KEGG mapping tools for uncovering hidden features in biological data

Abstract

In contrast to artificial intelligence and machine learning approaches, KEGG (https://www.kegg.jp) has relied on human intelligence to develop "models" of biological systems, especially in the form of KEGG pathway maps that are manually created by capturing knowledge from published literature. The KEGG models can then be used in biological big data analysis, for example, for uncovering systemic functions of an organism hidden in its genome sequence through the simple procedure of KEGG mapping. Here we present an updated version of KEGG Mapper, a suite of KEGG mapping tools reported previously (Kanehisa and Sato, Protein Sci 2020; 29:28-35), together with the new versions of the KEGG pathway map viewer and the BRITE hierarchy viewer. Significant enhancements have been made for BRITE mapping, where the mapping result can be examined by manipulation of hierarchical trees, such as pruning and zooming. The tree manipulation feature has also been implemented in the taxonomy mapping tool for linking KO (KEGG Orthology) groups and modules to phenotypes.

Keywords: BRITE hierarchical classification; KEGG; KEGG mapper; KEGG module; KEGG orthology; KEGG pathway map; genome annotation.

FIGURE 1

In the new versions of (a) the KEGG pathway map viewer and (b) the BRITE hierarchy viewer, the side panel is available for various client‐side operations, including KEGG mapping operations. The User data section of the pathway map viewer corresponds to the Color tool of KEGG Mapper applied to a single pathway map. The ID search and Join sections of the BRITE hierarchy viewer correspond to the Search and Join tools applied to a single hierarchy file. The plus sign in each section is used to open an window for user data input

FIGURE 2

An example of using the Join tool of KEGG Mapper, where the dataset of prodrug to active substance relations is joined with br‐prefixed BRITE hierarchy files. One of the matching BRITE files, br08303 for the ATC drug classification, is shown here. Since the KEGG Mapper result appears in the Join list, it may be examined by combining with other predefined datasets

FIGURE 3

The taxonomy mapping tool shows the distribution of KEGG organisms for a given set of KOs (K numbers) and modules (M numbers) as well as for user‐defined data. The tool works with a specially organized BRITE hierarchy file, br08611 for KEGG organisms in taxonomic groups. Here the mapping result is shown with (a) zooming in to the species level or (b) zooming out to the genus level, revealing what fraction of organisms are matched (colored in red) under the changing resolution of organism groups