The third condition is when some metabolites are known to exist but the reactions producing or degrading them are not identified, then predictions of these reactions are necessary to move back to the second conditional steps etc. We defined reference pathways to cope with the first set of annotation conditions and designed the KEGG PATHWAY and BRITE so that they generally do not focus on a specific organism, but are designed in a general selleckchem way to be applicable to

all organisms. Reference pathways are defined as the combined pathways that are present in a number of organisms and there exists a consensus among many published papers. Figure 4 describes the difference between a species-specific pathway and a reference pathway, and the relationships among various IDs. In the reference pathway, rectangles and circles represent gene products (mostly proteins) and other molecules (mostly metabolites), respectively. This graphic is one of the reference

pathways for which no organism has been specified. When the user selects to view a reference KU-60019 pathway, the colored rectangles indicate the links to the corresponding orthologue (KO) entries, enzyme classifications or reactions. When the user specifies an organism, the colored rectangles indicate the links to the corresponding KEGG GENE pages, which indicates the specified organism possesses the corresponding genes or proteins in the genome. White rectangles indicate that Racecadotril there are no genes annotated to the corresponding function. Note that this does not necessarily

mean the organism does not really have the corresponding genes. It is possible that the corresponding genes have not been identified yet. Manually defined KO entries (groups of orthologous genes) are the basic components of the systems information, i.e., PATHWAY network diagrams and BRITE functional classifications. Continuous refinement of reference pathways and orthologue information is the key to maintain the quality of this procedure. We designed the E-zyme tool (Kotera et al., 2004) in response to the second set of annotation conditions, the practical situation where the user wants to identify enzymes (enzyme genes, proteins or reaction mechanisms) from only a partial reaction equation. The user can input any compound pairs, and obtain the candidate EC classifications, generating a ‘clue’ to identify the enzyme genes or proteins. This needs the library of the RDM chemical transformation patterns calculated in advance, which is compared with the query transformation pattern, resulting in a list of possible EC classifications with specific scores. Recently, we have done a significant improvement in this E-zyme, where a more complicated voting scheme and EC-RDM profile based scoring system is applied to achieve higher coverage with a higher accuracy rate (Yamanishi et al.