7,608 research outputs found
Analysis of signalling pathways using the prism model checker
We describe a new modelling and analysis approach for signal
transduction networks in the presence of incomplete data. We illustrate
the approach with an example, the RKIP inhibited ERK pathway
[1]. Our models are based on high level descriptions of continuous time
Markov chains: reactions are modelled as synchronous processes and concentrations
are modelled by discrete, abstract quantities. The main advantage
of our approach is that using a (continuous time) stochastic logic
and the PRISM model checker, we can perform quantitative analysis of
queries such as if a concentration reaches a certain level, will it remain at
that level thereafter? We also perform standard simulations and compare
our results with a traditional ordinary differential equation model. An
interesting result is that for the example pathway, only a small number
of discrete data values is required to render the simulations practically
indistinguishable
Petri nets for systems and synthetic biology
We give a description of a Petri net-based framework for
modelling and analysing biochemical pathways, which uni¯es the qualita-
tive, stochastic and continuous paradigms. Each perspective adds its con-
tribution to the understanding of the system, thus the three approaches
do not compete, but complement each other. We illustrate our approach
by applying it to an extended model of the three stage cascade, which
forms the core of the ERK signal transduction pathway. Consequently
our focus is on transient behaviour analysis. We demonstrate how quali-
tative descriptions are abstractions over stochastic or continuous descrip-
tions, and show that the stochastic and continuous models approximate
each other. Although our framework is based on Petri nets, it can be
applied more widely to other formalisms which are used to model and
analyse biochemical networks
Modeling and simulating chemical reactions
Many students are familiar with the idea of modeling chemical reactions in terms of ordinary differential equations. However, these deterministic reaction rate equations are really a certain large-scale limit of a sequence of finer-scale probabilistic models. In studying this hierarchy of models, students can be exposed to a range of modern ideas in applied and computational mathematics. This article introduces some of the basic concepts in an accessible manner and points to some challenges that currently occupy researchers in this area. Short, downloadable MATLAB codes are listed and described
Modeling biological systems with delays in Bio-PEPA
Delays in biological systems may be used to model events for which the
underlying dynamics cannot be precisely observed, or to provide abstraction of
some behavior of the system resulting more compact models. In this paper we
enrich the stochastic process algebra Bio-PEPA, with the possibility of
assigning delays to actions, yielding a new non-Markovian process algebra:
Bio-PEPAd. This is a conservative extension meaning that the original syntax of
Bio-PEPA is retained and the delay specification which can now be associated
with actions may be added to existing Bio-PEPA models. The semantics of the
firing of the actions with delays is the delay-as-duration approach, earlier
presented in papers on the stochastic simulation of biological systems with
delays. These semantics of the algebra are given in the Starting-Terminating
style, meaning that the state and the completion of an action are observed as
two separate events, as required by delays. Furthermore we outline how to
perform stochastic simulation of Bio-PEPAd systems and how to automatically
translate a Bio-PEPAd system into a set of Delay Differential Equations, the
deterministic framework for modeling of biological systems with delays. We end
the paper with two example models of biological systems with delays to
illustrate the approach.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005
Jump-Diffusion Approximation of Stochastic Reaction Dynamics: Error bounds and Algorithms
Biochemical reactions can happen on different time scales and also the
abundance of species in these reactions can be very different from each other.
Classical approaches, such as deterministic or stochastic approach, fail to
account for or to exploit this multi-scale nature, respectively. In this paper,
we propose a jump-diffusion approximation for multi-scale Markov jump processes
that couples the two modeling approaches. An error bound of the proposed
approximation is derived and used to partition the reactions into fast and slow
sets, where the fast set is simulated by a stochastic differential equation and
the slow set is modeled by a discrete chain. The error bound leads to a very
efficient dynamic partitioning algorithm which has been implemented for several
multi-scale reaction systems. The gain in computational efficiency is
illustrated by a realistically sized model of a signal transduction cascade
coupled to a gene expression dynamics.Comment: 32 pages, 7 figure
Data-driven modelling of biological multi-scale processes
Biological processes involve a variety of spatial and temporal scales. A
holistic understanding of many biological processes therefore requires
multi-scale models which capture the relevant properties on all these scales.
In this manuscript we review mathematical modelling approaches used to describe
the individual spatial scales and how they are integrated into holistic models.
We discuss the relation between spatial and temporal scales and the implication
of that on multi-scale modelling. Based upon this overview over
state-of-the-art modelling approaches, we formulate key challenges in
mathematical and computational modelling of biological multi-scale and
multi-physics processes. In particular, we considered the availability of
analysis tools for multi-scale models and model-based multi-scale data
integration. We provide a compact review of methods for model-based data
integration and model-based hypothesis testing. Furthermore, novel approaches
and recent trends are discussed, including computation time reduction using
reduced order and surrogate models, which contribute to the solution of
inference problems. We conclude the manuscript by providing a few ideas for the
development of tailored multi-scale inference methods.Comment: This manuscript will appear in the Journal of Coupled Systems and
Multiscale Dynamics (American Scientific Publishers
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