22,305 research outputs found
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
How to understand the cell by breaking it: network analysis of gene perturbation screens
Modern high-throughput gene perturbation screens are key technologies at the
forefront of genetic research. Combined with rich phenotypic descriptors they
enable researchers to observe detailed cellular reactions to experimental
perturbations on a genome-wide scale. This review surveys the current
state-of-the-art in analyzing perturbation screens from a network point of
view. We describe approaches to make the step from the parts list to the wiring
diagram by using phenotypes for network inference and integrating them with
complementary data sources. The first part of the review describes methods to
analyze one- or low-dimensional phenotypes like viability or reporter activity;
the second part concentrates on high-dimensional phenotypes showing global
changes in cell morphology, transcriptome or proteome.Comment: Review based on ISMB 2009 tutorial; after two rounds of revisio
Nonparametric Bayesian inference for perturbed and orthologous gene regulatory networks
Motivation: The generation of time series transcriptomic datasets collected under multiple experimental conditions has proven to be a powerful approach for disentangling complex biological processes, allowing for the reverse engineering of gene regulatory networks (GRNs). Most methods for reverse engineering GRNs from multiple datasets assume that each of the time series were generated from networks with identical topology. In this study, we outline a hierarchical, non-parametric Bayesian approach for reverse engineering GRNs using multiple time series that can be applied in a number of novel situations including: (i) where different, but overlapping sets of transcription factors are expected to bind in the different experimental conditions; that is, where switching events could potentially arise under the different treatments and (ii) for inference in evolutionary related species in which orthologous GRNs exist. More generally, the method can be used to identify context-specific regulation by leveraging time series gene expression data alongside methods that can identify putative lists of transcription factors or transcription factor targets.
Results: The hierarchical inference outperforms related (but non-hierarchical) approaches when the networks used to generate the data were identical, and performs comparably even when the networks used to generate data were independent. The method was subsequently used alongside yeast one hybrid and microarray time series data to infer potential transcriptional switches in Arabidopsis thaliana response to stress. The results confirm previous biological studies and allow for additional insights into gene regulation under various abiotic stresses.
Availability: The methods outlined in this article have been implemented in Matlab and are available on request
A Posterior Probability Approach for Gene Regulatory Network Inference in Genetic Perturbation Data
Inferring gene regulatory networks is an important problem in systems
biology. However, these networks can be hard to infer from experimental data
because of the inherent variability in biological data as well as the large
number of genes involved. We propose a fast, simple method for inferring
regulatory relationships between genes from knockdown experiments in the NIH
LINCS dataset by calculating posterior probabilities, incorporating prior
information. We show that the method is able to find previously identified
edges from TRANSFAC and JASPAR and discuss the merits and limitations of this
approach
Brain covariance selection: better individual functional connectivity models using population prior
Spontaneous brain activity, as observed in functional neuroimaging, has been
shown to display reproducible structure that expresses brain architecture and
carries markers of brain pathologies. An important view of modern neuroscience
is that such large-scale structure of coherent activity reflects modularity
properties of brain connectivity graphs. However, to date, there has been no
demonstration that the limited and noisy data available in spontaneous activity
observations could be used to learn full-brain probabilistic models that
generalize to new data. Learning such models entails two main challenges: i)
modeling full brain connectivity is a difficult estimation problem that faces
the curse of dimensionality and ii) variability between subjects, coupled with
the variability of functional signals between experimental runs, makes the use
of multiple datasets challenging. We describe subject-level brain functional
connectivity structure as a multivariate Gaussian process and introduce a new
strategy to estimate it from group data, by imposing a common structure on the
graphical model in the population. We show that individual models learned from
functional Magnetic Resonance Imaging (fMRI) data using this population prior
generalize better to unseen data than models based on alternative
regularization schemes. To our knowledge, this is the first report of a
cross-validated model of spontaneous brain activity. Finally, we use the
estimated graphical model to explore the large-scale characteristics of
functional architecture and show for the first time that known cognitive
networks appear as the integrated communities of functional connectivity graph.Comment: in Advances in Neural Information Processing Systems, Vancouver :
Canada (2010
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