The KEGG MODULE database is a collection of KEGG modules, manually defined functional units of gene sets. Each module is identified by the M number and defined by the logical expression of K numbers. There are two types of modules.

• pathway modules – functional units of gene sets in metabolic pathways, mostly conserved subpathways of successive reaction steps and some molecular complexes
• signature modules – functional units of gene sets that characterize phenotypic features

Some signature modules are represented in a hierarchical manner, using the logical expression of K numbers and M numbers. A related dataset of reaction modules represents functional units of chemical reaction steps, which often correspond to functional units of gene sets. Each reaction module is identified by the RM number and defined by the logical expression of RC (Reaction Class) numbers. Currently available KEGG modules and reaction modules are summarized in the following Brite hierarchy files.

• 00002 KEGG modules
• 00003 KEGG reaction modules

The actual content of each KEGG module can be viewed by a dynamically generated graphical diagram, called the module diagram, such as M00002 for glycolysis core module involving three-carbon compounds. This reference module can be expanded by adding the KEGG organism code in the form of hsa_M00002, for example, for a human-specific module. Similar to organism-specific KEGG pathway maps, organism-specific modules are highlighted green.

KEGG pathway mapping is an enrichment analysis, which may require additional efforts to interpret how and where KO-linked boxes are highlighted. In contrast, module mapping is an evaluation of the logical expression, which give a clear-cut answer of whether the functional unit is present in the genome; thus, whether the metabolic capacity is present in the organism as described below.

In order to evaluate whether the gene set is complete, i.e., the functional unit is present, in a given genome, the completeness check is performed from a set of assigned K numbers. This is called module validation. In the logical expression a space or a plus sign, representing a connection in the pathway or the molecular complex, is treated as an AND operator and a comma, used for alternatives, is treated as an OR operator. A minus sign designates an optional item in the complex. The completeness check also requires identifying individual blocks separated by top-level spaces, each of which must be parenthesized before applying the AND operator. For a given set of K numbers, validated modules can be found from the following form or the following KEGG syntax tool that accepts file upload. Another representation of KEGG modules, called the module entry contains a list of organisms, including addendum and virus categories, with complete modules. Alternatively, each organism or virus may be viewed from Change pathway type button of the module diagram page. Here is an example of naming organism-specific modules.

M00793

Reference module

eco_M00793

Escherichia coli K-12 MG1655 (KEGG organism)

1877_M00793

Micromonospora echinospora (addendum category)

948870_M00793

Escherichia coli phage phi927 (virus category)

It is usually the case that modules representing specific biosynthetic pathways, biodegradation pathways, molecular complexes, etc. are found in specific organism groups. The taxonomy analysis tool shows the number of organisms having modules and/or KOs in the three pre-defined levels of taxonomic groups. The distribution of modules is shown below for the seven top levles: Animals, Plants, Fungi, Protists, Bacteria, Archaea and Viruses.