Likelihood based observability analysis and confidence intervals for predictions of dynamic models

Mechanistic dynamic models of biochemical networks such as Ordinary Differential Equations (ODEs) contain unknown parameters like the reaction rate constants and the initial concentrations of the compounds. The large number of parameters as well as their nonlinear impact on the model responses hamper the determination of confidence regions for parameter estimates. At the same time, classical approaches translating the uncertainty of the parameters into confidence intervals for model predictions are hardly feasible. In this article it is shown that a so-called prediction profile likelihood yields reliable confidence intervals for model predictions, despite arbitrarily complex and high-dimensional shapes of the confidence regions for the estimated parameters. Prediction confidence intervals of the dynamic states allow a data-based observability analysis. The approach renders the issue of sampling a high-dimensional parameter space into evaluating one-dimensional prediction spaces. The method is also applicable if there are non-identifiable parameters yielding to some insufficiently specified model predictions that can be interpreted as non-observability. Moreover, a validation profile likelihood is introduced that should be applied when noisy validation experiments are to be interpreted. The properties and applicability of the prediction and validation profile likelihood approaches are demonstrated by two examples, a small and instructive ODE model describing two consecutive reactions, and a realistic ODE model for the MAP kinase signal transduction pathway. The presented general approach constitutes a concept for observability analysis and for generating reliable confidence intervals of model predictions, not only, but especially suitable for mathematical models of biological systems

Probabilistic error estimation for non-intrusive reduced models learned from data of systems governed by linear parabolic partial differential equations

This work derives a residual-based a posteriori error estimator for reduced models learned with non-intrusive model reduction from data of high-dimensional systems governed by linear parabolic partial differential equations with control inputs. It is shown that quantities that are necessary for the error estimator can be either obtained exactly as the solutions of least-squares problems in a non-intrusive way from data such as initial conditions, control inputs, and high-dimensional solution trajectories or bounded in a probabilistic sense. The computational procedure follows an offline/online decomposition. In the offline (training) phase, the high-dimensional system is judiciously solved in a black-box fashion to generate data and to set up the error estimator. In the online phase, the estimator is used to bound the error of the reduced-model predictions for new initial conditions and new control inputs without recourse to the high-dimensional system. Numerical results demonstrate the workflow of the proposed approach from data to reduced models to certified predictions

Levy stable noise induced transitions: stochastic resonance, resonant activation and dynamic hysteresis

A standard approach to analysis of noise-induced effects in stochastic dynamics assumes a Gaussian character of the noise term describing interaction of the analyzed system with its complex surroundings. An additional assumption about the existence of timescale separation between the dynamics of the measured observable and the typical timescale of the noise allows external fluctuations to be modeled as temporally uncorrelated and therefore white. However, in many natural phenomena the assumptions concerning the abovementioned properties of "Gaussianity" and "whiteness" of the noise can be violated. In this context, in contrast to the spatiotemporal coupling characterizing general forms of non-Markovian or semi-Markovian L\'evy walks, so called L\'evy flights correspond to the class of Markov processes which still can be interpreted as white, but distributed according to a more general, infinitely divisible, stable and non-Gaussian law. L\'evy noise-driven non-equilibrium systems are known to manifest interesting physical properties and have been addressed in various scenarios of physical transport exhibiting a superdiffusive behavior. Here we present a brief overview of our recent investigations aimed to understand features of stochastic dynamics under the influence of L\'evy white noise perturbations. We find that the archetypal phenomena of noise-induced ordering are robust and can be detected also in systems driven by non-Gaussian, heavy-tailed fluctuations with infinite variance.Comment: 7 pages, 8 figure