References of "Vo, Thuy D."
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See detailGlobal reconstruction of the human metabolic network based on genomic and bibliomic data.
Duarte, Natalie C.; Becker, Scott A.; Jamshidi, Neema et al

in Proceedings of the National Academy of Sciences of the United States of America (2007), 104(6), 1777-82

Metabolism is a vital cellular process, and its malfunction is a major contributor to human disease. Metabolic networks are complex and highly interconnected, and thus systems-level computational ... [more ▼]

Metabolism is a vital cellular process, and its malfunction is a major contributor to human disease. Metabolic networks are complex and highly interconnected, and thus systems-level computational approaches are required to elucidate and understand metabolic genotype-phenotype relationships. We have manually reconstructed the global human metabolic network based on Build 35 of the genome annotation and a comprehensive evaluation of >50 years of legacy data (i.e., bibliomic data). Herein we describe the reconstruction process and demonstrate how the resulting genome-scale (or global) network can be used (i) for the discovery of missing information, (ii) for the formulation of an in silico model, and (iii) as a structured context for analyzing high-throughput biological data sets. Our comprehensive evaluation of the literature revealed many gaps in the current understanding of human metabolism that require future experimental investigation. Mathematical analysis of network structure elucidated the implications of intracellular compartmentalization and the potential use of correlated reaction sets for alternative drug target identification. Integrated analysis of high-throughput data sets within the context of the reconstruction enabled a global assessment of functional metabolic states. These results highlight some of the applications enabled by the reconstructed human metabolic network. The establishment of this network represents an important step toward genome-scale human systems biology. [less ▲]

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See detailExpanded metabolic reconstruction of Helicobacter pylori (iIT341 GSM/GPR): an in silico genome-scale characterization of single- and double-deletion mutants.
Thiele, Ines UL; Vo, Thuy D.; Price, Nathan D. et al

in Journal of Bacteriology (2005), 187(16), 5818-30

Helicobacter pylori is a human gastric pathogen infecting almost half of the world population. Herein, we present an updated version of the metabolic reconstruction of H. pylori strain 26695 based on the ... [more ▼]

Helicobacter pylori is a human gastric pathogen infecting almost half of the world population. Herein, we present an updated version of the metabolic reconstruction of H. pylori strain 26695 based on the revised genome annotation and new experimental data. This reconstruction, iIT341 GSM/GPR, represents a detailed review of the current literature about H. pylori as it integrates biochemical and genomic data in a comprehensive framework. In total, it accounts for 341 metabolic genes, 476 intracellular reactions, 78 exchange reactions, and 485 metabolites. Novel features of iIT341 GSM/GPR include (i) gene-protein-reaction associations, (ii) elementally and charge-balanced reactions, (iii) more accurate descriptions of isoprenoid and lipopolysaccharide metabolism, and (iv) quantitative assessments of the supporting data for each reaction. This metabolic reconstruction was used to carry out in silico deletion studies to identify essential and conditionally essential genes in H. pylori. A total of 128 essential and 75 conditionally essential metabolic genes were identified. Predicted growth phenotypes of single knockouts were validated using published experimental data. In addition, in silico double-deletion studies identified a total of 47 synthetic lethal mutants involving 67 different metabolic genes in rich medium. [less ▲]

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See detailCandidate metabolic network states in human mitochondria. Impact of diabetes, ischemia, and diet.
Thiele, Ines UL; Price, Nathan D.; Vo, Thuy D. et al

in Journal of Biological Chemistry (2005), 280(12), 11683-95

The human mitochondrial metabolic network was recently reconstructed based on proteomic and biochemical data. Linear programming and uniform random sampling were applied herein to identify candidate ... [more ▼]

The human mitochondrial metabolic network was recently reconstructed based on proteomic and biochemical data. Linear programming and uniform random sampling were applied herein to identify candidate steady states of the metabolic network that were consistent with the imposed physico-chemical constraints and available experimental data. The activity of the mitochondrion was studied under four metabolic conditions: normal physiologic, diabetic, ischemic, and dietetic. Pairwise correlations between steady-state reaction fluxes were calculated in each condition to evaluate the dependence among the reactions in the network. Applying constraints on exchange fluxes resulted in predictions for intracellular fluxes that agreed with experimental data. Analyses of the steady-state flux distributions showed that the experimentally observed reduced activity of pyruvate dehydrogenase in vivo could be a result of stoichiometric constraints and therefore would not necessarily require enzymatic inhibition. The observed changes in the energy metabolism of the mitochondrion under diabetic conditions were used to evaluate the impact of previously suggested treatments. The results showed that neither normalized glucose uptake nor decreased ketone body uptake have a positive effect on the mitochondrial energy metabolism or network flexibility. Taken together, this study showed that sampling of the steady-state flux space is a powerful method to investigate network properties under different conditions and provides a basis for in silico evaluations of effects of potential disease treatments. [less ▲]

Detailed reference viewed: 120 (1 UL)