Research
Stoichiometric Determinants of Metabolic Network States
The stoichiometric description of metabolic networks lends itself to direct, physical interpretations of the four fundamental subspaces of the mass balance equations. The right and left null spaces contain information about steady state capabilities of the biochemical network. The row and column spaces account for the network dynamics. High- and low-throughput data can be used to further constrain these networks and improve the sensivity and specificity of network predictions.
Drug Response Phenotypes: Assessment of altered platelet flux states in aspirin resistance
As an example of how genome-scale models can be used for precision medicine applications using multi-omics data. Although aspirin is a commonly taken pharmaceutical and frequently prescribed as a ‘first line’ prophylactic medication for clotting disorders, it is surprisingly estimated 10-20% of individuals may have diminished response to inhibition of cyclooxygenase (aspirin’s target). We developed a platelet reconstruction, iAT-PLT- 636, to assess the cellular alterations in subjects who have normal versus abnormal (‘resistant’) responses to aspirin. Findings from this work suggested that the metabolic consequences of aspirin-resistance on platelet metabolism are elicited by the diversion of metabolites to prostaglandin synthesis and the consequent flux decrease in oxidative metabolism and flux increase in the pentose sugar metabolism with corresponding shifts in redox pathways, glycolysis, and nucleotide salvage pathways.
