A case study in model-driven synthetic biology

We report on a case study in synthetic biology, demonstrating the modeldriven design of a self-powering electrochemical biosensor. An essential result of the design process is a general template of a biosensor, which can be instantiated to be adapted to specific pollutants. This template represents a gene expression network extended by metabolic activity. We illustrate the model-based analysis of this template using qualitative, stochastic and continuous Petri nets and related analysis techniques, contributing to a reliable and robust design

On functional module detection in metabolic networks

Functional modules of metabolic networks are essential for understanding the metabolism of an organism as a whole. With the vast amount of experimental data and the construction of complex and large-scale, often genome-wide, models, the computer-aided identification of functional modules becomes more and more important. Since steady states play a key role in biology, many methods have been developed in that context, for example, elementary flux modes, extreme pathways, transition invariants and place invariants. Metabolic networks can be studied also from the point of view of graph theory, and algorithms for graph decomposition have been applied for the identification of functional modules. A prominent and currently intensively discussed field of methods in graph theory addresses the Q-modularity. In this paper, we recall known concepts of module detection based on the steady-state assumption, focusing on transition-invariants (elementary modes) and their computation as minimal solutions of systems of Diophantine equations. We present the Fourier-Motzkin algorithm in detail. Afterwards, we introduce the Q-modularity as an example for a useful non-steady-state method and its application to metabolic networks. To illustrate and discuss the concepts of invariants and Q-modularity, we apply a part of the central carbon metabolism in potato tubers (Solanum tuberosum) as running example. The intention of the paper is to give a compact presentation of known steady-state concepts from a graph-theoretical viewpoint in the context of network decomposition and reduction and to introduce the application of Q-modularity to metabolic Petri net models

Abridged Petri Nets

A new graphical framework, Abridged Petri Nets (APNs) is introduced for bottom-up modeling of complex stochastic systems. APNs are similar to Stochastic Petri Nets (SPNs) in as much as they both rely on component-based representation of system state space, in contrast to Markov chains that explicitly model the states of an entire system. In both frameworks, so-called tokens (denoted as small circles) represent individual entities comprising the system; however, SPN graphs contain two distinct types of nodes (called places and transitions) with transitions serving the purpose of routing tokens among places. As a result, a pair of place nodes in SPNs can be linked to each other only via a transient stop, a transition node. In contrast, APN graphs link place nodes directly by arcs (transitions), similar to state space diagrams for Markov chains, and separate transition nodes are not needed. Tokens in APN are distinct and have labels that can assume both discrete values ("colors") and continuous values ("ages"), both of which can change during simulation. Component interactions are modeled in APNs using triggers, which are either inhibitors or enablers (the inhibitors' opposites). Hierarchical construction of APNs rely on using stacks (layers) of submodels with automatically matching color policies. As a result, APNs provide at least the same modeling power as SPNs, but, as demonstrated by means of several examples, the resulting models are often more compact and transparent, therefore facilitating more efficient performance evaluation of complex systems.Comment: 17 figure

Integration of a failure monitoring within a hybrid dynamic simulation environment

The complexity and the size of the industrial chemical processes induce the monitoring of a growing number of process variables. Their knowledge is generally based on the measurements of system variables and on the physico-chemical models of the process. Nevertheless this information is imprecise because of process and measurement noise. So the research ways aim at developing new and more powerful techniques for the detection of process fault. In this work, we present a method for the fault detection based on the comparison between the real system and the reference model evolution generated by the extended Kalman filter. The reference model is simulated by the dynamic hybrid simulator, PrODHyS. It is a general object-oriented environment which provides common and reusable components designed for the development and the management of dynamic simulation of industrial systems. The use of this method is illustrated through a didactic example relating to the field of Chemical Process System Engineering

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-

Representing Conversations for Scalable Overhearing

Open distributed multi-agent systems are gaining interest in the academic community and in industry. In such open settings, agents are often coordinated using standardized agent conversation protocols. The representation of such protocols (for analysis, validation, monitoring, etc) is an important aspect of multi-agent applications. Recently, Petri nets have been shown to be an interesting approach to such representation, and radically different approaches using Petri nets have been proposed. However, their relative strengths and weaknesses have not been examined. Moreover, their scalability and suitability for different tasks have not been addressed. This paper addresses both these challenges. First, we analyze existing Petri net representations in terms of their scalability and appropriateness for overhearing, an important task in monitoring open multi-agent systems. Then, building on the insights gained, we introduce a novel representation using Colored Petri nets that explicitly represent legal joint conversation states and messages. This representation approach offers significant improvements in scalability and is particularly suitable for overhearing. Furthermore, we show that this new representation offers a comprehensive coverage of all conversation features of FIPA conversation standards. We also present a procedure for transforming AUML conversation protocol diagrams (a standard human-readable representation), to our Colored Petri net representation