Types for BioAmbients

The BioAmbients calculus is a process algebra suitable for representing compartmentalization, molecular localization and movements between compartments. In this paper we enrich this calculus with a static type system classifying each ambient with group types specifying the kind of compartments in which the ambient can stay. The type system ensures that, in a well-typed process, ambients cannot be nested in a way that violates the type hierarchy. Exploiting the information given by the group types, we also extend the operational semantics of BioAmbients with rules signalling errors that may derive from undesired ambients' moves (i.e. merging incompatible tissues). Thus, the signal of errors can help the modeller to detect and locate unwanted situations that may arise in a biological system, and give practical hints on how to avoid the undesired behaviour

A Process Calculus for Molecular Interaction Maps

We present the MIM calculus, a modeling formalism with a strong biological basis, which provides biologically-meaningful operators for representing the interaction capabilities of molecular species. The operators of the calculus are inspired by the reaction symbols used in Molecular Interaction Maps (MIMs), a diagrammatic notation used by biologists. Models of the calculus can be easily derived from MIM diagrams, for which an unambiguous and executable interpretation is thus obtained. We give a formal definition of the syntax and semantics of the MIM calculus, and we study properties of the formalism. A case study is also presented to show the use of the calculus for modeling biomolecular networks.Comment: 15 pages; 8 figures; To be published on EPTCS, proceedings of MeCBIC 200

Stochastic Calculus of Wrapped Compartments

The Calculus of Wrapped Compartments (CWC) is a variant of the Calculus of Looping Sequences (CLS). While keeping the same expressiveness, CWC strongly simplifies the development of automatic tools for the analysis of biological systems. The main simplification consists in the removal of the sequencing operator, thus lightening the formal treatment of the patterns to be matched in a term (whose complexity in CLS is strongly affected by the variables matching in the sequences). We define a stochastic semantics for this new calculus. As an application we model the interaction between macrophages and apoptotic neutrophils and a mechanism of gene regulation in E.Coli

A Type System for a Stochastic CLS

The Stochastic Calculus of Looping Sequences is suitable to describe the evolution of microbiological systems, taking into account the speed of the described activities. We propose a type system for this calculus that models how the presence of positive and negative catalysers can modify these speeds. We claim that types are the right abstraction in order to represent the interaction between elements without specifying exactly the element positions. Our claim is supported through an example modelling the lactose operon

A Calculus of Looping Sequences with Local Rules

In this paper we present a variant of the Calculus of Looping Sequences (CLS for short) with global and local rewrite rules. While global rules, as in CLS, are applied anywhere in a given term, local rules can only be applied in the compartment on which they are defined. Local rules are dynamic: they can be added, moved and erased. We enrich the new calculus with a parallel semantics where a reduction step is lead by any number of global and local rules that could be performed in parallel. A type system is developed to enforce the property that a compartment must contain only local rules with specific features. As a running example we model some interactions happening in a cell starting from its nucleus and moving towards its mitochondria.Comment: In Proceedings DCM 2011, arXiv:1207.682

Process algebra modelling styles for biomolecular processes

We investigate how biomolecular processes are modelled in process algebras, focussing on chemical reactions. We consider various modelling styles and how design decisions made in the definition of the process algebra have an impact on how a modelling style can be applied. Our goal is to highlight the often implicit choices that modellers make in choosing a formalism, and illustrate, through the use of examples, how this can affect expressability as well as the type and complexity of the analysis that can be performed

Towards modular verification of pathways: fairness and assumptions

Modular verification is a technique used to face the state explosion problem often encountered in the verification of properties of complex systems such as concurrent interactive systems. The modular approach is based on the observation that properties of interest often concern a rather small portion of the system. As a consequence, reduced models can be constructed which approximate the overall system behaviour thus allowing more efficient verification. Biochemical pathways can be seen as complex concurrent interactive systems. Consequently, verification of their properties is often computationally very expensive and could take advantage of the modular approach. In this paper we report preliminary results on the development of a modular verification framework for biochemical pathways. We view biochemical pathways as concurrent systems of reactions competing for molecular resources. A modular verification technique could be based on reduced models containing only reactions involving molecular resources of interest. For a proper description of the system behaviour we argue that it is essential to consider a suitable notion of fairness, which is a well-established notion in concurrency theory but novel in the field of pathway modelling. We propose a modelling approach that includes fairness and we identify the assumptions under which verification of properties can be done in a modular way. We prove the correctness of the approach and demonstrate it on the model of the EGF receptor-induced MAP kinase cascade by Schoeberl et al.Comment: In Proceedings MeCBIC 2012, arXiv:1211.347

A Minimal OO Calculus for Modelling Biological Systems

In this paper we present a minimal object oriented core calculus for modelling the biological notion of type that arises from biological ontologies in formalisms based on term rewriting. This calculus implements encapsulation, method invocation, subtyping and a simple formof overriding inheritance, and it is applicable to models designed in the most popular term-rewriting formalisms. The classes implemented in a formalism can be used in several models, like programming libraries.Comment: In Proceedings CompMod 2011, arXiv:1109.104

On Designing Multicore-Aware Simulators for Systems Biology Endowed with OnLine Statistics

The paper arguments are on enabling methodologies for the design of a fully parallel, online, interactive tool aiming to support the bioinformatics scientists .In particular, the features of these methodologies, supported by the FastFlow parallel programming framework, are shown on a simulation tool to perform the modeling, the tuning, and the sensitivity analysis of stochastic biological models. A stochastic simulation needs thousands of independent simulation trajectories turning into big data that should be analysed by statistic and data mining tools. In the considered approach the two stages are pipelined in such a way that the simulation stage streams out the partial results of all simulation trajectories to the analysis stage that immediately produces a partial result. The simulation-analysis workflow is validated for performance and effectiveness of the online analysis in capturing biological systems behavior on a multicore platform and representative proof-of-concept biological systems. The exploited methodologies include pattern-based parallel programming and data streaming that provide key features to the software designers such as performance portability and efficient in-memory (big) data management and movement. Two paradigmatic classes of biological systems exhibiting multistable and oscillatory behavior are used as a testbed