Design Environments for Complex Systems

The paper describes an approach for modeling complex systems by hiding as much formal details as possible from the user, still allowing verification and simulation of the model. The interface is based on UML to make the environment available to the largest audience. To carry out analysis, verification and simulation we automatically extract process algebras specifications from UML models. The results of the analysis is then reflected back in the UML model by annotating diagrams. The formal model includes stochastic information to handle quantitative parameters. We present here the stochastic -calculus and we discuss the implementation of its probabilistic support that allows simulation of processes. We exploit the benefits of our approach in two applicative domains: global computing and systems biology

Proceedings of International Workshop "Global Computing: Programming Environments, Languages, Security and Analysis of Systems"

According to the IST/ FET proactive initiative on GLOBAL COMPUTING, the goal is to obtain techniques (models, frameworks, methods, algorithms) for constructing systems that are flexible, dependable, secure, robust and efficient. The dominant concerns are not those of representing and manipulating data efficiently but rather those of handling the co-ordination and interaction, security, reliability, robustness, failure modes, and control of risk of the entities in the system and the overall design, description and performance of the system itself. Completely different paradigms of computer science may have to be developed to tackle these issues effectively. The research should concentrate on systems having the following characteristics: • The systems are composed of autonomous computational entities where activity is not centrally controlled, either because global control is impossible or impractical, or because the entities are created or controlled by different owners. • The computational entities are mobile, due to the movement of the physical platforms or by movement of the entity from one platform to another. • The configuration varies over time. For instance, the system is open to the introduction of new computational entities and likewise their deletion. The behaviour of the entities may vary over time. • The systems operate with incomplete information about the environment. For instance, information becomes rapidly out of date and mobility requires information about the environment to be discovered. The ultimate goal of the research action is to provide a solid scientific foundation for the design of such systems, and to lay the groundwork for achieving effective principles for building and analysing such systems. This workshop covers the aspects related to languages and programming environments as well as analysis of systems and resources involving 9 projects (AGILE , DART, DEGAS , MIKADO, MRG, MYTHS, PEPITO, PROFUNDIS, SECURE) out of the 13 founded under the initiative. After an year from the start of the projects, the goal of the workshop is to fix the state of the art on the topics covered by the two clusters related to programming environments and analysis of systems as well as to devise strategies and new ideas to profitably continue the research effort towards the overall objective of the initiative. We acknowledge the Dipartimento di Informatica and Tlc of the University of Trento, the Comune di Rovereto, the project DEGAS for partially funding the event and the Events and Meetings Office of the University of Trento for the valuable collaboration

From Solvable to Executable Models of Biological Systems

Classical modeling approaches for biology are mainly grounded in mathematics, and specifically on ordinary differential equations (ODE). Process calculi-based conceptual and computational tools are an alternative and emergent approach. Here we focus our analysis on BlenX (a beta-binders inspired programming language) showing how it is possible to easily re-use ODE models within this framework. An example will show then the advantages of moving into a stochastic approach. This is the preliminary version of a paper that was published in Proceedings of Pacific Symposium on Biocomputing (PSB 2009), January, 2009. The original publication is available at http://psb.stanford.edu/psb-online/proceedings/psb09

Model Checking Dynamic-Epistemic Spatial Logic

In this paper we focus on Dynamic Spatial Logic, the extension of Hennessy-Milner logic with the parallel operator. We develop a sound complete Hilbert-style axiomatic system for it comprehending the behavior of spatial operators in relation with dynamic/temporal ones. Underpining on a new congruence we define over the class of processes - the structural bisimulation - we prove the finite model property for this logic that provides the decidability for satisfiability, validity and model checking against process semantics. Eventualy we propose algorithms for validity, satisfiability and model checking

Cell Cycle Control in Eukaryotes: a BioSpi model

This paper presents a stochastic model of the cell cycle control in eukaryotes. The framework used is based on stochastic process algebras for mobile systems. The automatic tool used in the simulation is the BioSpi. We compare our approach with classical ODE specications

BlenX-based compositional modeling of complex reaction mechanisms

Molecular interactions are wired in a fascinating way resulting in complex behavior of biological systems. Theoretical modeling provides a useful framework for understanding the dynamics and the function of such networks. The complexity of the biological networks calls for conceptual tools that manage the combinatorial explosion of the set of possible interactions. A suitable conceptual tool to attack complexity is compositionality, already successfully used in the process algebra field to model computer systems. We rely on the BlenX programming language, originated by the beta-binders process calculus, to specify and simulate high-level descriptions of biological circuits. The Gillespie's stochastic framework of BlenX requires the decomposition of phenomenological functions into basic elementary reactions. Systematic unpacking of complex reaction mechanisms into BlenX templates is shown in this study. The estimation/derivation of missing parameters and the challenges emerging from compositional model building in stochastic process algebras are discussed. A biological example on circadian clock is presented as a case study of BlenX compositionality

Simulation of non-Markovian Processes in BlenX

BlenX is a programming language explicitly designed for modeling biological processes inspired by Beta-binders. The actual framework assumes biochemical interactions being exponentially distributed, i.e., an underlying Markov process is associated with BlenX programs. In this paper we relax this condition by providing formal tools for managing non-Markovian processes within BlenX

Inferring rate coefficents of biochemical reactions from noisy data with KInfer

Dynamical models of inter- and intra-cellular processes contain the rate constants of the biochemical reactions. These kinetic parameters are often not accessible directly through experiments, but they can be inferred from time-resolved data. Time resolved data, that is, measurements of reactant concentration at series of time points, are usually affected by different types of error, whose source can be both experimental and biological. The noise in the input data makes the estimation of the model parameters a very difficult task, as if the inference method is not sufficiently robust to the noise, the resulting estimates are not reliable. Therefore "noise-robust" methods that estimate rate constants with the maximum precision and accuracy are needed. In this report we present the probabilistic generative model of parameter inference implemented by the software prototype KInfer and we show the ability of this tool of estimating the rate coefficients of models of biochemical network with a good accuracy even from very noisy input data

Efficient Finite Difference Method for Computing Sensitivities of Biochemical Reactions

Sensitivity analysis of biochemical reactions aims at quantifying the dependence of the reaction dynamics on the reaction rates. The computation of the parameter sensitivities, however, poses many computational challenges when taking stochastic noise into account. This paper proposes a new finite difference method for efficiently computing sensitivities of biochemical reactions. We employ propensity bounds of reactions to couple the simulation of the nominal and perturbed processes. The exactness of the simulation is reserved by applying the rejection-based mechanism. For each simulation step, the nominal and perturbed processes under our coupling strategy are synchronized and often jump together, increasing their positive correlation and hence reducing the variance of the estimator. The distinctive feature of our approach in comparison with existing coupling approaches is that it only needs to maintain a single data structure storing propensity bounds of reactions during the simulation of the nominal and perturbed processes. Our approach allows to computing sensitivities of many reaction rates simultaneously. Moreover, the data structure does not require to be updated frequently, hence improving the computational cost. This feature is especially useful when applied to large reaction networks. We benchmark our method on biological reaction models to prove its applicability and efficiency.Comment: 29 pages with 6 figures, 2 table