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Bioinformatics. 2018 Oct 15;34(20):3503-3510. doi: 10.1093/bioinformatics/bty372.

REGGAE: a novel approach for the identification of key transcriptional regulators.

Author information

1
Center for Bioinformatics, Saarland Informatics Campus, Saarland University, Saarbrücken D-66041, Germany.
2
Department of Genetics, Saarland University, Saarbrücken D-66041, Germany.
3
Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, and Comprehensive Cancer Center Mainfranken, Würzburg University, Würzburg, Germany.
4
Department of Human Genetics, Medical School, Saarland University, Homburg, Germany.
5
Institute for Immunology, Johannes Gutenberg University Mainz, Mainz, Germany.
6
Department of Internal Medicine III, School of Medicine, Technische Universität München, Munich, Germany.
7
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
8
Department of Pediatric Oncology and Hematology, Medical School, Saarland University, Homburg, Germany.

Abstract

Motivation:

Transcriptional regulators play a major role in most biological processes. Alterations in their activities are associated with a variety of diseases and in particular with tumor development and progression. Hence, it is important to assess the effects of deregulated regulators on pathological processes.

Results:

Here, we present REGulator-Gene Association Enrichment (REGGAE), a novel method for the identification of key transcriptional regulators that have a significant effect on the expression of a given set of genes, e.g. genes that are differentially expressed between two sample groups. REGGAE uses a Kolmogorov-Smirnov-like test statistic that implicitly combines associations between regulators and their target genes with an enrichment approach to prioritize the influence of transcriptional regulators. We evaluated our method in two different application scenarios, which demonstrate that REGGAE is well suited for uncovering the influence of transcriptional regulators and is a valuable tool for the elucidation of complex regulatory mechanisms.

Availability and implementation:

REGGAE is freely available at https://regulatortrail.bioinf.uni-sb.de.

Supplementary information:

Supplementary data are available at Bioinformatics online.

PMID:
29741575
PMCID:
PMC6184769
DOI:
10.1093/bioinformatics/bty372
[Indexed for MEDLINE]
Free PMC Article

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