Title
Constraint-based functional similarity of metabolic genes: going beyond network topology.
Abstract
Motivation: 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. Contact: olegro@cs.technion.ac.il Supplementary information: Supplementary data are available at Bioinformatics online.
Year
DOI
Venue
2007
10.1093/bioinformatics/btm319
BIOINFORMATICS
Keywords
Field
DocType
gene knockout,metabolic network,network topology
Gene,Biology,Metabolic Model,Gene knockout,Gene ontology,Gene expression,Metabolic network,Bioinformatics,Metabolic network modelling,In silico
Journal
Volume
Issue
ISSN
23
16
1367-4803
Citations 
PageRank 
References 
5
1.14
5
Authors
5
Name
Order
Citations
PageRank
Oleg Rokhlenko125017.03
Tomer Shlomi256328.44
Roded Sharan32792186.61
Eytan Ruppin41954173.51
Ron Pinter547852.83