 for EC:1.5.99.14. (C) Dendrogram obtained by hierarchical clustering of ag:CAD47941 and its neighbors in SSDB, where genes annotated with K19188 are distinguished by coloring.

Figure 4.

KEGG pathway maps for (A) non-small cell lung cancer (hsa05223) and (B) EGFR tyrosine kinase inhibitor resistance (hsa01521). Some of the well-known molecular target drugs are included in these maps.