Eugene – A Domain Specific Language for Specifying and Constraining Synthetic Biological Parts, Devices, and Systems

BACKGROUND: Synthetic biological systems are currently created by an ad-hoc, iterative process of specification, design, and assembly. These systems would greatly benefit from a more formalized and rigorous specification of the desired system components as well as constraints on their composition. Therefore, the creation of robust and efficient design flows and tools is imperative. We present a human readable language (Eugene) that allows for the specification of synthetic biological designs based on biological parts, as well as provides a very expressive constraint system to drive the automatic creation of composite Parts (Devices) from a collection of individual Parts. RESULTS: We illustrate Eugene's capabilities in three different areas: Device specification, design space exploration, and assembly and simulation integration. These results highlight Eugene's ability to create combinatorial design spaces and prune these spaces for simulation or physical assembly. Eugene creates functional designs quickly and cost-effectively. CONCLUSIONS: Eugene is intended for forward engineering of DNA-based devices, and through its data types and execution semantics, reflects the desired abstraction hierarchy in synthetic biology. Eugene provides a powerful constraint system which can be used to drive the creation of new devices at runtime. It accomplishes all of this while being part of a larger tool chain which includes support for design, simulation, and physical device assembly

Constraint-based genetic compilation

Synthetic biology aims at facilitating the design of new organisms via the standardization of biological parts and following engineering principles. We present atgc (Assistant To Genetic Compilation), a software tool that automatically builds a functional sequence of DNA from a minimal set of requirements. Through a simple language, the user provides in-house knowledge about their construct (e.g. relative placement of parts, number of restriction enzymes). atgc combines information from established biology, user knowledge and bioinformatics databases, and maps the problem to a constraint satisfaction setting. The solution is a functional DNA sequence ready to be assembled and transferred to a target organism

An Integrated Computer-Aided Design and Manufacturing Workflow for Synthetic Biology.

Biological computer-aided design and manufacturing (bioCAD/CAM) tools facilitate the design and build processes of engineering biological systems using iterative design-build-test-learn (DBTL) cycles. In this book chapter, we highlight some of the bioCAD/CAM tools developed and used at the US Department of Energy (DOE) Joint Genome Institute (JGI), Joint BioEnergy Institute (JBEI), and Agile BioFoundry (ABF). We demonstrate the use of these bioCAD/CAM tools on a common workflow for designing and building a multigene pathway in a hierarchical fashion. Each tool presented in this book chapter is specifically tailored to support one or more specific steps in a workflow, can be integrated with the others into design and build workflows, and can be deployed at academic, government, or commercial entities

Combinatorial-Hierarchical DNA Library Design Using the TeselaGen DESIGN Module with j5.

Modern DNA assembly techniques are known for their potential to link multiple large DNA fragments together into even larger constructs in single pot reactions that are easier to automate and work more reliably than traditional cloning methods. The simplicity of the chemistry is in contrast to the increased work needed to design optimal reactions that maximize DNA fragment reuse, minimize cost, and organize thousands of potential chemical reactions. Here we examine available DNA assembly methods and describe through example, the construction of a complex but not atypical combinatorial and hierarchical library using protocols that are generated automatically with the assistance of modern synthetic biology software