38,467 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
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
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
Modeling Infection with Multi-agent Dynamics
Developing the ability to comprehensively study infections in small
populations enables us to improve epidemic models and better advise individuals
about potential risks to their health. We currently have a limited
understanding of how infections spread within a small population because it has
been difficult to closely track an infection within a complete community. The
paper presents data closely tracking the spread of an infection centered on a
student dormitory, collected by leveraging the residents' use of cellular
phones. The data are based on daily symptom surveys taken over a period of four
months and proximity tracking through cellular phones. We demonstrate that
using a Bayesian, discrete-time multi-agent model of infection to model
real-world symptom reports and proximity tracking records gives us important
insights about infec-tions in small populations
Inferring Biologically Relevant Models: Nested Canalyzing Functions
Inferring dynamic biochemical networks is one of the main challenges in
systems biology. Given experimental data, the objective is to identify the
rules of interaction among the different entities of the network. However, the
number of possible models fitting the available data is huge and identifying a
biologically relevant model is of great interest. Nested canalyzing functions,
where variables in a given order dominate the function, have recently been
proposed as a framework for modeling gene regulatory networks. Previously we
described this class of functions as an algebraic toric variety. In this paper,
we present an algorithm that identifies all nested canalyzing models that fit
the given data. We demonstrate our methods using a well-known Boolean model of
the cell cycle in budding yeast
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