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DiRE: identifying distant regulatory elements of co-expressed genes.

ABSTRACT: Regulation of gene expression in eukaryotic genomes is established through a complex cooperative activity of proximal promoters and distant regulatory elements (REs) such as enhancers, repressors and silencers. We have developed a web server named DiRE, based on the Enhancer Identification (EI) method, for predicting distant regulatory elements in higher eukaryotic genomes, namely for determining their chromosomal location and functional characteristics. The server uses gene co-expression data, comparative genomics and profiles of transcription factor binding sites (TFBSs) to determine TFBS-association signatures that can be used for discriminating specific regulatory functions. DiRE's unique feature is its ability to detect REs outside of proximal promoter regions, as it takes advantage of the full gene locus to conduct the search. DiRE can predict common REs for any set of input genes for which the user has prior knowledge of co-expression, co-function or other biologically meaningful grouping. The server predicts function-specific REs consisting of clusters of specifically-associated TFBSs and it also scores the association of individual transcription factors (TFs) with the biological function shared by the group of input genes. Its integration with the Array2BIO server allows users to start their analysis with raw microarray expression data. The DiRE web server is freely available at http://dire.dcode.org.

SUBMITTER: Gotea V

PROVIDER: S-EPMC2447744 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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DiRE: identifying distant regulatory elements of co-expressed genes.

Gotea Valer V Ovcharenko Ivan I

Nucleic acids research 20080517 Web Server issue

Regulation of gene expression in eukaryotic genomes is established through a complex cooperative activity of proximal promoters and distant regulatory elements (REs) such as enhancers, repressors and silencers. We have developed a web server named DiRE, based on the Enhancer Identification (EI) method, for predicting distant regulatory elements in higher eukaryotic genomes, namely for determining their chromosomal location and functional characteristics. The server uses gene co-expression data, ...[more]

PMID: 18487623

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Project description:BackgroundThe male germ line in flowering plants is initiated within developing pollen grains via asymmetric division. The smaller cell then becomes totally encased within a much larger vegetative cell, forming a unique "cell within a cell structure". The generative cell subsequently divides to give rise to two non-motile diminutive sperm cells, which take part in double fertilization and lead to the seed set. Sperm cells are difficult to investigate because of their presence within the confines of the larger vegetative cell. However, recently developed techniques for the isolation of rice sperm cells and the fully annotated rice genome sequence have allowed for the characterization of the transcriptional repertoire of sperm cells. Microarray gene expression data has identified a subset of rice genes that show unique or highly preferential expression in sperm cells. This information has led to the identification of cis-regulatory elements (CREs), which are conserved in sperm-expressed genes and are putatively associated with the control of cell-specific expression.FindingsWe aimed to identify the CREs associated with rice sperm cell-specific gene expression data using in silico prediction tools. We analyzed 1-kb upstream regions of the top 40 sperm cell co-expressed genes for over-represented conserved and novel motifs. Analysis of upstream regions with the SIGNALSCAN program with the PLACE database, MEME and the Mclip tool helped to find combinatorial sets of known transcriptional factor-binding sites along with two novel motifs putatively associated with the co-expression of sperm cell-specific genes.ConclusionsOur data shows the occurrence of novel motifs, which are putative CREs and are likely targets of transcriptional factors regulating sperm cell gene expression. These motifs can be used to design the experimental verification of regulatory elements and the identification of transcriptional factors that regulate sperm cell-specific gene expression.

Project description:BackgroundThe landscape of biological and biomedical research is being changed rapidly with the invention of microarrays which enables simultaneous view on the transcription levels of a huge number of genes across different experimental conditions or time points. Using microarray data sets, clustering algorithms have been actively utilized in order to identify groups of co-expressed genes. This article poses the problem of fuzzy clustering in microarray data as a multiobjective optimization problem which simultaneously optimizes two internal fuzzy cluster validity indices to yield a set of Pareto-optimal clustering solutions. Each of these clustering solutions possesses some amount of information regarding the clustering structure of the input data. Motivated by this fact, a novel fuzzy majority voting approach is proposed to combine the clustering information from all the solutions in the resultant Pareto-optimal set. This approach first identifies the genes which are assigned to some particular cluster with high membership degree by most of the Pareto-optimal solutions. Using this set of genes as the training set, the remaining genes are classified by a supervised learning algorithm. In this work, we have used a Support Vector Machine (SVM) classifier for this purpose.ResultsThe performance of the proposed clustering technique has been demonstrated on five publicly available benchmark microarray data sets, viz., Yeast Sporulation, Yeast Cell Cycle, Arabidopsis Thaliana, Human Fibroblasts Serum and Rat Central Nervous System. Comparative studies of the use of different SVM kernels and several widely used microarray clustering techniques are reported. Moreover, statistical significance tests have been carried out to establish the statistical superiority of the proposed clustering approach. Finally, biological significance tests have been carried out using a web based gene annotation tool to show that the proposed method is able to produce biologically relevant clusters of co-expressed genes.ConclusionThe proposed clustering method has been shown to perform better than other well-known clustering algorithms in finding clusters of co-expressed genes efficiently. The clusters of genes produced by the proposed technique are also found to be biologically significant, i.e., consist of genes which belong to the same functional groups. This indicates that the proposed clustering method can be used efficiently to identify co-expressed genes in microarray gene expression data.Supplementary Website The pre-processed and normalized data sets, the matlab code and other related materials are available at http://anirbanmukhopadhyay.50webs.com/mogasvm.html.

Project description:RNA sequencing (RNA-Seq) measures genome-wide gene expression. RNA-Seq data is count-based rendering normal distribution models for analysis inappropriate. Normalization of RNA-Seq data to transform the data has limitations which can adversely impact the analysis. Furthermore, there are a few count-based methods for analysis of RNA-Seq data but they are essentially for pairwise analysis of treatment groups or multiclasses but not pattern-based to identify co-expressed genes.We adapted our extracting patterns and identifying genes methodology for RNA-Seq (EPIG-Seq) count data. The software uses count-based correlation to measure similarity between genes, quasi-Poisson modelling to estimate dispersion in the data and a location parameter to indicate magnitude of differential expression. EPIG-Seq is different than any other software currently available for pattern analysis of RNA-Seq data in that EPIG-Seq 1) uses count level data and supports cases of inflated zeros, 2) identifies statistically significant clusters of genes that are co-expressed across experimental conditions, 3) takes into account dispersion in the replicate data and 4) provides reliable results even with small sample sizes. EPIG-Seq operates in two steps: 1) extract the pattern profiles from data as seeds for clustering co-expressed genes and 2) cluster the genes to the pattern seeds and compute statistical significance of the pattern of co-expressed genes. EPIG-Seq provides a table of the genes with bootstrapped p-values and profile plots of the patterns of co-expressed genes. In addition, EPIG-Seq provides a heat map and principal component dimension reduction plot of the clustered genes as visual aids. We demonstrate the utility of EPIG-Seq through the analysis of toxicogenomics and cancer data sets to identify biologically relevant co-expressed genes. EPIG-Seq is available at: sourceforge.net/projects/epig-seq.EPIG-Seq is unlike any other software currently available for pattern analysis of RNA-Seq count level data across experimental groups. Using the EPIG-Seq software to analyze RNA-Seq count data across biological conditions permits the ability to extract biologically meaningful co-expressed genes associated with coordinated regulation.

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DiRE: identifying distant regulatory elements of co-expressed genes.

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DiRE: identifying distant regulatory elements of co-expressed genes.

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