Kanehisa M, Goto S, Furumichi M, Tanabe M, Hirakawa M.. KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res 38: D355-D360

Bioinformatics Center, Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.
Nucleic Acids Research (Impact Factor: 9.11). 10/2009; 38(Database issue):D355-60. DOI: 10.1093/nar/gkp896
Source: PubMed


Most human diseases are complex multi-factorial diseases resulting from the combination of various genetic and environmental
factors. In the KEGG database resource (, diseases are viewed as perturbed states of the molecular system, and drugs as perturbants to the molecular system. Disease
information is computerized in two forms: pathway maps and gene/molecule lists. The KEGG PATHWAY database contains pathway
maps for the molecular systems in both normal and perturbed states. In the KEGG DISEASE database, each disease is represented
by a list of known disease genes, any known environmental factors at the molecular level, diagnostic markers and therapeutic
drugs, which may reflect the underlying molecular system. The KEGG DRUG database contains chemical structures and/or chemical
components of all drugs in Japan, including crude drugs and TCM (Traditional Chinese Medicine) formulas, and drugs in the
USA and Europe. This database also captures knowledge about two types of molecular networks: the interaction network with
target molecules, metabolizing enzymes, other drugs, etc. and the chemical structure transformation network in the history
of drug development. The new disease/drug information resource named KEGG MEDICUS can be used as a reference knowledge base
for computational analysis of molecular networks, especially, by integrating large-scale experimental datasets.

Download full-text


Available from: Mika Hirakawa
  • Source
    • "(P < 0.05) of the DEGs was conducted [35]. A comprehensive comparison of a select set of KEGG pathways [36] in both of the antibiotics-treated amphioxus groups, on the basis of the time-course of the proportion of significantly regulated genes, is shown in Tables 1 and S3. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Chloramphenicol (Chl) is an effective antimicrobial agent widely used in veterinary medicine and commonly used in fish. Its use is restricted in the clinic because of adverse effects on the immune system and oxidative stress in mammals. However, the effects of Chl treatment on invertebrates remain unclear. Amphioxus, a basal chordate, is an ideal model to study the origin and evolution of the vertebrate immune system as it has a primary vertebrate-like arachidonic acid (AA) metabolic system. Here, we combined transcriptomic and lipidomic approaches to investigate the immune system and observe the oxygenated metabolites of AA to address the antibiotic effects on amphioxus. Tissue necrosis of the gill slits occurred in the Chl-treated amphioxus, but fewer epithelial cells were lost when treated with both Chl and ampicillin (Amp). The immune related pathways were dysregulated in both of the antibiotic treatment groups. The Chl alone treatment resulted in immunosuppression with down-regulation of the innate immune genes. In contrast, the Chl + Amp treatment resulted in immunostimulation to some extent, as shown by KEGG clustering. Furthermore, Chl induced a 3-fold reduction in the level of the eicosanoids, while the Chl + Amp treatment resulted in 1.7-fold increase of eicosanoid level. Thus in amphioxus, Amp might relieve the effects of the Chl-induced immune suppression and increase the level of eicosanoids from AA. Finally, the oxygenated metabolites from AA might be crucial to evaluate the effects of Chl treatment in animals.
    Full-text · Article · Aug 2015 · FEBS Open Bio
  • Source
    • "symbols were entered into the DAVID database and the resulting gene ontologies were analyzed for biological processes (BPs), cellular components (CCs), and molecular functions (MFs). Additional pathway analysis was carried out through the Kyoto encyclopedia of genes and genomes (KEGG) [29] [30] [31]. The EASE score, a modified Fisher exact p-value, adopted to measure the gene enrichment in annotation term was set below 0.01. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Large scale production and incorporation of titanium dioxide nanoparticles (NP-TiO2) in consumer products leads to their potential release into the environment and raises the question of their toxicity. The bactericidal mechanism of titanium dioxide nanoparticles (NP-TiO2) under UV light is known to involve oxidative stress due to the generation of reactive oxygen species. In the dark, several studies revealed that NP-TiO2 can exert toxicological effects. However, the mode of action of these nanoparticles is still controversial. In the present study, we used a combination of fluorescent probes to show that NP-TiO2 causes E. coli membrane depolarization and loss of integrity, leading to higher cell permeability. Using both transcriptomic and proteomic global approaches we showed that this phenomenon translates into a cellular response to osmotic stress, metabolism of cell envelope components and uptake/metabolism of endogenous and exogenous compounds. This primary mechanism of bacterial NP-TiO2 toxicity is supported by the observed massive cell leakage of K+ / Mg2+ concomitant with the entrance of extracellular Na+, and by the depletion of intracellular ATP level.This article is protected by copyright. All rights reserved
    Full-text · Article · Jan 2015 · Proteomics
  • Source
    • "We also exhibited the subcellular localization of these proteins by integrating the evidence from HPA portal [6], Uniprot [7], and GO cellular component (GO-CC) [8] since subcellular localization of a protein is quite important information for elucidation of its function. Moreover, we explored the biological processes carried out by gallbladder-specific proteins using the GO biological process (GO-BP) [8] and KEGG Pathways [9]. Finally, we identified metabolic reactions associated to the gallbladder-specific proteins through the use of the human metabolic reaction database (HMR) 2.0 [10] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Global protein analysis of human gallbladder tissue is vital for identification of molecular regulators and effectors of its physiological activity. Here, we employed a genome-wide deep RNA sequencing analysis in 28 human tissues to identify the genes overrepresented in the gallbladder and complemented it with antibody-based immunohistochemistry in 48 human tissues. We characterized human gallbladder proteins and identified 140 gallbladder-specific proteins with an elevated expression in the gallbladder as compared to the other analyzed tissues. Five genes were categorized as enriched, with at least five-fold higher levels in gallbladder, 60 genes were categorized as group enriched with elevated transcript levels in gallbladder shared with at least one other tissue and 75 genes were categorized as enhanced with higher expression than the average expression in other tissues. We explored the localization of the genes within the gallbladder through cell-type specific antibody-based protein profiling and the subcellular localization of the genes through immunofluorescent-based profiling. Finally, we revealed the biological processes and metabolic functions carried out by these genes through the use of Gene Ontology, KEGG Pathway and HMR2.0 that is compilation of the human metabolic reactions. We demonstrated the results of the combined analysis of the transcriptomics and affinity proteomics.This article is protected by copyright. All rights reserved
    Full-text · Article · Nov 2014 · Proteomics
Show more