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A Logic for Checking the Probabilistic Steady-State Properties of Reaction Networks

Vincent Picard, Anne Siegel, Jérémie Bourdon
2017 Journal of Computational Biology  
In order to assist in the construction of reaction network models, we introduce a logic that allows one to express asymptotic properties about the steady-state stochastic dynamics of a reaction network  ...  If a formula encoding for experimental observations on the system is not satisfiable then the reaction network model can be rejected.  ...  Phillipe Codognet for interesting discussions about solving systems of polynomial constraints.  ... 
doi:10.1089/cmb.2017.0099 pmid:28686462 fatcat:gcosf2ox4rc6ldlnclzub663de

A Study of the PDGF Signaling Pathway with PRISM

Qixia Yuan, Jun Pang, Sjouke Mauw, Panuwat Trairatphisan, Monique Wiesinger, Thomas Sauter
2011 Electronic Proceedings in Theoretical Computer Science  
In this paper, we apply the probabilistic model checker PRISM to the analysis of a biological system -- the Platelet-Derived Growth Factor (PDGF) signaling pathway, demonstrating in detail how this pathway  ...  We show that quantitative verification can yield a better understanding of the PDGF signaling pathway.  ...  Analysis is performed through model checking such systems against properties written in the probabilistic temporal logics PCTL if the model is a DTMC or an MDP, or CSL in the case of a CTMC, as well as  ... 
doi:10.4204/eptcs.67.7 fatcat:pgl4iaqqlvbitjkfjd4a37kjhe

A Property-Driven Methodology for Formal Analysis of Synthetic Biology Systems

Savas Konur, Marian Gheorghe
2015 IEEE/ACM Transactions on Computational Biology & Bioinformatics  
An integrative analysis perspective combining different model checking approaches based on different property categories is provided.  ...  The methodology is applied to the synthetic pulse generator system and several verification experiments are carried out to demonstrate the use of our approach to formally analyse various aspects of synthetic  ...  For example, steady-state and complex properties with embedded operators are not supported. PLASMA PLASMA [4] is a statistical model checker for probabilistic systems.  ... 
doi:10.1109/tcbb.2014.2362531 pmid:26357223 fatcat:iljr55mvq5co5jgkx3r3r5jvjq

Simulative Model Checking of Steady State and Time-Unbounded Temporal Operators [chapter]

Christian Rohr
2013 Lecture Notes in Computer Science  
While finite time horizon algorithms are well known for probabilistic linear-time temporal logic, we provide an infinite time horizon procedure as well as steady state computation, based on exact stochastic  ...  We demonstrate the approach on models of the RKIP inhibited ERK pathway and angiogenetic process.  ...  Conclusions In this paper we presented an infinite time horizon model checking algorithm plus steady state operator for probabilistic linear-time temporal logic.  ... 
doi:10.1007/978-3-642-40465-8_8 fatcat:csrpjlc36fdanaccuhxgzh7pw4

Comparative Analysis of Statistical Model Checking Tools [chapter]

Mehmet Emin Bakir, Marian Gheorghe, Savas Konur, Mike Stannett
2017 Lecture Notes in Computer Science  
Statistical model checking is a powerful and flexible approach for formal verification of computational models, e.g. P systems, which can have very large search spaces.  ...  modelling and property specification languages, but also because they may be designed to support only a certain subset of property types.  ...  However, statistical model checking can only be applied to a limited subset of properties; for example, it does not support steady-state and LTL-style path properties.  ... 
doi:10.1007/978-3-319-54072-6_8 fatcat:mtrtkgwr4zd7nemowsuazwu6ky

An overview of existing modeling tools making use of model checking in the analysis of biochemical networks

Miguel Carrillo, Pedro A. Góngora, David A. Rosenblueth
2012 Frontiers in Plant Science  
We conclude with advantages and drawbacks of model checking for the analysis of biochemical networks.  ...  Model checking is a well-established technique for automatically verifying complex systems.  ...  Members of the Biocham and GNA teams generously gave us helpful information. Finally, we are grateful to the reviewers, who gave us useful suggestions. FUNDING Pedro A.  ... 
doi:10.3389/fpls.2012.00155 pmid:22833747 pmcid:PMC3400939 fatcat:ubqooqdp2vhrbakjxvui4eq4wy

Statistical Model Checking in BioLab: Applications to the Automated Analysis of T-Cell Receptor Signaling Pathway [chapter]

Edmund M. Clarke, James R. Faeder, Christopher J. Langmead, Leonard A. Harris, Sumit Kumar Jha, Axel Legay
2008 Lecture Notes in Computer Science  
Temporal logic is a formalism for representing and reasoning about propositions qualified in terms of time.  ...  We present an algorithm, called BioLab, for verifying temporal properties of rule-based models of cellular signalling networks.  ...  Younes for answering many email questions on his work.  ... 
doi:10.1007/978-3-540-88562-7_18 fatcat:vc6ut2at75hb3nlpbgtn6mtmgq

Studying Irreversible Transitions in a Model of Cell Cycle Regulation

Paolo Ballarini, Tommaso Mazza, Alida Palmisano, Attila Csikasz-Nagy
2009 Electronical Notes in Theoretical Computer Science  
Through probabilistic model checking we provide a quantitative measure for the probability of irreversibility in the "Start" transition of the cell cycle.  ...  The transitions through the various cell cycle phases are controlled by a complex network of signalling pathways.  ...  Expressing properties of the cell-cycle in probabilistic temporal logic The Continuous Stochastic Logic (CSL) [1, 2] is a language for stating properties referring to CTMC models.  ... 
doi:10.1016/j.entcs.2009.02.049 fatcat:h7ifb7sabbfe3odwmrff4nn4mu

Integrated Simulation and Model-Checking for the Analysis of Biochemical Systems

Federica Ciocchetta, Stephen Gilmore, Maria Luisa Guerriero, Jane Hillston
2009 Electronical Notes in Theoretical Computer Science  
Moreover, the finite nature of the state representation used means that a priori bounds must be set for the numbers of molecules of each species to be observed in the system.  ...  The stochastic simulation identifies reasonable bounds for molecular populations in the context of the considered experiment.  ...  Acknowledgement The authors thank the anonymous reviewers of this paper for their insightful comments on the work. Federica Ciocchetta and Jane Hillston are supported by the U.K.  ... 
doi:10.1016/j.entcs.2009.02.048 fatcat:xaaqhay42rb27hsrzht7y7vddu

Analysis of Signalling Pathways Using Continuous Time Markov Chains [chapter]

Muffy Calder, Vladislav Vyshemirsky, David Gilbert, Richard Orton
2006 Lecture Notes in Computer Science  
We describe a quantitative modelling and analysis approach for signal transduction networks. We illustrate the approach with an example, the RKIP inhibited ERK pathway [CSK + 03].  ...  The main advantage of our approach is that using a (continuous time) stochastic logic and the PRISM model checker, we can perform quantitative analysis such as what is the probability that if a concentration  ...  Acknowledgements This research is supported by the project A Software Tool for Simulation and Analysis of Biochemical Networks, funded by the DTI Beacon Bioscience Programme.  ... 
doi:10.1007/11880646_3 fatcat:rd2ur64kmncqhano327w2yhag4

Stochastic analysis of Chemical Reaction Networks using Linear Noise Approximation

Luca Cardelli, Marta Kwiatkowska, Luca Laurenti
2016 Biosystems (Amsterdam. Print)  
We develop a probabilistic logic for CRNs that enables stochastic analysis of the evolution of populations of molecular species.  ...  Stochastic evolution of Chemical Reactions Networks (CRNs) over time is usually analyzed through solving the Chemical Master Equation (CME) or performing extensive simulations.  ...  Acknowledgements The authors would like to thank Luca Bortolussi for helpful discussions. This research is supported by a Royal Society Research Professorship and ERC AdG VERIWARE.  ... 
doi:10.1016/j.biosystems.2016.09.004 pmid:27816736 fatcat:z7szay3mgvbfbob5h2fjk7nx64

Organisation-Oriented Coarse Graining and Refinement of Stochastic Reaction Networks

Chunyan Mu, Peter Dittrich, David Parker, Jonathan E. Rowe
2018 IEEE/ACM Transactions on Computational Biology & Bioinformatics  
We then construct and formalise a coarse-grained Markov chain model of hierarchic organisations for a given reaction network, which can be used to approximate the behaviour of the original reaction network  ...  As an application of the coarse-grained model, we predict the behaviour of the reaction network systems over time via the master equation.  ...  ACKNOWLEDGMENTS The authors acknowledge support from the European Union through funding under FP7-ICT-2011-8 project HIERATIC  ... 
doi:10.1109/tcbb.2018.2804395 pmid:29994367 fatcat:ceomvhxo2bcu5pt4l3km3776lu

Formal Quantitative Analysis of Reaction Networks Using Chemical Organisation Theory [chapter]

Chunyan Mu, Peter Dittrich, David Parker, Jonathan E. Rowe
2016 Lecture Notes in Computer Science  
Probabilistic Model Checking Probabilistic model checking is a variant of model checking [5], a well-established formal method to automatically verify the correctness of real-life systems.  ...  be used to approximate and predict the behaviour of the original reaction network.  ...  We also thank the anonymous reviewers for their helpful and detailed comments.  ... 
doi:10.1007/978-3-319-45177-0_15 fatcat:cn4nivol4zdbnk2n6hczzlngmy

Model Checking of Biological Systems [chapter]

Luboš Brim, Milan Češka, David Šafránek
2013 Lecture Notes in Computer Science  
We present a selection of approaches used for modeling biological systems and formalizing their interesting properties in temporal logics.  ...  We also give a brief account of high performance model checking techniques and add a few case studies that demonstrate the use of model checking in computational systems biology.  ...  The logic also includes the steady-state operator S describing the steady-state behavior of a CTMC.  ... 
doi:10.1007/978-3-642-38874-3_3 fatcat:gko33i5f6fe33jl4zi2cdte6ha

From software verification to 'everyware' verification

Marta Kwiatkowska
2013 Computer Science - Research and Development  
In this paper we describe the objectives and initial progress of the research aimed at extending the capabilities of quantitative, probabilistic verification to challenging ubiquitous computing scenarios  ...  Ubiquitous computing is a vision of computing in which the computer disappears from view and becomes embedded in our environment, in the equipment we use, in our clothes, and even in our body.  ...  [ F ≤t Φ ], where t is real-valued, and a steady state operator S=? [ Φ ] for computing long-run probability of residing in states satisfying Φ. Examples of CSL properties are: -P =?  ... 
doi:10.1007/s00450-013-0249-1 fatcat:yijv5tfqwjb5rlopsnmy6gpsf4
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