Kyoto Encyclopedia of Genes and Genomes (KEGG)

The central component of KEGG, consisting of manually drawn pathway maps representing molecular interaction, reaction, and relation networks. These maps cover six broad categories: Metabolism, Genetic Information Processing, Environmental Information Processing, Cellular Processes, Organismal Systems, and Human Diseases. Each map is a collection of KO (KEGG Orthology) nodes connected by edges representing enzyme-catalyzed reactions, protein-protein interactions, or gene regulatory relationships. Unlike purely computational networks, these maps are curated from published experimental evidence and provide a canonical reference for pathway enrichment analysis.

A system of functional ortholog identifiers that serves as the backbone linking genomes to pathways. Each KO entry (e.g., K00844 for hexokinase) represents a manually defined functional group of genes that perform the same role across different organisms. KO groups are defined by combining sequence similarity with functional conservation in terms of position within pathways and complexes. This abstraction layer allows KEGG to map genomic content directly onto pathway maps, enabling cross-species comparisons and functional annotation of newly sequenced genomes. KO identifiers are the primary nodes in KEGG PATHWAY diagrams.

A collection of gene catalogs for complete genomes of organisms across all domains of life. Each organism is assigned a three- or four-letter KEGG organism code (e.g., 'hsa' for Homo sapiens, 'eco' for E. coli). Gene entries link to KO identifiers, enabling the computational assignment of genomic content to pathway maps. This component also includes KEGG GENOME, which organizes organisms taxonomically and provides summary statistics on the number of genes, RNAs, and KO assignments per genome. It is the foundational layer for comparative genomics and metagenomic functional profiling.

The chemical building blocks of KEGG's metabolic networks. This subsystem includes:

• KEGG COMPOUND: Small molecules, metabolites, and other chemical substances (e.g., C00031 for D-Glucose).
• KEGG REACTION: Biochemical transformations defined by substrate-product pairs and stoichiometry (e.g., R00299).
• KEGG ENZYME: Enzyme nomenclature linked to EC numbers and reaction specificity. These entities form the edges and substrate nodes in metabolic pathway maps, enabling the reconstruction of organism-specific metabolic models and the interpretation of metabolomics data within a pathway context.

KEGG BRITE is a hierarchical classification system representing functional hierarchies and ontologies beyond pathways, including protein families, drug classifications, and disease taxonomies. It organizes biological entities into structured trees (e.g., cytochrome P450 family hierarchy). KEGG MODULE defines tighter functional units—conserved sub-pathways or molecular complexes that function as discrete biological building blocks (e.g., M00001 for Glycolysis core module). Modules are particularly useful for metagenomic functional profiling, as they capture pathway completeness and organismal functional capacity more robustly than individual KO assignments.

The translational medicine components of KEGG that connect molecular networks to human health. KEGG DISEASE catalogs human diseases as perturbations of molecular pathways, classifying them by affected systems (e.g., H00001 for Colorectal cancer). Each disease entry links to relevant pathway maps, genes, and environmental factors. KEGG DRUG contains chemical structures, target information, and therapeutic categories for approved pharmaceuticals, linked to their molecular targets within KEGG PATHWAY maps. This integration enables drug repurposing analysis and the identification of druggable targets within enriched pathways.