Simulation-based inference for stochastic nonlinear mixed-effects models with applications in systems biology

Fuente: arXiv
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Autores principales: Häggström, Henrik, Persson, Sebastian, Cvijovic, Marija, Picchini, Umberto
Formato: Preprint
Publicado: 2025
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author Häggström, Henrik
Persson, Sebastian
Cvijovic, Marija
Picchini, Umberto
author_facet Häggström, Henrik
Persson, Sebastian
Cvijovic, Marija
Picchini, Umberto
contents The analysis of data from multiple experiments, such as observations of several individuals, is commonly approached using mixed-effects models, which account for variation between individuals through hierarchical representations. This makes mixed-effects models widely applied in fields such as biology, pharmacokinetics, and sociology. In this work, we propose a novel methodology for scalable Bayesian inference in hierarchical mixed-effects models. Our framework first constructs amortized approximations of the likelihood and the posterior distribution, which are then rapidly refined for each individual dataset, to ultimately approximate the parameters posterior across many individuals. The framework is easily trainable, as it uses mixtures of experts but without neural networks, leading to parsimonious yet expressive surrogate models of the likelihood and the posterior. We demonstrate the effectiveness of our methodology using challenging stochastic models, such as mixed-effects stochastic differential equations emerging in systems biology-driven problems. However, the approach is broadly applicable and can accommodate both stochastic and deterministic models. We show that our approach can seamlessly handle inference for many parameters. Additionally, we applied our method to a real-data case study of mRNA transfection. When compared to exact pseudomarginal Bayesian inference, our approach proved to be both fast and competitive in terms of statistical accuracy.
format Preprint
id arxiv_https___arxiv_org_abs_2504_11279
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Simulation-based inference for stochastic nonlinear mixed-effects models with applications in systems biology
Häggström, Henrik
Persson, Sebastian
Cvijovic, Marija
Picchini, Umberto
Computation
Methodology
Machine Learning
The analysis of data from multiple experiments, such as observations of several individuals, is commonly approached using mixed-effects models, which account for variation between individuals through hierarchical representations. This makes mixed-effects models widely applied in fields such as biology, pharmacokinetics, and sociology. In this work, we propose a novel methodology for scalable Bayesian inference in hierarchical mixed-effects models. Our framework first constructs amortized approximations of the likelihood and the posterior distribution, which are then rapidly refined for each individual dataset, to ultimately approximate the parameters posterior across many individuals. The framework is easily trainable, as it uses mixtures of experts but without neural networks, leading to parsimonious yet expressive surrogate models of the likelihood and the posterior. We demonstrate the effectiveness of our methodology using challenging stochastic models, such as mixed-effects stochastic differential equations emerging in systems biology-driven problems. However, the approach is broadly applicable and can accommodate both stochastic and deterministic models. We show that our approach can seamlessly handle inference for many parameters. Additionally, we applied our method to a real-data case study of mRNA transfection. When compared to exact pseudomarginal Bayesian inference, our approach proved to be both fast and competitive in terms of statistical accuracy.
title Simulation-based inference for stochastic nonlinear mixed-effects models with applications in systems biology
topic Computation
Methodology
Machine Learning
url https://arxiv.org/abs/2504.11279