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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
Article, Bibliographie

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.

Item Type: Article
Erschienen: 2023
Creators: Engelmann, Nicolai ; Schwarz, Tobias ; Kubaczka, Erik ; Hochberger, Christian ; Koeppl, Heinz
Type of entry: Bibliographie
Title: Context-Aware Technology Mapping in Genetic Design Automation
Language: English
Date: 17 February 2023
Publisher: ACS Publications
Journal or Publication Title: ACS Synthetic Biology
Volume of the journal: 12
Issue Number: 2
DOI: 10.1021/acssynbio.2c00361
URL / URN: https://pubs.acs.org/doi/10.1021/acssynbio.2c00361
Corresponding Links:
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.

Uncontrolled Keywords: genetic design automation, equilibrium thermodynamics, branch and bound technology, mapping context effects crosstalk
Identification Number: pmid:36693176
Divisions: 18 Department of Electrical Engineering and Information Technology
18 Department of Electrical Engineering and Information Technology > Institute for Telecommunications > Bioinspired Communication Systems
18 Department of Electrical Engineering and Information Technology > Institute of Computer Engineering
18 Department of Electrical Engineering and Information Technology > Institute for Telecommunications
18 Department of Electrical Engineering and Information Technology > Institute of Computer Engineering > Computer Systems Group
18 Department of Electrical Engineering and Information Technology > Self-Organizing Systems Lab
Date Deposited: 27 Feb 2023 15:38
Last Modified: 25 Apr 2023 14:21
PPN: 507273400
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