Syntactic Markovian Bisimulation for Chemical Reaction Networks

In chemical reaction networks (CRNs) with stochastic semantics based on continuous-time Markov chains (CTMCs), the typically large populations of species cause combinatorially large state spaces. This makes the analysis very difficult in practice and represents the major bottleneck for the applicability of minimization techniques based, for instance, on lumpability. In this paper we present syntactic Markovian bisimulation (SMB), a notion of bisimulation developed in the Larsen-Skou style of probabilistic bisimulation, defined over the structure of a CRN rather than over its underlying CTMC. SMB identifies a lumpable partition of the CTMC state space a priori, in the sense that it is an equivalence relation over species implying that two CTMC states are lumpable when they are invariant with respect to the total population of species within the same equivalence class. We develop an efficient partition-refinement algorithm which computes the largest SMB of a CRN in polynomial time in the number of species and reactions. We also provide an algorithm for obtaining a quotient network from an SMB that induces the lumped CTMC directly, thus avoiding the generation of the state space of the original CRN altogether. In practice, we show that SMB allows significant reductions in a number of models from the literature. Finally, we study SMB with respect to the deterministic semantics of CRNs based on ordinary differential equations (ODEs), where each equation gives the time-course evolution of the concentration of a species. SMB implies forward CRN bisimulation, a recently developed behavioral notion of equivalence for the ODE semantics, in an analogous sense: it yields a smaller ODE system that keeps track of the sums of the solutions for equivalent species.Comment: Extended version (with proofs), of the corresponding paper published at KimFest 2017 (http://kimfest.cs.aau.dk/

White-Box Validation of Collective Adaptive Systems by Statistical Model Checking and Process Mining

Modeling and analyzing collective adaptive systems with heterogeneous components poses challenges to language designers, software engineers, and computer scientists interested in the formal verification of the modeled systems. This requires the integration of computational, reasoning, and analysis tools, but also of techniques to validate and shed light on the actual behavior described by a model. We build on a methodology built in collaboration with Rocco De Nicola, based on his influential contributions in the modeling and programming of distributed and adaptive systems. Such methodology allows to model and analyze collective adaptive systems equipped with reasoning capabilities. It combines SCEL, a language for programming collective adaptive systems, with Pirlo, a reasoner that can enrich agents with reasoning capabilities, and MultiVeStA, a statistical model checker that can analyze the obtained models by simulating them. Here, we further enrich this methodology with techniques from process-oriented data science, and in particular process mining, to ease the validation and debugging of such models. This follows recent proposals from the literature that validate models by explaining graphically the behaviors observed by a statistical model checker. We demonstrate our approach by considering a simple collision-avoidance robotic scenario where a group of robots moves in an arena while aiming at minimizing the number of collisions

Efficient Network Embedding by Approximate Equitable Partitions

Structural network embedding is a crucial step in enabling effective downstream tasks for complex systems that aim to project a network into a lower-dimensional space while preserving similarities among nodes. We introduce a simple and efficient embedding technique based on approximate variants of equitable partitions. The approximation consists in introducing a user-tunable tolerance parameter relaxing the otherwise strict condition for exact equitable partitions that can be hardly found in real-world networks. We exploit a relationship between equitable partitions and equivalence relations for Markov chains and ordinary differential equations to develop a partition refinement algorithm for computing an approximate equitable partition in polynomial time. We compare our method against state-of-the-art embedding techniques on benchmark networks. We report comparable-when not superior-performance for visualization, classification, and regression tasks at a cost between one and three orders of magnitude smaller using a prototype implementation, enabling the embedding of large-scale networks that could not be efficiently handled by most of the competing techniques

Symbolic computation of differential equivalences

Ordinary differential equations (ODEs) are widespread in many natural sciences including chemistry, ecology, and systems biology, and in disciplines such as control theory and electrical engineering. Building on the celebrated molecules-as-processes paradigm, they have become increasingly popular in computer science, with high-level languages and formal methods such as Petri nets, process algebra, and rule-based systems that are interpreted as ODEs. We consider the problem of comparing and minimizing ODEs automatically. Influenced by traditional approaches in the theory of programming, we propose differential equivalence relations. We study them for a basic intermediate language, for which we have decidability results, that can be targeted by a class of high-level specifications. An ODE implicitly represents an uncountable state space, hence reasoning techniques cannot be borrowed from established domains such as probabilistic programs with finite-state Markov chain semantics. We provide novel symbolic procedures to check an equivalence and compute the largest one via partition refinement algorithms that use satisfiability modulo theories. We illustrate the generality of our framework by showing that differential equivalences include (i) well-known notions for the minimization of continuous-time Markov chains (lumpability), (ii) bisimulations for chemical reaction networks recently proposed by Cardelli et al., and (iii) behavioral relations for process algebra with ODE semantics. Using ERODE, the tool that implements our techniques, we are able to detect equivalences in biochemical models from the literature that cannot be reduced using competing automatic techniques

Formal lumping of polynomial differential equations through approximate equivalences

It is well known that exact notions of model abstraction and reduction for dynamical systems may not be robust enough in practice because they are highly sensitive to the specific choice of parameters. In this paper we consider this problem for nonlinear ordinary differential equations (ODEs) with polynomial derivatives. We introduce a model reduction technique based on approximate differential equivalence, i.e., a partition of the set of ODE variables that performs an aggregation when the variables are governed by nearby derivatives. We develop algorithms to (i) compute the largest approximate differential equivalence; (ii) construct an approximately reduced model from the original one via an appropriate perturbation of the coefficients of the polynomials; and (iii) provide a formal certificate on the quality of the approximation as an error bound, computed as an over-approximation of the reachable set of the reduced model. Finally, we apply approximate differential equivalences to case studies on electric circuits, biological models, and polymerization reaction networks

Forward and Backward Constrained Bisimulations for Quantum Circuits

Efficient methods for the simulation of quantum circuits on classic computers are crucial for their analysis due to the exponential growth of the problem size with the number of qubits. Here we study lumping methods based on bisimulation, an established class of techniques that has been proven successful for (classic) stochastic and deterministic systems such as Markov chains and ordinary differential equations. Forward constrained bisimulation yields a lower-dimensional model which exactly preserves quantum measurements projected on a linear subspace of interest. Backward constrained bisimulation gives a reduction that is valid on a subspace containing the circuit input, from which the circuit result can be fully recovered. We provide an algorithm to compute the constraint bisimulations yielding coarsest reductions in both cases, using a duality result relating the two notions. As applications, we provide theoretical bounds on the size of the reduced state space for well-known quantum algorithms for search, optimization, and factorization. Using a prototype implementation, we report significant reductions on a set of benchmarks. Furthermore, we show that constraint bisimulation complements state-of-the-art methods for the simulation of quantum circuits based on decision diagrams.</p

Mean-Field Limits Beyond Ordinary Differential Equations

16th International School on Formal Methods for the Design of Computer, Communication, and Software Systems, SFM 2016, Bertinoro, Italy, June 20-24, 2016, Advanced LecturesInternational audienceWe study the limiting behaviour of stochastic models of populations of interacting agents, as the number of agents goes to infinity. Classical mean-field results have established that this limiting behaviour is described by an ordinary differential equation (ODE) under two conditions: (1) that the dynamics is smooth; and (2) that the population is composed of a finite number of homogeneous sub-populations, each containing a large number of agents. This paper reviews recent work showing what happens if these conditions do not hold. In these cases, it is still possible to exhibit a limiting regime at the price of replacing the ODE by a more complex dynamical system. In the case of non-smooth or uncertain dynamics, the limiting regime is given by a differential inclusion. In the case of multiple population scales, the ODE is replaced by a stochastic hybrid automaton

Approximate Reductions of Rational Dynamical Systems in CLUE

In life sciences, deriving insights from dynamical systems can be challenging due to the large number of state variables involved. To address this, model reduction techniques can be used to project the system onto a lower-dimensional state space. CLUE is a tool that computes exact reductions for rational systems of ordinary differential equations. In this paper, we present an extension of CLUE to include approximate reductions which allow for larger aggregating power at the expense of a bounded error. Additionally, our extension includes new functionalities such as an interface to the model database ODEBase repository and simulation techniques for exploratory analyses

Efficient Syntax-Driven Lumping of Differential Equations

We present an algorithm to compute exact aggregations of a class of systems of ordinary differential equations (ODEs). Our approach consists in an extension of Paige and Tarjan’s seminal solution to the coarsest refinement problem by encoding an ODE system into a suitable discrete-state representation. In particular, we consider a simple extension of the syntax of elementary chemical reaction networks because (i) it can express ODEs with derivatives given by polynomials of degree at most two, which are relevant in many applications in natural sciences and engineering; and (ii) we can build on two recently introduced bisimulations, which yield two complementary notions of ODE lumping. Our algorithm computes the largest bisimulations in O(r⋅s⋅logs)O(r⋅s⋅log⁡s) time, where r is the number of monomials and s is the number of variables in the ODEs. Numerical experiments on real-world models from biochemistry, electrical engineering, and structural mechanics show that our prototype is able to handle ODEs with millions of variables and monomials, providing significant model reductions

Optimality-Preserving Reduction of Chemical Reaction Networks

Across many disciplines, chemical reaction networks (CRNs) are an established population model defined as a system of coupled nonlinear ordinary differential equations. In many applications, for example, in systems biology and epidemiology, CRN parameters such as the kinetic reaction rates can be used as control inputs to steer the system toward a given target. Unfortunately, the resulting optimal control problem is nonlinear, therefore, computationally very challenging. We address this issue by introducing an optimality-preserving reduction algorithm for CRNs. The algorithm partitions the original state variables into a reduced set of macro-variables for which one can define a reduced optimal control problem with provably identical optimal values. The reduction algorithm runs with polynomial time complexity in the size of the CRN. We use this result to reduce verification and control problems of large-scale vaccination models over real-world networks