A Multiple Alignment Algorithm for Metabolic Pathway Analysis Using Enzyme Hierarchy

In many of the chemical reactions in living cells, enzymes act as catalysts in the conversion of certain compounds (substrates) into other compounds (products). Comparative analyses of the metabolic pathways formed by such reactions give important information on their evolution and on pharmacological targets (Dandekar et al. 1999). Each of the enzymes that constitute a pathway is classified according to the EC (Enzyme Commission) numbering system, which consists of four sets of numbers that categorize the type of the chemical reaction catalyzed. In this study, we consider that reaction similarities can be expressed by the similarities between EC numbers of the respective enzymes. Therefore, in order to find a common pattern among pathways, it is desirable to be able to use the functional hierarchy of EC numbers to express the reaction similarities. In this paper, we propose a multiple alignment algorithm utilizing information content that is extended to symbols having a hierarchical structure. The effectiveness of our method is demonstrated by applying the method to pathway analyses of sugar, DNA and amino acid metabolisms.

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