During the past two years, the ortholog annotation procedure has been significantly improved by the newly developed KOALA (KEGG Orthology and Links Annotation) tool. There are two types of annotation in KEGG. One is a genome-based annotation, assigning K numbers to genes in a given genome. The other is a KO-based annotation, assigning a given K number (such as in a pathway map) to genes in all organisms. In order to cope with an increasing number of complete genomes, the first annotation is now partially automated (except for selected reference organisms) with continuous efforts to manually improve the second cross-species annotation. The current KEGG annotation procedure is as follows. Gene information for completely sequenced genomes is computationally generated from RefSeq (7) and other public resources, and stored in the KEGG GENES database.Sequence similarity scores and best-hit relations are computationally generated from KEGG GENES by pair-wise genome comparisons using SSEARCH, and stored in the KEGG SSDB database.Automatic genome-based annotation is performed for a limited set (currently, about one-third) of K numbers, which are considered safe for such purpose based on the
