Design Automation in Synthetic Biology

Appleton, Evan; Madsen, Curtis; Roehner, Nicholas; Densmore, Douglas

doi:10.1101/cshperspect.a023978

Cited by 78 publications

(65 citation statements)

References 111 publications

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“…Additionally, DNA-BOT offers high accuracy and efficiency, derived from the underlying BASIC DNA assembly method 5 . Convenient features at bench scale, they become a key advantage once automated DNA assembly is integrated into more automated Design-Built-Test-Learn workflows 19 .…”

Section: Resultsmentioning

confidence: 99%

DNA-BOT: A low-cost, automated DNA assembly platform for synthetic biology

Storch

Haines

Baldwin

2019

Preprint

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Multi-part DNA assembly is the physical starting point for many projects in Synthetic and Molecular Biology. The ability to explore a genetic design space by building extensive libraries of DNA constructs is essential for creating programmed biological systems that perform the desired functions. With multiple DNA assembly methods and standards adopted in the Synthetic Biology community, automation of the DNA assembly process has received serious attention in recent years. Importantly, automating DNA assembly enables larger builds using less researcher time, increasing the accessible design space.However, these benefits currently incur high costs for both equipment and consumables. Here, we address this limitation by introducing low-cost DNA assembly with BASIC on OpenTrons (DNA-BOT).For this purpose, we developed an open-source software package dnabot (https://github.com/BASIC-DNA-ASSEMBLY/dnabot). We demonstrate the performance of DNA-BOT by simultaneously assembling 88 constructs composed of 10 genetic parts, exploring the promoter, ribosome binding site (RBS) and gene order design space for a 3-gene operon. All 88 constructs were assembled with high accuracy, at a cost of $1.50 -$5.50 per construct. This illustrates the efficiency, accuracy and affordability of DNA-BOT making it accessible for most labs and democratising automated DNA assembly.

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Section: Resultsmentioning

confidence: 99%

DNA-BOT: A low-cost, automated DNA assembly platform for synthetic biology

Storch

Haines

Baldwin

2019

Preprint

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“…This is one of the major bottlenecks that restrict the depth of genetic logic circuits and limit scalability, since not every gate within a library will be compatible with another. The analysis of inter-gate compatibility is therefore fundamental for circuit design and is an integral part of current synthetic biology Computer Aided Design tools 1,29 . However, knowledge about the effect of context on gate compatibility has until now been lacking.…”

Section: Enhanced Gate Compatibility By Fine-tuning Contextual Dependmentioning

confidence: 99%

Contextual dependencies expand the re-usability of genetic inverters

Tas

Grozinger

Stoof

et al. 2020

Preprint

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The design and implementation of Boolean logic functions in living cells has become a very active field within synthetic biology. By controlling networks of regulatory proteins, novel genetic circuits are engineered to generate predefined output responses. Although many current implementations focus solely on the genetic components of the circuit, the host context in which the circuit performs is crucial for its outcome. Here, we characterise 20 genetic NOT logic gates (inverters) in up to 7 bacterial-based contexts each, to finally generate 135 different functions. The contexts we focus on are particular combinations of four plasmid backbones and three hosts, two Escherichia coli and one Pseudomonas putida strains. Each NOT logic gate shows seven different logic behaviours, depending on the context. That is, gates can be reconfigured to fit response requirements by changing only contextual parameters. Computational analysis shows that this range of behaviours improves the compatibility between gates, because there are considerably more possibilities for combination than when considering a unique function per genetic construct. Finally, we address the issue of interoperability and portability by measuring, scoring, and comparing gate performance across contexts. Rather than being a limitation, we argue that the effect of the genetic background on synthetic constructs expand the scope of the functions that can be engineered in complex cellular environments, and advocate for considering context as a fundamental design parameter for synthetic biology.

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“…Following the electronic design automation (EDA) concept, which was an essential contribution that spurred the digital society we live in, there are many design automation tools for circuit and pathway, these are extensively reviewed in Appleton et al 1 and Lin et al 2 respectively. As an example, Cello 3 applies the EDA approach to genetic circuits.…”

Section: Introductionmentioning

confidence: 99%

“…As pointed in Appleton et al 1 , most of the tools mentioned above feature dedicated support for designing genetic regulatory networks/circuits, but they do not feature the same level of support for designing biosynthetic/metabolic pathways. One of the purposes of the Galaxy-SynBioCAD portal is addressing this shortcoming by providing a suite of interoperable and standardized tools to design pathways from the design specification (choice of the compound, strain) to the DNA parts to be assembled.…”

Section: Introductionmentioning

confidence: 99%

Galaxy-SynBioCAD: Synthetic Biology Design Automation tools in Galaxy workflows

Duigou

Hérisson

et al. 2020

Preprint

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Many computer-aided design tools are available for synthetic biology and metabolic engineering. Yet, these tools can be difficult to apprehend, sometimes requiring a level of expertise that limits their use by a wider community. Furthermore, some of the tools, although complementary, rely on different input and output formats and cannot communicate with one another. Scientific workflows address these shortcomings while offering a novel design strategy. Among the workflow systems available, Galaxy is a web-based platform for performing findable and accessible data analyses for all scientists regardless of their informatics expertise, along with interoperable and reproducible computations regardless of the particular platform that is being used.Here, we introduce the Galaxy-SynBioCAD a portal, the first Galaxy toolshed for synthetic biology and metabolic engineering. It allows one to easily create workflows or use those already developed by the community. The portal is a growing community effort where developers can add new tools and users can evaluate the tools performing design for their specific projects. The tools and workflows currently shared on the Galaxy-SynBioCAD portal cover an end-to-end metabolic pathway design process from the selection of strain and target to the calculation of DNA parts to be assembled to build libraries of strains to be engineered to produce the target.Standard formats are used throughout to enforce the compatibility of the tools. These include SBML for strain and pathway and SBOL for genetic layouts. The portal has been benchmarked on a galaxy-synbiocad.org 81 literature pathways, overall, we find we have a 65% (and 88%) success rate in retrieving the literature pathways among the top 10 (50) pathways predicted and generated by the workflows.

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Design Automation in Synthetic Biology

Cited by 78 publications

References 111 publications

DNA-BOT: A low-cost, automated DNA assembly platform for synthetic biology

DNA-BOT: A low-cost, automated DNA assembly platform for synthetic biology

Contextual dependencies expand the re-usability of genetic inverters

Galaxy-SynBioCAD: Synthetic Biology Design Automation tools in Galaxy workflows

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