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Local Riemannian geometry of model manifolds and its implications for practical parameter identifiability

When non-linear models are fitted to experimental data, parameter estimates can be poorly constrained albeit being identifiable in principle. This means that along certain paths in parameter space, the log-likelihood does not exceed a given statistical threshold but remains bounded. This situation,...

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Autores principales: Lill, Daniel, Timmer, Jens, Kaschek, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546239/
https://www.ncbi.nlm.nih.gov/pubmed/31158252
http://dx.doi.org/10.1371/journal.pone.0217837
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author Lill, Daniel
Timmer, Jens
Kaschek, Daniel
author_facet Lill, Daniel
Timmer, Jens
Kaschek, Daniel
author_sort Lill, Daniel
collection PubMed
description When non-linear models are fitted to experimental data, parameter estimates can be poorly constrained albeit being identifiable in principle. This means that along certain paths in parameter space, the log-likelihood does not exceed a given statistical threshold but remains bounded. This situation, denoted as practical non-identifiability, can be detected by Monte Carlo sampling or by systematic scanning using the profile likelihood method. In contrast, any method based on a Taylor expansion of the log-likelihood around the optimum, e.g., parameter uncertainty estimation by the Fisher Information Matrix, reveals no information about the boundedness at all. In this work, we present a geometric approach, approximating the original log-likelihood by geodesic coordinates of the model manifold. The Christoffel Symbols in the geodesic equation are fixed to those obtained from second order model sensitivities at the optimum. Based on three exemplary non-linear models we show that the information about the log-likelihood bounds and flat parameter directions can already be contained in this local information. Whereas the unbounded case represented by the Fisher Information Matrix is embedded in the geometric framework as vanishing Christoffel Symbols, non-vanishing constant Christoffel Symbols prove to define prototype non-linear models featuring boundedness and flat parameter directions of the log-likelihood. Finally, we investigate if those models could allow to approximate and replace computationally expensive objective functions originating from non-linear models by a surrogate objective function in parameter estimation problems.
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spelling pubmed-65462392019-06-17 Local Riemannian geometry of model manifolds and its implications for practical parameter identifiability Lill, Daniel Timmer, Jens Kaschek, Daniel PLoS One Research Article When non-linear models are fitted to experimental data, parameter estimates can be poorly constrained albeit being identifiable in principle. This means that along certain paths in parameter space, the log-likelihood does not exceed a given statistical threshold but remains bounded. This situation, denoted as practical non-identifiability, can be detected by Monte Carlo sampling or by systematic scanning using the profile likelihood method. In contrast, any method based on a Taylor expansion of the log-likelihood around the optimum, e.g., parameter uncertainty estimation by the Fisher Information Matrix, reveals no information about the boundedness at all. In this work, we present a geometric approach, approximating the original log-likelihood by geodesic coordinates of the model manifold. The Christoffel Symbols in the geodesic equation are fixed to those obtained from second order model sensitivities at the optimum. Based on three exemplary non-linear models we show that the information about the log-likelihood bounds and flat parameter directions can already be contained in this local information. Whereas the unbounded case represented by the Fisher Information Matrix is embedded in the geometric framework as vanishing Christoffel Symbols, non-vanishing constant Christoffel Symbols prove to define prototype non-linear models featuring boundedness and flat parameter directions of the log-likelihood. Finally, we investigate if those models could allow to approximate and replace computationally expensive objective functions originating from non-linear models by a surrogate objective function in parameter estimation problems. Public Library of Science 2019-06-03 /pmc/articles/PMC6546239/ /pubmed/31158252 http://dx.doi.org/10.1371/journal.pone.0217837 Text en © 2019 Lill et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lill, Daniel
Timmer, Jens
Kaschek, Daniel
Local Riemannian geometry of model manifolds and its implications for practical parameter identifiability
title Local Riemannian geometry of model manifolds and its implications for practical parameter identifiability
title_full Local Riemannian geometry of model manifolds and its implications for practical parameter identifiability
title_fullStr Local Riemannian geometry of model manifolds and its implications for practical parameter identifiability
title_full_unstemmed Local Riemannian geometry of model manifolds and its implications for practical parameter identifiability
title_short Local Riemannian geometry of model manifolds and its implications for practical parameter identifiability
title_sort local riemannian geometry of model manifolds and its implications for practical parameter identifiability
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546239/
https://www.ncbi.nlm.nih.gov/pubmed/31158252
http://dx.doi.org/10.1371/journal.pone.0217837
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