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2017 ; 287
(ä): 130-146
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Nonparametric dynamic modeling
#MMPMID27590775
Faraji M
; Voit EO
Math Biosci
2017[May]; 287
(ä): 130-146
PMID27590775
show ga
Challenging as it typically is, the estimation of parameter values seems to be an
unavoidable step in the design and implementation of any dynamic model. Here, we
demonstrate that it is possible to set up, diagnose, and simulate dynamic models
without the need to estimate parameter values, if the situation is favorable.
Specifically, it is possible to establish nonparametric models for nonlinear
compartment models, including metabolic pathway models, if sufficiently many
high-quality time series data are available that describe the biological
phenomenon under investigation in an appropriate and representative manner. The
proposed nonparametric strategy is a variant of the method of Dynamic Flux
Estimation (DFE), which permits the estimation of numerical flux profiles from
metabolic time series data. However, instead of attempting to formulate these
numerical profiles as explicit functions and to optimize their parameter values,
as it is done in DFE, the metabolite and flux profiles are used here directly as
a scaffold for a library from which values are interpolated and retrieved for the
simulation of the differential equations describing the model. Beyond
simulations, the proposed methods render it possible to determine steady states
from non-steady state data, perform sensitivity analyses, and estimate the
Jacobian of the system at a steady state.