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Efficient Bayesian inference for mechanistic modelling with high-throughput data

Bayesian methods are routinely used to combine experimental data with detailed mathematical models to obtain insights into physical phenomena. However, the computational cost of Bayesian computation with detailed models has been a notorious problem. Moreover, while high-throughput data presents oppo...

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Detalles Bibliográficos
Autores principales: Martina Perez, Simon, Sailem, Heba, Baker, Ruth E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249175/
https://www.ncbi.nlm.nih.gov/pubmed/35727839
http://dx.doi.org/10.1371/journal.pcbi.1010191
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author Martina Perez, Simon
Sailem, Heba
Baker, Ruth E.
author_facet Martina Perez, Simon
Sailem, Heba
Baker, Ruth E.
author_sort Martina Perez, Simon
collection PubMed
description Bayesian methods are routinely used to combine experimental data with detailed mathematical models to obtain insights into physical phenomena. However, the computational cost of Bayesian computation with detailed models has been a notorious problem. Moreover, while high-throughput data presents opportunities to calibrate sophisticated models, comparing large amounts of data with model simulations quickly becomes computationally prohibitive. Inspired by the method of Stochastic Gradient Descent, we propose a minibatch approach to approximate Bayesian computation. Through a case study of a high-throughput imaging scratch assay experiment, we show that reliable inference can be performed at a fraction of the computational cost of a traditional Bayesian inference scheme. By applying a detailed mathematical model of single cell motility, proliferation and death to a data set of 118 gene knockdowns, we characterise functional subgroups of gene knockdowns, each displaying its own typical combination of local cell density-dependent and -independent motility and proliferation patterns. By comparing these patterns to experimental measurements of cell counts and wound closure, we find that density-dependent interactions play a crucial role in the process of wound healing.
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spelling pubmed-92491752022-07-02 Efficient Bayesian inference for mechanistic modelling with high-throughput data Martina Perez, Simon Sailem, Heba Baker, Ruth E. PLoS Comput Biol Research Article Bayesian methods are routinely used to combine experimental data with detailed mathematical models to obtain insights into physical phenomena. However, the computational cost of Bayesian computation with detailed models has been a notorious problem. Moreover, while high-throughput data presents opportunities to calibrate sophisticated models, comparing large amounts of data with model simulations quickly becomes computationally prohibitive. Inspired by the method of Stochastic Gradient Descent, we propose a minibatch approach to approximate Bayesian computation. Through a case study of a high-throughput imaging scratch assay experiment, we show that reliable inference can be performed at a fraction of the computational cost of a traditional Bayesian inference scheme. By applying a detailed mathematical model of single cell motility, proliferation and death to a data set of 118 gene knockdowns, we characterise functional subgroups of gene knockdowns, each displaying its own typical combination of local cell density-dependent and -independent motility and proliferation patterns. By comparing these patterns to experimental measurements of cell counts and wound closure, we find that density-dependent interactions play a crucial role in the process of wound healing. Public Library of Science 2022-06-21 /pmc/articles/PMC9249175/ /pubmed/35727839 http://dx.doi.org/10.1371/journal.pcbi.1010191 Text en © 2022 Martina Perez et al 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
Martina Perez, Simon
Sailem, Heba
Baker, Ruth E.
Efficient Bayesian inference for mechanistic modelling with high-throughput data
title Efficient Bayesian inference for mechanistic modelling with high-throughput data
title_full Efficient Bayesian inference for mechanistic modelling with high-throughput data
title_fullStr Efficient Bayesian inference for mechanistic modelling with high-throughput data
title_full_unstemmed Efficient Bayesian inference for mechanistic modelling with high-throughput data
title_short Efficient Bayesian inference for mechanistic modelling with high-throughput data
title_sort efficient bayesian inference for mechanistic modelling with high-throughput data
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249175/
https://www.ncbi.nlm.nih.gov/pubmed/35727839
http://dx.doi.org/10.1371/journal.pcbi.1010191
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