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 result of SSDB computation and the criteria of the KOALA tool.Manual annotation is performed across species for other K numbers using the KOALA and GFIT (8) tools. This step may involve addition/revision of ortholog groups, which is essential to increase the number of safe K numbers.