Compiling and Verifying DNA-Based Chemical Reaction Network Implementations

One goal of molecular programming and synthetic biology is to build chemical circuits that can control chemical processes at the molecular level. Remarkably, it has been shown that synthesized DNA molecules can be used to construct complex chemical circuits that operate without any enzyme or cellular component. However, designing DNA molecules at the individual nucleotide base level is often difficult and laborious, and thus chemical reaction networks (CRNs) have been proposed as a higher-level programming language. So far, several general-purpose schemes have been described for designing synthetic DNA molecules that simulate the behavior of arbitrary CRNs, and many more are being actively investigated. Here, we solve two problems related to this topic. First, we present a general-purpose CRN-to-DNA compiler that can apply user-defined compilation schemes for translating formal CRNs to domain-level specifications for DNA molecules. In doing so, we develop a language in which such schemes can be concisely and precisely described. This compiler can greatly reduce the amount of tedious manual labor faced by researchers working in the field. Second, we present a general method for the formal verification of the correctness of such compilation. We first show that this problem reduces to testing a notion of behavioral equivalence between two CRNs, and then we construct a mathematical formalism in which that notion can be precisely defined. Finally, we provide algorithms for testing that notion. This verification process can be thought of as an equivalent of model checking in molecular computation, and we hope that the generality of our verification techniques will eventually allow us to apply them not only to DNA-based CRN implementations but to a wider class of molecular programs.