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Context-Aware Technology Mapping in Genetic Design Automation

Engelmann, Nicolai ; Schwarz, Tobias ; Kubaczka, Erik ; Hochberger, Christian ; Koeppl, Heinz (2023)
Context-Aware Technology Mapping in Genetic Design Automation.
In: ACS Synthetic Biology, 12 (2)
doi: 10.1021/acssynbio.2c00361
Artikel, Bibliographie

Dies ist die neueste Version dieses Eintrags.

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: 2023
Autor(en): Engelmann, Nicolai ; Schwarz, Tobias ; Kubaczka, Erik ; Hochberger, Christian ; Koeppl, Heinz
Art des Eintrags: Bibliographie
Titel: Context-Aware Technology Mapping in Genetic Design Automation
Sprache: Englisch
Publikationsjahr: 17 Februar 2023
Verlag: ACS Publications
Titel der Zeitschrift, Zeitung oder Schriftenreihe: ACS Synthetic Biology
Jahrgang/Volume einer Zeitschrift: 12
(Heft-)Nummer: 2
Kollation: 14 Seiten
DOI: 10.1021/acssynbio.2c00361
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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.

Freie Schlagworte: genetic design automation, equilibrium thermodynamics, branch and bound, technology mapping, context effects, crosstalk
ID-Nummer: pmid:36693176
Zusätzliche Informationen:

Erstveröffentlichung

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 Datentechnik
18 Fachbereich Elektrotechnik und Informationstechnik > Institut für Nachrichtentechnik
18 Fachbereich Elektrotechnik und Informationstechnik > Institut für Datentechnik > Rechnersysteme
18 Fachbereich Elektrotechnik und Informationstechnik > Self-Organizing Systems Lab
Interdisziplinäre Forschungsprojekte
Interdisziplinäre Forschungsprojekte > Centre for Synthetic Biology
Hinterlegungsdatum: 27 Feb 2023 15:38
Letzte Änderung: 11 Okt 2024 14:52
PPN: 507273400
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