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Top-Down Analysis of Temporal Hierarchy in Biochemical Reaction Networks

The study of dynamic functions of large-scale biological networks has intensified in recent years. A critical component in developing an understanding of such dynamics involves the study of their hierarchical organization. We investigate the temporal hierarchy in biochemical reaction networks focusi...

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Detalles Bibliográficos
Autores principales: Jamshidi, Neema, Palsson, Bernhard Ø.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518853/
https://www.ncbi.nlm.nih.gov/pubmed/18787685
http://dx.doi.org/10.1371/journal.pcbi.1000177
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author Jamshidi, Neema
Palsson, Bernhard Ø.
author_facet Jamshidi, Neema
Palsson, Bernhard Ø.
author_sort Jamshidi, Neema
collection PubMed
description The study of dynamic functions of large-scale biological networks has intensified in recent years. A critical component in developing an understanding of such dynamics involves the study of their hierarchical organization. We investigate the temporal hierarchy in biochemical reaction networks focusing on: (1) the elucidation of the existence of “pools” (i.e., aggregate variables) formed from component concentrations and (2) the determination of their composition and interactions over different time scales. To date the identification of such pools without prior knowledge of their composition has been a challenge. A new approach is developed for the algorithmic identification of pool formation using correlations between elements of the modal matrix that correspond to a pair of concentrations and how such correlations form over the hierarchy of time scales. The analysis elucidates a temporal hierarchy of events that range from chemical equilibration events to the formation of physiologically meaningful pools, culminating in a network-scale (dynamic) structure–(physiological) function relationship. This method is validated on a model of human red blood cell metabolism and further applied to kinetic models of yeast glycolysis and human folate metabolism, enabling the simplification of these models. The understanding of temporal hierarchy and the formation of dynamic aggregates on different time scales is foundational to the study of network dynamics and has relevance in multiple areas ranging from bacterial strain design and metabolic engineering to the understanding of disease processes in humans.
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spelling pubmed-25188532008-09-12 Top-Down Analysis of Temporal Hierarchy in Biochemical Reaction Networks Jamshidi, Neema Palsson, Bernhard Ø. PLoS Comput Biol Research Article The study of dynamic functions of large-scale biological networks has intensified in recent years. A critical component in developing an understanding of such dynamics involves the study of their hierarchical organization. We investigate the temporal hierarchy in biochemical reaction networks focusing on: (1) the elucidation of the existence of “pools” (i.e., aggregate variables) formed from component concentrations and (2) the determination of their composition and interactions over different time scales. To date the identification of such pools without prior knowledge of their composition has been a challenge. A new approach is developed for the algorithmic identification of pool formation using correlations between elements of the modal matrix that correspond to a pair of concentrations and how such correlations form over the hierarchy of time scales. The analysis elucidates a temporal hierarchy of events that range from chemical equilibration events to the formation of physiologically meaningful pools, culminating in a network-scale (dynamic) structure–(physiological) function relationship. This method is validated on a model of human red blood cell metabolism and further applied to kinetic models of yeast glycolysis and human folate metabolism, enabling the simplification of these models. The understanding of temporal hierarchy and the formation of dynamic aggregates on different time scales is foundational to the study of network dynamics and has relevance in multiple areas ranging from bacterial strain design and metabolic engineering to the understanding of disease processes in humans. Public Library of Science 2008-09-12 /pmc/articles/PMC2518853/ /pubmed/18787685 http://dx.doi.org/10.1371/journal.pcbi.1000177 Text en Jamshidi, Palsson. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Jamshidi, Neema
Palsson, Bernhard Ø.
Top-Down Analysis of Temporal Hierarchy in Biochemical Reaction Networks
title Top-Down Analysis of Temporal Hierarchy in Biochemical Reaction Networks
title_full Top-Down Analysis of Temporal Hierarchy in Biochemical Reaction Networks
title_fullStr Top-Down Analysis of Temporal Hierarchy in Biochemical Reaction Networks
title_full_unstemmed Top-Down Analysis of Temporal Hierarchy in Biochemical Reaction Networks
title_short Top-Down Analysis of Temporal Hierarchy in Biochemical Reaction Networks
title_sort top-down analysis of temporal hierarchy in biochemical reaction networks
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518853/
https://www.ncbi.nlm.nih.gov/pubmed/18787685
http://dx.doi.org/10.1371/journal.pcbi.1000177
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