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

Qualitative and quantitative analysis of systems and synthetic biology constructs using P systems

YesComputational models are perceived as an attractive alternative to mathematical models (e.g., ordinary differential equations). These models incorporate a set of methods for specifying, modeling, testing, and simulating biological systems. In addition, they can be analyzed using algorithmic techniques (e.g., formal verification). This paper shows how formal verification is utilized in systems and synthetic biology through qualitative vs quantitative analysis. Here, we choose two well-known case studies: quorum sensing in P. aeruginosas and pulse generator. The paper reports verification analysis of two systems carried out using some model checking tools, integrated to the Infobiotics Workbench platform, where system models are based on stochastic P systems.EPSR

A property-driven methodology for formal analysis of synthetic biology systems

yesThis paper proposes a formal methodology to analyse bio-systems, in particular synthetic biology systems. 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 biology systems.EPSR

A review of modelling and verification approaches for computational biology

This paper reviews most frequently used computational modelling approaches and formal verification techniques in computational biology. The paper also compares a number of model checking tools and software suits used in analysing biological systems and biochemical networks and verifiying a wide range of biological properties

A synthesis of logic and biology in the design of dependable systems

The technologies of model-based design and dependability analysis in the design of dependable systems, including software intensive systems, have advanced in recent years. Much of this development can be attributed to the application of advances in formal logic and its application to fault forecasting and verification of systems. In parallel, work on bio-inspired technologies has shown potential for the evolutionary design of engineering systems via automated exploration of potentially large design spaces. We have not yet seen the emergence of a design paradigm that combines effectively and throughout the design lifecycle these two techniques which are schematically founded on the two pillars of formal logic and biology. Such a design paradigm would apply these techniques synergistically and systematically from the early stages of design to enable optimal refinement of new designs which can be driven effectively by dependability requirements. The paper sketches such a model-centric paradigm for the design of dependable systems that brings these technologies together to realise their combined potential benefits

Experimental Biological Protocols with Formal Semantics

Both experimental and computational biology is becoming increasingly automated. Laboratory experiments are now performed automatically on high-throughput machinery, while computational models are synthesized or inferred automatically from data. However, integration between automated tasks in the process of biological discovery is still lacking, largely due to incompatible or missing formal representations. While theories are expressed formally as computational models, existing languages for encoding and automating experimental protocols often lack formal semantics. This makes it challenging to extract novel understanding by identifying when theory and experimental evidence disagree due to errors in the models or the protocols used to validate them. To address this, we formalize the syntax of a core protocol language, which provides a unified description for the models of biochemical systems being experimented on, together with the discrete events representing the liquid-handling steps of biological protocols. We present both a deterministic and a stochastic semantics to this language, both defined in terms of hybrid processes. In particular, the stochastic semantics captures uncertainties in equipment tolerances, making it a suitable tool for both experimental and computational biologists. We illustrate how the proposed protocol language can be used for automated verification and synthesis of laboratory experiments on case studies from the fields of chemistry and molecular programming

A synthesis of logic and bio-inspired techniques in the design of dependable systems

Much of the development of model-based design and dependability analysis in the design of dependable systems, including software intensive systems, can be attributed to the application of advances in formal logic and its application to fault forecasting and verification of systems. In parallel, work on bio-inspired technologies has shown potential for the evolutionary design of engineering systems via automated exploration of potentially large design spaces. We have not yet seen the emergence of a design paradigm that effectively combines these two techniques, schematically founded on the two pillars of formal logic and biology, from the early stages of, and throughout, the design lifecycle. Such a design paradigm would apply these techniques synergistically and systematically to enable optimal refinement of new designs which can be driven effectively by dependability requirements. The paper sketches such a model-centric paradigm for the design of dependable systems, presented in the scope of the HiP-HOPS tool and technique, that brings these technologies together to realise their combined potential benefits. The paper begins by identifying current challenges in model-based safety assessment and then overviews the use of meta-heuristics at various stages of the design lifecycle covering topics that span from allocation of dependability requirements, through dependability analysis, to multi-objective optimisation of system architectures and maintenance schedules

Formal verification of genetic circuits

pre-printResearchers are beginning to be able to engineer synthetic genetic circuits for a range of applications in the environmental, medical, and energy domains [1]. Crucial to the success of these efforts is the development of methods and tools to verify the correctness of these designs. This verification though is complicated by the fact that genetic circuit components are inherently noisy making their behavior asynchronous, analog, and stochastic in nature [2]. Therefore, rather than definite results, researchers are often interested in the probability of the system reaching a given state within a certain amount of time. Usually, this involves simulating the system to produce some time series data and analyzing this data to discern the state probabilities. However, as the complexity of models of genetic circuits grow, it becomes more difficult for researchers to reason about the different states by looking only at time series simulation results of the models. To address this problem, techniques from the formal verification community, such as stochastic model checking, can be leveraged [3, 4]. This tutorial will introduce the basic biology concepts needed to understand genetic circuits, as well as, the modeling and analysis techniques currently being employed. Finally, it will give insight into how formal verification techniques can be applied to genetic circuits

Computational Modeling, Formal Analysis, and Tools for Systems Biology.

As the amount of biological data in the public domain grows, so does the range of modeling and analysis techniques employed in systems biology. In recent years, a number of theoretical computer science developments have enabled modeling methodology to keep pace. The growing interest in systems biology in executable models and their analysis has necessitated the borrowing of terms and methods from computer science, such as formal analysis, model checking, static analysis, and runtime verification. Here, we discuss the most important and exciting computational methods and tools currently available to systems biologists. We believe that a deeper understanding of the concepts and theory highlighted in this review will produce better software practice, improved investigation of complex biological processes, and even new ideas and better feedback into computer science