A Global Occurrence Counting Analysis for Brane Calculi

We propose a polynomial static analysis for Brane Calculi, based on Abstract Interpretation techniques. The analysis provides a description of the possible hierarchical structure of membranes and of the processes possibly associated to each membrane, together with global occurrence counting information. Our analysis can be applied in the biological setting to investigate systems in which the information on the number of membranes occurring in the system plays a crucial role

A static analysis for Brane Calculi providing global occurrence counting information

In this paper we propose a static analysis for Brane Calculi [1], based on Abstract Interpretation [2] techniques. Our analysis statically approximates the dynamic behaviour of Brane systems, by providing a description of the possible hierarchical structure of membranes and of the processes possibly associated to each membrane, together with global occurrence counting information. Our analysis can be computed in polynomial time. We apply it to investigate several biological systems in which occurrence counting information plays a crucial role. In particular, our case study concerns the formation of the haemoglobin polymer in presence of alterations and investigate the influence that such alterations have on the ability of the haemoglobin polymer to bind oxygen molecules

A flat process calculus for nested membrane interactions

The link-calculus has been recently proposed as a process calculus for representing interactions that are open (i.e. that the number of processes may vary), and multiparty (i.e. that may involve more than two processes). Here, we apply the link-calculus for expressing, possibly hierarchical and non dyadic, biological interactions. In particular, we provide a natural encoding of Cardelli's Brane calculus, a compartment-based calculus, introduced to model the behaviour of nested membranes. Notably, the link-calculus is at, but we can model membranes just as special processes taking part in the biological reaction. Moreover, we give evidence that the link-calculus allows one to directly model biological phenomena at the more appropriate level of abstraction

Mutual Mobile Membranes with Timers

A feature of current membrane systems is the fact that objects and membranes are persistent. However, this is not true in the real world. In fact, cells and intracellular proteins have a well-defined lifetime. Inspired from these biological facts, we define a model of systems of mobile membranes in which each membrane and each object has a timer representing their lifetime. We show that systems of mutual mobile membranes with and without timers have the same computational power. An encoding of timed safe mobile ambients into systems of mutual mobile membranes with timers offers a relationship between two formalisms used in describing biological systems

Stochastic models for the in silico simulation of synaptic processes

Background: Research in life sciences is benefiting from a large availability of formal description techniques and analysis methodologies. These allow both the phenomena investigated to be precisely modeled and virtual experiments to be performed in silico. Such experiments may result in easier, faster, and satisfying approximations of their in vitro/vivo counterparts. A promising approach is represented by the study of biological phenomena as a collection of interactive entities through process calculi equipped with stochastic semantics. These exploit formal grounds developed in the theory of concurrency in computer science, account for the not continuous, nor discrete, nature of many phenomena, enjoy nice compositional properties and allow for simulations that have been demonstrated to be coherent with data in literature. Results: Motivated by the need to address some aspects of the functioning of neural synapses, we have developed one such model for synaptic processes in the calyx of Held, which is a glutamatergic synapse in the auditory pathway of the mammalia. We have developed such a stochastic model starting from existing kinetic models based on ODEs of some sub-components of the synapse, integrating other data from literature and making some assumptions about non-fully understood processes. Experiments have confirmed the coherence of our model with known biological data, also validating the assumptions made. Our model overcomes some limitations of the kinetic ones and, to our knowledge, represents the first model of synaptic processes based on process calculi. The compositionality of the approach has permitted us to independently focus on tuning the models of the pre- and post- synaptic traits, and then to naturally connect them, by dealing with “interface” issues. Furthermore, we have improved the expressiveness of the model, e.g. by embedding easy control of element concentration time courses. Sensitivity analysis over several parameters of the model has provided results that may help clarify the dynamics of synaptic transmission, while experiments with the model of the complete synapse seem worth explaining short-term plasticity mechanisms. Conclusions: Specific presynaptic and postsynaptic mechanisms can be further analysed under various conditions, for instance by studying the presynaptic behaviour under repeated activations. The level of details of the description can be refined, for instance by further specifying the neurotransmitter generation and release steps. Taking advantage of the compositionality of the approach, an enhanced model could then be composed with other neural models, designed within the same framework, in order to obtain a more detailed and comprehensive model. In the long term, we are interested, in particular, in addressing models of synaptic plasticity, i.e. activity dependent mechanisms, which are the bases of memory and learning processes. More on the computer science side, we plan to follow some directions to improve the underlying computational model and the linguistic primitives it provides as suggested by the experiments carried out, e.g. by introducing a suitable notion of (spatial) locality

A Flat Process Calculus for Nested Membrane Interactions

The link-calculus has been recently proposed as a process calculus for representing interactions that are open (i.e., that the number of processes may vary), and multiparty (i.e., that may involve more than two processes). Here, we apply the link-calculus for expressing, possibly hierarchical and non dyadic, biological interactions. In particular, we provide a natural encoding of Cardelli's Brane calculus, a compartment-based calculus, introduced to model the behaviour of nested membranes. Notably, the link-calculus is flat, but we can model membranes just as special processes taking part in the biological reaction. Moreover, we give evidence that the link-calculus allows one to directly model biological phenomena at the more appropriate level of abstraction

Causal static analysis for Brane Calculi

We present here a static analysis, based on Abstract Interpretation, obtained by defining an abstract version of the causal semantics for the Mate/Bud/Drip (MBD) version of Brane Calculi, proposed by Busi. Our analysis statically approximates the dynamic behaviour of MBD systems. More precisely, the analysis is able to describe the essential behaviour of the represented membranes, in terms of their possible interactions. Furthermore, our analysis is able to statically capture the possible causal dependencies among interactions, whose determination can be exploited to better understand the modelled biological phenomena. Finally, we apply our analysis to an abstract specification of the receptor-mediated endocytosis mechanism

BioAmbients: an abstraction for biological compartments

AbstractBiomolecular systems, composed of networks of proteins, underlie the major functions of living cells. Compartments are key to the organization of such systems. We have previously developed an abstraction for biomolecular systems using the π-calculus process algebra, which successfully handled their molecular and biochemical aspects, but provided only a limited solution for representing compartments. In this work, we extend this abstraction to handle compartments. We are motivated by the ambient calculus, a process algebra for the specification of process location and movement through computational domains. We present the BioAmbients calculus, which is suitable for representing various aspects of molecular localization and compartmentalization, including the movement of molecules between compartments, the dynamic rearrangement of cellular compartments, and the interaction between molecules in a compartmentalized setting. Guided by the calculus, we adapt the BioSpi simulation system, to provide an extended modular framework for molecular and cellular compartmentalization, and we use it to model and study a complex multi-cellular system