Abstract
BackgroundAn increasing number of genetic components are available in several depositories of such components to facilitate synthetic biology research, but picking out those that will allow a designed circuit to achieve the specified function still requires multiple cycles of testing. Here, we addressed this problem by developing a computational pipeline to mathematically simulate a gene circuit for a comprehensive range and combination of the kinetic parameters of the biological components that constitute the gene circuit.ResultsWe showed that, using a well-studied transcriptional repression cascade as an example, the sets of kinetic parameters that could produce the specified system dynamics of the gene circuit formed clusters of recurrent combinations, referred to as kinetic motifs, which appear to be associated with both the specific topology and specified dynamics of the circuit. Furthermore, the use of the resulting "handbook" of performance-ranked kinetic motifs in finding suitable circuit components was illustrated in two application scenarios.ConclusionsThese results show that the computational pipeline developed here can provide a rational-based guide to aid in the design and improvement of synthetic gene circuits.
Highlights
An increasing number of genetic components are available in several depositories of such components to facilitate synthetic biology research, but picking out those that will allow a designed circuit to achieve the specified function still requires multiple cycles of testing
By identifying the set of kinetic parameters required to produce the user-specified dynamic behaviour for a given network topology in both the presence and absence of random perturbations and using statistical analysis to identify recurrent patterns of these kinetic parameters and understand their mechanics, Kinetic Motif and Functional Analysis (KMFA) provides a “handbook” of kinetic motifs in which one can look up a biological components library to choose suitable parts for optimal performance of the designed circuit
For this 4-gene circuit, only 2,355 (0.6%) of the 390,625 (58) possible combinations of the kinetic parameters could produce the prescribed steady-state concentration of each gene product as the output of the circuit under both perturbed and unperturbed conditions and that these kinetic solutions formed clusters of motifs, which could be ranked according to their relative performance, yielding a “handbook” of performance-ranked kinetic motifs that can be used to select library components for the circuit
Summary
An increasing number of genetic components are available in several depositories of such components to facilitate synthetic biology research, but picking out those that will allow a designed circuit to achieve the specified function still requires multiple cycles of testing We addressed this problem by developing a computational pipeline to mathematically simulate a gene circuit for a comprehensive range and combination of the kinetic parameters of the biological components that constitute the gene circuit. KMFA is a useful computational tool with a rational design capability to choose circuit components in synthetic biology research
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
