KEGG spider: interpretation of genomics data in the context of the global gene metabolic network

Abstract

KEGG spider is a web-based tool for interpretation of experimentally derived gene lists in order to gain understanding of metabolism variations at a genomic level. KEGG spider implements a 'pathway-free' framework that overcomes a major bottleneck of enrichment analyses: it provides global models uniting genes from different metabolic pathways. Analyzing a number of experimentally derived gene lists, we demonstrate that KEGG spider provides deeper insights into metabolism variations in comparison to existing methods.

Figure 1

Artificial example. The genes ME1, MDH1, FH, ASL, ASS1, CTH, CDO1, CBS and SHMT1 are presented as red boxes. Five KEGG pathway ('urea cycle', 'citrate cycle', 'pyruvate metabolism', 'cysteine metabolism', 'glycine, serine and threonine metabolism') wiring diagrams are manually linked together to demonstrate that all nine genes form a non-interrupted metabolic network.

Figure 2

Network model D₂ of 150 commonly up- or down-regulated genes in diffuse-type gastric cancers [35]. Twenty-eight genes can be mapped to KEGG metabolic pathways; the model D₂ covers 24 genes (p-value < 0.001). Genes from the input list are presented as rectangles, intermediate genes as triangles and chemical compounds as circles. Different colors are used to specify different KEGG canonical pathways.

Figure 3

Network model D₂ of 21 down-regulated proteins in a comparison of unaffected versus affected hepatic segments [36]. The network model D₂ covers 17 proteins (p-value < 0.001). Proteins from the input list are indicated by rectangles, intermediate proteins by triangles, and chemical compounds by circles. The colors are used to specify KEGG canonical pathways.