5,337 research outputs found
Stochastic Simulation of Process Calculi for Biology
Biological systems typically involve large numbers of components with
complex, highly parallel interactions and intrinsic stochasticity. To model
this complexity, numerous programming languages based on process calculi have
been developed, many of which are expressive enough to generate unbounded
numbers of molecular species and reactions. As a result of this expressiveness,
such calculi cannot rely on standard reaction-based simulation methods, which
require fixed numbers of species and reactions. Rather than implementing custom
stochastic simulation algorithms for each process calculus, we propose to use a
generic abstract machine that can be instantiated to a range of process calculi
and a range of reaction-based simulation algorithms. The abstract machine
functions as a just-in-time compiler, which dynamically updates the set of
possible reactions and chooses the next reaction in an iterative cycle. In this
short paper we give a brief summary of the generic abstract machine, and show
how it can be instantiated with the stochastic simulation algorithm known as
Gillespie's Direct Method. We also discuss the wider implications of such an
abstract machine, and outline how it can be used to simulate multiple calculi
simultaneously within a common framework.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005
Compositionality, stochasticity and cooperativity in dynamic models of gene regulation
We present an approach for constructing dynamic models for the simulation of
gene regulatory networks from simple computational elements. Each element is
called a ``gene gate'' and defines an input/output-relationship corresponding
to the binding and production of transcription factors. The proposed reaction
kinetics of the gene gates can be mapped onto stochastic processes and the
standard ode-description. While the ode-approach requires fixing the system's
topology before its correct implementation, expressing them in stochastic
pi-calculus leads to a fully compositional scheme: network elements become
autonomous and only the input/output relationships fix their wiring. The
modularity of our approach allows to pass easily from a basic first-level
description to refined models which capture more details of the biological
system. As an illustrative application we present the stochastic repressilator,
an artificial cellular clock, which oscillates readily without any cooperative
effects.Comment: 15 pages, 8 figures. Accepted by the HFSP journal (13/09/07
Model checking probabilistic and stochastic extensions of the pi-calculus
We present an implementation of model checking for probabilistic and stochastic extensions of the pi-calculus, a process algebra which supports modelling of concurrency and mobility. Formal verification techniques for such extensions have clear applications in several domains, including mobile ad-hoc network protocols, probabilistic security protocols and biological pathways. Despite this, no implementation of automated verification exists. Building upon the pi-calculus model checker MMC, we first show an automated procedure for constructing the underlying semantic model of a probabilistic or stochastic pi-calculus process. This can then be verified using existing probabilistic model checkers such as PRISM. Secondly, we demonstrate how for processes of a specific structure a more efficient, compositional approach is applicable, which uses our extension of MMC on each parallel component of the system and then translates the results into a high-level modular description for the PRISM tool. The feasibility of our techniques is demonstrated through a number of case studies from the pi-calculus literature
Parallel BioScape: A Stochastic and Parallel Language for Mobile and Spatial Interactions
BioScape is a concurrent language motivated by the biological landscapes
found at the interface of biology and biomaterials. It has been motivated by
the need to model antibacterial surfaces, biofilm formation, and the effect of
DNAse in treating and preventing biofilm infections. As its predecessor, SPiM,
BioScape has a sequential semantics based on Gillespie's algorithm, and its
implementation does not scale beyond 1000 agents. However, in order to model
larger and more realistic systems, a semantics that may take advantage of the
new multi-core and GPU architectures is needed. This motivates the introduction
of parallel semantics, which is the contribution of this paper: Parallel
BioScape, an extension with fully parallel semantics.Comment: In Proceedings MeCBIC 2012, arXiv:1211.347
Abstract Interpretation for Probabilistic Termination of Biological Systems
In a previous paper the authors applied the Abstract Interpretation approach
for approximating the probabilistic semantics of biological systems, modeled
specifically using the Chemical Ground Form calculus. The methodology is based
on the idea of representing a set of experiments, which differ only for the
initial concentrations, by abstracting the multiplicity of reagents present in
a solution, using intervals. In this paper, we refine the approach in order to
address probabilistic termination properties. More in details, we introduce a
refinement of the abstract LTS semantics and we abstract the probabilistic
semantics using a variant of Interval Markov Chains. The abstract probabilistic
model safely approximates a set of concrete experiments and reports
conservative lower and upper bounds for probabilistic termination
Computational Modeling for the Activation Cycle of G-proteins by G-protein-coupled Receptors
In this paper, we survey five different computational modeling methods. For
comparison, we use the activation cycle of G-proteins that regulate cellular
signaling events downstream of G-protein-coupled receptors (GPCRs) as a driving
example. Starting from an existing Ordinary Differential Equations (ODEs)
model, we implement the G-protein cycle in the stochastic Pi-calculus using
SPiM, as Petri-nets using Cell Illustrator, in the Kappa Language using
Cellucidate, and in Bio-PEPA using the Bio-PEPA eclipse plug in. We also
provide a high-level notation to abstract away from communication primitives
that may be unfamiliar to the average biologist, and we show how to translate
high-level programs into stochastic Pi-calculus processes and chemical
reactions.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005
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
Flux Analysis in Process Models via Causality
We present an approach for flux analysis in process algebra models of
biological systems. We perceive flux as the flow of resources in stochastic
simulations. We resort to an established correspondence between event
structures, a broadly recognised model of concurrency, and state transitions of
process models, seen as Petri nets. We show that we can this way extract the
causal resource dependencies in simulations between individual state
transitions as partial orders of events. We propose transformations on the
partial orders that provide means for further analysis, and introduce a
software tool, which implements these ideas. By means of an example of a
published model of the Rho GTP-binding proteins, we argue that this approach
can provide the substitute for flux analysis techniques on ordinary
differential equation models within the stochastic setting of process algebras
On Designing Multicore-aware Simulators for Biological Systems
The stochastic simulation of biological systems is an increasingly popular
technique in bioinformatics. It often is an enlightening technique, which may
however result in being computational expensive. We discuss the main
opportunities to speed it up on multi-core platforms, which pose new challenges
for parallelisation techniques. These opportunities are developed in two
general families of solutions involving both the single simulation and a bulk
of independent simulations (either replicas of derived from parameter sweep).
Proposed solutions are tested on the parallelisation of the CWC simulator
(Calculus of Wrapped Compartments) that is carried out according to proposed
solutions by way of the FastFlow programming framework making possible fast
development and efficient execution on multi-cores.Comment: 19 pages + cover pag
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