KEGG Virus is a resource for integrated analysis of virses and cellular organisms. It is part of the GENES, KO, GENOME, BRITE, PATHWAY, MODULE, NETWORK, DISEASE and DRUG databases in KEGG. It also contains a computationally generated dataset of virus ortholog group (VOG).

The virus category of the GENES and GENOME databases is generated from the bimonthly release of the NCBI RefSeq database. RefSeq GeneID's are used as gene identifiers and the organism code "vg" is used for the entire set of virus genes. Thus, each virus gene in KEGG is identified by vg:<gene_id> where <gene_id> is the NCBI GeneID. In order to distinguish virus genomes, the Vtax identifier is used in the GENOME database in the form of gn:<vtax>. Vtax is the same as the NCBI taxonomy ID, thus may occasionally contain multiple genome sequences determined separately.

All viruses are classified according to the NCBI taxonomy, which is based on the ICTV (International Committee on Taxonomy of Viruses) taxonomy, supplemented by KEGG with the traditional Baltimore classification. The correspondence between the ICTV realm, kingdom, phylum, class ranks and the seven types of Baltimore classification is shown below. Additional family-level assingments without higher ranks are also included. The resulting classification is shown in the following Brite hierarchy files, where 08621 is used as a default file.

• 08620 KEGG viruses in the NCBI taxonomy
• 08621 KEGG viruses in taxonomic ranks (fixed levels of taxonomic ranks reorganized from 08620)

In both files, it is now possible to exclude the Baltimore classificaation to view the ICTV taxonomy. Use the link at the bottom right corner.

The Vtax identifiers used in these taxonomy files are not stable identifiers, for they may change when NCBI changes the taxonomy IDs. Thus, the T4 identifiers are given to selected viruses, especially for the purpose of creating links to/from the DISEASE database.

• 08622 KEGG selected viruses

Based on experimental evidence virus specific KOs are defined as summarized in the following BRITE hierarchy file.

• 03200 Viral proteins

Most virus KOs are defined at the family or genus level, but sometimes at the species level as well. Furthermore, some KOs are defined for the "vp" category of the GENES database, which contains mature peptides cleaved from polyproteins for selected viruses. Such distictions are made to better represent functional orthologs in the pathway maps and other protein interaction networks.

Due to the lack of experimental evidence, defining and assigning KOs for virus genes will be very limited. In order to supplement KOs, a new attempt has been made to computationally generate virus ortholog groups (formerly called virus ortholog clusters) using the same annotation resource of GFIT tables (see KO assignment tools). Currently, virus ortholog groups are generated by a simple procedure shown below.

1. The result of vg-vg comparison is stored in the the paralog GFIT table, a variant form of which may be viewed from the "Paralog" button of each vg entry page.
2. The measure of similarity is defined by a modified identity with weighting of min(1, overlap*2/(aalen1+aalen2)) for the identity of the overlap (aligned) region.
3. For each gene its GFIT table is used to collect similar genes above a given threshold of modified identity.
4. GFIT tables of similar genes are then used to collect additional similar genes and this process is repeated until no addition is made.
5. This can be viewed as single-linkage clustering of truncated GFIT tables, which are processed in the order of the decreasing table size.

Virus ortholog group (VOG) data are shown in the VOG page linked from the "Vog" button of each vg entry page such as the following:

• VOG page example for vg:944565

Note that the VOG number identifiers starting with 3, 5 and 7 for the threshold values of 30%, 50% and 70%, respectively, are not stable identifiers and will change when the original RefSeq data are updated.

The most important usage of VOGs is described in KEGG Syntax involving the analysis of conserved genes and gene orders among viruses and also between viruses and cellular organisms.

Annotation