Filter inference: a scalable nonlinear mixed effects inference approach for snapshot time series data

Variability is an intrinsic property of biological systems and is often at the heart of their complex behaviour. Examples range from cell-to-cell variability in cell signalling pathways to variability in the response to treatment across patients. A popular approach to model and understand this varia...

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Main Authors: Augustin, D, Lambert, B, Wang, K, Walz, A-C, Robinson, M, Gavaghan, D
Format: Journal article
Language:English
Published: Public Library of Science 2023
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author Augustin, D
Lambert, B
Wang, K
Walz, A-C
Robinson, M
Gavaghan, D
author_facet Augustin, D
Lambert, B
Wang, K
Walz, A-C
Robinson, M
Gavaghan, D
author_sort Augustin, D
collection OXFORD
description Variability is an intrinsic property of biological systems and is often at the heart of their complex behaviour. Examples range from cell-to-cell variability in cell signalling pathways to variability in the response to treatment across patients. A popular approach to model and understand this variability is nonlinear mixed effects (NLME) modelling. However, estimating the parameters of NLME models from measurements quickly becomes computationally expensive as the number of measured individuals grows, making NLME inference intractable for datasets with thousands of measured individuals. This shortcoming is particularly limiting for snapshot datasets, common e.g. in cell biology, where high-throughput measurement techniques provide large numbers of single cell measurements. We introduce a novel approach for the estimation of NLME model parameters from snapshot measurements, which we call filter inference. Filter inference uses measurements of simulated individuals to define an approximate likelihood for the model parameters, avoiding the computational limitations of traditional NLME inference approaches and making efficient inferences from snapshot measurements possible. Filter inference also scales well with the number of model parameters, using state-of-the-art gradient-based MCMC algorithms such as the No-U-Turn Sampler (NUTS). We demonstrate the properties of filter inference using examples from early cancer growth modelling and from epidermal growth factor signalling pathway modelling.
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spelling oxford-uuid:213f99f6-3546-4187-9882-a4d93b6e47422023-11-22T06:10:05ZFilter inference: a scalable nonlinear mixed effects inference approach for snapshot time series dataJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:213f99f6-3546-4187-9882-a4d93b6e4742EnglishSymplectic ElementsPublic Library of Science2023Augustin, DLambert, BWang, KWalz, A-CRobinson, MGavaghan, DVariability is an intrinsic property of biological systems and is often at the heart of their complex behaviour. Examples range from cell-to-cell variability in cell signalling pathways to variability in the response to treatment across patients. A popular approach to model and understand this variability is nonlinear mixed effects (NLME) modelling. However, estimating the parameters of NLME models from measurements quickly becomes computationally expensive as the number of measured individuals grows, making NLME inference intractable for datasets with thousands of measured individuals. This shortcoming is particularly limiting for snapshot datasets, common e.g. in cell biology, where high-throughput measurement techniques provide large numbers of single cell measurements. We introduce a novel approach for the estimation of NLME model parameters from snapshot measurements, which we call filter inference. Filter inference uses measurements of simulated individuals to define an approximate likelihood for the model parameters, avoiding the computational limitations of traditional NLME inference approaches and making efficient inferences from snapshot measurements possible. Filter inference also scales well with the number of model parameters, using state-of-the-art gradient-based MCMC algorithms such as the No-U-Turn Sampler (NUTS). We demonstrate the properties of filter inference using examples from early cancer growth modelling and from epidermal growth factor signalling pathway modelling.
spellingShingle Augustin, D
Lambert, B
Wang, K
Walz, A-C
Robinson, M
Gavaghan, D
Filter inference: a scalable nonlinear mixed effects inference approach for snapshot time series data
title Filter inference: a scalable nonlinear mixed effects inference approach for snapshot time series data
title_full Filter inference: a scalable nonlinear mixed effects inference approach for snapshot time series data
title_fullStr Filter inference: a scalable nonlinear mixed effects inference approach for snapshot time series data
title_full_unstemmed Filter inference: a scalable nonlinear mixed effects inference approach for snapshot time series data
title_short Filter inference: a scalable nonlinear mixed effects inference approach for snapshot time series data
title_sort filter inference a scalable nonlinear mixed effects inference approach for snapshot time series data
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