Computational Complexity of Atomic Chemical Reaction Networks

Informally, a chemical reaction network is "atomic" if each reaction may be interpreted as the rearrangement of indivisible units of matter. There are several reasonable definitions formalizing this idea. We investigate the computational complexity of deciding whether a given network is atomic according to each of these definitions. Our first definition, primitive atomic, which requires each reaction to preserve the total number of atoms, is to shown to be equivalent to mass conservation. Since it is known that it can be decided in polynomial time whether a given chemical reaction network is mass-conserving, the equivalence gives an efficient algorithm to decide primitive atomicity. Another definition, subset atomic, further requires that all atoms are species. We show that deciding whether a given network is subset atomic is in $\textsf{NP}$, and the problem "is a network subset atomic with respect to a given atom set" is strongly $\textsf{NP}$-$\textsf{Complete}$. A third definition, reachably atomic, studied by Adleman, Gopalkrishnan et al., further requires that each species has a sequence of reactions splitting it into its constituent atoms. We show that there is a $\textbf{polynomial-time algorithm}$ to decide whether a given network is reachably atomic, improving upon the result of Adleman et al. that the problem is $\textbf{decidable}$. We show that the reachability problem for reachably atomic networks is $\textsf{Pspace}$-$\textsf{Complete}$. Finally, we demonstrate equivalence relationships between our definitions and some special cases of another existing definition of atomicity due to Gnacadja

Programmability of Chemical Reaction Networks

Motivated by the intriguing complexity of biochemical circuitry within individual cells we study Stochastic Chemical Reaction Networks (SCRNs), a formal model that considers a set of chemical reactions acting on a finite number of molecules in a well-stirred solution according to standard chemical kinetics equations. SCRNs have been widely used for describing naturally occurring (bio)chemical systems, and with the advent of synthetic biology they become a promising language for the design of artificial biochemical circuits. Our interest here is the computational power of SCRNs and how they relate to more conventional models of computation. We survey known connections and give new connections between SCRNs and Boolean Logic Circuits, Vector Addition Systems, Petri Nets, Gate Implementability, Primitive Recursive Functions, Register Machines, Fractran, and Turing Machines. A theme to these investigations is the thin line between decidable and undecidable questions about SCRN behavior

Synthesizing and tuning chemical reaction networks with specified behaviours

We consider how to generate chemical reaction networks (CRNs) from functional specifications. We propose a two-stage approach that combines synthesis by satisfiability modulo theories and Markov chain Monte Carlo based optimisation. First, we identify candidate CRNs that have the possibility to produce correct computations for a given finite set of inputs. We then optimise the reaction rates of each CRN using a combination of stochastic search techniques applied to the chemical master equation, simultaneously improving the of correct behaviour and ruling out spurious solutions. In addition, we use techniques from continuous time Markov chain theory to study the expected termination time for each CRN. We illustrate our approach by identifying CRNs for majority decision-making and division computation, which includes the identification of both known and unknown networks.Comment: 17 pages, 6 figures, appeared the proceedings of the 21st conference on DNA Computing and Molecular Programming, 201

Viability, Invariance and Reachability for Controlled Piecewise Deterministic Markov Processes Associated to Gene Networks

We aim at characterizing viability, invariance and some reachability properties of controlled piecewise deterministic Markov processes (PDMPs). Using analytical methods from the theory of viscosity solutions, we establish criteria for viability and invariance in terms of the first order normal cone. We also investigate reachability of arbitrary open sets. The method is based on viscosity techniques and duality for some associated linearized problem. The theoretical results are applied to general On/Off systems, Cook's model for haploinssuficiency, and a stochastic model for bacteriophage lambda.Comment: submitte

BioDiVinE: A Framework for Parallel Analysis of Biological Models

In this paper a novel tool BioDiVinEfor parallel analysis of biological models is presented. The tool allows analysis of biological models specified in terms of a set of chemical reactions. Chemical reactions are transformed into a system of multi-affine differential equations. BioDiVinE employs techniques for finite discrete abstraction of the continuous state space. At that level, parallel analysis algorithms based on model checking are provided. In the paper, the key tool features are described and their application is demonstrated by means of a case study

Reachability in Restricted Chemical Reaction Networks

The popularity of molecular computation has given rise to several models of abstraction, one of the more recent ones being Chemical Reaction Networks (CRNs). These are equivalent to other popular computational models, such as Vector Addition Systems and Petri-Nets, and restricted versions are equivalent to Population Protocols. This paper continues the work on core reachability questions related to Chemical Reaction Networks; given two configurations, can one reach the other according to the system's rules? With no restrictions, reachability was recently shown to be Ackermann-complete, this resolving a decades-old problem. Here, we fully characterize monotone reachability problems based on various restrictions such as the rule size, the number of rules that may create a species (k-source) or consume a species (k-consuming), the volume, and whether the rules have an acyclic production order (feed-forward). We show PSPACE-completeness of reachability with only bimolecular reactions with two-source and two-consuming rules. This proves hardness of reachability in Population Protocols, which was unknown. Further, this shows reachability in CRNs is PSPACE-complete with size-2 rules, which was previously only known with size-5 rules. This is achieved using techniques within the motion planning framework. We provide many important results for feed-forward CRNs where rules are single-source or single-consuming. We show that reachability is solvable in polynomial time if the system does not contain special void or autogenesis rules. We then fully characterize all systems of this type and show that if you allow void/autogenesis rules, or have more than one source and one consuming, the problems become NP-complete. Finally, we show several interesting special cases of CRNs based on these restrictions or slight relaxations and note future significant open questions related to this taxonomy.Comment: This research was supported in part by National Science Foundation Grant CCF-181760