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Mélanie Prague

Mélanie Prague contributes to research discovery and scholarly infrastructure.

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Published work

2 published item(s)

preprint2026arXiv

Bayesian Nonparametric Mixed-Effect ODEs with Gaussian Processes

Dynamical modelling is central to many scientific domains, including pharmacometrics, systems biology, physiology, and epidemiology. In these settings, heterogeneity is often intrinsic: different subjects or units follow related but distinct continuous-time dynamics. Classical nonlinear mixed-effects Ordinary Differential Equation (ODE) models address this by combining population-level structure with subject-specific effects, but they rely on a parametric vector field and are therefore vulnerable to structural misspecification and unmodelled mechanisms. This motivates nonparametric approaches that can retain principled uncertainty quantification, yet existing nonparametric ODE methods typically assume a single shared dynamical system rather than an explicit mixed-effect hierarchy over subject-specific dynamics. We propose MEGPODE, a Bayesian nonparametric mixed-effect ODE model in which each subject's vector field is decomposed into a shared population component and a subject-specific deviation, both endowed with Gaussian process (GP) priors. To avoid repeated ODE solves per subject during training, we combine state-space GP trajectory priors with virtual collocation observations, yielding Kalman-smoothing trajectory updates and closed-form regressions for the vector fields. Across controlled heterogeneous ODE benchmarks spanning oscillatory, biomedical systems, MEGPODE improves population-field recovery and subject-level trajectory prediction relative to strong baselines.

preprint2021arXiv

Parameter estimation in nonlinear mixed effect models based on ordinary differential equations: an optimal control approach

We present a parameter estimation method for nonlinear mixed effect models based on ordinary differential equations (NLME-ODEs). The method presented here aims at regularizing the estimation problem in presence of model misspecifications, practical identifiability issues and unknown initial conditions. For doing so, we define our estimator as the minimizer of a cost function which incorporates a possible gap between the assumed model at the population level and the specific individual dynamic. The cost function computation leads to formulate and solve optimal control problems at the subject level. This control theory approach allows to bypass the need to know or estimate initial conditions for each subject and it regularizes the estimation problem in presence of poorly identifiable parameters. Comparing to maximum likelihood, we show on simulation examples that our method improves estimation accuracy in possibly partially observed systems with unknown initial conditions or poorly identifiable parameters with or without model error. We conclude this work with a real application on antibody concentration data after vaccination against Ebola virus coming from phase 1 trials. We use the estimated model discrepancy at the subject level to analyze the presence of model misspecification.