14,006 research outputs found
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
Reverse engineering of genetic networks with Bayesian networks
This paper provides a brief introduction to learning Bayesian networks from gene-expression data. The method is contrasted with other approaches to the reverse engineering of biochemical networks, and the Bayesian learning paradigm is briefly described. The article demonstrates an application to a simple synthetic toy problem and evaluates the inference performance in terms of ROC (receiver operator characteristic) curves
Reverse-engineering of polynomial dynamical systems
Multivariate polynomial dynamical systems over finite fields have been
studied in several contexts, including engineering and mathematical biology. An
important problem is to construct models of such systems from a partial
specification of dynamic properties, e.g., from a collection of state
transition measurements. Here, we consider static models, which are directed
graphs that represent the causal relationships between system variables,
so-called wiring diagrams. This paper contains an algorithm which computes all
possible minimal wiring diagrams for a given set of state transition
measurements. The paper also contains several statistical measures for model
selection. The algorithm uses primary decomposition of monomial ideals as the
principal tool. An application to the reverse-engineering of a gene regulatory
network is included. The algorithm and the statistical measures are implemented
in Macaulay2 and are available from the authors
Integrating heterogeneous knowledges for understanding biological behaviors: a probabilistic approach
Despite recent molecular technique improvements, biological knowledge remains
incomplete. Reasoning on living systems hence implies to integrate
heterogeneous and partial informations. Although current investigations
successfully focus on qualitative behaviors of macromolecular networks, others
approaches show partial quantitative informations like protein concentration
variations over times. We consider that both informations, qualitative and
quantitative, have to be combined into a modeling method to provide a better
understanding of the biological system. We propose here such a method using a
probabilistic-like approach. After its exhaustive description, we illustrate
its advantages by modeling the carbon starvation response in Escherichia coli.
In this purpose, we build an original qualitative model based on available
observations. After the formal verification of its qualitative properties, the
probabilistic model shows quantitative results corresponding to biological
expectations which confirm the interest of our probabilistic approach.Comment: 10 page
Mathematical modelling plant signalling networks
During the last two decades, molecular genetic studies and the completion of the sequencing of the Arabidopsis thaliana genome have increased knowledge of hormonal regulation in plants. These signal transduction pathways act in concert through gene regulatory and signalling networks whose main components have begun to be elucidated. Our understanding of the resulting cellular processes is hindered by the complex, and sometimes counter-intuitive, dynamics of the networks, which may be interconnected through feedback controls and cross-regulation. Mathematical modelling provides a valuable tool to investigate such dynamics and to perform in silico experiments that may not be easily carried out in a laboratory. In this article, we firstly review general methods for modelling gene and signalling networks and their application in plants. We then describe specific models of hormonal perception and cross-talk in plants. This sub-cellular analysis paves the way for more comprehensive mathematical studies of hormonal transport and signalling in a multi-scale setting
Discovering Graphical Granger Causality Using the Truncating Lasso Penalty
Components of biological systems interact with each other in order to carry
out vital cell functions. Such information can be used to improve estimation
and inference, and to obtain better insights into the underlying cellular
mechanisms. Discovering regulatory interactions among genes is therefore an
important problem in systems biology. Whole-genome expression data over time
provides an opportunity to determine how the expression levels of genes are
affected by changes in transcription levels of other genes, and can therefore
be used to discover regulatory interactions among genes.
In this paper, we propose a novel penalization method, called truncating
lasso, for estimation of causal relationships from time-course gene expression
data. The proposed penalty can correctly determine the order of the underlying
time series, and improves the performance of the lasso-type estimators.
Moreover, the resulting estimate provides information on the time lag between
activation of transcription factors and their effects on regulated genes. We
provide an efficient algorithm for estimation of model parameters, and show
that the proposed method can consistently discover causal relationships in the
large , small setting. The performance of the proposed model is
evaluated favorably in simulated, as well as real, data examples. The proposed
truncating lasso method is implemented in the R-package grangerTlasso and is
available at http://www.stat.lsa.umich.edu/~shojaie.Comment: 12 pages, 4 figures, 1 tabl
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