4,849 research outputs found
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
BioSimulator.jl: Stochastic simulation in Julia
Biological systems with intertwined feedback loops pose a challenge to
mathematical modeling efforts. Moreover, rare events, such as mutation and
extinction, complicate system dynamics. Stochastic simulation algorithms are
useful in generating time-evolution trajectories for these systems because they
can adequately capture the influence of random fluctuations and quantify rare
events. We present a simple and flexible package, BioSimulator.jl, for
implementing the Gillespie algorithm, -leaping, and related stochastic
simulation algorithms. The objective of this work is to provide scientists
across domains with fast, user-friendly simulation tools. We used the
high-performance programming language Julia because of its emphasis on
scientific computing. Our software package implements a suite of stochastic
simulation algorithms based on Markov chain theory. We provide the ability to
(a) diagram Petri Nets describing interactions, (b) plot average trajectories
and attached standard deviations of each participating species over time, and
(c) generate frequency distributions of each species at a specified time.
BioSimulator.jl's interface allows users to build models programmatically
within Julia. A model is then passed to the simulate routine to generate
simulation data. The built-in tools allow one to visualize results and compute
summary statistics. Our examples highlight the broad applicability of our
software to systems of varying complexity from ecology, systems biology,
chemistry, and genetics. The user-friendly nature of BioSimulator.jl encourages
the use of stochastic simulation, minimizes tedious programming efforts, and
reduces errors during model specification.Comment: 27 pages, 5 figures, 3 table
Analysis of signalling pathways using continuous time Markov chains
We describe a quantitative modelling and analysis approach for signal transduction networks.
We illustrate the approach with an example, the RKIP inhibited ERK pathway [CSK+03]. Our models are high level descriptions of continuous time Markov chains: proteins are modelled by synchronous processes and reactions by transitions. 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 such as what is the probability that if a concentration reaches a certain level, it will remain at that level thereafter? or how does varying a given reaction rate affect that probability? 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
Analysis of Petri Net Models through Stochastic Differential Equations
It is well known, mainly because of the work of Kurtz, that density dependent
Markov chains can be approximated by sets of ordinary differential equations
(ODEs) when their indexing parameter grows very large. This approximation
cannot capture the stochastic nature of the process and, consequently, it can
provide an erroneous view of the behavior of the Markov chain if the indexing
parameter is not sufficiently high. Important phenomena that cannot be revealed
include non-negligible variance and bi-modal population distributions. A
less-known approximation proposed by Kurtz applies stochastic differential
equations (SDEs) and provides information about the stochastic nature of the
process. In this paper we apply and extend this diffusion approximation to
study stochastic Petri nets. We identify a class of nets whose underlying
stochastic process is a density dependent Markov chain whose indexing parameter
is a multiplicative constant which identifies the population level expressed by
the initial marking and we provide means to automatically construct the
associated set of SDEs. Since the diffusion approximation of Kurtz considers
the process only up to the time when it first exits an open interval, we extend
the approximation by a machinery that mimics the behavior of the Markov chain
at the boundary and allows thus to apply the approach to a wider set of
problems. The resulting process is of the jump-diffusion type. We illustrate by
examples that the jump-diffusion approximation which extends to bounded domains
can be much more informative than that based on ODEs as it can provide accurate
quantity distributions even when they are multi-modal and even for relatively
small population levels. Moreover, we show that the method is faster than
simulating the original Markov chain
Versatile Markovian models for networks with asymmetric TCP sources
In this paper we use Stochastic Petri Nets (SPNs) to study the interaction of multiple TCP sources that share one or two buffers, thereby considerably extending earlier work. We first consider two sources sharing a buffer and investigate the consequences of two popular assumptions for the loss process in terms of fairness and link utilization. The results obtained by our model are in agreement with existing analytic models or are closer to results obtained by ns-2 simulations. We then study a network consisting of three sources and two buffers and provide evidence that link sharing is approximately minimum-potential-delay-fair in case of equal round-trip times. \u
A model checker for performance and dependability properties
Markov chains are widely used in the context of
performance and reliability evaluation of systems of various
nature. Model checking of such chains with respect to
a given (branching) temporal logic formula has been proposed
for both the discrete [8] and the continuous time setting
[1], [3]. In this short paper, we describe the prototype
model checker for discrete and continuous-time
Markov chains, where properties are expressed in appropriate
extensions of CTL.We illustrate the general benefits
of this approach and discuss the structure of the tool
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
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