The tool Snoopy provides a unifying Petri net framework which has particularly many application scenarios in systems and synthetic biology. The framework consists of two levels: uncoloured and coloured. Each level comprises a family of related Petri net classes, sharing structure, but being specialized by their kinetic information. Petri nets of all net classes within one level can be converted into each other, while changing the level involves user-guided folding or automatic unfolding. Models can be hierarchically structured, allowing for the mastering of larger networks. Snoopy supports the simultaneous use of several Petri net classes; the graphical user interface adapts dynamically to the active one. Built-in animation and simulation (depending on the net class) are complemented by export to various analysis tools. Snoopy facilitates the extension by new Petri net classes thanks to its generic design.

Snoopy --- a unifying petri net tool

https://www.pure.ed.ac.uk/ws/files/7838519/mean_field_tutorial.pdf

Continuous approximation of collective system behaviour: A tutorial

We describe the Calculus of Looping Sequences (CLS) which is suitable for modeling microbiological systems and their evolution. We present two extensions, CLS with links (LCLS) and Stochastic CLS. LCLS simplifies the description of protein interaction at a lower level of abstraction, namely at the domain level. Stochastic CLS allows us to describe quantitative aspects of the modeled systems, such as the frequency of chemical reactions. As examples of application to real biological systems, we show the simulation of the activity of the lactose operon in E.coli and the quorum sensing process in P.aeruginosa, both described with Stochastic CLS.

/pdf/the-calculus-of-looping-sequences-4yvjch1w3s.pdf

The calculus of looping sequences

Motivation: Fabrication of synthetic biological systems is greatly enhanced by incorporating engineering design principles and techniques such as computer-aided design. To this end, the ongoing standardization of biological parts presents an opportunity to develop libraries of standard virtual parts in the form of mathematical models that can be combined to inform system design.

Results: We present an online Repository, populated with a collection of standardized models that can readily be recombined to model different biological systems using the inherent modularity support of the CellML 1.1 model exchange format. The applicability of this approach is demonstrated by modeling gold-medal winning iGEM machines.

Availability and Implementation: The Repository is available online as part of http://models.cellml.org. We hope to stimulate the worldwide community to reuse and extend the models therein, and contribute to the Repository of Standard Virtual Parts thus founded. Systems Model architecture information for the Systems Model described here, along with an additional example and a tutorial, is also available as Supplementary information. The example Systems Model from this manuscript can be found at http://models.cellml.org/workspace/bugbuster. The Template models used in the example can be found at http://models.cellml.org/workspace/SVP_Templates200906.

Contact: m.cooling@auckland.ac.nz

Supplementary information:Supplementary data are available at Bioinformatics online.

Standard virtual biological parts

Rule-based modelling has already proved to be successful for taming the combinatorial complexity, typical of cellular signalling networks, caused by the combination of physical protein-protein interactions and modifications that generate astronomical numbers of distinct molecular species. However, traditional rule-based approaches, based on an unstructured space of agents and rules, remain susceptible to other combinatorial explosions caused by mutated and/or splice variant agents, that share most but not all of their rules with their wild-type counterparts; and by drugs, which must be clearly distinguished from physiological ligands.

In this paper, we define a syntactic extension of Kappa, an established rule-based modelling platform, that enables the expression of a structured space of agents and rules that allows us to express mutated agents, splice variants, families of related proteins and ligand/drug interventions uniformly. This also enables a mode of model construction where, starting from the current consensus model, we attempt to reproduce in numero the mutational--and more generally the ligand/drug perturbational--analyses that were used in the process of inferring those pathways in the first place.

/pdf/rule-based-modelling-and-model-perturbation-4nypla6b06.pdf

Rule-Based Modelling and Model Perturbation

We present Spatial P systems, a variant of P systems which embodies the concept of space and position inside a membrane. Objects in membranes are associated with positions. Rules specify, in the usual way, the objects which are consumed and the ones which are produced; in addition, they can specify the positions of the produced objects. Objects belong to two different sets: the set of ordinary objects and the set of mutually exclusive objects. Every position inside a membrane can accommodate an arbitrary number of ordinary objects, but at most one mutually exclusive object. We prove that Spatial P systems are universal even if only non-cooperating rules are allowed. We also show how Spatial P systems can be used to model the evolution of populations in presence of geographical separations.

http://www.cs.unicam.it/tesei/updown/Barbuti2010.pdf

Spatial P systems

The Calculus of Looping Sequences (CLS) enables the description of biological systems and of their evolution. This paper presents the Spatial CLS, an extension of CLS that allows the description of the position of biological elements, and of the space they take up in a 2D/3D space. The elements may move autonomously during the passage of time, and may interact when constraints on their positions are satisfied. The space occupied by each element is modeled as a hard sphere, hence space conflicts may arise during system evolution. These conflicts are resolved by an appropriate algorithm, which rearranges the position of the elements by assuming that they push each other when they are too close. Moreover, rewrite rules are endowed with a parameter describing their reaction rate. The aim of Spatial CLS is to enable a more accurate description of those biological processes whose behaviour depends on the exact position of the elements. As example applications of the calculus, we present a model of cell proliferation, and a model of the quorum sensing process in Pseudomonas aeruginosa.

Spatial Calculus of Looping Sequences

http://pages.di.unipi.it/milazzo/papers/SpatialCLS-fbtc08.pdf

Giovanni Pardini

Papers

The calculus of looping sequences

Spatial P systems

Spatial Calculus of Looping Sequences

Spatial Calculus of Looping Sequences

Spatial Calculus of Looping Sequences