Dynamic simulation of regulatory networks using SQUAD

BACKGROUND: The ambition of most molecular biologists is the understanding of the intricate network of molecular interactions that control biological systems. As scientists uncover the components and the connectivity of these networks, it becomes possible to study their dynamical behavior as a whole and discover what is the specific role of each of their components. Since the behavior of a network is by no means intuitive, it becomes necessary to use computational models to understand its behavior and to be able to make predictions about it. Unfortunately, most current computational models describe small networks due to the scarcity of kinetic data available. To overcome this problem, we previously published a methodology to convert a signaling network into a dynamical system, even in the total absence of kinetic information. In this paper we present a software implementation of such methodology. RESULTS: We developed SQUAD, a software for the dynamic simulation of signaling networks using the standardized qualitative dynamical systems approach. SQUAD converts the network into a discrete dynamical system, and it uses a binary decision diagram algorithm to identify all the steady states of the system. Then, the software creates a continuous dynamical system and localizes its steady states which are located near the steady states of the discrete system. The software permits to make simulations on the continuous system, allowing for the modification of several parameters. Importantly, SQUAD includes a framework for perturbing networks in a manner similar to what is performed in experimental laboratory protocols, for example by activating receptors or knocking out molecular components. Using this software we have been able to successfully reproduce the behavior of the regulatory network implicated in T-helper cell differentiation. CONCLUSION: The simulation of regulatory networks aims at predicting the behavior of a whole system when subject to stimuli, such as drugs, or determine the role of specific components within the network. The predictions can then be used to interpret and/or drive laboratory experiments. SQUAD provides a user-friendly graphical interface, accessible to both computational and experimental biologists for the fast qualitative simulation of large regulatory networks for which kinetic data is not necessarily available

M\'ethodologie de mod\'elisation et d'impl\'ementation d'adaptateurs spatio-temporels

The re-use of pre-designed blocks is a well-known concept of the software development. This technique has been applied to System-on-Chip (SoC) design whose complexity and heterogeneity are growing. The re-use is made thanks to high level components, called virtual components (IP), available in more or less flexible forms. These components are dedicated blocks: digital signal processing (DCT, FFT), telecommunications (Viterbi, TurboCodes),... These blocks rest on a model of fixed architecture with very few degrees of personalization. This rigidity is particularly true for the communication interface whose orders of acquisition and production of data, the temporal behavior and protocols of exchanges are fixed. The successful integration of such an IP requires that the designer (1) synchronizes the components (2) converts the protocols between "incompatible" blocks (3) temporizes the data to guarantee the temporal constraints and the order of the data. This phase remains however very manual and source of errors. Our approach proposes a formal modeling, based on an original Ressource Compatibility Graph. The synthesis flow is based on a set of transformations of the initial graph to lead to an interface architecture allowing the space-time adaptation of the data exchanges between several components

Input-output Conformance Testing for Channel-based Service Connectors

Service-based systems are software systems composed of autonomous components or services provided by different vendors, deployed on remote machines and accessible through the web. One of the challenges of modern software engineering is to ensure that such a system behaves as intended by its designer. The Reo coordination language is an extensible notation for formal modeling and execution of service compositions. Services that have no prior knowledge about each other communicate through advanced channel connectors which guarantee that each participant, service or client, receives the right data at the right time. Each channel is a binary relation that imposes synchronization and data constraints on input and output messages. Furthermore, channels are composed together to realize arbitrarily complex behavioral protocols. During this process, a designer may introduce errors into the connector model or the code for their execution, and thus affect the behavior of a composed service. In this paper, we present an approach for model-based testing of coordination protocols designed in Reo. Our approach is based on the input-output conformance (ioco) testing theory and exploits the mapping of automata-based semantic models for Reo to equivalent process algebra specifications

Port Protocols for Deadlock-Freedom of Component Systems

In component-based development, approaches for property verification exist that avoid building the global system behavior of the component model. Typically, these approaches rely on the analysis of the local behavior of fixed sized subsystems of components. In our approach, we want to avoid not only the analysis of the global behavior but also of the local behaviors of the components. Instead, we consider very small parts of the local behaviors called port protocols that suffice to verify properties.Comment: In Proceedings ICE 2010, arXiv:1010.530

Components Interoperability through Mediating Connector Patterns

A key objective for ubiquitous environments is to enable system interoperability between system's components that are highly heterogeneous. In particular, the challenge is to embed in the system architecture the necessary support to cope with behavioral diversity in order to allow components to coordinate and communicate. The continuously evolving environment further asks for an automated and on-the-fly approach. In this paper we present the design building blocks for the dynamic and on-the-fly interoperability between heterogeneous components. Specifically, we describe an Architectural Pattern called Mediating Connector, that is the key enabler for communication. In addition, we present a set of Basic Mediator Patterns, that describe the basic mismatches which can occur when components try to interact, and their corresponding solutions.Comment: In Proceedings WCSI 2010, arXiv:1010.233