5,583 research outputs found
On Projection-Based Model Reduction of Biochemical Networks-- Part II: The Stochastic Case
In this paper, we consider the problem of model order reduction of stochastic
biochemical networks. In particular, we reduce the order of (the number of
equations in) the Linear Noise Approximation of the Chemical Master Equation,
which is often used to describe biochemical networks. In contrast to other
biochemical network reduction methods, the presented one is projection-based.
Projection-based methods are powerful tools, but the cost of their use is the
loss of physical interpretation of the nodes in the network. In order alleviate
this drawback, we employ structured projectors, which means that some nodes in
the network will keep their physical interpretation. For many models in
engineering, finding structured projectors is not always feasible; however, in
the context of biochemical networks it is much more likely as the networks are
often (almost) monotonic. To summarise, the method can serve as a trade-off
between approximation quality and physical interpretation, which is illustrated
on numerical examples.Comment: Submitted to the 53rd CD
Model reduction for stochastic CaMKII reaction kinetics in synapses by graph-constrained correlation dynamics.
A stochastic reaction network model of Ca(2+) dynamics in synapses (Pepke et al PLoS Comput. Biol. 6 e1000675) is expressed and simulated using rule-based reaction modeling notation in dynamical grammars and in MCell. The model tracks the response of calmodulin and CaMKII to calcium influx in synapses. Data from numerically intensive simulations is used to train a reduced model that, out of sample, correctly predicts the evolution of interaction parameters characterizing the instantaneous probability distribution over molecular states in the much larger fine-scale models. The novel model reduction method, 'graph-constrained correlation dynamics', requires a graph of plausible state variables and interactions as input. It parametrically optimizes a set of constant coefficients appearing in differential equations governing the time-varying interaction parameters that determine all correlations between variables in the reduced model at any time slice
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
Uniformisation techniques for stochastic simulation of chemical reaction networks
This work considers the method of uniformisation for continuous-time Markov
chains in the context of chemical reaction networks. Previous work in the
literature has shown that uniformisation can be beneficial in the context of
time-inhomogeneous models, such as chemical reaction networks incorporating
extrinsic noise. This paper lays focus on the understanding of uniformisation
from the viewpoint of sample paths of chemical reaction networks. In
particular, an efficient pathwise stochastic simulation algorithm for
time-homogeneous models is presented which is complexity-wise equal to
Gillespie's direct method. This new approach therefore enlarges the class of
problems for which the uniformisation approach forms a computationally
attractive choice. Furthermore, as a new application of the uniformisation
method, we provide a novel variance reduction method for (raw) moment
estimators of chemical reaction networks based upon the combination of
stratification and uniformisation
Predicting unobserved exposures from seasonal epidemic data
We consider a stochastic Susceptible-Exposed-Infected-Recovered (SEIR)
epidemiological model with a contact rate that fluctuates seasonally. Through
the use of a nonlinear, stochastic projection, we are able to analytically
determine the lower dimensional manifold on which the deterministic and
stochastic dynamics correctly interact. Our method produces a low dimensional
stochastic model that captures the same timing of disease outbreak and the same
amplitude and phase of recurrent behavior seen in the high dimensional model.
Given seasonal epidemic data consisting of the number of infectious
individuals, our method enables a data-based model prediction of the number of
unobserved exposed individuals over very long times.Comment: 24 pages, 6 figures; Final version in Bulletin of Mathematical
Biolog
On Monotonicity and Propagation of Order Properties
In this paper, a link between monotonicity of deterministic dynamical systems
and propagation of order by Markov processes is established. The order
propagation has received considerable attention in the literature, however,
this notion is still not fully understood. The main contribution of this paper
is a study of the order propagation in the deterministic setting, which
potentially can provide new techniques for analysis in the stochastic one. We
take a close look at the propagation of the so-called increasing and increasing
convex orders. Infinitesimal characterisations of these orders are derived,
which resemble the well-known Kamke conditions for monotonicity. It is shown
that increasing order is equivalent to the standard monotonicity, while the
class of systems propagating the increasing convex order is equivalent to the
class of monotone systems with convex vector fields. The paper is concluded by
deriving a novel result on order propagating diffusion processes and an
application of this result to biological processes.Comment: Part of the paper is to appear in American Control Conference 201
Simulation of networks of spiking neurons: A review of tools and strategies
We review different aspects of the simulation of spiking neural networks. We
start by reviewing the different types of simulation strategies and algorithms
that are currently implemented. We next review the precision of those
simulation strategies, in particular in cases where plasticity depends on the
exact timing of the spikes. We overview different simulators and simulation
environments presently available (restricted to those freely available, open
source and documented). For each simulation tool, its advantages and pitfalls
are reviewed, with an aim to allow the reader to identify which simulator is
appropriate for a given task. Finally, we provide a series of benchmark
simulations of different types of networks of spiking neurons, including
Hodgkin-Huxley type, integrate-and-fire models, interacting with current-based
or conductance-based synapses, using clock-driven or event-driven integration
strategies. The same set of models are implemented on the different simulators,
and the codes are made available. The ultimate goal of this review is to
provide a resource to facilitate identifying the appropriate integration
strategy and simulation tool to use for a given modeling problem related to
spiking neural networks.Comment: 49 pages, 24 figures, 1 table; review article, Journal of
Computational Neuroscience, in press (2007
Fast stochastic simulation of biochemical reaction systems by\ud alternative formulations of the Chemical Langevin Equation
The Chemical Langevin Equation (CLE), which is a stochastic differential equation (SDE) driven by a multidimensional Wiener process, acts as a bridge between the discrete Stochastic Simulation Algorithm and the deterministic reaction rate equation when simulating (bio)chemical kinetics. The CLE model is valid in the regime where molecular populations are abundant enough to assume their concentrations change continuously, but stochastic fluctuations still play a major role. The contribution of this work is that we observe and explore that the CLE is not a single equation, but a parametric family of equations, all of which give the same finite-dimensional distribution of the variables. On the theoretical side, we prove that as many Wiener processes are sufficient to formulate the CLE as there are independent variables in the equation. On the practical side, we show that in the case where there are m1 pairs of reversible reactions and m2 irreversible reactions only m1+m2 Wiener processes are required in the formulation of the CLE, whereas the standard approach uses 2m1 + m2. We illustrate our findings by considering alternative formulations of the CLE for a\ud
HERG ion channel model and the Goldbeter–Koshland switch. We show that there are considerable computational savings when using our insights
- …