Design of experiments for identification of complex biochemical systems with applications to mitochondrial bioenergetics.
Identification of a complex biochemical system model requires appropriate experimental data. Models constructed on the basis of data from the literature often contain parameters that are not identifiable with high sensitivity and therefore require additional experimental data to identify those parameters. Here we report the application of a local sensitivity analysis to design experiments that will improve the identifiability of previously unidentifiable model parameters in a model of mitochondrial oxidative phosphorylation and tricaboxylic acid cycle. Experiments were designed based on measurable biochemical reactants in a dilute suspension of purified cardiac mitochondria with experimentally feasible perturbations to this system. Experimental perturbations and variables yielding the most number of parameters above a 5% sensitivity level are presented and discussed.
Vinnakota
Kalyan C
KC
Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. kvinnakota@mcw.edu
Beard
Daniel A
DA
Dash
Ranjan K
RK
D000465:Algorithms; D000818:Animals; D001698:Biomedical Engineering / Q000379:methods; D002021:Buffers; D004594:Electrophysiology / Q000379:methods; D004734:Energy Metabolism; D004867:Equipment Design; D006321:Heart / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010766:Phosphorylation; D015203:Reproducibility of Results; D013997:Time Factors; D014233:Tricarboxylic Acids / Q000378:metabolism
D002021:Buffers; D014233:Tricarboxylic Acids