Foreword

Abstract

The four papers in this special issue apply tools and techniques from computer performance evaluation in the very different domain of modelling biological systems. This might seem to be a very odd thing to do but the practice of analysing biological systems in this way is becoming increasing common. As data about the internal components of biological systems is becoming more readily available, biologists are increasingly asking questions about how systems function. In addition to conducting laboratory experiments, they are supported in this exploration by in silico experimentation based on models. The view taken of the biological processes focusses on the stimuli and responses, a view akin to that taken of engineered systems in systems engineering. Thus this new endeavour in biology is known as Systems Biology . Performance analysts have a long tradition of modelling systems in order to understand and predict their function. Their focus is particularly on the dynamic aspects of the system, the use of, and contention for, resources, and the impact of uncertainty or randomness. These issues are important in the biological setting also, and so it is perhaps inevitable that we see some people and techniques from performance modelling being applied in systems biology. In particular some of the high-level modelling formalisms which have supported Markovian performance modelling in the last few decades (stochastic Petri nets, stochastic process algebras, etc.) are being applied in the biological domain. Furthermore analysis techniques, such as Markovian analysis, Monte Carlo simulation and probabilistic model checking have also been adoped. In this volume we have sought to give a snapshot of a variety of work which is going on at this interface between systems biology and more traditional quantitative analysis techniques. It is by no means an exhaustive account of this exciting area, but rather a taster which will hopefully whet your appetite to find out more. To open the volume, the editors provide a survey paper describing the motivations and goals of the systems biology endeavour, summarising the existing modelling techniques and outlining some instances of cross-over between performance modelling and systems biology. This includes an account of the use of ordinary differential equations (ODE) and stochastic simulation to analyse biological systems, and the adoption of high-level modelling formalisms such as Petri nets and process algebras to drive these ODE models and simulations. In their paper Kwiatkowska, Norman and Parker show the application of logic and probabilistic model checking to the analysis of biological signalling pathways. They use the PRISM probabilistic model-checker to check formulae of the CSL logic against CTMC-based models of the MAPK cascade, a sequence of biochemical reactions which sends a message within a cell. The paper provides an introduction to the CSL logic as well as the reactive modules language implemented by the PRISM model checker. Performance measures of interest are described using reward structures and the analysis achieved by PRISM is able to show how the percentage of activated MAPK, a key component of the pathway, and the number of MAPK-MAPKK reactions, vary as a function of time, for different values of the initial number of MAPKs. The paper by Jeschke, Ewald, Park, Fujimoto and Uhrmacher addresses the drive for increased physical accuracy in simulation models which represent the spatial aspects of cell biology. Standard approaches to stochastic simulation of cellular systems assume that the cell is a homogeneous soup of biochemical components. The truth is far removed from this, as the cell has a lot of internal structure which can have a profound effect on the dynamics of reactions. Setting aside the assumption that the reacting chemical species are well-stirred, spatial approaches divide the volume into sub-volumes and apply a structured method which identifies the next reaction to occur in each subvolume. The cost of such an increase in accuracy in the simulation model is a much increased running time so the authors use a parallel and distributed approach to improve performance. To close this special issue we have a paper by DemattB, Priami and Romanel which uses the BlenX language and the Beta Workbench software to analyse the MAPK pathway considered also by Kwiatkowska, Norman and Parker. The BlenX language, and the Beta-binders process calculus which was its inspiration, are examples of a new generation of languages which have been designed specifically for the biological domain, as an alternative to using existing languages designed for modelling computer systems. The paper shows how a well-designed platform for modelling and simulation can lift the user's experience and make their use of process calculi more valuable, delivering insights which would not have been seen otherwise.