Specifying real-time properties with metric temporal logic
Real-Time Systems
The algorithmic analysis of hybrid systems
Theoretical Computer Science - Special issue on hybrid systems
Proving Liveness Properties of Concurrent Programs
ACM Transactions on Programming Languages and Systems (TOPLAS)
Symbolic Model Checking for Probabilistic Processes
ICALP '97 Proceedings of the 24th International Colloquium on Automata, Languages and Programming
Beyond HYTECH: Hybrid Systems Analysis Using Interval Numerical Methods
HSCC '00 Proceedings of the Third International Workshop on Hybrid Systems: Computation and Control
Level Set Methods for Computation in Hybrid Systems
HSCC '00 Proceedings of the Third International Workshop on Hybrid Systems: Computation and Control
Symbolic Techniques for Parametric Reasoning about Counter and Clock Systems
CAV '00 Proceedings of the 12th International Conference on Computer Aided Verification
Counterexample-Guided Abstraction Refinement
CAV '00 Proceedings of the 12th International Conference on Computer Aided Verification
Symbolic Model Checking of Biochemical Networks
CMSB '03 Proceedings of the First International Workshop on Computational Methods in Systems Biology
Probabilistic Verification of Discrete Event Systems Using Acceptance Sampling
CAV '02 Proceedings of the 14th International Conference on Computer Aided Verification
Model-Checking Algorithms for Continuous-Time Markov Chains
IEEE Transactions on Software Engineering
PRISM 2.0: A Tool for Probabilistic Model Checking
QEST '04 Proceedings of the The Quantitative Evaluation of Systems, First International Conference
Protein Explorer: A Petaflops Special-Purpose Computer System for Molecular Dynamics Simulations
Proceedings of the 2003 ACM/IEEE conference on Supercomputing
Verification and planning for stochastic processes with asynchronous events
Verification and planning for stochastic processes with asynchronous events
Numerical vs. statistical probabilistic model checking
International Journal on Software Tools for Technology Transfer (STTT)
LiQuor: A tool for Qualitative and Quantitative Linear Time analysis of Reactive Systems
QEST '06 Proceedings of the 3rd international conference on the Quantitative Evaluation of Systems
Statistical probabilistic model checking with a focus on time-bounded properties
Information and Computation
Hybridization methods for the analysis of nonlinear systems
Acta Informatica - Hybrid Systems
Anton, a special-purpose machine for molecular dynamics simulation
Proceedings of the 34th annual international symposium on Computer architecture
Probabilistic model checking of complex biological pathways
Theoretical Computer Science
Robustness analysis and tuning of synthetic gene networks
Bioinformatics
The temporal logic of programs
SFCS '77 Proceedings of the 18th Annual Symposium on Foundations of Computer Science
A Counterexample-Guided Approach to Parameter Synthesis for Linear Hybrid Automata
HSCC '08 Proceedings of the 11th international workshop on Hybrid Systems: Computation and Control
CMSB '08 Proceedings of the 6th International Conference on Computational Methods in Systems Biology
CMSB '08 Proceedings of the 6th International Conference on Computational Methods in Systems Biology
A Model Checking Approach to the Parameter Estimation of Biochemical Pathways
CMSB '08 Proceedings of the 6th International Conference on Computational Methods in Systems Biology
Approximate Parameter Synthesis for Probabilistic Time-Bounded Reachability
RTSS '08 Proceedings of the 2008 Real-Time Systems Symposium
Parameter Synthesis in Nonlinear Dynamical Systems: Application to Systems Biology
RECOMB 2'09 Proceedings of the 13th Annual International Conference on Research in Computational Molecular Biology
A Bayesian Approach to Model Checking Biological Systems
CMSB '09 Proceedings of the 7th International Conference on Computational Methods in Systems Biology
Monitoring Algorithms for Metric Temporal Logic Specifications
Electronic Notes in Theoretical Computer Science (ENTCS)
Systematic simulation using sensitivity analysis
HSCC'07 Proceedings of the 10th international conference on Hybrid systems: computation and control
Reachability for linear hybrid automata using iterative relaxation abstraction
HSCC'07 Proceedings of the 10th international conference on Hybrid systems: computation and control
Automated symbolic reachability analysis: with application to delta-notch signaling automata
HSCC'03 Proceedings of the 6th international conference on Hybrid systems: computation and control
Efficient representation and computation of reachable sets for hybrid systems
HSCC'03 Proceedings of the 6th international conference on Hybrid systems: computation and control
Symbolic reachability analysis of lazy linear hybrid automata
FORMATS'07 Proceedings of the 5th international conference on Formal modeling and analysis of timed systems
Reconstruction of switching thresholds in piecewise-affine models of genetic regulatory networks
HSCC'06 Proceedings of the 9th international conference on Hybrid Systems: computation and control
Probabilistic model checking of complex biological pathways
CMSB'06 Proceedings of the 2006 international conference on Computational Methods in Systems Biology
TACAS'05 Proceedings of the 11th international conference on Tools and Algorithms for the Construction and Analysis of Systems
On statistical model checking of stochastic systems
CAV'05 Proceedings of the 17th international conference on Computer Aided Verification
Synthesis of insulin pump controllers from safety specifications using Bayesian model validation
International Journal of Bioinformatics Research and Applications
Learning and designing stochastic processes from logical constraints
QEST'13 Proceedings of the 10th international conference on Quantitative Evaluation of Systems
Hi-index | 5.23 |
The stochastic dynamics of biochemical reaction networks can be modeled using a number of succinct formalisms all of whose semantics are expressed as Continuous Time Markov Chains (CTMC). While some kinetic parameters for such models can be measured experimentally, most are estimated by either fitting to experimental data or by performing ad hoc, and often manual search procedures. We consider an alternative strategy to the problem, and introduce algorithms for automatically synthesizing the set of all kinetic parameters such that the model satisfies a given high-level behavioral specification. Our algorithms, which integrate statistical model checking and abstraction refinement, can also report the infeasibility of the model if no such combination of parameters exists. Behavioral specifications can be given in any finitely monitorable logic for stochastic systems, including the probabilistic and bounded fragments of linear and metric temporal logics. The correctness of our algorithms is established using a novel combination of arguments based on survey sampling and uniform continuity. We prove that the probability of a measurable set of paths is uniformly and jointly continuous with respect to the kinetic parameters. Under a suitable technical condition, we also show that the unbiased statistical estimator for the probability of a measurable set of paths is monotonic in the parameter space. We apply our algorithms to two benchmark models of biochemical signaling, and demonstrate that they can efficiently find parameter regimes satisfying a given high-level behavioral specification. In particular, we show that our algorithms can synthesize up to 6 parameters, simultaneously, which is more than that reported by any other synthesis algorithm for stochastic systems. Moreover, when parameter estimation is desired, as opposed to synthesis, we show that our approach can scale to even higher dimensional spaces, by identifying the single parameter combination that maximizes the probability of the behavior being true in an 11-dimensional system.