A Formal Framework for Analysis and Design of Synthetic Gene Networks PDF Download

Author: Boyan Yordanov Yordanov
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ISBN:
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Languages : en
Pages : 320

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Book Description
Abstract: Synthetic biology has recently emerged as an attempt to study biological systems by construction rather than through observation. Work in the field has demonstrated that synthetic gene networks with a specific function can be designed and constructed experimentally and is expected to lead to important application in bioremediation, biosensing, clean fuel and drug bioproduction, and therapeutics. However, designing biological systems that work as expected remains a challenge. Mathematical modeling is often used to guide the design efforts in synthetic biology but the types of models arc often complex and cannot be easily analyzed. In addition, only simple specifications such as the existence of equilibria, limit cycles, or invariance sets are usually considered. In contrast, methods for proving (or disproving) the correctness of software programs and digital circuits have been developed in the field of formal verification. Such systems can be modeled as simple finite transition graphs and algorithms for automatically deciding whether a model satisfies a specification, expressed in temporal logic, are available. Temporal logics are rich enough to capture properties of biological systems relevant to synthetic biology. However, only simple, unrealistic models are directly amenable to formal verification. In this work, we bridge the gap and develop a theoretical framework and a set of computational tools allowing the analysis of realistic models from rich temporal logic specifications. We consider discrete time, piece-wise affine (PWA) systems, which evolve along different affine dynamics in different regions of the continuous state space. This structure results in models that are globally complex and can approximate nonlinear systems with arbitrary accuracy, but are also locally simple, which allows us to construct finite abstractions. Based on this, we develop formal methods for the analysis, parameter synthesis and control of PWA systems from temporal logic specifications.We apply our methods to analyze the synthetic gene networks that can be constructed from a set of available parts. We demonstrate how our tools can identify device designs that fail to meet the required specifications. Such an approach can be used to filter flawed designs before they are implemented experimentally, thereby decreasing the time and cost involved in synthetic biology projects.