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Identifying submodules of cellular regulatory networks

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TLDR
This paper integrates network architecture data with genome-wide gene expression measurements in order to determine which regulatory relations are actually confirmed by the expression data, and obtains non-trivial submodules of the regulatory network using two distinct algorithms, a naive exhaustive algorithm and a spectral algorithm based on the eigendecomposition of an affinity matrix.
Abstract
Recent high throughput techniques in molecular biology have brought about the possibility of directly identifying the architecture of regulatory networks on a genome-wide scale. However, the computational task of estimating fine-grained models on a genome-wide scale is daunting. Therefore, it is of great importance to be able to reliably identify submodules of the network that can be effectively modelled as independent subunits. In this paper we present a procedure to obtain submodules of a cellular network by using information from gene-expression measurements. We integrate network architecture data with genome-wide gene expression measurements in order to determine which regulatory relations are actually confirmed by the expression data. We then use this information to obtain non-trivial submodules of the regulatory network using two distinct algorithms, a naive exhaustive algorithm and a spectral algorithm based on the eigendecomposition of an affinity matrix. We test our method on two yeast biological data sets, using regulatory information obtained from chromatin immunoprecipitation.

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Citations
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Singular Value Decomposition for Genome-Wide Expression Data Processing and Modeling

TL;DR: Using singular value decomposition in transforming genome-wide expression data from genes x arrays space to reduced diagonalized "eigengenes" x "eigenarrays" space gives a global picture of the dynamics of gene expression, in which individual genes and arrays appear to be classified into groups of similar regulation and function, or similar cellular state and biological phenotype.
Journal ArticleDOI

MMG: a probabilistic tool to identify submodules of metabolic pathways.

TL;DR: Mixture Model on Graphs (MMG), a novel probabilistic model to identify differentially expressed submodules of biological networks and pathways is introduced, which can easily incorporate information about weights in the network, is robust against missing data and can be easily generalized to directed networks.
References
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Journal ArticleDOI

Comprehensive Identification of Cell Cycle–regulated Genes of the Yeast Saccharomyces cerevisiae by Microarray Hybridization

TL;DR: A comprehensive catalog of yeast genes whose transcript levels vary periodically within the cell cycle is created, and it is found that the mRNA levels of more than half of these 800 genes respond to one or both of these cyclins.
Journal ArticleDOI

An efficient algorithm for large-scale detection of protein families

TL;DR: This work presents a novel approach called TRIBE-MCL for rapid and accurate clustering of protein sequences into families based on precomputed sequence similarity information that has been rigorously tested and validated on a number of very large databases.
Journal ArticleDOI

Transcriptional Regulatory Networks in Saccharomyces cerevisiae

TL;DR: This work determines how most of the transcriptional regulators encoded in the eukaryote Saccharomyces cerevisiae associate with genes across the genome in living cells, and identifies network motifs, the simplest units of network architecture, and demonstrates that an automated process can use motifs to assemble a transcriptional regulatory network structure.
Journal ArticleDOI

Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals

TL;DR: In this article, a comparative analysis of the human, mouse, rat and dog genomes is presented to create a systematic catalogue of common regulatory motifs in promoters and 3' untranslated regions (3' UTRs).
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