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Topological augmentation to infer hidden processes in biological systems


Sunnaker, M; Zamora-Sillero, E; Lopez Garcia de Lomana, A; Rudroff, F; Sauer, U; Stelling, J; Wagner, A (2014). Topological augmentation to infer hidden processes in biological systems. Bioinformatics, 30(2):221-227.

Abstract

MOTIVATION:
A common problem in understanding a biochemical system is to infer its correct structure or topology. This topology consists of all relevant state variables-usually molecules and their interactions. Here we present a method called topological augmentation to infer this structure in a statistically rigorous and systematic way from prior knowledge and experimental data.
RESULTS:
Topological augmentation starts from a simple model that is unable to explain the experimental data and augments its topology by adding new terms that capture the experimental behavior. This process is guided by representing the uncertainty in the model topology through stochastic differential equations whose trajectories contain information about missing model parts. We first apply this semiautomatic procedure to a pharmacokinetic model. This example illustrates that a global sampling of the parameter space is critical for inferring a correct model structure. We also use our method to improve our understanding of glutamine transport in yeast. This analysis shows that transport dynamics is determined by glutamine permeases with two different kinds of kinetics. Topological augmentation can not only be applied to biochemical systems, but also to any system that can be described by ordinary differential equations. Availability and implementation: Matlab code and examples are available at: http://www.csb.ethz.ch/tools/index.

Abstract

MOTIVATION:
A common problem in understanding a biochemical system is to infer its correct structure or topology. This topology consists of all relevant state variables-usually molecules and their interactions. Here we present a method called topological augmentation to infer this structure in a statistically rigorous and systematic way from prior knowledge and experimental data.
RESULTS:
Topological augmentation starts from a simple model that is unable to explain the experimental data and augments its topology by adding new terms that capture the experimental behavior. This process is guided by representing the uncertainty in the model topology through stochastic differential equations whose trajectories contain information about missing model parts. We first apply this semiautomatic procedure to a pharmacokinetic model. This example illustrates that a global sampling of the parameter space is critical for inferring a correct model structure. We also use our method to improve our understanding of glutamine transport in yeast. This analysis shows that transport dynamics is determined by glutamine permeases with two different kinds of kinetics. Topological augmentation can not only be applied to biochemical systems, but also to any system that can be described by ordinary differential equations. Availability and implementation: Matlab code and examples are available at: http://www.csb.ethz.ch/tools/index.

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5 citations in Web of Science®
7 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Evolutionary Biology and Environmental Studies
Dewey Decimal Classification:570 Life sciences; biology
590 Animals (Zoology)
Language:English
Date:2014
Deposited On:20 Jan 2014 08:33
Last Modified:21 Nov 2017 17:04
Publisher:Oxford University Press
ISSN:1367-4803
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/bioinformatics/btt638
PubMed ID:24297519

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