Sieve estimation of constant and time-varying coefficients in nonlinear ordinary differential equation models by considering both numerical error and measurement error

This article considers estimation of constant and time-varying coefficients in nonlinear ordinary differential equation (ODE) models where analytic closed-form solutions are not available. The numerical solution-based nonlinear least squares (NLS) estimator is investigated in this study. A numerical algorithm such as the Runge--Kutta method is used to approximate the ODE solution. The asymptotic properties are established for the proposed estimators considering both numerical error and measurement error. The B-spline is used to approximate the time-varying coefficients, and the corresponding asymptotic theories in this case are investigated under the framework of the sieve approach. Our results show that if the maximum step size of the $p$-order numerical algorithm goes to zero at a rate faster than $n^{-1/(p\wedge4)}$, the numerical error is negligible compared to the measurement error. This result provides a theoretical guidance in selection of the step size for numerical evaluations of ODEs. Moreover, we have shown that the numerical solution-based NLS estimator and the sieve NLS estimator are strongly consistent. The sieve estimator of constant parameters is asymptotically normal with the same asymptotic co-variance as that of the case where the true ODE solution is exactly known, while the estimator of the time-varying parameter has the optimal convergence rate under some regularity conditions. The theoretical results are also developed for the case when the step size of the ODE numerical solver does not go to zero fast enough or the numerical error is comparable to the measurement error. We illustrate our approach with both simulation studies and clinical data on HIV viral dynamics.Comment: Published in at http://dx.doi.org/10.1214/09-AOS784 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Gradient matching methods for computational inference in mechanistic models for systems biology: a review and comparative analysis

Parameter inference in mathematical models of biological pathways, expressed as coupled ordinary differential equations (ODEs), is a challenging problem in contemporary systems biology. Conventional methods involve repeatedly solving the ODEs by numerical integration, which is computationally onerous and does not scale up to complex systems. Aimed at reducing the computational costs, new concepts based on gradient matching have recently been proposed in the computational statistics and machine learning literature. In a preliminary smoothing step, the time series data are interpolated; then, in a second step, the parameters of the ODEs are optimised so as to minimise some metric measuring the difference between the slopes of the tangents to the interpolants, and the time derivatives from the ODEs. In this way, the ODEs never have to be solved explicitly. This review provides a concise methodological overview of the current state-of-the-art methods for gradient matching in ODEs, followed by an empirical comparative evaluation based on a set of widely used and representative benchmark data

Blended General Linear Methods based on Boundary Value Methods in the GBDF family

Among the methods for solving ODE-IVPs, the class of General Linear Methods (GLMs) is able to encompass most of them, ranging from Linear Multistep Formulae (LMF) to RK formulae. Moreover, it is possible to obtain methods able to overcome typical drawbacks of the previous classes of methods. For example, order barriers for stable LMF and the problem of order reduction for RK methods. Nevertheless, these goals are usually achieved at the price of a higher computational cost. Consequently, many efforts have been made in order to derive GLMs with particular features, to be exploited for their efficient implementation. In recent years, the derivation of GLMs from particular Boundary Value Methods (BVMs), namely the family of Generalized BDF (GBDF), has been proposed for the numerical solution of stiff ODE-IVPs. In particular, this approach has been recently developed, resulting in a new family of L-stable GLMs of arbitrarily high order, whose theory is here completed and fully worked-out. Moreover, for each one of such methods, it is possible to define a corresponding Blended GLM which is equivalent to it from the point of view of the stability and order properties. These blended methods, in turn, allow the definition of efficient nonlinear splittings for solving the generated discrete problems. A few numerical tests, confirming the excellent potential of such blended methods, are also reported.Comment: 22 pages, 8 figure

A Hybrid Algorithm Based on Optimal Quadratic Spline Collocation and Parareal Deferred Correction for Parabolic PDEs

Parareal is a kind of time parallel numerical methods for time-dependent systems. In this paper, we consider a general linear parabolic PDE, use optimal quadratic spline collocation (QSC) method for the space discretization, and proceed with the parareal technique on the time domain. Meanwhile, deferred correction technique is also used to improve the accuracy during the iterations. In fact, the optimal QSC method is a correction of general QSC method. Along the temporal direction we embed the iterations of deferred correction into parareal to construct a hybrid method, parareal deferred correction (PDC) method. The error estimation is presented and the stability is analyzed. To save computational cost, we find out a simple way to balance the two kinds of iterations as much as possible. We also argue that the hybrid algorithm has better system efficiency and costs less running time. Numerical experiments by multicore computers are attached to exhibit the effectiveness of the hybrid algorithm

Probabilistic Numerics and Uncertainty in Computations

We deliver a call to arms for probabilistic numerical methods: algorithms for numerical tasks, including linear algebra, integration, optimization and solving differential equations, that return uncertainties in their calculations. Such uncertainties, arising from the loss of precision induced by numerical calculation with limited time or hardware, are important for much contemporary science and industry. Within applications such as climate science and astrophysics, the need to make decisions on the basis of computations with large and complex data has led to a renewed focus on the management of numerical uncertainty. We describe how several seminal classic numerical methods can be interpreted naturally as probabilistic inference. We then show that the probabilistic view suggests new algorithms that can flexibly be adapted to suit application specifics, while delivering improved empirical performance. We provide concrete illustrations of the benefits of probabilistic numeric algorithms on real scientific problems from astrometry and astronomical imaging, while highlighting open problems with these new algorithms. Finally, we describe how probabilistic numerical methods provide a coherent framework for identifying the uncertainty in calculations performed with a combination of numerical algorithms (e.g. both numerical optimisers and differential equation solvers), potentially allowing the diagnosis (and control) of error sources in computations.Comment: Author Generated Postprint. 17 pages, 4 Figures, 1 Tabl