105 research outputs found
Trend-based analysis of a population model of the AKAP scaffold protein
No full textWe formalise a continuous-time Markov chain with multi-dimensional discrete state space model of the AKAP scaffold protein as a crosstalk mediator between two biochemical signalling pathways. The analysis by temporal properties of the AKAP model requires reasoning about whether the counts of individuals of the same type (species) are increasing or decreasing. For this purpose we propose the concept of stochastic trends based on formulating the probabilities of transitions that increase (resp. decrease) the counts of individuals of the same type, and express these probabilities as formulae such that the state space of the model is not altered. We define a number of stochastic trend formulae (e.g. weakly increasing, strictly increasing, weakly decreasing, etc.) and use them to extend the set of state formulae of Continuous Stochastic Logic. We show how stochastic trends can be implemented in a guarded-command style specification language for transition systems. We illustrate the application of stochastic trends with numerous small examples and then we analyse the AKAP model in order to characterise and show causality and pulsating behaviours in this biochemical system
A generic approach for the automatic verification of featured, parameterised systems
No full textA general technique is presented that allows property based feature analysis of systems consisting of an arbitrary number of components. Each component may have an arbitrary set of safe features. The components are defined in a guarded command form and the technique combines model checking and abstraction. Features must fulfill certain criteria in order to be safe, the criteria express constraints on the variables which occur in feature guards. The main result is a generalisation theorem which we apply to a well known example: the ubiquitous, featured telephone system
Modelling and analysis of biochemical signalling pathway cross-talk
No full textSignalling pathways are abstractions that help life scientists structure the coordination of cellular activity. Cross-talk between pathways accounts for many of the complex behaviours exhibited by signalling pathways and is often critical in producing the correct signal-response relationship. Formal models of signalling pathways and cross-talk in particular can aid understanding and drive experimentation. We define an approach to modelling based on the concept that a pathway is the (synchronising) parallel composition of instances of generic modules (with internal and external labels). Pathways are then composed by (synchronising) parallel composition and renaming; different types of cross-talk result from different combinations of synchronisation and renaming. We define a number of generic modules in PRISM and five types of cross-talk: signal flow, substrate availability, receptor function, gene expression and intracellular communication. We show that Continuous Stochastic Logic properties can both detect and distinguish the types of cross-talk. The approach is illustrated with small examples and an analysis of the cross-talk between the TGF-b/BMP, WNT and MAPK pathways
Generalising feature interactions in email
No full textWe report on a property-based approach to feature interaction analysis for a client-server email system. The model is based upon Hall's email model presented at FIW'00, but the implementation is at a lower level of abstraction, employing non-determinism and asynchronous communication; it is a challenge to avoid deadlock and race conditions. The analysis is more extensive in two ways: interaction analysis is fully automated, based on model-checking the entire state-space, and results are scalable, that is they generalise to email systems consisting of any number of email clients. Abstraction techniques are used to prove general results. The key idea is to model-check a system consisting of a constant number (m) of client processes, in parallel with a mailer process and an ``abstract'' process which represents the product of any number of other (unfeatured, isomorphic) client processes. We give a lower bound for the value of m. All of the models -- for any specified set of client processes and selected features -- are generated automatically using Perl scripts
Modular modelling of signalling pathways and their crosstalk
No full textSignalling pathways are well-known abstractions that explain the mechanisms whereby cells respond to signals. Collections of pathways form networks, and interactions between pathways in a network, known as cross-talk, enables further complex signalling behaviours. While there are several formal modelling approaches for signalling pathways, none make cross-talk explicit; the aim of this paper is to define and categorise cross-talk in a rigorous way. We define a modular approach to pathway and network modelling, based on the module construct in the PRISM modelling language, and a set of generic signalling modules. Five different types of cross-talk are defined according to various biologically meaningful combinations of variable sharing, synchronisation labels and reaction renaming. The approach is illustrated with a case-study analysis of cross-talk between the TGF-β, WNT and MAPK pathways
Formalising the Chisel Feature Notation
No full textThe CHISEL notation was developed by Bellcore as an informal graphical notation for describing telecomms services and features. CRESS (CHISEL Representation Employing Systematic Specification) is an enhanced version of CHISEL with tightly defined rules for the syntax and static semantics of diagrams. More importantly, CRESS has formal denotations given by SDL (Specification and Description Language) and LOTOS (Language Of Temporal Ordering Specification). This permits rigorous checking, analysis and prototyping of descriptions. The accompanying toolset has been written in an open and extensible manner
Process algebra modelling styles for biomolecular processes
No full textWe investigate how biomolecular processes are modelled in process algebras, focussing on chemical reactions. We consider various modelling styles and how design decisions made in the definition of the process algebra have an impact on how a modelling style can be applied. Our goal is to highlight the often implicit choices that modellers make in choosing a formalism, and illustrate, through the use of examples, how this can affect expressability as well as the type and complexity of the analysis that can be performed
Feature interaction detection by pairwise analysis of LTL properties—A case study
No full textA Promela specification and a set of temporal properties are developed for a basic call service with a number of features. The properties are expressed in the logic LTL.
Interactions between features are detected by pairwise analysis of features and properties. The analysis quickly results in both state-space and property case explosion. To overcome this state-spaces are minimised, model checking results generalised through symmetry and bisimulation, and analysis performed automatically using scripts. The result is a more extensive feature interaction analysis than others in the field
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