Identifying optimal models to represent biochemical systems.

Biochemical systems involving a high number of components with intricate interactions often lead to complex models containing a large number of parameters. Although a large model could describe in detail the mechanisms that underlie the system, its very large size may hinder us in understanding the...

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Main Authors: Mochamad Apri, Maarten de Gee, Simon van Mourik, Jaap Molenaar
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3885518?pdf=render
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author Mochamad Apri
Maarten de Gee
Simon van Mourik
Jaap Molenaar
author_facet Mochamad Apri
Maarten de Gee
Simon van Mourik
Jaap Molenaar
author_sort Mochamad Apri
collection DOAJ
description Biochemical systems involving a high number of components with intricate interactions often lead to complex models containing a large number of parameters. Although a large model could describe in detail the mechanisms that underlie the system, its very large size may hinder us in understanding the key elements of the system. Also in terms of parameter identification, large models are often problematic. Therefore, a reduced model may be preferred to represent the system. Yet, in order to efficaciously replace the large model, the reduced model should have the same ability as the large model to produce reliable predictions for a broad set of testable experimental conditions. We present a novel method to extract an "optimal" reduced model from a large model to represent biochemical systems by combining a reduction method and a model discrimination method. The former assures that the reduced model contains only those components that are important to produce the dynamics observed in given experiments, whereas the latter ensures that the reduced model gives a good prediction for any feasible experimental conditions that are relevant to answer questions at hand. These two techniques are applied iteratively. The method reveals the biological core of a model mathematically, indicating the processes that are likely to be responsible for certain behavior. We demonstrate the algorithm on two realistic model examples. We show that in both cases the core is substantially smaller than the full model.
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spelling doaj.art-3c24aab88bdf489eb6b2a41f1ce7a7b62022-12-21T19:10:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8366410.1371/journal.pone.0083664Identifying optimal models to represent biochemical systems.Mochamad ApriMaarten de GeeSimon van MourikJaap MolenaarBiochemical systems involving a high number of components with intricate interactions often lead to complex models containing a large number of parameters. Although a large model could describe in detail the mechanisms that underlie the system, its very large size may hinder us in understanding the key elements of the system. Also in terms of parameter identification, large models are often problematic. Therefore, a reduced model may be preferred to represent the system. Yet, in order to efficaciously replace the large model, the reduced model should have the same ability as the large model to produce reliable predictions for a broad set of testable experimental conditions. We present a novel method to extract an "optimal" reduced model from a large model to represent biochemical systems by combining a reduction method and a model discrimination method. The former assures that the reduced model contains only those components that are important to produce the dynamics observed in given experiments, whereas the latter ensures that the reduced model gives a good prediction for any feasible experimental conditions that are relevant to answer questions at hand. These two techniques are applied iteratively. The method reveals the biological core of a model mathematically, indicating the processes that are likely to be responsible for certain behavior. We demonstrate the algorithm on two realistic model examples. We show that in both cases the core is substantially smaller than the full model.http://europepmc.org/articles/PMC3885518?pdf=render
spellingShingle Mochamad Apri
Maarten de Gee
Simon van Mourik
Jaap Molenaar
Identifying optimal models to represent biochemical systems.
PLoS ONE
title Identifying optimal models to represent biochemical systems.
title_full Identifying optimal models to represent biochemical systems.
title_fullStr Identifying optimal models to represent biochemical systems.
title_full_unstemmed Identifying optimal models to represent biochemical systems.
title_short Identifying optimal models to represent biochemical systems.
title_sort identifying optimal models to represent biochemical systems
url http://europepmc.org/articles/PMC3885518?pdf=render
work_keys_str_mv AT mochamadapri identifyingoptimalmodelstorepresentbiochemicalsystems
AT maartendegee identifyingoptimalmodelstorepresentbiochemicalsystems
AT simonvanmourik identifyingoptimalmodelstorepresentbiochemicalsystems
AT jaapmolenaar identifyingoptimalmodelstorepresentbiochemicalsystems