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Expressive Statistical Model Checking of Genetic Networks with Delayed Stochastic Dynamics [chapter]

Paolo Ballarini, Jarno Mäkelä, Andre S. Ribeiro
2012 Lecture Notes in Computer Science  
To this aim we consider the analysis of a model of gene expression with delayed stochastic dynamics, a class of systems whose dynamics includes both Markovian and non-Markovian events.  ...  We identify a number of relevant properties related to this model, formally express them in HASL terms and, assess them with COSMOS, a statistical model checker for HASL model checking.  ...  Genetic Networks with Delayed Stochastic Dynamics Gene expression is the process by which proteins are synthesized from a sequence in the DNA.  ... 
doi:10.1007/978-3-642-33636-2_4 fatcat:aqri4y6m65fnpby6icgmt6qf3u

Statistical Model Checking for Stochastic Hybrid Systems

Alexandre David, Dehui Du, Kim G. Larsen, Axel Legay, Marius Mikučionis, Danny Bøgsted Poulsen, Sean Sedwards
2012 Electronic Proceedings in Theoretical Computer Science  
This paper presents novel extensions and applications of the UPPAAL-SMC model checker. The extensions allow for statistical model checking of stochastic hybrid systems.  ...  We show how our race-based stochastic semantics extends to networks of hybrid systems, and indicate the integration technique applied for implementing this semantics in the UPPAAL-SMC simulation engine  ...  Conclusions This paper presents an extensions of the UPPAAL-SMC model checker supporting statistical model checking for stochastic hybrid automata, where dynamic of systems can be specified with ODEs.  ... 
doi:10.4204/eptcs.92.9 fatcat:caia5evy3fgpxmdiga7btpvzde

Taming Living Logic Using Formal Methods [chapter]

Hasan Baig, Jan Madsen
2017 Lecture Notes in Computer Science  
Therefore, the verification of genetic circuit models is usually performed by the statistical approach of model checking.  ...  The state space of stochastic genetic circuit models is usually too large to be handled by classical model checking techniques.  ...  Chris Myers (University of Utah) for providing us the SBML models of the genetic circuits, and Associate Prof.  ... 
doi:10.1007/978-3-319-63121-9_25 fatcat:pggneohe45ex5djnqihneoivje

A General Modeling Strategy for Gene Regulatory Networks with Stochastic Dynamics

Andre Ribeiro, Rui Zhu, Stuart A. Kauffman
2006 Journal of Computational Biology  
A stochastic genetic toggle switch model that consists of two identical, mutually repressive genes is built using the Gillespie algorithm with time delays as an example of a simple stochastic gene regulatory  ...  Although its dynamics is very rich and allows applying the ensemble approach, useful at determining general dynamical behavior, real genetic networks are not synchronous and genes' level of expression  ...  ACKNOWLEDGMENTS A.S.R. is currently funded by FCT, Portuguese Foundation for Science and Technology, with a Post Doctoral Fellowship (SFRH/BPD/14565/2003).  ... 
doi:10.1089/cmb.2006.13.1630 pmid:17147485 fatcat:kgngxxlyrjf2tj2efp4tvdd6de

Uppaal SMC tutorial

Alexandre David, Kim G. Larsen, Axel Legay, Marius Mikučionis, Danny Bøgsted Poulsen
2015 International Journal on Software Tools for Technology Transfer (STTT)  
This tutorial paper surveys the main features of Uppaal SMC, a model checking approach in Uppaal family that allows us to reason on networks of complex real-timed systems with a stochastic semantic.  ...  We demonstrate the modeling features of the tool, new verification algorithms and ways of applying them to potentially complex case studies.  ...  Extension to Hybrid Systems Uppaal SMC allows for statistical model checking of stochastic hybrid systems, i.e. extensions of (stochastic) timed automata, where the rate of clocks may be given by general  ... 
doi:10.1007/s10009-014-0361-y fatcat:idacg5lwdndldddufdx2hlg4xy

Statistical model checking for biological systems

Alexandre David, Kim G. Larsen, Axel Legay, Marius Mikučionis, Danny Bøgsted Poulsen, Sean Sedwards
2014 International Journal on Software Tools for Technology Transfer (STTT)  
Statistical Model Checking (SMC) is a highly scalable simulation-based verification approach for testing and estimating the probability that a stochastic system satisfy a given linear temporal property  ...  In this paper we enable the application of SMC to complex biological systems, by combining Uppaal SMC with ANIMO, a plugin of the tool Cytoscape used by biologists, as well as with SimBiology R , a plugin  ...  Acknowledgement The authors of this paper are grateful for the detailed comments from the anonymous reviewers.  ... 
doi:10.1007/s10009-014-0323-4 fatcat:cgvz3tpfpfaofojxmtgsepde4y

Stochastic Oscillations Induced by Intrinsic Fluctuations in a Self-Repressing Gene

Jingkui Wang, Marc Lefranc, Quentin Thommen
2014 Biophysical Journal  
Here, we study the stochastic dynamics of a self-repressing gene with arbitrarily long or short response time.  ...  To gain insight into this phenomenon at the crossroads of determinism and stochasticity, we use an intermediate theoretical approach, based on a moment-closure approximation of the master equation, which  ...  Here, we study how stochastic fluctuations in gene activity feed-back into the deterministic dynamics of the smallest genetic network, which consists of a single gene repressed by its own protein product  ... 
doi:10.1016/j.bpj.2014.09.042 pmid:25418309 pmcid:PMC4241447 fatcat:rwq5z5vv5vdj5hybxzmujduzku

A tunable synthetic mammalian oscillator

Marcel Tigges, Tatiana T. Marquez-Lago, Jörg Stelling, Martin Fussenegger
2009 Nature  
After detailed systems design with experimental analyses and mathematical modelling, we monitored oscillating concentrations of green fluorescent protein with tunable frequency and amplitude by time-lapse  ...  The precise molecular mechanism and expression dynamics of this mammalian circadian clock are still not fully understood.  ...  This underlines the importance of stochastic effects on the quantitative behaviour of systems with complicated dynamics 22 .  ... 
doi:10.1038/nature07616 pmid:19148099 fatcat:xuvqnwbawzhhdfvhfw3p2w5dlm

Time delay induced transition of gene switch and stochastic resonance in a genetic transcriptional regulatory model

Canjun Wang, Ming Yi, Keli Yang, Lijian Yang
2012 BMC Systems Biology  
of gene expression.  ...  Conclusions: The stochastic delay dynamic approach can identify key physiological control parameters to which the behavior of special genetic regulatory systems is particularly sensitive.  ...  Figure 4 4 Model of genetic regulation with a positive autoregulatory feedback loop and time delays.  ... 
doi:10.1186/1752-0509-6-s1-s9 pmid:23281598 pmcid:PMC3521184 fatcat:7qs2hbllczccbkj2dcrymzdiw4

Time delay-accelerated transition of gene switch and -enhanced stochastic resonance in a bistable gene regulatory model

Canjun Wang, Ming Yi, Keli Yang
2011 2011 IEEE International Conference on Systems Biology (ISB)  
The roles of time delay on gene switch and stochastic resonance are systematically explored based on a famous gene transcriptional regulatory model with noises.  ...  The theoretical results by using small-delay timeapproximation approach are consistent well with our numerical simulation.  ...  The simplest kinetic model of genetic regulation with time delay can be described by Fig.4 .  ... 
doi:10.1109/isb.2011.6033129 fatcat:e5srxqit6fgepn4pabdzglqfmi

Model Checking of Biological Systems [chapter]

Luboš Brim, Milan Češka, David Šafránek
2013 Lecture Notes in Computer Science  
Model checking together with other formal methods and techniques is being adapted for applications to biological systems.  ...  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.  ...  GNA (de Jong et al. [116]) Genetic Network Analyzer (GNA) provides support for modeling and simulation of genetic regulatory networks using knowledge about regulatory interactions in combination with gene  ... 
doi:10.1007/978-3-642-38874-3_3 fatcat:gko33i5f6fe33jl4zi2cdte6ha

Stochastic delay differential equations for genetic regulatory networks

Tianhai Tian, Kevin Burrage, Pamela M. Burrage, Margherita Carletti
2007 Journal of Computational and Applied Mathematics  
Two simple genetic regulatory networks are used to study the impact of intrinsic noise on the system dynamics where there are delays.  ...  In this paper we introduce a general mathematical formalism via stochastic delay differential equations for describing time delays in genetic regulatory networks.  ...  Acknowledgements One of the authors (K.B.) would like to acknowledge support of the Australian Research Council for the award of a Federation Fellowship.  ... 
doi:10.1016/j.cam.2006.02.063 fatcat:ncrjhudgwrfwxlcl4aqb33crdy

Statistical model checking for biological applications

Paolo Zuliani
2014 International Journal on Software Tools for Technology Transfer (STTT)  
In this paper we survey recent work on the use of statistical model checking techniques for biological applications.  ...  We begin with an overview of the basic modelling techniques for biochemical reactions and their corresponding stochastic simulation algorithm - the Gillespie algorithm.  ...  The authors demonstrate their technique by analysing stochastic models of gene networks with delayed dynamics.  ... 
doi:10.1007/s10009-014-0343-0 fatcat:sdcqgtwswzehtaamju6ymqfpgu

Stochastic Dynamic Modeling of Short Gene Expression Time-Series Data

Zidong Wang, Fuwen Yang, D.W.C. Ho, S. Swift, A. Tucker, Xiaohui Liu
2008 IEEE Transactions on Nanobioscience  
The gene regulatory network is viewed as a stochastic dynamic model, which consists of the noisy gene measurement from microarray and the gene regulation first-order autoregressive (AR) stochastic dynamic  ...  The gene expression stochastic dynamic models for four real-world gene expression data sets are constructed to demonstrate the advantages of the introduced algorithm.  ...  In Section II, a stochastic dynamic model is described for genetic regulatory network, which takes into account the noisy measurement as well as the inherently stochastic phenomenon of the genetic regulatory  ... 
doi:10.1109/tnb.2008.2000149 pmid:18334455 fatcat:pj7hoipuwje3dlylli5loqvlny

Stochastic Dynamic Modeling of Short Gene Expression Time Series Data [chapter]

2010 Chapman & Hall/CRC Computer Science & Data Analysis  
The gene regulatory network is viewed as a stochastic dynamic model, which consists of the noisy gene measurement from microarray and the gene regulation first-order autoregressive (AR) stochastic dynamic  ...  The gene expression stochastic dynamic models for four real-world gene expression data sets are constructed to demonstrate the advantages of the introduced algorithm.  ...  In Section II, a stochastic dynamic model is described for genetic regulatory network, which takes into account the noisy measurement as well as the inherently stochastic phenomenon of the genetic regulatory  ... 
doi:10.1201/9781420091540-c10 fatcat:amzbqtnkvjhlxflrzxnau2wyaa
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