KEGG: integrating viruses and cellular organisms

Abstract

KEGG (https://www.kegg.jp/) is a manually curated resource integrating eighteen databases categorized into systems, genomic, chemical and health information. It also provides KEGG mapping tools, which enable understanding of cellular and organism-level functions from genome sequences and other molecular datasets. KEGG mapping is a predictive method of reconstructing molecular network systems from molecular building blocks based on the concept of functional orthologs. Since the introduction of the KEGG NETWORK database, various diseases have been associated with network variants, which are perturbed molecular networks caused by human gene variants, viruses, other pathogens and environmental factors. The network variation maps are created as aligned sets of related networks showing, for example, how different viruses inhibit or activate specific cellular signaling pathways. The KEGG pathway maps are now integrated with network variation maps in the NETWORK database, as well as with conserved functional units of KEGG modules and reaction modules in the MODULE database. The KO database for functional orthologs continues to be improved and virus KOs are being expanded for better understanding of virus-cell interactions and for enabling prediction of viral perturbations.

Figure 1.

KEGG consists of eighteen original databases in four categories. The health information category, called KEGG MEDICUS, is supplemented with two outside databases of drug labels: Japanese drug labels obtained from JAPIC (http://www.japic.or.jp) and FDA drug labels linked to the DailyMed database (https://dailymed.nlm.nih.gov). The identifier of each entry in the KEGG database generally takes the form of a prefix followed by a five-digit number and is called, for example, map number, M number and K number for the PATHWAY, MODULE and KO databases, respectively.

Figure 2.

The new pathway map viewer with a side panel for client-side operations. Here the human pathway map hsa00600 for sphingolipid metabolism is shown with the module M00094 for ceramide biosynthesis in red and the network N00642 for saposin (PSAP) stimulation of GBA (3.2.1.45) and GALC (3.2.1.46) in purple. The saposin node and regulatory links are not present in the original map and are displayed only when this network is selected.

Figure 3.

The global map of metabolic pathways can now be viewed in two modes: normal link mode and the module link mode, the latter treating the map as consisting of modules rather than individual genes or KOs. Here the global map of a Tara Oceans sample (T30798_01100) is shown in the module link mode with the coloring of pink for the background of all modules, green for mapped genes, and brown for complete modules identified in the sample.

Figure 4.

The network variation map nt06131 for Apoptosis (viruses and bacteria) showing aligned sets of reference networks in green and variant networks with viral or bacterial proteins in purple. Variant networks are linked to disease types, mostly viral infections but including five bacterial infections.

Figure 5.

Selected networks in the variation map nt06131 are shown on the pathway maps: (A) inhibition of apoptosis by KSHV in the pathway map of hsa05167 for Kaposi sarcoma-associated herpesvirus infection and (B) activation of apoptosis by HIV in the pathway map of hsa05170 for Human immunodeficiency virus 1 infection.

Figure 6.

The correspondence between the seven groups of Baltimore classification (colored) and the hierarchy of ICTV virus classification consisting of realm (-viria), kingdom (-virae), phylum (-viricota), class (-viricetes) and family (-viridae).