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      Computational Methods in Systems Biology 

      Strong Turing Completeness of Continuous Chemical Reaction Networks and Compilation of Mixed Analog-Digital Programs

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          Programmable chemical controllers made from DNA.

          Biological organisms use complex molecular networks to navigate their environment and regulate their internal state. The development of synthetic systems with similar capabilities could lead to applications such as smart therapeutics or fabrication methods based on self-organization. To achieve this, molecular control circuits need to be engineered to perform integrated sensing, computation and actuation. Here we report a DNA-based technology for implementing the computational core of such controllers. We use the formalism of chemical reaction networks as a 'programming language' and our DNA architecture can, in principle, implement any behaviour that can be mathematically expressed as such. Unlike logic circuits, our formulation naturally allows complex signal processing of intrinsically analogue biological and chemical inputs. Controller components can be derived from biologically synthesized (plasmid) DNA, which reduces errors associated with chemically synthesized DNA. We implement several building-block reaction types and then combine them into a network that realizes, at the molecular level, an algorithm used in distributed control systems for achieving consensus between multiple agents.
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            Ultrasensitivity in the mitogen-activated protein kinase cascade.

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              The chemical abstract machine

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                Book Chapter
                2017
                September 01 2017
                : 108-127
                10.1007/978-3-319-67471-1_7
                5e581ae4-1e16-4e04-ab88-959f80e4237c
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