Simulating bacterial transcription and translation in a stochastic pi-calculus

International audienceStochastic simulation of genetic networks based on models in the stochastic pi-calculus is a promising recent approach. This paper contributes an extensible model of the central mechanisms of gene ex- pression i.e. transcription and translation, at the prototypical instance of bacteria. We reach extensibility through object-oriented abstractions, that are expressible in a stochastic π-calculus with pattern guarded inputs. We illustrate our generic model by simulating the effect of translational bursting in bacterial gene expression

Gene Regulation in the Pi Calculus: Simulating Cooperativity at the Lambda Switch

Part of the Lecture Notes in Computer Science book series (LNCS, volume 4230).Also part of the Lecture Notes in Bioinformatics book sub series (volume 4230).International audienceWe propose to model the dynamics of gene regulatory networks as concurrent processes in the stochastic pi calculus. As a first case study, we show how to express the control of transcription initiation at the lambda switch, a prototypical example where cooperative enhancement is crucial. This requires concurrent programming techniques that are new to systems biology, and necessitates stochastic parameters that we derive from the literature. We test all components of our model by exhaustive stochastic simulations. A comparison with previous results reported in the literature, experimental and simulation based, confirms the appropriateness of our modeling approach

Cellular modelling using P systems and process algebra.

In this paper various molecular chemical interactions are modelled under different computational paradigms. P systems and -calculus are used to describe intra-cellular reactions like protein-protein interactions and gene regulation control

Theoretical basis of the community effect in development

Peer reviewedPublisher PD

Rule-based Modeling of Transcriptional Attenuation at the Tryptophan Operon

Transcriptional attenuation at E.coli\u27s tryptophan operon is a prime example of RNA-mediated gene regulation. In this paper, we present a discrete stochastic model for this phenomenon based on chemical reactions. Our model is compact and intelligible, due to n-ary reactions (which preclude object-centric approaches) and to rule schemas that define finite sets of chemical reactions. Stochastic simulations with our model confirm results that were previously obtained by master equations or differential equations. In addition, our approach permits to reflect mutation experiments by simple model modifications, and to re-use model components for transcriptional attenuation in other genes and organisms

A Stochastic Pi Calculus for Concurrent Objects

International audienceWe present SpiCO, a new modeling and simulation language for system biology, based on the stochastic pi-calculus. SpiCO supports higher level modeling via multi-profile concurrent objects with static inheritance. We present a semantics for SpiCO in terms of continuous time Markov chains, and show how to compile SpiCO back into the biochemical stochastic pi-calculus while preserving semantics

06161 Abstracts Collection -- Simulation and Verification of Dynamic Systems

From 17.04.06 to 22.04.06, the Dagstuhl Seminar 06161 ``Simulation and Verification of Dynamic Systems\u27\u27 was held in the International Conference and Research Center (IBFI), Schloss Dagstuhl. During the seminar, several participants presented their current research, and ongoing work and open problems were discussed. Abstracts of the presentations given during the seminar as well as abstracts of seminar results and ideas are put together in this paper. The first section describes the seminar topics and goals in general. Links to extended abstracts or full papers are provided, if available

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 Stochastic Pi Calculus for Concurrent Objects

International audienceWe present SpiCO, a new modeling and simulation language for system biology, based on the stochastic pi-calculus. SpiCO supports higher level modeling via multi-profile concurrent objects with static inheritance. We present a semantics for SpiCO in terms of continuous time Markov chains, and show how to compile SpiCO back into the biochemical stochastic pi-calculus while preserving semantics

Infobiotics : computer-aided synthetic systems biology

Until very recently Systems Biology has, despite its stated goals, been too reductive in terms of the models being constructed and the methods used have been, on the one hand, unsuited for large scale adoption or integration of knowledge across scales, and on the other hand, too fragmented. The thesis of this dissertation is that better computational languages and seamlessly integrated tools are required by systems and synthetic biologists to enable them to meet the significant challenges involved in understanding life as it is, and by designing, modelling and manufacturing novel organisms, to understand life as it could be. We call this goal, where everything necessary to conduct model-driven investigations of cellular circuitry and emergent effects in populations of cells is available without significant context-switching, “one-pot” in silico synthetic systems biology in analogy to “one-pot” chemistry and “one-pot” biology. Our strategy is to increase the understandability and reusability of models and experiments, thereby avoiding unnecessary duplication of effort, with practical gains in the efficiency of delivering usable prototype models and systems. Key to this endeavour are graphical interfaces that assists novice users by hiding complexity of the underlying tools and limiting choices to only what is appropriate and useful, thus ensuring that the results of in silico experiments are consistent, comparable and reproducible. This dissertation describes the conception, software engineering and use of two novel software platforms for systems and synthetic biology: the Infobiotics Workbench for modelling, in silico experimentation and analysis of multi-cellular biological systems; and DNA Library Designer with the DNALD language for the compact programmatic specification of combinatorial DNA libraries, as the first stage of a DNA synthesis pipeline, enabling methodical exploration biological problem spaces. Infobiotics models are formalised as Lattice Population P systems, a novel framework for the specification of spatially-discrete and multi-compartmental rule-based models, imbued with a stochastic execution semantics. This framework was developed to meet the needs of real systems biology problems: hormone transport and signalling in the root of Arabidopsis thaliana, and quorum sensing in the pathogenic bacterium Pseudomonas aeruginosa. Our tools have also been used to prototype a novel synthetic biological system for pattern formation, that has been successfully implemented in vitro. Taken together these novel software platforms provide a complete toolchain, from design to wet-lab implementation, of synthetic biological circuits, enabling a step change in the scale of biological investigations that is orders of magnitude greater than could previously be performed in one in silico “pot”