3,623 research outputs found
Reduction of dynamical biochemical reaction networks in computational biology
Biochemical networks are used in computational biology, to model the static
and dynamical details of systems involved in cell signaling, metabolism, and
regulation of gene expression. Parametric and structural uncertainty, as well
as combinatorial explosion are strong obstacles against analyzing the dynamics
of large models of this type. Multi-scaleness is another property of these
networks, that can be used to get past some of these obstacles. Networks with
many well separated time scales, can be reduced to simpler networks, in a way
that depends only on the orders of magnitude and not on the exact values of the
kinetic parameters. The main idea used for such robust simplifications of
networks is the concept of dominance among model elements, allowing
hierarchical organization of these elements according to their effects on the
network dynamics. This concept finds a natural formulation in tropical
geometry. We revisit, in the light of these new ideas, the main approaches to
model reduction of reaction networks, such as quasi-steady state and
quasi-equilibrium approximations, and provide practical recipes for model
reduction of linear and nonlinear networks. We also discuss the application of
model reduction to backward pruning machine learning techniques
Moment-Based Variational Inference for Markov Jump Processes
We propose moment-based variational inference as a flexible framework for
approximate smoothing of latent Markov jump processes. The main ingredient of
our approach is to partition the set of all transitions of the latent process
into classes. This allows to express the Kullback-Leibler divergence between
the approximate and the exact posterior process in terms of a set of moment
functions that arise naturally from the chosen partition. To illustrate
possible choices of the partition, we consider special classes of jump
processes that frequently occur in applications. We then extend the results to
parameter inference and demonstrate the method on several examples.Comment: Accepted by the 36th International Conference on Machine Learning
(ICML 2019
Analysis of Brownian dynamics simulations of reversible biomolecular reactions
A class of Brownian dynamics algorithms for stochastic reaction-diffusion models which include reversible bimolecular reactions is presented and analyzed. The method is a generalization of the λ-rho model for irreversible bimolecular reactions which was introduced in [11]. The formulae relating the experimentally measurable quantities (reaction rate constants and diffusion constants) with the algorithm parameters are derived. The probability of geminate recombination is also investigated
Analysis of Brownian Dynamics Simulations of Reversible Bimolecular Reactions
A class of Brownian dynamics algorithms for stochastic reaction-diffusion
models which include reversible bimolecular reactions is presented and
analyzed. The method is a generalization of the --\newrho model for
irreversible bimolecular reactions which was introduced in [arXiv:0903.1298].
The formulae relating the experimentally measurable quantities (reaction rate
constants and diffusion constants) with the algorithm parameters are derived.
The probability of geminate recombination is also investigated.Comment: 16 pages, 13 figures, submitted to SIAM Appl Mat
On functional module detection in metabolic networks
Functional modules of metabolic networks are essential for understanding the metabolism of an organism as a whole. With the vast amount of experimental data and the construction of complex and large-scale, often genome-wide, models, the computer-aided identification of functional modules becomes more and more important. Since steady states play a key role in biology, many methods have been developed in that context, for example, elementary flux modes, extreme pathways, transition invariants and place invariants. Metabolic networks can be studied also from the point of view of graph theory, and algorithms for graph decomposition have been applied for the identification of functional modules. A prominent and currently intensively discussed field of methods in graph theory addresses the Q-modularity. In this paper, we recall known concepts of module detection based on the steady-state assumption, focusing on transition-invariants (elementary modes) and their computation as minimal solutions of systems of Diophantine equations. We present the Fourier-Motzkin algorithm in detail. Afterwards, we introduce the Q-modularity as an example for a useful non-steady-state method and its application to metabolic networks. To illustrate and discuss the concepts of invariants and Q-modularity, we apply a part of the central carbon metabolism in potato tubers (Solanum tuberosum) as running example. The intention of the paper is to give a compact presentation of known steady-state concepts from a graph-theoretical viewpoint in the context of network decomposition and reduction and to introduce the application of Q-modularity to metabolic Petri net models
Controllability Metrics on Networks with Linear Decision Process-type Interactions and Multiplicative Noise
This paper aims at the study of controllability properties and induced
controllability metrics on complex networks governed by a class of (discrete
time) linear decision processes with mul-tiplicative noise. The dynamics are
given by a couple consisting of a Markov trend and a linear decision process
for which both the "deterministic" and the noise components rely on
trend-dependent matrices. We discuss approximate, approximate null and exact
null-controllability. Several examples are given to illustrate the links
between these concepts and to compare our results with their continuous-time
counterpart (given in [16]). We introduce a class of backward stochastic
Riccati difference schemes (BSRDS) and study their solvability for particular
frameworks. These BSRDS allow one to introduce Gramian-like controllability
metrics. As application of these metrics, we propose a minimal
intervention-targeted reduction in the study of gene networks
Sampling rare switching events in biochemical networks
Bistable biochemical switches are ubiquitous in gene regulatory networks and
signal transduction pathways. Their switching dynamics, however, are difficult
to study directly in experiments or conventional computer simulations, because
switching events are rapid, yet infrequent. We present a simulation technique
that makes it possible to predict the rate and mechanism of flipping of
biochemical switches. The method uses a series of interfaces in phase space
between the two stable steady states of the switch to generate transition
trajectories in a ratchet-like manner. We demonstrate its use by calculating
the spontaneous flipping rate of a symmetric model of a genetic switch
consisting of two mutually repressing genes. The rate constant can be obtained
orders of magnitude more efficiently than using brute-force simulations. For
this model switch, we show that the switching mechanism, and consequently the
switching rate, depends crucially on whether the binding of one regulatory
protein to the DNA excludes the binding of the other one. Our technique could
also be used to study rare events and non-equilibrium processes in soft
condensed matter systems.Comment: 9 pages, 6 figures, last page contains supplementary informatio
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