Year of Publication
Doctor of Philosophy (PhD)
Arts and Sciences
Dr. Arnold Stromberg
Dr. Chi Wang
Kinetic modeling of the time dependence of metabolite concentrations including the unstable isotope labeled species is an important approach to simulate metabolic pathway dynamics. It is also essential for quantitative metabolic flux analysis using tracer data. However, as the metabolic networks are complex including extensive compartmentation and interconnections, the parameter estimation for enzymes that catalyze individual reactions needed for kinetic modeling is challenging. As the pa- rameter space is large and multi-dimensional while kinetic data are comparatively sparse, the estimation procedure (especially the point estimation methods) often en- counters multiple local maximum such that standard maximum likelihood methods may yield unreliable results. We proposed a Bayesian approach that leverages existing expert-constructed kinetic models for specifying an informative prior distribution for kinetic parameters. This prior knowledge prioritizes regions of parameter space that encompass the most likely parameter values, thereby facilitating robust parameter es- timation. A component-wise  adaptive Metropolis algorithm was used to generate the posterior samples of the kinetic parameters and conduct hypothesis tests under different treatments. Simulation studies using defined networks were used to test the performance of this algorithm under conditions of variable noise.
Digital Object Identifier (DOI)
This research was supported by NIH 1P01CA163223-01A1 from Jan 2018 to April 2019.
Zhang, Xu, "BAYESIAN KINETIC MODELING FOR TRACER-BASED METABOLOMIC DATA" (2020). Theses and Dissertations--Statistics. 45.