Schladt, Tobias ; Engelmann, Nicolai ; Kubaczka, Erik ; Hochberger, Christian ; Koeppl, Heinz (2024)
Automated Design of Robust Genetic Circuits: Structural Variants and Parameter Uncertainty.
In: ACS Synthetic Biology, 2021, 10 (12)
doi: 10.26083/tuprints-00026627
Artikel, Zweitveröffentlichung, Verlagsversion
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Kurzbeschreibung (Abstract)
Genetic design automation methods for combinational circuits often rely on standard algorithms from electronic design automation in their circuit synthesis and technology mapping. However, those algorithms are domain-specific and are hence often not directly suitable for the biological context. In this work we identify aspects of those algorithms that require domain-adaptation. We first demonstrate that enumerating structural variants for a given Boolean specification allows us to find better performing circuits and that stochastic gate assignment methods need to be properly adjusted in order to find the best assignment. Second, we present a general circuit scoring scheme that accounts for the limited accuracy of biological device models including the variability across cells and show that circuits selected according to this score exhibit higher robustness with respect to parametric variations. If gate characteristics in a library are just given in terms of intervals, we provide means to efficiently propagate signals through such a circuit and compute corresponding scores. We demonstrate the novel design approach using the Cello gate library and 33 logic functions that were synthesized and implemented in vivo recently (Nielsen, A., et al., Science, 2016, 352 (6281), DOI: 10.1126/science.aac7341). Across this set of functions, 32 of them can be improved by simply considering structural variants yielding performance gains of up to 7.9-fold, whereas 22 of them can be improved with gains up to 26-fold when selecting circuits according to the novel robustness score. We furthermore report on the synergistic combination of the two proposed improvements.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2024 |
| Autor(en): | Schladt, Tobias ; Engelmann, Nicolai ; Kubaczka, Erik ; Hochberger, Christian ; Koeppl, Heinz |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Automated Design of Robust Genetic Circuits: Structural Variants and Parameter Uncertainty |
| Sprache: | Englisch |
| Publikationsjahr: | 13 Mai 2024 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 2021 |
| Ort der Erstveröffentlichung: | Washington, DC |
| Verlag: | American Chemical Society |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | ACS Synthetic Biology |
| Jahrgang/Volume einer Zeitschrift: | 10 |
| (Heft-)Nummer: | 12 |
| Kollation: | 14 Seiten |
| DOI: | 10.26083/tuprints-00026627 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/26627 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichungsservice |
| Kurzbeschreibung (Abstract): | Genetic design automation methods for combinational circuits often rely on standard algorithms from electronic design automation in their circuit synthesis and technology mapping. However, those algorithms are domain-specific and are hence often not directly suitable for the biological context. In this work we identify aspects of those algorithms that require domain-adaptation. We first demonstrate that enumerating structural variants for a given Boolean specification allows us to find better performing circuits and that stochastic gate assignment methods need to be properly adjusted in order to find the best assignment. Second, we present a general circuit scoring scheme that accounts for the limited accuracy of biological device models including the variability across cells and show that circuits selected according to this score exhibit higher robustness with respect to parametric variations. If gate characteristics in a library are just given in terms of intervals, we provide means to efficiently propagate signals through such a circuit and compute corresponding scores. We demonstrate the novel design approach using the Cello gate library and 33 logic functions that were synthesized and implemented in vivo recently (Nielsen, A., et al., Science, 2016, 352 (6281), DOI: 10.1126/science.aac7341). Across this set of functions, 32 of them can be improved by simply considering structural variants yielding performance gains of up to 7.9-fold, whereas 22 of them can be improved with gains up to 26-fold when selecting circuits according to the novel robustness score. We furthermore report on the synergistic combination of the two proposed improvements. |
| Freie Schlagworte: | genetic design automation, synthetic biology, circuit synthesis, structural variants, cell-to-cell variability, robust genetic circuit |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-266274 |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 660 Technische Chemie |
| Fachbereich(e)/-gebiet(e): | 18 Fachbereich Elektrotechnik und Informationstechnik 18 Fachbereich Elektrotechnik und Informationstechnik > Self-Organizing Systems Lab Interdisziplinäre Forschungsprojekte Interdisziplinäre Forschungsprojekte > Centre for Synthetic Biology |
| Hinterlegungsdatum: | 13 Mai 2024 09:45 |
| Letzte Änderung: | 17 Mai 2024 10:18 |
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| Suche nach Titel in: | TUfind oder in Google |
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- Automated Design of Robust Genetic Circuits: Structural Variants and Parameter Uncertainty. (deposited 13 Mai 2024 09:45) [Gegenwärtig angezeigt]
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