6,888 research outputs found
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
Dynamic Bayesian networks in molecular plant science: inferring gene regulatory networks from multiple gene expression time series
To understand the processes of growth and biomass production in plants, we ultimately need to elucidate the structure of the underlying regulatory networks at the molecular level. The advent of high-throughput postgenomic technologies has spurred substantial interest in reverse engineering these networks from data, and several techniques from machine learning and multivariate statistics have recently been proposed. The present article discusses the problem of inferring gene regulatory networks from gene expression time series, and we focus our exposition on the methodology of Bayesian networks. We describe dynamic Bayesian networks and explain their advantages over other statistical methods. We introduce a novel information sharing scheme, which allows us to infer gene regulatory networks from multiple sources of gene expression data more accurately. We illustrate and test this method on a set of synthetic data, using three different measures to quantify the network reconstruction accuracy. The main application of our method is related to the problem of circadian regulation in plants, where we aim to reconstruct the regulatory networks of nine circadian genes in Arabidopsis thaliana from four gene expression time series obtained under different experimental conditions
Reconstructing dynamical networks via feature ranking
Empirical data on real complex systems are becoming increasingly available.
Parallel to this is the need for new methods of reconstructing (inferring) the
topology of networks from time-resolved observations of their node-dynamics.
The methods based on physical insights often rely on strong assumptions about
the properties and dynamics of the scrutinized network. Here, we use the
insights from machine learning to design a new method of network reconstruction
that essentially makes no such assumptions. Specifically, we interpret the
available trajectories (data) as features, and use two independent feature
ranking approaches -- Random forest and RReliefF -- to rank the importance of
each node for predicting the value of each other node, which yields the
reconstructed adjacency matrix. We show that our method is fairly robust to
coupling strength, system size, trajectory length and noise. We also find that
the reconstruction quality strongly depends on the dynamical regime
Validating module network learning algorithms using simulated data
In recent years, several authors have used probabilistic graphical models to
learn expression modules and their regulatory programs from gene expression
data. Here, we demonstrate the use of the synthetic data generator SynTReN for
the purpose of testing and comparing module network learning algorithms. We
introduce a software package for learning module networks, called LeMoNe, which
incorporates a novel strategy for learning regulatory programs. Novelties
include the use of a bottom-up Bayesian hierarchical clustering to construct
the regulatory programs, and the use of a conditional entropy measure to assign
regulators to the regulation program nodes. Using SynTReN data, we test the
performance of LeMoNe in a completely controlled situation and assess the
effect of the methodological changes we made with respect to an existing
software package, namely Genomica. Additionally, we assess the effect of
various parameters, such as the size of the data set and the amount of noise,
on the inference performance. Overall, application of Genomica and LeMoNe to
simulated data sets gave comparable results. However, LeMoNe offers some
advantages, one of them being that the learning process is considerably faster
for larger data sets. Additionally, we show that the location of the regulators
in the LeMoNe regulation programs and their conditional entropy may be used to
prioritize regulators for functional validation, and that the combination of
the bottom-up clustering strategy with the conditional entropy-based assignment
of regulators improves the handling of missing or hidden regulators.Comment: 13 pages, 6 figures + 2 pages, 2 figures supplementary informatio
- …