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Open Access Highly Accessed Methodology article

Metabolic pathway alignment between species using a comprehensive and flexible similarity measure

Yunlei Li123*, Dick de Ridder123, Marco JL de Groot134 and Marcel JT Reinders123

Author Affiliations

1 Information and Communication Theory Group, Faculty of Electrical Engineering, Mathematics and Computer Science, Delft University of Technology, Mekelweg 4, 2628 CD Delft, the Netherlands

2 Netherlands Bioinformatics Centre, 260 NBIC, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands

3 Kluyver Centre for Genomics of Industrial Fermentation, Julianalaan 67, 2628 BC Delft, the Netherlands

4 Bioprocess Technology Group, Department of Biotechnology, Faculty of Applied Sciences, Delft University of Technology, Julianalaan 67, 2628 BC Delft, the Netherlands

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BMC Systems Biology 2008, 2:111  doi:10.1186/1752-0509-2-111

Published: 24 December 2008



Comparative analysis of metabolic networks in multiple species yields important information on their evolution, and has great practical value in metabolic engineering, human disease analysis, drug design etc. In this work, we aim to systematically search for conserved pathways in two species, quantify their similarities, and focus on the variations between them.


We present an efficient framework, Metabolic Pathway Alignment and Scoring (M-PAS), for identifying and ranking conserved metabolic pathways. M-PAS aligns all reactions in entire metabolic networks of two species and assembles them into pathways, taking mismatches, gaps and crossovers into account. It uses a comprehensive scoring function, which quantifies pathway similarity such that we can focus on different pathways given different biological motivations. Using M-PAS, we detected 1198 length-four pathways fully conserved between Saccharomyces cerevisiae and Escherichia coli, and also revealed 1399 cases of a species using a unique route in otherwise highly conserved pathways.


Our method efficiently automates the process of exploring reaction arrangement possibilities, both between species and within species, to find conserved pathways. We not only reconstruct conventional pathways such as those found in KEGG, but also discover new pathway possibilities. Our results can help to generate hypotheses on missing reactions and manifest differences in highly conserved pathways, which is useful for biology and life science applications.