Hafner, M. ; Koeppl, H. ; Hasler, M. ; Wagner, A. (2009)
'Glocal' robustness analysis and model discrimination for circadian oscillators.
In: PLoS Computational Biology, 5 (10)
doi: 10.1371/journal.pcbi.1000534
Artikel, Bibliographie

Kurzbeschreibung (Abstract)

To characterize the behavior and robustness of cellular circuits with many unknown parameters is a major challenge for systems biology. Its difficulty rises exponentially with the number of circuit components. We here propose a novel analysis method to meet this challenge. Our method identifies the region of a high-dimensional parameter space where a circuit displays an experimentally observed behavior. It does so via a Monte Carlo approach guided by principal component analysis, in order to allow efficient sampling of this space. This 'global' analysis is then supplemented by a 'local' analysis, in which circuit robustness is determined for each of the thousands of parameter sets sampled in the global analysis. We apply this method to two prominent, recent models of the cyanobacterial circadian oscillator, an autocatalytic model, and a model centered on consecutive phosphorylation at two sites of the KaiC protein, a key circadian regulator. For these models, we find that the two-sites architecture is much more robust than the autocatalytic one, both globally and locally, based on five different quantifiers of robustness, including robustness to parameter perturbations and to molecular noise. Our 'glocal' combination of global and local analyses can also identify key causes of high or low robustness. In doing so, our approach helps to unravel the architectural origin of robust circuit behavior. Complementarily, identifying fragile aspects of system behavior can aid in designing perturbation experiments that may discriminate between competing mechanisms and different parameter sets.

Typ des Eintrags:	Artikel
Erschienen:	2009
Autor(en):	Hafner, M. ; Koeppl, H. ; Hasler, M. ; Wagner, A.
Art des Eintrags:	Bibliographie
Titel:	'Glocal' robustness analysis and model discrimination for circadian oscillators
Sprache:	Englisch
Publikationsjahr:	Oktober 2009
Titel der Zeitschrift, Zeitung oder Schriftenreihe:	PLoS Computational Biology
Jahrgang/Volume einer Zeitschrift:	5
(Heft-)Nummer:	10
DOI:	10.1371/journal.pcbi.1000534
URL / URN:	http://journals.plos.org/ploscompbiol/article?id=10.1371/jou...
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Kurzbeschreibung (Abstract):	To characterize the behavior and robustness of cellular circuits with many unknown parameters is a major challenge for systems biology. Its difficulty rises exponentially with the number of circuit components. We here propose a novel analysis method to meet this challenge. Our method identifies the region of a high-dimensional parameter space where a circuit displays an experimentally observed behavior. It does so via a Monte Carlo approach guided by principal component analysis, in order to allow efficient sampling of this space. This 'global' analysis is then supplemented by a 'local' analysis, in which circuit robustness is determined for each of the thousands of parameter sets sampled in the global analysis. We apply this method to two prominent, recent models of the cyanobacterial circadian oscillator, an autocatalytic model, and a model centered on consecutive phosphorylation at two sites of the KaiC protein, a key circadian regulator. For these models, we find that the two-sites architecture is much more robust than the autocatalytic one, both globally and locally, based on five different quantifiers of robustness, including robustness to parameter perturbations and to molecular noise. Our 'glocal' combination of global and local analyses can also identify key causes of high or low robustness. In doing so, our approach helps to unravel the architectural origin of robust circuit behavior. Complementarily, identifying fragile aspects of system behavior can aid in designing perturbation experiments that may discriminate between competing mechanisms and different parameter sets.
Freie Schlagworte:	Circadian Rhythm,Models,Theoretical
Fachbereich(e)/-gebiet(e):	18 Fachbereich Elektrotechnik und Informationstechnik 18 Fachbereich Elektrotechnik und Informationstechnik > Institut für Nachrichtentechnik > Bioinspirierte Kommunikationssysteme 18 Fachbereich Elektrotechnik und Informationstechnik > Institut für Nachrichtentechnik
Hinterlegungsdatum:	04 Apr 2014 13:02
Letzte Änderung:	07 Aug 2024 11:32
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• ‘Glocal’ Robustness Analysis and Model Discrimination for Circadian Oscillators. (deposited 13 Mai 2024 09:58)
  • 'Glocal' robustness analysis and model discrimination for circadian oscillators. (deposited 04 Apr 2014 13:02) [Gegenwärtig angezeigt]

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