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On algorithmic analysis of transcriptional regulation by LTL model checking

J. Barnat, L. Brim, I. Černá, S. Dražan, J. Fabriková, D. Šafránek
2009 Theoretical Computer Science  
This paper is focused on the model checking approach for analysis of piecewise-linear deterministic models of genetic regulatory networks.  ...  Efficiency of the new algorithm when implemented in the parallel model checking environment is demonstrated on a set of experiments performed on randomly modified biological models.  ...  This work has been supported by the FP6 project No. NEST-043235 (EC-MOAN) and by the Grant Academy of Czech Republic grant No. 201/09/1389. Appendix. Additional proofs  ... 
doi:10.1016/j.tcs.2009.02.017 fatcat:bg45abxftfac7m37v5pqehv6mi

Qualitative analysis of gene regulatory networks by temporal logic

Sohei Ito, Takuma Ichinose, Masaya Shimakawa, Naoko Izumi, Shigeki Hagihara, Naoki Yonezaki
2015 Theoretical Computer Science  
We model the possible behaviours of networks by logical formulae in linear temporal logic (LTL).  ...  Owing to the complexity of LTL satisfiability checking, analysis of large networks is generally intractable in this method. To mitigate this computational difficulty, we developed two methods.  ...  We show the strong specification of this network motif (we set n = 2 but generalisation is easy): G(¬on y → F (on y ∨ ¬y z 1 )), G((¬on y ∧ ¬y z 1 ) → (¬y z 1 U (on y ∨ ¬x z 2 ))), G((¬on y ∧ ¬y z 2 )  ... 
doi:10.1016/j.tcs.2015.06.017 fatcat:vpc7vzxtxvaudpisd5z664nyky

Experimentally driven verification of synthetic biological circuits

B. Yordanov, E. Appleton, R. Ganguly, E. A. Gol, S. B. Carr, S. Bhatia, T. Haddock, C. Belta, D. Densmore
2012 2012 Design, Automation & Test in Europe Conference & Exhibition (DATE)  
We delineate algorithms to create finite abstractions of these models, and novel analysis techniques inspired from model-checking to verify behavioral specifications using Linear Temporal Logic (LTL) formulae  ...  We describe experimental procedures to acquire characterization data for the assigned parts and construct mathematical models capturing all possible behaviors of the generated GRN.  ...  This material is based upon work supported by the Office of Naval Research under Grant No. N00014-11-1-0725.  ... 
doi:10.1109/date.2012.6176468 dblp:conf/date/YordanovAGGCBHBD12 fatcat:fo4yakstijh47n3x6hyuc735dy

Model Checking of Biological Systems [chapter]

Luboš Brim, Milan Češka, David Šafránek
2013 Lecture Notes in Computer Science  
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.  ...  Model checking together with other formal methods and techniques is being adapted for applications to biological systems.  ...  Parallel Algorithms for LTL Model Checking.  ... 
doi:10.1007/978-3-642-38874-3_3 fatcat:gko33i5f6fe33jl4zi2cdte6ha

Efficient Analysis of Homeostasis of Gene Networks with Compositional Approach

Sohei Ito, Kenji Osari, Shigeki Hagihara, Naoki Yonezaki
2017 Proceedings of the 10th International Joint Conference on Biomedical Engineering Systems and Technologies  
To tackle this issue, we introduce a new clustering algorithm based on a characteristic function on formulae, which calculates the size of formulae and the variation of propositions.  ...  For this purpose, we proposed a qualitative approach to model gene regulatory networks with logical formulae and formulate the homeostasis in terms of a kind of logical property -called realisability of  ...  QUALITATIVE ANALYSIS OF HOMEOSTASIS IN GENE NETWORKS In this section we review how we model the gene networks and analyse homeostasis of them by LTL.  ... 
doi:10.5220/0006093600170028 dblp:conf/biostec/ItoOHY17 fatcat:qxaw774osncwvhyt7bqjfzufyq

Robustness analysis and tuning of synthetic gene networks

G. Batt, B. Yordanov, R. Weiss, C. Belta
2007 Bioinformatics  
These algorithms are implemented in the tool RoVerGeNe, and their practical applicability and biological relevance are demonstrated on the analysis of the tuning of a synthetic transcriptional cascade  ...  Results: We propose an approach for the analysis of a class of uncertain piecewise-multiaffine differential equation models.  ...  We acknowledge financial support by NSF 0432070. Conflict of Interest: none declared.  ... 
doi:10.1093/bioinformatics/btm362 pmid:17660209 fatcat:gcjrb5oy4jew5prk7r3nr7cdh4

Formal analysis of Piecewise Affine systems under parameter uncertainty with application to gene networks

Boyan Yordanov, Calin Belta
2008 2008 American Control Conference  
Our method is based on the iterative computation and model checking of finite transition systems simulating the original PWA system.  ...  We illustrate our method by computing the basins of attraction for the two equilibria of a PWA model of a two-gene network.  ...  Additionally, for most gene networks, dynamics are affine, with the exception of gene regulation function (GRF), which captures the effect of concentrations of various transcription factors on the activity  ... 
doi:10.1109/acc.2008.4586912 dblp:conf/amcc/YordanovB08 fatcat:yiscpneo5rhinfpglwfig4zg3a

Temporal Logic Analysis of Gene Networks Under Parameter Uncertainty

GrÉgory Batt, Calin Belta, Ron Weiss
2008 IEEE Transactions on Automatic Control  
The proposed method uses discrete abstractions and model checking and allows for efficient search of the parameter space.  ...  The lack of precise numerical information for the values of biological parameters severely limits the development and analysis of models of genetic regulatory networks.  ...  Yordanov for contributions to the development of earlier versions of the mathematical model of the transcriptional cascade.  ... 
doi:10.1109/tac.2007.911330 fatcat:adlpf4b4tba7dgxamdfi5nwbwy

A Logical Paradigm for Systems Biology (Invited Talk)

François Fages, Marc Herbstritt
2010 International Conference on Logic Programming  
These graphical notations encompass two types of information: interactions (e.g. protein complexation, modification, binding to a gene, etc.) and regulations (of an interaction or a transcription).  ...  Based on these structures, mathematical models can be developed by equipping such molecular interaction networks with kinetic expressions leading to quantitative models of mainly two kinds: ordinary differential  ...  By generalizing model-checking techniques to temporal logic constraint solving [3, 4] , a continuous degree of satisfaction could be defined for temporal logic formulae, opening the field of model-checking  ... 
doi:10.4230/lipics.iclp.2010.2 dblp:conf/iclp/Fages10 fatcat:j2p4jn3lfrczhnbrj6nmd72ogu

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  
Next, our overview focuses on direct applications of existing model checkers, as well as on algorithms for biochemical network analysis influenced by model checking, such as those using binary decision  ...  We conclude with advantages and drawbacks of model checking for the analysis of biochemical networks.  ...  Góngora was supported by Conacyt.  ... 
doi:10.3389/fpls.2012.00155 pmid:22833747 pmcid:PMC3400939 fatcat:ubqooqdp2vhrbakjxvui4eq4wy

Design, optimization and predictions of a coupled model of the cell cycle, circadian clock, DNA repair system, irinotecan metabolism and exposure control under temporal logic constraints

Elisabetta De Maria, François Fages, Aurélien Rizk, Sylvain Soliman
2011 Theoretical Computer Science  
In systems biology, the number of available models of cellular processes has increased rapidly, but re-using models in different contexts or for different questions remains a challenging issue.  ...  In this paper, we study the coupling of different models playing a role in the mammalian cell cycle and in cancer therapies.  ...  Acknowledgements This work was supported by the EU FP6 STREP project TEMPO on cancer chronotherapies and is now supported by the ERASysBio project C5Sys concerning circadian and cell cycle clock systems  ... 
doi:10.1016/j.tcs.2010.10.036 fatcat:m2u5433xzfaejikulbewakei6a

Parallel Model Checking Large-Scale Genetic Regulatory Networks with DiVinE

J. Barnat, L. Brim, I. Černá, S. Dražan, D. Šafránek
2008 Electronical Notes in Theoretical Computer Science  
The use of model checking for the analysis of biological networks has attracted much attention recently. One of the practical limitations is the size of the model.  ...  Open access under CC BY-NC-ND license. computational methods, the hardware infrastructure is available (clusters, GRID, multi-core computers), but the parallel (distributed) algorithms for model analysis  ...  Large models require powerful implements several efficient parallel LTL model-checking algorithms.  ... 
doi:10.1016/j.entcs.2007.12.001 fatcat:frszpqf27bc4jlovonwz4wngo4

High-performance analysis of biological systems dynamics with the DiVinE model checker

J. Barnat, L. Brim, D. Safranek
2010 Briefings in Bioinformatics  
The tool employs high-performance computing techniques to enable analysis of large models.  ...  Since the key aspect of biological modelling is based on unifying several kinds of data captured in terms of large-scale biological networks, scalable and automatized methods are necessary to obtain novel  ...  The technique of model checking can provide a powerful scalable tool for analysis of biological systems dynamics.  ... 
doi:10.1093/bib/bbp074 pmid:20478855 fatcat:ufnwwxw3pfffvjjbv3koejbjrm

On Parameter Synthesis by Parallel Model Checking

J. Barnat, L. Brim, A. Krejci, A. Streck, D. Safranek, M. Vejnar, T. Vejpustek
2012 IEEE/ACM Transactions on Computational Biology & Bioinformatics  
This paper presents a novel algorithm for parameter synthesis based on parallel model checking. The algorithm is conceptually universal with respect to the modelling approach employed.  ...  We introduce the algorithm, show its scalability, and examine its applicability on several biological models.  ...  ACKNOWLEDGMENT This work has been supported by the Czech Science Foundation grant No. 201/09/1389.  ... 
doi:10.1109/tcbb.2011.110 pmid:21788679 fatcat:czmmgchba5amrbtkqvdij6kt2i

Model checking the evolution of gene regulatory networks

Mirco Giacobbe, Călin C. Guet, Ashutosh Gupta, Thomas A. Henzinger, Tiago Paixão, Tatjana Petrov
2016 Acta Informatica  
We employ symbolic bounded model checking and SMT solving to compute the space of GRNs that satisfy the property, which amounts to synthesizing a set of linear constraints on the weights.  ...  We focus on Wagner's weighted GRN model with varying weights, which is used in evolutionary biology.  ...  Acknowledgments Open access funding provided by Institute of Science and Technology (IST Austria).  ... 
doi:10.1007/s00236-016-0278-x fatcat:h5oh6rsxnjblxea5qspuqd47la
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