title: Inferring meaningful pathways in weighted metabolic networks.
abstract: An approach is presented for computing meaningful pathways in the network of small molecule metabolism comprising the chemical reactions characterized in all organisms. The metabolic network is described as a weighted graph in which all the compounds are included, but each compound is assigned a weight equal to the number of reactions in which it participates. Path finding is performed in this graph by searching for one or more paths with lowest weight. Performance is evaluated systematically by computing paths between the first and last reactions in annotated metabolic pathways, and comparing the intermediate reactions in the computed pathways to those in the annotated ones. For the sake of comparison, paths are computed also in the un-weighted raw (all compounds and reactions) and filtered (highly connected pool metabolites removed) metabolic graphs, respectively. The correspondence between the computed and annotated pathways is very poor (<30%) in the raw graph; increasing to approximately 65% in the filtered graph; reaching approximately 85% in the weighted graph. Considering the best-matching path among the five lightest paths increases the correspondence to 92%, on average. We then show that the average distance between pairs of metabolites is significantly larger in the weighted graph than in the raw unfiltered graph, suggesting that the small-world properties previously reported for metabolic networks probably result from irrelevant shortcuts through pool metabolites. In addition, we provide evidence that the length of the shortest path in the weighted graph represents a valid measure of the "metabolic distance" between enzymes. We suggest that the success of our simplistic approach is rooted in the high degree of specificity of the reactions in metabolic pathways, presumably reflecting thermodynamic constraints operating in these pathways. We expect our approach to find useful applications in inferring metabolic pathways in newly sequenced genomes.
authors.affiliation: SCMBB-Université Libre de Bruxelles, Campus Plaine, CP 263, Boulevard du Triomphe, 1050 Bruxelles, Belgium.
authors.forename: Didier
authors.initials: D
authors.lastname: Croes
authors.forename: Fabian
authors.initials: F
authors.lastname: Couche
authors.forename: Shoshana J
authors.initials: SJ
authors.lastname: Wodak
authors.forename: Jacques
authors.initials: J
authors.lastname: van Helden
mesh_terms: D000596:Amino Acids / Q000096:biosynthesis; D019295:Computational Biology / Q000379:methods*; D004926:Escherichia coli / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D011506:Proteins