A White-Box Approach to Function-Parameter Co-Estimation for Kinetic Models of Biochemical Networks
Hopkins, Calvin Michael
2012
- Kinetic modeling attempts to describe the time-dependent behavior of every enzyme-catalyzed reaction in the network. Systems of ordinary differential equations express each reaction rate as a function of metabolite concentrations and rate constant parameters. The mechanistic knowledge of enzyme kinetics however is not always available. Furthermore, estimating a consistent set of rate parameters ... read morefrom time-series data requires a large experimental effort for even a moderately-sized network. This work develops approximate kinetic expressions for a module (connected groups of reactions) instead of developing kinetic expressions for each reaction within the module. Our modeling utilizes Convenience Kinetics to capture system dynamics. We develop a genetic algorithm to explore the trade offs between expression accuracy and simplicity, in terms of including variables representing the concentration of metabolites internal to the module. When eliminating an internal variable, our algorithm compensates by calculating a new set of parameter values and shifting the roles of remaining metabolites as activators and inhibitors. Our validation efforts on three test cases demonstrate such tradeoffs, and show that modest loss of accuracy is possible when some internal metabolite concentrations are eliminated and when the resulting system is gamed to compensate for the missing variables.read less
- ID:
- bc386w173
- Component ID:
- tufts:UA005.035.011.00001
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