Statistical Model Checking of Membrane Systems with Peripheral Proteins: Quantifying the Role of Estrogen in Cellular Mitosis and DNA Damage

Abstract

Systems biology is a natural application of membrane systems, allowing the analysis of biological systems using the formal technique of model checking.To overcome the intractable model size of typical biological systems, statistical model checking may be used to efficiently estimate the probability of properties of interest with arbitrary levels of confidence. In this chapter we analyse a biological system linked to breast cancer, using statistical model checking (SMC) applied to membrane systems. To do this, we have constructed a computational platform that integrates an SMC library with a stochastic simulator of membrane systems with peripheral proteins. We present the methodology to investigate the role of estrogen in cellular mitosis and DNA damage and we use our statistical model checker to find the most appropriate time-dependent dosage of antagonist that should be used to minimize the uncontrolled replication of abnormal cells.

Infobiotics Workbench: A P Systems Based Tool for Systems and Synthetic Biology

“…Such an analysis method is the formal verification approach based on computational models [44,43], especially model checking. So far, only IBW and, very recently, Cyto-Sim [23] support this type of analysis. In IBW this analysis is fully integrated with the rest, the translation into PRISM is automatically obtained from the specification and the queries formulated for each model are expressed using natural language patterns.…”

“…It is difficult to compare the expressiveness of the modelling languages used by these tools, as although they all use the same P systems paradigm, they implement different features -some use deterministic execution style [11], whereas many rely on probabilistic or stochastic behaviour [7,28,14,23,68]; SRSim uses strings as opposed to all the others employing multisets; some use explicitly geometric elements [68,14] or a topology of the environment [28], but the others make use only of the membrane structure.…”

“…An integrated software environment, called MeCoSim, is supporting the modelling language with an editor and different visualisation options [96]. -Probabilistic P systems with peripheral proteins focuses on trans-membrane operations where a Gillespie algorithm is used for describing the system behaviour; a specification language is integrated into the simulation environment Cyto-sim [23].…”

Comparative Analysis of Statistical Model Checking Tools

“…The number of tools using statistical model checking has been increasing steadily, as has their application to biological systems [14,53]. Although the variety of SMC tools gives a certain amount of flexibility and control to users, each model checker has its own specific pros and cons.…”