KEGG for integration and interpretation of large-scale molecular data sets

Abstract

Kyoto Encyclopedia of Genes and Genomes (KEGG, http://www.genome.jp/kegg/ or http://www.kegg.jp/) is a database resource that integrates genomic, chemical and systemic functional information. In particular, gene catalogs from completely sequenced genomes are linked to higher-level systemic functions of the cell, the organism and the ecosystem. Major efforts have been undertaken to manually create a knowledge base for such systemic functions by capturing and organizing experimental knowledge in computable forms; namely, in the forms of KEGG pathway maps, BRITE functional hierarchies and KEGG modules. Continuous efforts have also been made to develop and improve the cross-species annotation procedure for linking genomes to the molecular networks through the KEGG Orthology system. Here we report KEGG Mapper, a collection of tools for KEGG PATHWAY, BRITE and MODULE mapping, enabling integration and interpretation of large-scale data sets. We also report a variant of the KEGG mapping procedure to extend the knowledge base, where different types of data and knowledge, such as disease genes and drug targets, are integrated as part of the KEGG molecular networks. Finally, we describe recent enhancements to the KEGG content, especially the incorporation of disease and drug information used in practice and in society, to support translational bioinformatics.

Figure 1.

The Color Pathway tool in KEGG Mapper accepts numerical values associated with genes, which can be displayed by color-shading or 3D mapping. Here somatic mutation frequency observed in chronic myeloid leukemia (obtained from the COSMIC database, http://www.sanger.ac.uk/genetics/CGP/cosmic/) is shown on top of the global cancer pathway map (hsa05200).

Figure 2.

Comparison of metabolic pathways reconstructed from the complete genomes of Homo sapiens (hsa) and E. coli (eco). Here the global metabolic pathway map (map01100) and the terpenoid backbone biosynthesis map (map00900) are shown, where human-specific pathways are colored in green, E. coli specific pathways in pink, and shared pathways in blue or split coloring.

Figure 3.

Disease/drug mapping is the process to map all known disease genes (pink) and all known drug targets (light blue) against all KEGG pathway maps. This is the mapping result of the Alzheimer's disease pathway map (hsa05010), which reveals relationships with other neurodegenerative diseases.