A clustering method for comparative analysis between genomes and pathways

This paper presents a clustering method for the comparative analysis of genomes and metabolic pathways. Our method consists of several steps: (1) extract linear sequences of metabolic reactions (non-branching pathways) from a network of metabolic pathways, (2) perform pairwise alignments of every pair of non-branching pathways, and (3) explore a set of genes for each aligned non-branching pathways such that those genes encode enzymes of the pathway and the genes are closely located on a genome (such as operons or gene clusters). To measure the similarity between pathways, we formalized a scoring system by using the functional hierarchy of the EC numbers of enzymes. By applying our method to the metabolic pathways in Escherichia coli, we have obtained several pairs of pathways with similar reactions having enzymes encoded by neighbor genes on the E. coli genome. The resulting pathway pairs were mainly found in metabolisms between similar amino acids (tryptophan and histidine) and between similar sugars (fucose and rhamnose).