Modeling biological systems with delays in Bio-PEPA

Delays in biological systems may be used to model events for which the underlying dynamics cannot be precisely observed, or to provide abstraction of some behavior of the system resulting more compact models. In this paper we enrich the stochastic process algebra Bio-PEPA, with the possibility of assigning delays to actions, yielding a new non-Markovian process algebra: Bio-PEPAd. This is a conservative extension meaning that the original syntax of Bio-PEPA is retained and the delay specification which can now be associated with actions may be added to existing Bio-PEPA models. The semantics of the firing of the actions with delays is the delay-as-duration approach, earlier presented in papers on the stochastic simulation of biological systems with delays. These semantics of the algebra are given in the Starting-Terminating style, meaning that the state and the completion of an action are observed as two separate events, as required by delays. Furthermore we outline how to perform stochastic simulation of Bio-PEPAd systems and how to automatically translate a Bio-PEPAd system into a set of Delay Differential Equations, the deterministic framework for modeling of biological systems with delays. We end the paper with two example models of biological systems with delays to illustrate the approach.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005

Extended Differential Aggregations in Process Algebra for Performance and Biology

We study aggregations for ordinary differential equations induced by fluid semantics for Markovian process algebra which can capture the dynamics of performance models and chemical reaction networks. Whilst previous work has required perfect symmetry for exact aggregation, we present approximate fluid lumpability, which makes nearby processes perfectly symmetric after a perturbation of their parameters. We prove that small perturbations yield nearby differential trajectories. Numerically, we show that many heterogeneous processes can be aggregated with negligible errors.Comment: In Proceedings QAPL 2014, arXiv:1406.156

Analysis of Timed and Long-Run Objectives for Markov Automata

Markov automata (MAs) extend labelled transition systems with random delays and probabilistic branching. Action-labelled transitions are instantaneous and yield a distribution over states, whereas timed transitions impose a random delay governed by an exponential distribution. MAs are thus a nondeterministic variation of continuous-time Markov chains. MAs are compositional and are used to provide a semantics for engineering frameworks such as (dynamic) fault trees, (generalised) stochastic Petri nets, and the Architecture Analysis & Design Language (AADL). This paper considers the quantitative analysis of MAs. We consider three objectives: expected time, long-run average, and timed (interval) reachability. Expected time objectives focus on determining the minimal (or maximal) expected time to reach a set of states. Long-run objectives determine the fraction of time to be in a set of states when considering an infinite time horizon. Timed reachability objectives are about computing the probability to reach a set of states within a given time interval. This paper presents the foundations and details of the algorithms and their correctness proofs. We report on several case studies conducted using a prototypical tool implementation of the algorithms, driven by the MAPA modelling language for efficiently generating MAs.Comment: arXiv admin note: substantial text overlap with arXiv:1305.705

Rate-Based Transition Systems for Stochastic Process Calculi

A variant of Rate Transition Systems (RTS), proposed by Klin and Sassone, is introduced and used as the basic model for defining stochastic behaviour of processes. The transition relation used in our variant associates to each process, for each action, the set of possible futures paired with a measure indicating their rates. We show how RTS can be used for providing the operational semantics of stochastic extensions of classical formalisms, namely CSP and CCS. We also show that our semantics for stochastic CCS guarantees associativity of parallel composition. Similarly, in contrast with the original definition by Priami, we argue that a semantics for stochastic π-calculus can be provided that guarantees associativity of parallel composition

Efficient Modelling and Generation of Markov Automata (extended version)

This paper introduces a framework for the efficient modelling and generation of Markov automata. It consists of (1) the data-rich process-algebraic language MAPA, allowing concise modelling of systems with nondeterminism, probability and Markovian timing; (2) a restricted form of the language, the MLPPE, enabling easy state space generation and parallel composition; and (3) several syntactic reduction techniques on the MLPPE format, for generating equivalent but smaller models. Technically, the framework relies on an encoding of MAPA into the existing prCRL language for probabilistic automata. First, we identify a class of transformations on prCRL that can be lifted to the Markovian realm using our encoding. Then, we employ this result to reuse prCRL's linearisation procedure to transform any MAPA specification to an equivalent MLPPE, and to lift three prCRL reduction techniques to MAPA. Additionally, we define two novel reduction techniques for MLPPEs. All our techniques treat data as well as Markovian and interactive behaviour in a fully symbolic manner, working on specifications instead of models and thus reducing state spaces prior to their construction. The framework has been implemented in our tool SCOOP, and a case study on polling systems and mutual exclusion protocols shows its practical applicability

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/

Compositional Performance Modelling with the TIPPtool

Stochastic process algebras have been proposed as compositional specification formalisms for performance models. In this paper, we describe a tool which aims at realising all beneficial aspects of compositional performance modelling, the TIPPtool. It incorporates methods for compositional specification as well as solution, based on state-of-the-art techniques, and wrapped in a user-friendly graphical front end. Apart from highlighting the general benefits of the tool, we also discuss some lessons learned during development and application of the TIPPtool. A non-trivial model of a real life communication system serves as a case study to illustrate benefits and limitations