Reference - Detail
|Author||Imieliński M, Belta C, Halász A, Rubin H.|
|Title||Investigating metabolite essentiality through genome-scale analysis of Escherichia coli production capabilities.|
MOTIVATION:A phenotype mechanism is classically derived through the study of a set of mutants and comparison of their biochemical capabilities. One method of comparing mutant capabilities is to characterize producible and knocked out metabolites. However such an effect is difficult to manually assess, especially for a large biochemical network and a complex media. Current algorithmic approaches towards analyzing metabolic networks either do not address this specific property or are computationally infeasible on the genome-scale.
RESULTS:We have developed a novel genome-scale computational approach that identifies the full set of biochemical species that are knocked out from the metabolome following a gene deletion. Results from this approach are combined with data from in vivo mutant screens to examine the essentiality of metabolite production for a phenotype. This approach can also be a useful tool for metabolic network annotation validation and refinement in newly sequenced organisms. Combining an in silico genome-scale model of Escherichia coli metabolism with in vivo survival data, we uncover possible essential roles for several cell membranes, cell walls, and quinone species. We also identify specific biomass components whose production appears to be non-essential for survival, contrary to the assumptions of previous models.
AVAILABILITY:Programs are available upon request from the authors in the form of Matlab script files.
|MeSH||Algorithms* Cell Survival / physiology Chromosome Mapping / methods* Computer Simulation Escherichia coli / physiology* Escherichia coli Proteins / genetics* Escherichia coli Proteins / metabolism* Gene Deletion Gene Expression Regulation / physiology* Models, Biological* Mutagenesis, Site-Directed Recombinant Proteins / metabolism Signal Transduction / physiology*|
|WOS Category||COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS STATISTICS & PROBABILITY MATHEMATICAL & COMPUTATIONAL BIOLOGY BIOCHEMICAL RESEARCH METHODS BIOTECHNOLOGY & APPLIED MICROBIOLOGY|