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

Yunlei Li*, Dick de Ridder, Marco J. de Groot, Marcel J.T. Reinders*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

21 Citations (Scopus)
8 Downloads (Pure)

Abstract

Background
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.

Results
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.

Conclusion
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.
Original languageEnglish
Article number111
JournalBMC Systems Biology
DOIs
Publication statusPublished - 24 Dec 2008
Externally publishedYes

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