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Stochastic Methods for Parameter Estimation and Design of Experiments in Systems Biology
von Andrei KramerMarkov Chain Monte Carlo (MCMC) methods are sampling based techniques,
which use random numbers to approximate deterministic but unknown
values. They can be used to obtain expected values, estimate
parameters or to simply inspect the properties of a non-standard, high
dimensional probability distribution. Bayesian analysis of model
parameters provides the mathematical foundation for parameter
estimation using such probabilistic sampling.
The strengths of these stochastic methods are their robustness and relative simplicity even for nonlinear problems with dozens of parameters as well as a built-in uncertainty analysis. Because Bayesian model analysis necessarily involves the notion of prior knowledge, the estimation of unidentifiable parameters can be regularised (by priors) in a straight forward way.
This work draws the focus on typical cases in systems biology:
In biology the data is almost exclusively relative, the raw measurements (e. g. western blot intensities) are normalised by control experiments or a reference value within a series and require the model to do the same when comparing its output to the data.
Several sampling algorithms are compared in terms of effective sampling speed and necessary adaptations to relative and steady state data are explained.
The strengths of these stochastic methods are their robustness and relative simplicity even for nonlinear problems with dozens of parameters as well as a built-in uncertainty analysis. Because Bayesian model analysis necessarily involves the notion of prior knowledge, the estimation of unidentifiable parameters can be regularised (by priors) in a straight forward way.
This work draws the focus on typical cases in systems biology:
In biology the data is almost exclusively relative, the raw measurements (e. g. western blot intensities) are normalised by control experiments or a reference value within a series and require the model to do the same when comparing its output to the data.
Several sampling algorithms are compared in terms of effective sampling speed and necessary adaptations to relative and steady state data are explained.