GUBS, a Behavior-based Language for Open System Dedicated to Synthetic Biology

In this article, we propose a domain specific language, GUBS (Genomic Unified Behavior Specification), dedicated to the behavioral specification of synthetic biological devices, viewed as discrete open dynamical systems. GUBS is a rule-based declarative language. By contrast to a closed system, a program is always a partial description of the behavior of the system. The semantics of the language accounts the existence of some hidden non-specified actions possibly altering the behavior of the programmed device. The compilation framework follows a scheme similar to automatic theorem proving, aiming at improving synthetic biological design safety.Comment: In Proceedings MeCBIC 2012, arXiv:1211.347

BioScript: programming safe chemistry on laboratories-on-a-chip

This paper introduces BioScript, a domain-specific language (DSL) for programmable biochemistry which executes on emerging microfluidic platforms. The goal of this research is to provide a simple, intuitive, and type-safe DSL that is accessible to life science practitioners. The novel feature of the language is its syntax, which aims to optimize human readability; the technical contributions of the paper include the BioScript type system and relevant portions of its compiler. The type system ensures that certain types of errors, specific to biochemistry, do not occur, including the interaction of chemicals that may be unsafe. The compiler includes novel optimizations that place biochemical operations to execute concurrently on a spatial 2D array platform on the granularity of a control flow graph, as opposed to individual basic blocks. Results are obtained using both a cycle-accurate microfluidic simulator and a software interface to a real-world platform

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

A Mathematical Framework for Agent Based Models of Complex Biological Networks

Agent-based modeling and simulation is a useful method to study biological phenomena in a wide range of fields, from molecular biology to ecology. Since there is currently no agreed-upon standard way to specify such models it is not always easy to use published models. Also, since model descriptions are not usually given in mathematical terms, it is difficult to bring mathematical analysis tools to bear, so that models are typically studied through simulation. In order to address this issue, Grimm et al. proposed a protocol for model specification, the so-called ODD protocol, which provides a standard way to describe models. This paper proposes an addition to the ODD protocol which allows the description of an agent-based model as a dynamical system, which provides access to computational and theoretical tools for its analysis. The mathematical framework is that of algebraic models, that is, time-discrete dynamical systems with algebraic structure. It is shown by way of several examples how this mathematical specification can help with model analysis.Comment: To appear in Bulletin of Mathematical Biolog

BioNetGen 2.2: Advances in Rule-Based Modeling

BioNetGen is an open-source software package for rule-based modeling of complex biochemical systems. Version 2.2 of the software introduces numerous new features for both model specification and simulation. Here, we report on these additions, discussing how they facilitate the construction, simulation, and analysis of larger and more complex models than previously possible.Comment: 3 pages, 1 figure, 1 supplementary text file. Supplementary text includes a brief discussion of the RK-PLA along with a performance analysis, two tables listing all new actions/arguments added in BioNetGen 2.2, and the "BioNetGen Quick Reference Guide". Accepted for publication in Bioinformatic

A framework for protein and membrane interactions

We introduce the BioBeta Framework, a meta-model for both protein-level and membrane-level interactions of living cells. This formalism aims to provide a formal setting where to encode, compare and merge models at different abstraction levels; in particular, higher-level (e.g. membrane) activities can be given a formal biological justification in terms of low-level (i.e., protein) interactions. A BioBeta specification provides a protein signature together a set of protein reactions, in the spirit of the kappa-calculus. Moreover, the specification describes when a protein configuration triggers one of the only two membrane interaction allowed, that is "pinch" and "fuse". In this paper we define the syntax and semantics of BioBeta, analyse its properties, give it an interpretation as biobigraphical reactive systems, and discuss its expressivity by comparing with kappa-calculus and modelling significant examples. Notably, BioBeta has been designed after a bigraphical metamodel for the same purposes. Hence, each instance of the calculus corresponds to a bigraphical reactive system, and vice versa (almost). Therefore, we can inherith the rich theory of bigraphs, such as the automatic construction of labelled transition systems and behavioural congruences

DeviceEditor visual biological CAD canvas

<p>Abstract</p> <p>Background</p> <p>Biological Computer Aided Design (bioCAD) assists the <it>de novo </it>design and selection of existing genetic components to achieve a desired biological activity, as part of an integrated design-build-test cycle. To meet the emerging needs of Synthetic Biology, bioCAD tools must address the increasing prevalence of combinatorial library design, design rule specification, and scar-less multi-part DNA assembly.</p> <p>Results</p> <p>We report the development and deployment of web-based bioCAD software, DeviceEditor, which provides a graphical design environment that mimics the intuitive visual whiteboard design process practiced in biological laboratories. The key innovations of DeviceEditor include visual combinatorial library design, direct integration with scar-less multi-part DNA assembly design automation, and a graphical user interface for the creation and modification of design specification rules. We demonstrate how biological designs are rendered on the DeviceEditor canvas, and we present effective visualizations of genetic component ordering and combinatorial variations within complex designs.</p> <p>Conclusions</p> <p>DeviceEditor liberates researchers from DNA base-pair manipulation, and enables users to create successful prototypes using standardized, functional, and visual abstractions. Open and documented software interfaces support further integration of DeviceEditor with other bioCAD tools and software platforms. DeviceEditor saves researcher time and institutional resources through correct-by-construction design, the automation of tedious tasks, design reuse, and the minimization of DNA assembly costs.</p

An integrated model checking toolset for kernel P systems

P systems are the computational models introduced in the context of membrane computing, a computational paradigm within the more general area of unconventional computing. Kernel P (kP) systems are defined to unify the specification of different variants of P systems, motivated by challenging theoretical aspects and the need to model different problems. kP systems are supported by a software framework, called kPWORKBENCH, which integrates a set of related simulation and verification methodologies and tools. In this paper, we present an extension to kPWORKBENCH with a new model checking framework supporting the formal verification of kP system models. This framework supports both LTL and CTL properties. To make the property specification an easier task, we propose a property language, composed of natural language statements. We demonstrate our proposed methodology with an example