Papin, Jason A. ; Hafner, Marc ; Koeppl, Heinz ; Hasler, Martin ; Wagner, Andreas (2024)
‘Glocal’ Robustness Analysis and Model Discrimination for Circadian Oscillators.
In: PLoS Computational Biology, 2009, 5 (10)
doi: 10.26083/tuprints-00026926
Artikel, Zweitveröffentlichung, Verlagsversion
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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.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2024 |
| Autor(en): | Papin, Jason A. ; Hafner, Marc ; Koeppl, Heinz ; Hasler, Martin ; Wagner, Andreas |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | ‘Glocal’ Robustness Analysis and Model Discrimination for Circadian Oscillators |
| Sprache: | Englisch |
| Publikationsjahr: | 13 Mai 2024 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 2009 |
| Ort der Erstveröffentlichung: | San Francisco, Calif. |
| Verlag: | PLoS |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | PLoS Computational Biology |
| Jahrgang/Volume einer Zeitschrift: | 5 |
| (Heft-)Nummer: | 10 |
| Kollation: | 10 Seiten |
| DOI: | 10.26083/tuprints-00026926 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/26926 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichungsservice |
| 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. |
| ID-Nummer: | Artikel-ID: e1000534 |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-269264 |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 621.3 Elektrotechnik, Elektronik |
| Hinterlegungsdatum: | 13 Mai 2024 09:58 |
| Letzte Änderung: | 09 Aug 2024 06:41 |
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| Suche nach Titel in: | TUfind oder in Google |
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