Constraint-based functional similarity of metabolic genes: going beyond network topology.
BACKGROUND
Several recent studies attempted to establish measures for the similarity between genes that are based on the topological properties of metabolic networks. However, these approaches offer only a static description of the properties of interest and offer moderate (albeit significant) correlations with pertinent experimental data.


RESULTS
Using a constraint-based large-scale metabolic model, we present two effectively computable measures of functional gene similarity, one based on the response of the metabolic network to gene knockouts and the other based on the metabolic flux activity across a variety of growth media. We applied these measures to 750 genes comprising the metabolic network of the budding yeast. Comparing the in silico computed functional similarities to Gene Ontology (GO) annotations and gene expression data, we show that our computational method captures functional similarities between metabolic genes that go beyond those obtained by the topological analysis of metabolic networks alone, thus revealing dynamic characteristics of gene function. Interestingly, the measure based on the network response to different growth environments markedly outperforms the measure based on its response to gene knockouts, though both have some added synergistic value in depicting the functional relationships between metabolic genes.


BACKGROUND
Supplementary data are available at Bioinformatics online.
Rokhlenko
Oleg
O
Department of Computer Science, Technion, Haifa 32000, Israel. olegro@cs.technion.ac.il
Shlomi
Tomer
T
Sharan
Roded
R
Ruppin
Eytan
E
Pinter
Ron Y
RY
D003198:Computer Simulation; D004734:Energy Metabolism / Q000502:physiology; D008954:Models, Biological; D005810:Multigene Family / Q000502:physiology*; D025941:Protein Interaction Mapping / Q000379:methods*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*