Journal Article

Genetic circuit design automation with Cello 2.0

Densmore, Douglas, Jones, Timothy S., Voigt, Christopher A., Oliveira, Samuel M. D., Myers, Chris J.

2022

Overview

Cells interact with their environment, communicate among themselves, track time and make decisions through functions controlled by natural regulatory genetic circuits consisting of interacting biological components. Synthetic programmable circuits used in therapeutics and other applications can be automatically designed by computer-aided tools. The Cello software designs the DNA sequences for programmable circuits based on a high-level software description and a library of characterized DNA parts representing Boolean logic gates. This process allows for design specification reuse, modular DNA part library curation and formalized circuit transformations based on experimental data. This protocol describes Cello 2.0, a freely available cross-platform software written in Java. Cello 2.0 enables flexible descriptions of the logic gates’ structure and their mathematical models representing dynamic behavior, new formal rules for describing the placement of gates in a genome, a new graphical user interface, support for Verilog 2005 syntax and a connection to the SynBioHub parts repository software environment. Collectively, these features expand Cello’s capabilities beyond Escherichia coli plasmids to new organisms and broader genetic contexts, including the genome. Designing circuits with Cello 2.0 produces an abstract Boolean network from a Verilog file, assigns biological parts to each node in the Boolean network, constructs a DNA sequence and generates highly structured and annotated sequence representations suitable for downstream processing and fabrication, respectively. The result is a sequence implementing the specified Boolean function in the organism and predictions of circuit performance. Depending on the size of the design space and users’ expertise, jobs may take minutes or hours to complete. This protocol describes how to design genetic circuits using the web implementation of the Cello 2.0 software, which allows users to construct a DNA sequence for a genetic circuit composed of defined elements and predicts the circuit’s performance in new organisms and genetic contexts.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/1647/794 / 631/553/117 / 631/553/552 / Analytical Chemistry / Automation / Biochemistry & Molecular Biology / Biological Techniques / Biomedical and Life Sciences / Boolean / Boolean algebra / Boolean functions / CAD / Circuit design / Circuits / Computational Biology/Bioinformatics / Computer aided design / Deoxyribonucleic acid / Design specifications / DNA / DNA - genetics / Downstream effects / E coli / Escherichia coli - genetics / Fabrication / Gates / Gates (circuits) / Gene Regulatory Networks / Gene sequencing / Genomes / Graphical user interface / Libraries / Life Sciences / Logic circuits / Mathematical models / Microarrays / Modular design / Nucleotide sequence / Organic Chemistry / Organisms / Plasmids / Protocol / Software / Synthetic Biology