Engelmann, Nicolai ; Schwarz, Tobias ; Kubaczka, Erik ; Hochberger, Christian ; Koeppl, Heinz (2024)
Context-Aware Technology Mapping in Genetic Design Automation.
In: ACS Synthetic Biology, 2023, 12 (2)
doi: 10.26083/tuprints-00026517
Artikel, Zweitveröffentlichung, Verlagsversion
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Kurzbeschreibung (Abstract)
Genetic design automation (GDA) tools hold promise to speed-up circuit design in synthetic biology. Their widespread adoption is hampered by their limited predictive power, resulting in frequent deviations between the in silico and in vivo performance of a genetic circuit. Context effects, i.e., the change in overall circuit functioning, due to the intracellular environment of the host and due to cross-talk among circuits components are believed to be a major source for the aforementioned deviations. Incorporating these effects in computational models of GDA tools is challenging but is expected to boost their predictive power and hence their deployment. Using fine-grained thermodynamic models of promoter activity, we show in this work how to account for two major components of cellular context effects: (i) crosstalk due to limited specificity of used regulators and (ii) titration of circuit regulators to off-target binding sites on the host genome. We show how we can compensate the incurred increase in computational complexity through dedicated branch-and-bound techniques during the technology mapping process. Using the synthesis of several combinational logic circuits based on Cello’s device library as a case study, we analyze the effect of different intensities and distributions of crosstalk on circuit performance and on the usability of a given device library.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2024 |
| Autor(en): | Engelmann, Nicolai ; Schwarz, Tobias ; Kubaczka, Erik ; Hochberger, Christian ; Koeppl, Heinz |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Context-Aware Technology Mapping in Genetic Design Automation |
| Sprache: | Englisch |
| Publikationsjahr: | 30 September 2024 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 2023 |
| Ort der Erstveröffentlichung: | Washington, DC |
| Verlag: | American Chemical Society |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | ACS Synthetic Biology |
| Jahrgang/Volume einer Zeitschrift: | 12 |
| (Heft-)Nummer: | 2 |
| Kollation: | 14 Seiten |
| DOI: | 10.26083/tuprints-00026517 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/26517 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichungsservice |
| Kurzbeschreibung (Abstract): | Genetic design automation (GDA) tools hold promise to speed-up circuit design in synthetic biology. Their widespread adoption is hampered by their limited predictive power, resulting in frequent deviations between the in silico and in vivo performance of a genetic circuit. Context effects, i.e., the change in overall circuit functioning, due to the intracellular environment of the host and due to cross-talk among circuits components are believed to be a major source for the aforementioned deviations. Incorporating these effects in computational models of GDA tools is challenging but is expected to boost their predictive power and hence their deployment. Using fine-grained thermodynamic models of promoter activity, we show in this work how to account for two major components of cellular context effects: (i) crosstalk due to limited specificity of used regulators and (ii) titration of circuit regulators to off-target binding sites on the host genome. We show how we can compensate the incurred increase in computational complexity through dedicated branch-and-bound techniques during the technology mapping process. Using the synthesis of several combinational logic circuits based on Cello’s device library as a case study, we analyze the effect of different intensities and distributions of crosstalk on circuit performance and on the usability of a given device library. |
| Freie Schlagworte: | genetic design automation, equilibrium thermodynamics, branch and bound, technology mapping, context effects, crosstalk |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-265171 |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 540 Chemie 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 621.3 Elektrotechnik, Elektronik |
| Fachbereich(e)/-gebiet(e): | 18 Fachbereich Elektrotechnik und Informationstechnik Interdisziplinäre Forschungsprojekte Interdisziplinäre Forschungsprojekte > Centre for Synthetic Biology |
| Hinterlegungsdatum: | 30 Sep 2024 09:53 |
| Letzte Änderung: | 11 Okt 2024 14:46 |
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| Suche nach Titel in: | TUfind oder in Google |
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