Petri Nets for Biologically Motivated Computing

Petri nets are a general and well-established model of concurrent and distributed computation and behaviour, including that taking place in biological systems. In this survey paper, we are concerned with intrinsic relationships between Petri nets and two formal models inspired by aspects of the functioning of the living cell: membrane systems and reaction systems. In particular, we are interested in the benefits that can result from establishing strong semantical links between Petri nets and membrane systems and reaction systems. We first discuss Petri nets with localities reflecting the compartmentalisation modelled in membrane systems. Then special attention is given to set-nets, a new Petri net model for reaction systems and their qualitative approach to the investigation of the processes carried out by biochemical reactions taking place in the living cell

Membrane Systems and Petri Net Synthesis

Automated synthesis from behavioural specifications is an attractive and powerful way of constructing concurrent systems. Here we focus on the problem of synthesising a membrane system from a behavioural specification given in the form of a transition system which specifies the desired state space of the system to be constructed. We demonstrate how a Petri net solution to this problem, based on the notion of region of a transition system, yields a method of automated synthesis of membrane systems from state spaces.Comment: In Proceedings MeCBIC 2012, arXiv:1211.347

Petri nets for systems and synthetic biology

We give a description of a Petri net-based framework for modelling and analysing biochemical pathways, which uni¯es the qualita- tive, stochastic and continuous paradigms. Each perspective adds its con- tribution to the understanding of the system, thus the three approaches do not compete, but complement each other. We illustrate our approach by applying it to an extended model of the three stage cascade, which forms the core of the ERK signal transduction pathway. Consequently our focus is on transient behaviour analysis. We demonstrate how quali- tative descriptions are abstractions over stochastic or continuous descrip- tions, and show that the stochastic and continuous models approximate each other. Although our framework is based on Petri nets, it can be applied more widely to other formalisms which are used to model and analyse biochemical networks

Design and Development of Software Tools for Bio-PEPA

This paper surveys the design of software tools for the Bio-PEPA process algebra. Bio-PEPA is a high-level language for modelling biological systems such as metabolic pathways and other biochemical reaction networks. Through providing tools for this modelling language we hope to allow easier use of a range of simulators and model-checkers thereby freeing the modeller from the responsibility of developing a custom simulator for the problem of interest. Further, by providing mappings to a range of different analysis tools the Bio-PEPA language allows modellers to compare analysis results which have been computed using independent numerical analysers, which enhances the reliability and robustness of the results computed.

09091 Abstracts Collection -- Formal Methods in Molecular Biology

From 23. February to 27. February 2009, the Dagstuhl Seminar 09091 ``Formal Methods in Molecular Biology \u27\u27 was held in Schloss Dagstuhl~--~Leibniz Center for Informatics. During the seminar, several participants presented their current research, and ongoing work and open problems were discussed. Abstracts of the presentations given during the seminar as well as abstracts of seminar results and ideas are put together in this paper. The first section describes the seminar topics and goals in general. Links to extended abstracts or full papers are provided, if available

A Type System for a Stochastic CLS

The Stochastic Calculus of Looping Sequences is suitable to describe the evolution of microbiological systems, taking into account the speed of the described activities. We propose a type system for this calculus that models how the presence of positive and negative catalysers can modify these speeds. We claim that types are the right abstraction in order to represent the interaction between elements without specifying exactly the element positions. Our claim is supported through an example modelling the lactose operon

Exploring the concept of interaction computing through the discrete algebraic analysis of the Belousov–Zhabotinsky reaction

Interaction computing (IC) aims to map the properties of integrable low-dimensional non-linear dynamical systems to the discrete domain of finite-state automata in an attempt to reproduce in software the self-organizing and dynamically stable properties of sub-cellular biochemical systems. As the work reported in this paper is still at the early stages of theory development it focuses on the analysis of a particularly simple chemical oscillator, the Belousov-Zhabotinsky (BZ) reaction. After retracing the rationale for IC developed over the past several years from the physical, biological, mathematical, and computer science points of view, the paper presents an elementary discussion of the Krohn-Rhodes decomposition of finite-state automata, including the holonomy decomposition of a simple automaton, and of its interpretation as an abstract positional number system. The method is then applied to the analysis of the algebraic properties of discrete finite-state automata derived from a simplified Petri net model of the BZ reaction. In the simplest possible and symmetrical case the corresponding automaton is, not surprisingly, found to contain exclusively cyclic groups. In a second, asymmetrical case, the decomposition is much more complex and includes five different simple non-abelian groups whose potential relevance arises from their ability to encode functionally complete algebras. The possible computational relevance of these findings is discussed and possible conclusions are drawn

Biologically Relevant Classes of Boolean Functions

A large influx of experimental data has prompted the development of innovative computational techniques for modeling and reverse engineering biological networks. While finite dynamical systems, in particular Boolean networks, have gained attention as relevant models of network dynamics, not all Boolean functions reflect the behaviors of real biological systems. In this work, we focus on two classes of Boolean functions and study their applicability as biologically relevant network models: the nested and partially nested canalyzing functions. We begin by analyzing the nested canalyzing functions} (NCFs), which have been proposed as gene regulatory network models due to their stability properties. We introduce two biologically motivated measures of network stability, the average height and average cycle length on a state space graph and show that, on average, networks comprised of NCFs are more stable than general Boolean networks. Next, we introduce the partially nested canalyzing functions (PNCFs), a generalization of the NCFs, and the nested canalyzing depth, which measures the extent to which it retains a nested canalyzing structure. We characterize the structure of functions with a given depth and compute the expected activities and sensitivities of the variables. This analysis quantifies how canalyzation leads to higher stability in Boolean networks. We find that functions become decreasingly sensitive to input perturbations as the canalyzing depth increases, but exhibit rapidly diminishing returns in stability. Additionally, we show that as depth increases, the dynamics of networks using these functions quickly approach the critical regime, suggesting that real networks exhibit some degree of canalyzing depth, and that NCFs are not significantly better than PNCFs of sufficient depth for many applications to biological networks. Finally, we propose a method for the reverse engineering of networks of PNCFs using techniques from computational algebra. Given discretized time series data, this method finds a network model using PNCFs. Our ability to use these functions in reverse engineering applications further establishes their relevance as biological network models