5 research outputs found
A Methodology to Annotate Systems Biology Markup Language Models with the Synthetic Biology Open Language
Recently, we have begun to witness
the potential of synthetic biology,
noted here in the form of bacteria and yeast that have been genetically
engineered to produce biofuels, manufacture drug precursors, and even
invade tumor cells. The success of these projects, however, has often
failed in translation and application to new projects, a problem exacerbated
by a lack of engineering standards that combine descriptions of the
structure and function of DNA. To address this need, this paper describes
a methodology to connect the <i>systems biology markup language</i> (SBML) to the <i>synthetic biology open language</i> (SBOL),
existing standards that describe biochemical models and DNA components,
respectively. Our methodology involves first annotating SBML model
elements such as species and reactions with SBOL DNA components. A
graph is then constructed from the model, with vertices corresponding
to elements within the model and edges corresponding to the cause-and-effect
relationships between these elements. Lastly, the graph is traversed
to assemble the annotating DNA components into a composite DNA component,
which is used to annotate the model itself and can be referenced by
other composite models and DNA components. In this way, our methodology
can be used to build up a hierarchical library of models annotated
with DNA components. Such a library is a useful input to any future
genetic technology mapping algorithm that would automate the process
of composing DNA components to satisfy a behavioral specification.
Our methodology for SBML-to-SBOL annotation is implemented in the
latest version of our <i>genetic design automation</i> (GDA)
software tool, iBioSim
Directed Acyclic Graph-Based Technology Mapping of Genetic Circuit Models
As
engineering foundations such as standards and abstraction begin
to mature within synthetic biology, it is vital that genetic design
automation (GDA) tools be developed to enable synthetic biologists
to automatically select standardized DNA components from a library
to meet the behavioral specification for a genetic circuit. To this
end, we have developed a genetic technology mapping algorithm that
builds on the directed acyclic graph (DAG) based mapping techniques
originally used to select parts for digital electronic circuit designs
and implemented it in our GDA tool, iBioSim. It is among the first
genetic technology mapping algorithms to adapt techniques from electronic
circuit design, in particular the use of a cost function to guide
the search for an optimal solution, and perhaps that which makes the
greatest use of standards for describing genetic function and structure
to represent design specifications and component libraries. This paper
demonstrates the use of our algorithm to map the specifications for
three different genetic circuits against four randomly generated libraries
of increasing size to evaluate its performance against both exhaustive
search and greedy variants for finding optimal and near-optimal solutions
A Converter from the Systems Biology Markup Language to the Synthetic Biology Open Language
Standards are important to synthetic
biology because they enable
exchange and reproducibility of genetic designs. This paper describes
a procedure for converting between two standards: the Systems Biology
Markup Language (SBML) and the Synthetic Biology Open Language (SBOL).
SBML is a standard for behavioral models of biological systems at
the molecular level. SBOL describes structural and basic qualitative
behavioral aspects of a biological design. Converting SBML to SBOL
enables a consistent connection between behavioral and structural
information for a biological design. The conversion process described
in this paper leverages Systems Biology Ontology (SBO) annotations
to enable inference of a designs qualitative function
Double Dutch: A Tool for Designing Combinatorial Libraries of Biological Systems
Recently, semirational
approaches that rely on combinatorial assembly
of characterized DNA components have been used to engineer biosynthetic
pathways. In practice, however, it is not practical to assemble and
test millions of pathway variants in order to elucidate how different
DNA components affect the behavior of a pathway. To address this challenge,
we apply a rigorous mathematical approach known as design of experiments
(DOE) that can be used to construct empirical models of system behavior
without testing all variants. To support this approach, we have developed
a tool named Double Dutch, which uses a formal grammar and heuristic
algorithms to automate the process of DOE library design. Compared
to designing by hand, Double Dutch enables users to more efficiently
and scalably design libraries of pathway variants that can be used
in a DOE framework and uniquely provides a means to flexibly balance
design considerations of statistical analysis, construction cost,
and risk of homologous recombination, thereby demonstrating the utility
of automating decision making when faced with complex design trade-offs
SBOL: A community standard for communicating designs in synthetic biology
<p>Abstract</p>
<p>The Synthetic Biology Open Language (SBOL) is a proposed data standard for exchanging designs within the synthetic biology community. SBOL represents synthetic biology designs in a community-adopted, formalized format for exchange between software tools, research groups, and commercial service providers. The re-use of previously validated designs is critical to the evolution of synthetic biology from a research discipline to an engineering practice. As a community-driven standard, SBOL adapts as synthetic biology evolves, providing specific capabilities for different aspects of the synthetic biology workflow. The SBOL Developers Group has implemented SBOL 1.1 as an XML/RDF serialization and provides software libraries and specification documentation to help developers implement SBOL in their own software. This paper also reports on early successes, including a demonstration of the utility of SBOL for information exchange between three different tools from three academic sites.</p>
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