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ISMARA: Automated modeling of genomic signals as a democracy of regulatory motifs

Balwierz, Piotr J. and Pachkov, Mikhail and Arnold, Phild and Gruber, Andreas J. and Zavolan, Mihaela and van Nimwegen, Erik. (2014) ISMARA: Automated modeling of genomic signals as a democracy of regulatory motifs. Genome research, Vol. 24, H. 5. S. 869-884.

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Official URL: http://edoc.unibas.ch/dok/A6243441

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Abstract

Accurate reconstruction of the regulatory networks that control gene expression is one of the key current challenges in molecular biology. Although gene expression and chromatin state dynamics are ultimately encoded by constellations of binding sites recognized by regulators such as transcriptions factors (TFs) and microRNAs (miRNAs), our understanding of this regulatory code and its context-dependent read-out remains very limited. Given that there are thousands of potential regulators in mammals, it is not practical to use direct experimentation to identify which of these play a key role for a particular system of interest. We developed a methodology that models gene expression or chromatin modifications in terms of genome-wide predictions of regulatory sites, and completely automated it into a web-based tool called ISMARA (Integrated System for Motif Activity Response Analysis), located at http://ismara.unibas.ch. Given as input only gene expression or chromatin state data across a set of samples, ISMARA identifies the key TFs and miRNAs driving expression/chromatin changes and makes detailed predictions regarding their regulatory roles. These include predicted activities of the regulators across the samples, their genome-wide targets, enriched gene categories among the targets, and direct interactions between the regulators. Applying ISMARA to data sets from well-studied systems, we show that it consistently identifies known key regulators ab initio. We also present a number of novel predictions including regulatory interactions in innate immunity, a master regulator of mucociliary differentiation, TFs consistently disregulated in cancer, and TFs that mediate specific chromatin modifications.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (van Nimwegen)
05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
UniBasel Contributors:Zavolan, Mihaela and Balwierz, Piotr PJ and Pachkov, Mikhail and Gruber, Andreas J. and van Nimwegen, Erik
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:Cold Spring Harbor Laboratory Press
ISSN:1088-9051
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:18 Jul 2014 09:10
Deposited On:18 Jul 2014 09:10

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