Many scientific fields collect longitudinal multivariate count data where the total number of counts is arbitrary (e.g., multinomial observations). These data are often called count compositional as the information in the data relates to the relative frequencies of the categories (Silverman et al., 2018). These data occur frequently in molecular biology (Espinoza et al., 2020), microbiome studies (Silverman et al., 2018; Joseph et al., 2020; Äijö et al., 2018), natural language processing (Linderman et al., 2015), biomedicine (Fokianos and Kedem, 2003), and social sciences (Cargnoni et al., 1997). Although the counting process used to collect these data is often modeled as multinomial, other sources of noise in the system being studied often lead to extra-multinomial variation. While some account for this extra-multinomial variability with multinomial-Dirichlet models (Mosimann, 1962), multinomial logistic-normal models are often superior, as they can account for both positive and negative covariation between multinomial categories (Aitchison and Shen, 1980; Cargnoni et al., 1997; Joseph et al., 2020; Silverman et al., 2018). Moreover, under suitable transformation (i.e., link function), the logistic-normal is multivariate Gaussian.

Ordinary differential equations (ODEs) are widely used to describe dynamical systems in science, but identifying parameters that explain experimental measurements is challenging. In particular, although ODEs are differentiable and would allow for gradient-based parameter optimization, the nonlinear dynamics of ODEs often lead to many local minima and extreme sensitivity to initial conditions. We therefore propose diffusion tempering, a novel regularization technique for probabilistic numerical methods which improves convergence of gradient-based parameter optimization in ODEs. By iteratively reducing a noise parameter of the probabilistic integrator, the proposed method converges more reliably to the true parameters. We demonstrate that our method is effective for dynamical systems of different complexity and show that it obtains reliable parameter estimates for a Hodgkin-Huxley model with a practically relevant number of parameters.

Estimating the parameters of ordinary differential equations (ODEs) is of fundamental importance in many scientific applications. While ODEs are typically approximated with deterministic algorithms, new research on probabilistic solvers indicates that they produce more reliable parameter estimates by better accounting for numerical errors. However, many ODE systems are highly sensitive to their parameter values. This produces deep local maxima in the likelihood function -- a problem which existing probabilistic solvers have yet to resolve. Here we present a novel probabilistic ODE likelihood approximation, DALTON, which can dramatically reduce parameter sensitivity by learning from noisy ODE measurements in a data-adaptive manner. Our approximation scales linearly in both ODE variables and time discretization points, and is applicable to ODEs with both partially-unobserved components and non-Gaussian measurement models. Several examples demonstrate that DALTON produces more accurate parameter estimates via numerical optimization than existing probabilistic ODE solvers, and even in some cases than the exact ODE likelihood itself.

We show how probabilistic numerics can be used to convert an initial value problem into a Gauss--Markov process parametrised by the dynamics of the initial value problem. Consequently, the often difficult problem of parameter estimation in ordinary differential equations is reduced to hyperparameter estimation in Gauss--Markov regression, which tends to be considerably easier. The method's relation and benefits in comparison to classical numerical integration and gradient matching approaches is elucidated. In particular, the method can, in contrast to gradient matching, handle partial observations, and has certain routes for escaping local optima not available to classical numerical integration. Experimental results demonstrate that the method is on par or moderately better than competing approaches.