Dataset Information

DISCLOSE : DISsection of CLusters Obtained by SEries of transcriptome data using functional annotations and putative transcription factor binding sites.

ABSTRACT: BACKGROUND: A typical step in the analysis of gene expression data is the determination of clusters of genes that exhibit similar expression patterns. Researchers are confronted with the seemingly arbitrary choice between numerous algorithms to perform cluster analysis. RESULTS: We developed an exploratory application that benchmarks the results of clustering methods using functional annotations. In addition, a de novo DNA motif discovery algorithm is integrated in our program which identifies overrepresented DNA binding sites in the upstream DNA sequences of genes from the clusters that are indicative of sites of transcriptional control. The performance of our program was evaluated by comparing the original results of a time course experiment with the findings of our application. CONCLUSION: DISCLOSE assists researchers in the prokaryotic research community in systematically evaluating results of the application of a range of clustering algorithms to transcriptome data. Different performance measures allow to quickly and comprehensively determine the best suited clustering approach for a given dataset.

SUBMITTER: Blom EJ

PROVIDER: S-EPMC2661003 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Publications

DISCLOSE : DISsection of CLusters Obtained by SEries of transcriptome data using functional annotations and putative transcription factor binding sites.

Blom Evert-Jan EJ van Hijum Sacha A F T SA Hofstede Klaas J KJ Silvis Remko R Roerdink Jos B T M JB Kuipers Oscar P OP

BMC bioinformatics 20081216

<h4>Background</h4>A typical step in the analysis of gene expression data is the determination of clusters of genes that exhibit similar expression patterns. Researchers are confronted with the seemingly arbitrary choice between numerous algorithms to perform cluster analysis.<h4>Results</h4>We developed an exploratory application that benchmarks the results of clustering methods using functional annotations. In addition, a de novo DNA motif discovery algorithm is integrated in our program which ...[more]

PMID: 19087282

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Project description:BackgroundUnderstanding transcriptional regulation of gene expression is one of the greatest challenges of modern molecular biology. A central role in this mechanism is played by transcription factors, which typically bind to specific, short DNA sequence motifs usually located in the upstream region of the regulated genes. We discuss here a simple and powerful approach for the ab initio identification of these cis-regulatory motifs. The method we present integrates several elements: human-mouse comparison, statistical analysis of genomic sequences and the concept of coregulation. We apply it to a complete scan of the human genome.ResultsBy using the catalogue of conserved upstream sequences collected in the CORG database we construct sets of genes sharing the same overrepresented motif (short DNA sequence) in their upstream regions both in human and in mouse. We perform this construction for all possible motifs from 5 to 8 nucleotides in length and then filter the resulting sets looking for two types of evidence of coregulation: first, we analyze the Gene Ontology annotation of the genes in the set, searching for statistically significant common annotations; second, we analyze the expression profiles of the genes in the set as measured by microarray experiments, searching for evidence of coexpression. The sets which pass one or both filters are conjectured to contain a significant fraction of coregulated genes, and the upstream motifs characterizing the sets are thus good candidates to be the binding sites of the TF's involved in such regulation. In this way we find various known motifs and also some new candidate binding sites.ConclusionWe have discussed a new integrated algorithm for the "ab initio" identification of transcription factor binding sites in the human genome. The method is based on three ingredients: comparative genomics, overrepresentation, different types of coregulation. The method is applied to a full-scan of the human genome, giving satisfactory results.

Dataset Information

DISCLOSE : DISsection of CLusters Obtained by SEries of transcriptome data using functional annotations and putative transcription factor binding sites.

Publications

DISCLOSE : DISsection of CLusters Obtained by SEries of transcriptome data using functional annotations and putative transcription factor binding sites.

Similar Datasets

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