15,154 research outputs found
Stochastic models and numerical algorithms for a class of regulatory gene networks
Regulatory gene networks contain generic modules like those involving
feedback loops, which are essential for the regulation of many biological
functions. We consider a class of self-regulated genes which are the building
blocks of many regulatory gene networks, and study the steady state
distributions of the associated Gillespie algorithm by providing efficient
numerical algorithms. We also study a regulatory gene network of interest in
synthetic biology and in gene therapy, using mean-field models with time
delays. Convergence of the related time-nonhomogeneous Markov chain is
established for a class of linear catalytic networks with feedback loop
Stochastic Models and Numerical Algorithms for a Class ofRegulatory Gene Networks
Regulatory gene networks contain generic modules, like those involving feedback loops, which are essential for the regulation of many biological functions (Guido etal. in Nature 439:856-860, 2006). We consider a class of self-regulated genes which are the building blocks of many regulatory gene networks, and study the steady-state distribution of the associated Gillespie algorithm by providing efficient numerical algorithms. We also study a regulatory gene network of interest in gene therapy, using mean-field models with time delays. Convergence of the related time-nonhomogeneous Markov chain is established for a class of linear catalytic networks with feedback loop
Steady-State Analysis of Genetic Regulatory Networks Modelled by Probabilistic Boolean Networks
Probabilistic Boolean networks (PBNs) have recently been introduced as a promising class of models of genetic regulatory networks. The dynamic behaviour of PBNs can
be analysed in the context of Markov chains. A key goal is the determination of the
steady-state (long-run) behaviour of a PBN by analysing the corresponding Markov
chain. This allows one to compute the long-term influence of a gene on another
gene or determine the long-term joint probabilistic behaviour of a few selected genes.
Because matrix-based methods quickly become prohibitive for large sizes of networks,
we propose the use of Monte Carlo methods. However, the rate of convergence to
the stationary distribution becomes a central issue. We discuss several approaches
for determining the number of iterations necessary to achieve convergence of the
Markov chain corresponding to a PBN. Using a recently introduced method based on
the theory of two-state Markov chains, we illustrate the approach on a sub-network
designed from human glioma gene expression data and determine the joint steadystate
probabilities for several groups of genes
Inference of Temporally Varying Bayesian Networks
When analysing gene expression time series data an often overlooked but
crucial aspect of the model is that the regulatory network structure may change
over time. Whilst some approaches have addressed this problem previously in the
literature, many are not well suited to the sequential nature of the data. Here
we present a method that allows us to infer regulatory network structures that
may vary between time points, utilising a set of hidden states that describe
the network structure at a given time point. To model the distribution of the
hidden states we have applied the Hierarchical Dirichlet Process Hideen Markov
Model, a nonparametric extension of the traditional Hidden Markov Model, that
does not require us to fix the number of hidden states in advance. We apply our
method to exisiting microarray expression data as well as demonstrating is
efficacy on simulated test data
Relative Stability of Network States in Boolean Network Models of Gene Regulation in Development
Progress in cell type reprogramming has revived the interest in Waddington's
concept of the epigenetic landscape. Recently researchers developed the
quasi-potential theory to represent the Waddington's landscape. The
Quasi-potential U(x), derived from interactions in the gene regulatory network
(GRN) of a cell, quantifies the relative stability of network states, which
determine the effort required for state transitions in a multi-stable dynamical
system. However, quasi-potential landscapes, originally developed for
continuous systems, are not suitable for discrete-valued networks which are
important tools to study complex systems. In this paper, we provide a framework
to quantify the landscape for discrete Boolean networks (BNs). We apply our
framework to study pancreas cell differentiation where an ensemble of BN models
is considered based on the structure of a minimal GRN for pancreas development.
We impose biologically motivated structural constraints (corresponding to
specific type of Boolean functions) and dynamical constraints (corresponding to
stable attractor states) to limit the space of BN models for pancreas
development. In addition, we enforce a novel functional constraint
corresponding to the relative ordering of attractor states in BN models to
restrict the space of BN models to the biological relevant class. We find that
BNs with canalyzing/sign-compatible Boolean functions best capture the dynamics
of pancreas cell differentiation. This framework can also determine the genes'
influence on cell state transitions, and thus can facilitate the rational
design of cell reprogramming protocols.Comment: 24 pages, 6 figures, 1 tabl
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