Comparative Analysis of Statistical Model Checking Tools

Statistical model checking is a powerful and flexible approach for formal verification of computational models like P systems, which can have very large search spaces. Various statistical model checking tools have been developed, but choosing between them and using the most appropriate one requires a significant degree of experience, not only because different tools have different modelling and property specification languages, but also because they may be designed to support only a certain subset of property types. Furthermore, their performance can vary depending on the property types and membrane systems being verified. In this paper we evaluate the performance of various common statistical model checkers against a pool of biological models. Our aim is to help users select the most suitable SMC tools from among the available options, by comparing their modelling and property specification languages, capabilities and performances

Automatic Selection of Verification Tools for Efficient Analysis of Biochemical Models

YesMotivation: Formal verification is a computational approach that checks system correctness (in relation to a desired functionality). It has been widely used in engineering applications to verify that systems work correctly. Model checking, an algorithmic approach to verification, looks at whether a system model satisfies its requirements specification. This approach has been applied to a large number of models in systems and synthetic biology as well as in systems medicine. Model checking is, however, computationally very expensive, and is not scalable to large models and systems. Consequently, statistical model checking (SMC), which relaxes some of the constraints of model checking, has been introduced to address this drawback. Several SMC tools have been developed; however, the performance of each tool significantly varies according to the system model in question and the type of requirements being verified. This makes it hard to know, a priori, which one to use for a given model and requirement, as choosing the most efficient tool for any biological application requires a significant degree of computational expertise, not usually available in biology labs. The objective of this paper is to introduce a method and provide a tool leading to the automatic selection of the most appropriate model checker for the system of interest. Results: We provide a system that can automatically predict the fastest model checking tool for a given biological model. Our results show that one can make predictions of high confidence, with over 90% accuracy. This implies significant performance gain in verification time and substantially reduces the “usability barrier” enabling biologists to have access to this powerful computational technology.EPSRC, Innovate U

A Novel Method to Verify Multilevel Computational Models of Biological Systems Using Multiscale Spatio-Temporal Meta Model Checking

Insights gained from multilevel computational models of biological systems can be translated into real-life applications only if the model correctness has been verified first. One of the most frequently employed in silico techniques for computational model verification is model checking. Traditional model checking approaches only consider the evolution of numeric values, such as concentrations, over time and are appropriate for computational models of small scale systems (e.g. intracellular networks). However for gaining a systems level understanding of how biological organisms function it is essential to consider more complex large scale biological systems (e.g. organs). Verifying computational models of such systems requires capturing both how numeric values and properties of (emergent) spatial structures (e.g. area of multicellular population) change over time and across multiple levels of organization, which are not considered by existing model checking approaches. To address this limitation we have developed a novel approximate probabilistic multiscale spatio-temporal meta model checking methodology for verifying multilevel computational models relative to specifications describing the desired/expected system behaviour. The methodology is generic and supports computational models encoded using various high-level modelling formalisms because it is defined relative to time series data and not the models used to generate it. In addition, the methodology can be automatically adapted to case study specific types of spatial structures and properties using the spatio-temporal meta model checking concept. To automate the computational model verification process we have implemented the model checking approach in the software tool Mule (http://mule.modelchecking.org). Its applicability is illustrated against four systems biology computational models previously published in the literature encoding the rat cardiovascular system dynamics, the uterine contractions of labour, the Xenopus laevis cell cycle and the acute inflammation of the gut and lung. Our methodology and software will enable computational biologists to efficiently develop reliable multilevel computational models of biological systems

Computational model validation using a novel multiscale multidimensional spatio-temporal meta model checking approach

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonComputational models of complex biological systems can provide a better understanding of how living systems function but need to be validated before they are employed for real-life (e.g. clinical) applications. One of the most frequently employed in silico approaches for validating such models is model checking. Traditional model checking approaches are limited to uniscale non-spatial computational models because they do not explicitly distinguish between different scales, and do not take properties of (emergent) spatial structures (e.g. density of multicellular population) into account. This thesis defines a novel multiscale multidimensional spatio-temporal meta model checking methodology which enables validating multiscale (spatial) computational models of biological systems relative to how both numeric (e.g. concentrations) and spatial system properties are expected to change over time and across multiple scales. The methodology has two important advantages. First it supports computational models encoded using various high-level modelling formalisms because it is defined relative to time series data and not the models used to produce them. Secondly the methodology is generic because it can be automatically reconfigured according to case study specific types of spatial structures and properties using the meta model checking approach. In addition the methodology could be employed for multiple domains of science, but we illustrate its applicability here only against biological case studies. To automate the computational model validation process, the approach was implemented in software tools, which are made freely available online. Their efficacy is illustrated against two uniscale and four multiscale quantitative computational models encoding phase variation in bacterial colonies and the chemotactic aggregation of cells, respectively the rat cardiovascular system dynamics, the uterine contractions of labour, the Xenopus laevis cell cycle and the acute inflammation of the gut and lung. This novel model checking approach will enable the efficient construction of reliable multiscale computational models of complex systems.Brunel University Londo

Statistical verification and differential privacy in cyber-physical systems

This thesis studies the statistical verification and differential privacy in Cyber-Physical Systems. The first part focuses on the statistical verification of stochastic hybrid system, a class of formal models for Cyber-Physical Systems. Model reduction techniques are performed on both Discrete-Time and Continuous-Time Stochastic Hybrid Systems to reduce them to Discrete-Time Markov Chains and Continuous-Time Markov Chains, respectively; and statistical verification algorithms are proposed to verify Linear Inequality LTL and Metric Interval Temporal Logic on these discrete probabilistic models. In addition, the advantage of stratified sampling in verifying Probabilistic Computation Tree Logic on Labeled Discrete-Time Markov Chains is studied; this method can potentially be extended to other statistical verification algorithms to reduce computational costs. The second part focuses on the Differential Privacy in multi-agent systems that involve share information sharing to achieve overall control goals. A general formulation of the systems and a notion of Differential Privacy are proposed, and a trade-off between the Differential Privacy and the tracking performance of the systems is demonstrated. In addition, it is proved that there is a trade-off between Differential Privacy and the entropy of the unbiased estimator of the private data, and an optimal algorithm to achieve the best trade-off is given