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The impact of experimental design choices on parameter inference for models of growing cell colonies

To better understand development, repair and disease progression, it is useful to quantify the behaviour of proliferative and motile cell populations as they grow and expand to fill their local environment. Inferring parameters associated with mechanistic models of cell colony growth using quantitat...

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Detalles Bibliográficos
Autores principales: Parker, Andrew, Simpson, Matthew J., Baker, Ruth E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124093/
https://www.ncbi.nlm.nih.gov/pubmed/30225025
http://dx.doi.org/10.1098/rsos.180384
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author Parker, Andrew
Simpson, Matthew J.
Baker, Ruth E.
author_facet Parker, Andrew
Simpson, Matthew J.
Baker, Ruth E.
author_sort Parker, Andrew
collection PubMed
description To better understand development, repair and disease progression, it is useful to quantify the behaviour of proliferative and motile cell populations as they grow and expand to fill their local environment. Inferring parameters associated with mechanistic models of cell colony growth using quantitative data collected from carefully designed experiments provides a natural means to elucidate the relative contributions of various processes to the growth of the colony. In this work, we explore how experimental design impacts our ability to infer parameters for simple models of the growth of proliferative and motile cell populations. We adopt a Bayesian approach, which allows us to characterize the uncertainty associated with estimates of the model parameters. Our results suggest that experimental designs that incorporate initial spatial heterogeneities in cell positions facilitate parameter inference without the requirement of cell tracking, while designs that involve uniform initial placement of cells require cell tracking for accurate parameter inference. As cell tracking is an experimental bottleneck in many studies of this type, our recommendations for experimental design provide for significant potential time and cost savings in the analysis of cell colony growth.
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spelling pubmed-61240932018-09-17 The impact of experimental design choices on parameter inference for models of growing cell colonies Parker, Andrew Simpson, Matthew J. Baker, Ruth E. R Soc Open Sci Cellular and Molecular Biology To better understand development, repair and disease progression, it is useful to quantify the behaviour of proliferative and motile cell populations as they grow and expand to fill their local environment. Inferring parameters associated with mechanistic models of cell colony growth using quantitative data collected from carefully designed experiments provides a natural means to elucidate the relative contributions of various processes to the growth of the colony. In this work, we explore how experimental design impacts our ability to infer parameters for simple models of the growth of proliferative and motile cell populations. We adopt a Bayesian approach, which allows us to characterize the uncertainty associated with estimates of the model parameters. Our results suggest that experimental designs that incorporate initial spatial heterogeneities in cell positions facilitate parameter inference without the requirement of cell tracking, while designs that involve uniform initial placement of cells require cell tracking for accurate parameter inference. As cell tracking is an experimental bottleneck in many studies of this type, our recommendations for experimental design provide for significant potential time and cost savings in the analysis of cell colony growth. The Royal Society 2018-08-29 /pmc/articles/PMC6124093/ /pubmed/30225025 http://dx.doi.org/10.1098/rsos.180384 Text en © 2018 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Cellular and Molecular Biology
Parker, Andrew
Simpson, Matthew J.
Baker, Ruth E.
The impact of experimental design choices on parameter inference for models of growing cell colonies
title The impact of experimental design choices on parameter inference for models of growing cell colonies
title_full The impact of experimental design choices on parameter inference for models of growing cell colonies
title_fullStr The impact of experimental design choices on parameter inference for models of growing cell colonies
title_full_unstemmed The impact of experimental design choices on parameter inference for models of growing cell colonies
title_short The impact of experimental design choices on parameter inference for models of growing cell colonies
title_sort impact of experimental design choices on parameter inference for models of growing cell colonies
topic Cellular and Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124093/
https://www.ncbi.nlm.nih.gov/pubmed/30225025
http://dx.doi.org/10.1098/rsos.180384
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