External Control in Process Algebra for Systems Biology

A critical aspect in the modeling of biological systems is the description view point. On the one hand, the Stochastic \u3c0-calculus formalism provides an intuitive and compact representation from an internal perspective. On the other hand, other proposed languages such as Hybrid Automata and Stochastic Concurrent Constraint Programming introduce in the system description an external control and provide more structured models. This work aims at bridging the above discussed gap. In particular, we propose a different approach for the encoding of biological systems in Stochastic \u3c0-calculus in the direction of introducing an external control and comparing different formalisms. We show the effectiveness of our method on some examples

Investigating modularity in the analysis of process algebra models of biochemical systems

Compositionality is a key feature of process algebras which is often cited as one of their advantages as a modelling technique. It is certainly true that in biochemical systems, as in many other systems, model construction is made easier in a formalism which allows the problem to be tackled compositionally. In this paper we consider the extent to which the compositional structure which is inherent in process algebra models of biochemical systems can be exploited during model solution. In essence this means using the compositional structure to guide decomposed solution and analysis. Unfortunately the dynamic behaviour of biochemical systems exhibits strong interdependencies between the components of the model making decomposed solution a difficult task. Nevertheless we believe that if such decomposition based on process algebras could be established it would demonstrate substantial benefits for systems biology modelling. In this paper we present our preliminary investigations based on a case study of the pheromone pathway in yeast, modelling in the stochastic process algebra Bio-PEPA

Design and Development of Software Tools for Bio-PEPA

This paper surveys the design of software tools for the Bio-PEPA process algebra. Bio-PEPA is a high-level language for modelling biological systems such as metabolic pathways and other biochemical reaction networks. Through providing tools for this modelling language we hope to allow easier use of a range of simulators and model-checkers thereby freeing the modeller from the responsibility of developing a custom simulator for the problem of interest. Further, by providing mappings to a range of different analysis tools the Bio-PEPA language allows modellers to compare analysis results which have been computed using independent numerical analysers, which enhances the reliability and robustness of the results computed.

Overcoming the Newtonian Paradigm: The Unfinished Project of Theoretical Biology from a Schellingian Perspective

Defending Robert Rosen’s claim that in every confrontation between physics and biology it is physics that has always had to give ground, it is shown that many of the most important advances in mathematics and physics over the last two centuries have followed from Schelling’s demand for a new physics that could make the emergence of life intelligible. Consequently, while reductionism prevails in biology, many biophysicists are resolutely anti-reductionist. This history is used to identify and defend a fragmented but progressive tradition of anti-reductionist biomathematics. It is shown that the mathematicoephysico echemical morphology research program, the biosemiotics movement, and the relational biology of Rosen, although they have developed independently of each other, are built on and advance this antireductionist tradition of thought. It is suggested that understanding this history and its relationship to the broader history of post-Newtonian science could provide guidance for and justify both the integration of these strands and radically new work in post-reductionist biomathematics

Process Calculi Abstractions for Biology

Several approaches have been proposed to model biological systems by means of the formal techniques and tools available in computer science. To mention just a few of them, some representations are inspired by Petri Nets theory, and some other by stochastic processes. A most recent approach consists in interpreting the living entities as terms of process calculi where the behavior of the represented systems can be inferred by applying syntax-driven rules. A comprehensive picture of the state of the art of the process calculi approach to biological modeling is still missing. This paper goes in the direction of providing such a picture by presenting a comparative survey of the process calculi that have been used and proposed to describe the behavior of living entities. This is the preliminary version of a paper that was published in Algorithmic Bioprocesses. The original publication is available at http://www.springer.com/computer/foundations/book/978-3-540-88868-

Quantifying the implicit process flow abstraction in SBGN-PD diagrams with Bio-PEPA

For a long time biologists have used visual representations of biochemical networks to gain a quick overview of important structural properties. Recently SBGN, the Systems Biology Graphical Notation, has been developed to standardise the way in which such graphical maps are drawn in order to facilitate the exchange of information. Its qualitative Process Diagrams (SBGN-PD) are based on an implicit Process Flow Abstraction (PFA) that can also be used to construct quantitative representations, which can be used for automated analyses of the system. Here we explicitly describe the PFA that underpins SBGN-PD and define attributes for SBGN-PD glyphs that make it possible to capture the quantitative details of a biochemical reaction network. We implemented SBGNtext2BioPEPA, a tool that demonstrates how such quantitative details can be used to automatically generate working Bio-PEPA code from a textual representation of SBGN-PD that we developed. Bio-PEPA is a process algebra that was designed for implementing quantitative models of concurrent biochemical reaction systems. We use this approach to compute the expected delay between input and output using deterministic and stochastic simulations of the MAPK signal transduction cascade. The scheme developed here is general and can be easily adapted to other output formalisms

From Simple to Complex and Ultra-complex Systems:\ud A Paradigm Shift Towards Non-Abelian Systems Dynamics

Atoms, molecules, organisms distinguish layers of reality because of the causal links that govern their behavior, both horizontally (atom-atom, molecule-molecule, organism-organism) and vertically (atom-molecule-organism). This is the first intuition of the theory of levels. Even if the further development of the theory will require imposing a number of qualifications to this initial intuition, the idea of a series of entities organized on different levels of complexity will prove correct. Living systems as well as social systems and the human mind present features remarkably different from those characterizing non-living, simple physical and chemical systems. We propose that super-complexity requires at least four different categorical frameworks, provided by the theories of levels of reality, chronotopoids, (generalized) interactions, and anticipation

From Simple to Complex and Ultra-complex Systems:\ud A Paradigm Shift Towards Non-Abelian Systems Dynamics

Atoms, molecules, organisms distinguish layers of reality because of the causal links that govern their behavior, both horizontally (atom-atom, molecule-molecule, organism-organism) and vertically (atom-molecule-organism). This is the first intuition of the theory of levels. Even if the further development of the theory will require imposing a number of qualifications to this initial intuition, the idea of a series of entities organized on different levels of complexity will prove correct. Living systems as well as social systems and the human mind present features remarkably different from those characterizing non-living, simple physical and chemical systems. We propose that super-complexity requires at least four different categorical frameworks, provided by the theories of levels of reality, chronotopoids, (generalized) interactions, and anticipation

Entering the blackboard jungle: canonical dysfunction in conscious machines

The central paradigm of Artificial Intelligence is rapidly shifting toward biological models for both robotic devices and systems performing such critical tasks as network management and process control. Here we apply recent mathematical analysis of the necessary conditions for consciousness in humans in an attempt to gain some understanding of the likely canonical failure modes inherent to a broad class of global workspace/blackboard machines designed to emulate biological functions. Similar problems are likely to confront other possible architectures, although their mathematical description may be far less straightforward