A Process Algebraical Approach to Modelling Compartmentalized Biological Systems

This paper introduces Protein Calculus, a special modeling language designed for encoding and calculating the behaviors of compartmentilized biological systems. The formalism combines, in a unified framework, two successful computational paradigms - process algebras and membrane systems. The goal of Protein Calculus is to provide a formal tool for transforming collected information from in vivo experiments into coded definition of the different types of proteins, complexes of proteins, and membrane-organized systems of such entities. Using this encoded information as input, our calculus computes, in silico, the possible behaviors of a living system. This is the preliminary version of a paper that was published in Proceedings of International Conference of Computational Methods in Sciences and Engineering (ICCMSE), American Institute of Physics, AIP Proceedings, N 2: 642-646, 2007 (http://scitation.aip.org/dbt/dbt.jsp?KEY=APCPCS&Volume=963&Issue=2)

Formal Modeling of Connectionism using Concurrency Theory, an Approach Based on Automata and Model Checking

This paper illustrates a framework for applying formal methods techniques, which are symbolic in nature, to specifying and verifying neural networks, which are sub-symbolic in nature. The paper describes a communicating automata [Bowman & Gomez, 2006] model of neural networks. We also implement the model using timed automata [Alur & Dill, 1994] and then undertake a verification of these models using the model checker Uppaal [Pettersson, 2000] in order to evaluate the performance of learning algorithms. This paper also presents discussion of a number of broad issues concerning cognitive neuroscience and the debate as to whether symbolic processing or connectionism is a suitable representation of cognitive systems. Additionally, the issue of integrating symbolic techniques, such as formal methods, with complex neural networks is discussed. We then argue that symbolic verifications may give theoretically well-founded ways to evaluate and justify neural learning systems in the field of both theoretical research and real world applications

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

An introduction to Biomodel engineering, illustrated for signal transduction pathways

BioModel Engineering is the science of designing, constructing and analyzing computational models of biological systems. It is inspired by concepts from software engineering and computing science. This paper illustrates a major theme in BioModel Engineering, namely that identifying a quantitative model of a dynamic system means building the structure, finding an initial state, and parameter fitting. In our approach, the structure is obtained by piecewise construction of models from modular parts, the initial state is obtained by analysis of the structure and parameter fitting comprises determining the rate parameters of the kinetic equations. We illustrate this with an example in the area of intracellular signalling pathways

Stochastic Calculus of Wrapped Compartments

The Calculus of Wrapped Compartments (CWC) is a variant of the Calculus of Looping Sequences (CLS). While keeping the same expressiveness, CWC strongly simplifies the development of automatic tools for the analysis of biological systems. The main simplification consists in the removal of the sequencing operator, thus lightening the formal treatment of the patterns to be matched in a term (whose complexity in CLS is strongly affected by the variables matching in the sequences). We define a stochastic semantics for this new calculus. As an application we model the interaction between macrophages and apoptotic neutrophils and a mechanism of gene regulation in E.Coli

Verification of Spatial and Temporal Modalities in Biochemical Systems

AbstractBiochemical systems such as metabolic and signaling pathways tend to be arranged in a physical space: the product of one reaction must be in the right place to become the reactant for the subsequent reaction in the pathway. Moreover, in some cases, the behavior of the systems can depend on both, the location of the reactants as well as on the time needed for the reaction to occur. We address the problem of specifying and verifying properties of biochemical systems that exhibit both temporal and spatial modalities at the same time. For that, we use as specification language a fragment of intuitionistic linear logic with subexponentials (SELL). The subexponential signature allows us to capture the spatial relations among the different components of the system and the timed constraints for reactions to occur. We show that our framework is general enough to give a declarative semantics to P-Systems and we show that such logical characterization has a strong level of adequacy. Hence, derivations in SELL follow exactly the behavior of the modeled system