10,735 research outputs found
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
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
Detection of regulator genes and eQTLs in gene networks
Genetic differences between individuals associated to quantitative phenotypic
traits, including disease states, are usually found in non-coding genomic
regions. These genetic variants are often also associated to differences in
expression levels of nearby genes (they are "expression quantitative trait
loci" or eQTLs for short) and presumably play a gene regulatory role, affecting
the status of molecular networks of interacting genes, proteins and
metabolites. Computational systems biology approaches to reconstruct causal
gene networks from large-scale omics data have therefore become essential to
understand the structure of networks controlled by eQTLs together with other
regulatory genes, and to generate detailed hypotheses about the molecular
mechanisms that lead from genotype to phenotype. Here we review the main
analytical methods and softwares to identify eQTLs and their associated genes,
to reconstruct co-expression networks and modules, to reconstruct causal
Bayesian gene and module networks, and to validate predicted networks in
silico.Comment: minor revision with typos corrected; review article; 24 pages, 2
figure
Combining Bayesian Approaches and Evolutionary Techniques for the Inference of Breast Cancer Networks
Gene and protein networks are very important to model complex large-scale
systems in molecular biology. Inferring or reverseengineering such networks can
be defined as the process of identifying gene/protein interactions from
experimental data through computational analysis. However, this task is
typically complicated by the enormously large scale of the unknowns in a rather
small sample size. Furthermore, when the goal is to study causal relationships
within the network, tools capable of overcoming the limitations of correlation
networks are required. In this work, we make use of Bayesian Graphical Models
to attach this problem and, specifically, we perform a comparative study of
different state-of-the-art heuristics, analyzing their performance in inferring
the structure of the Bayesian Network from breast cancer data
Causal graphical models in systems genetics: A unified framework for joint inference of causal network and genetic architecture for correlated phenotypes
Causal inference approaches in systems genetics exploit quantitative trait
loci (QTL) genotypes to infer causal relationships among phenotypes. The
genetic architecture of each phenotype may be complex, and poorly estimated
genetic architectures may compromise the inference of causal relationships
among phenotypes. Existing methods assume QTLs are known or inferred without
regard to the phenotype network structure. In this paper we develop a
QTL-driven phenotype network method (QTLnet) to jointly infer a causal
phenotype network and associated genetic architecture for sets of correlated
phenotypes. Randomization of alleles during meiosis and the unidirectional
influence of genotype on phenotype allow the inference of QTLs causal to
phenotypes. Causal relationships among phenotypes can be inferred using these
QTL nodes, enabling us to distinguish among phenotype networks that would
otherwise be distribution equivalent. We jointly model phenotypes and QTLs
using homogeneous conditional Gaussian regression models, and we derive a
graphical criterion for distribution equivalence. We validate the QTLnet
approach in a simulation study. Finally, we illustrate with simulated data and
a real example how QTLnet can be used to infer both direct and indirect effects
of QTLs and phenotypes that co-map to a genomic region.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS288 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
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