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Geometric analysis enables biological insight from complex non-identifiable models using simple surrogates

An enduring challenge in computational biology is to balance data quality and quantity with model complexity. Tools such as identifiability analysis and information criterion have been developed to harmonise this juxtaposition, yet cannot always resolve the mismatch between available data and the gr...

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Autores principales: Browning, Alexander P., Simpson, Matthew J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9891533/
https://www.ncbi.nlm.nih.gov/pubmed/36662831
http://dx.doi.org/10.1371/journal.pcbi.1010844
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author Browning, Alexander P.
Simpson, Matthew J.
author_facet Browning, Alexander P.
Simpson, Matthew J.
author_sort Browning, Alexander P.
collection PubMed
description An enduring challenge in computational biology is to balance data quality and quantity with model complexity. Tools such as identifiability analysis and information criterion have been developed to harmonise this juxtaposition, yet cannot always resolve the mismatch between available data and the granularity required in mathematical models to answer important biological questions. Often, it is only simple phenomenological models, such as the logistic and Gompertz growth models, that are identifiable from standard experimental measurements. To draw insights from complex, non-identifiable models that incorporate key biological mechanisms of interest, we study the geometry of a map in parameter space from the complex model to a simple, identifiable, surrogate model. By studying how non-identifiable parameters in the complex model quantitatively relate to identifiable parameters in surrogate, we introduce and exploit a layer of interpretation between the set of non-identifiable parameters and the goodness-of-fit metric or likelihood studied in typical identifiability analysis. We demonstrate our approach by analysing a hierarchy of mathematical models for multicellular tumour spheroid growth experiments. Typical data from tumour spheroid experiments are limited and noisy, and corresponding mathematical models are very often made arbitrarily complex. Our geometric approach is able to predict non-identifiabilities, classify non-identifiable parameter spaces into identifiable parameter combinations that relate to features in the data characterised by parameters in a surrogate model, and overall provide additional biological insight from complex non-identifiable models.
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spelling pubmed-98915332023-02-02 Geometric analysis enables biological insight from complex non-identifiable models using simple surrogates Browning, Alexander P. Simpson, Matthew J. PLoS Comput Biol Research Article An enduring challenge in computational biology is to balance data quality and quantity with model complexity. Tools such as identifiability analysis and information criterion have been developed to harmonise this juxtaposition, yet cannot always resolve the mismatch between available data and the granularity required in mathematical models to answer important biological questions. Often, it is only simple phenomenological models, such as the logistic and Gompertz growth models, that are identifiable from standard experimental measurements. To draw insights from complex, non-identifiable models that incorporate key biological mechanisms of interest, we study the geometry of a map in parameter space from the complex model to a simple, identifiable, surrogate model. By studying how non-identifiable parameters in the complex model quantitatively relate to identifiable parameters in surrogate, we introduce and exploit a layer of interpretation between the set of non-identifiable parameters and the goodness-of-fit metric or likelihood studied in typical identifiability analysis. We demonstrate our approach by analysing a hierarchy of mathematical models for multicellular tumour spheroid growth experiments. Typical data from tumour spheroid experiments are limited and noisy, and corresponding mathematical models are very often made arbitrarily complex. Our geometric approach is able to predict non-identifiabilities, classify non-identifiable parameter spaces into identifiable parameter combinations that relate to features in the data characterised by parameters in a surrogate model, and overall provide additional biological insight from complex non-identifiable models. Public Library of Science 2023-01-20 /pmc/articles/PMC9891533/ /pubmed/36662831 http://dx.doi.org/10.1371/journal.pcbi.1010844 Text en © 2023 Browning, Simpson https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://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
Browning, Alexander P.
Simpson, Matthew J.
Geometric analysis enables biological insight from complex non-identifiable models using simple surrogates
title Geometric analysis enables biological insight from complex non-identifiable models using simple surrogates
title_full Geometric analysis enables biological insight from complex non-identifiable models using simple surrogates
title_fullStr Geometric analysis enables biological insight from complex non-identifiable models using simple surrogates
title_full_unstemmed Geometric analysis enables biological insight from complex non-identifiable models using simple surrogates
title_short Geometric analysis enables biological insight from complex non-identifiable models using simple surrogates
title_sort geometric analysis enables biological insight from complex non-identifiable models using simple surrogates
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9891533/
https://www.ncbi.nlm.nih.gov/pubmed/36662831
http://dx.doi.org/10.1371/journal.pcbi.1010844
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