4,891 research outputs found
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
Towards knowledge-based gene expression data mining
The field of gene expression data analysis has grown in the past few years from being purely data-centric to integrative, aiming at complementing microarray analysis with data and knowledge from diverse available sources. In this review, we report on the plethora of gene expression data mining techniques and focus on their evolution toward knowledge-based data analysis approaches. In particular, we discuss recent developments in gene expression-based analysis methods used in association and classification studies, phenotyping and reverse engineering of gene networks
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
Application of new probabilistic graphical models in the genetic regulatory networks studies
This paper introduces two new probabilistic graphical models for
reconstruction of genetic regulatory networks using DNA microarray data. One is
an Independence Graph (IG) model with either a forward or a backward search
algorithm and the other one is a Gaussian Network (GN) model with a novel
greedy search method. The performances of both models were evaluated on four
MAPK pathways in yeast and three simulated data sets. Generally, an IG model
provides a sparse graph but a GN model produces a dense graph where more
information about gene-gene interactions is preserved. Additionally, we found
two key limitations in the prediction of genetic regulatory networks using DNA
microarray data, the first is the sufficiency of sample size and the second is
the complexity of network structures may not be captured without additional
data at the protein level. Those limitations are present in all prediction
methods which used only DNA microarray data.Comment: 38 pages, 3 figure
A survey of models for inference of gene regulatory networks
In this article, I present the biological backgrounds of microarray, ChIP-chip and ChIPSeq technologies and the application of computational methods in reverse engineering of gene regulatory networks (GRNs). The most commonly used GRNs models based on Boolean networks, Bayesian networks, relevance networks, differential and difference equations are described. A novel model for integration of prior biological knowledge in the GRNs inference is presented, too. The advantages and disadvantages of the described models are compared. The GRNs validation criteria are depicted. Current trends and further directions for GRNs inference using prior knowledge are given at the end of the paper
Defining a robust biological prior from Pathway Analysis to drive Network Inference
Inferring genetic networks from gene expression data is one of the most
challenging work in the post-genomic era, partly due to the vast space of
possible networks and the relatively small amount of data available. In this
field, Gaussian Graphical Model (GGM) provides a convenient framework for the
discovery of biological networks. In this paper, we propose an original
approach for inferring gene regulation networks using a robust biological prior
on their structure in order to limit the set of candidate networks.
Pathways, that represent biological knowledge on the regulatory networks,
will be used as an informative prior knowledge to drive Network Inference. This
approach is based on the selection of a relevant set of genes, called the
"molecular signature", associated with a condition of interest (for instance,
the genes involved in disease development). In this context, differential
expression analysis is a well established strategy. However outcome signatures
are often not consistent and show little overlap between studies. Thus, we will
dedicate the first part of our work to the improvement of the standard process
of biomarker identification to guarantee the robustness and reproducibility of
the molecular signature.
Our approach enables to compare the networks inferred between two conditions
of interest (for instance case and control networks) and help along the
biological interpretation of results. Thus it allows to identify differential
regulations that occur in these conditions. We illustrate the proposed approach
by applying our method to a study of breast cancer's response to treatment
A survey of models for inference of gene regulatory networks
In this article, I present the biological backgrounds of microarray, ChIP-chip and ChIPSeq technologies and the application of computational methods in reverse engineering of gene regulatory networks (GRNs). The most commonly used GRNs models based on Boolean networks, Bayesian networks, relevance networks, differential and difference equations are described. A novel model for integration of prior biological knowledge in the GRNs inference is presented, too. The advantages and disadvantages of the described models are compared. The GRNs validation criteria are depicted. Current trends and further directions for GRNs inference using prior knowledge are given at the end of the paper
Bayesian network prior: network analysis of biological data using external knowledge
Motivation: Reverse engineering GI networks from experimental data is a challenging task due to the complex nature of the networks and the noise inherent in the data. One way to overcome these hurdles would be incorporating the vast amounts of external biological knowledge when building interaction networks. We propose a framework where GI networks are learned from experimental data using Bayesian networks (BNs) and the incorporation of external knowledge is also done via a BN that we call Bayesian Network Prior (BNP). BNP depicts the relation between various evidence types that contribute to the event ‘gene interaction’ and is used to calculate the probability of a candidate graph (G) in the structure learning process.
Results: Our simulation results on synthetic, simulated and real biological data show that the proposed approach can identify the underlying interaction network with high accuracy even when the prior information is distorted and outperforms existing methods
- …