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REGGAE: a Novel Approach for the Identification of Key Transcriptional Regulators

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.

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References
1.
Mathelier A, Fornes O, Arenillas D, Chen C, Denay G, Lee J . JASPAR 2016: a major expansion and update of the open-access database of transcription factor binding profiles. Nucleic Acids Res. 2015; 44(D1):D110-5. PMC: 4702842. DOI: 10.1093/nar/gkv1176. View

2.
Opgen-Rhein R, Strimmer K . Accurate ranking of differentially expressed genes by a distribution-free shrinkage approach. Stat Appl Genet Mol Biol. 2007; 6:Article9. DOI: 10.2202/1544-6115.1252. View

3.
Fazekas D, Koltai M, Turei D, Modos D, Palfy M, Dul Z . SignaLink 2 - a signaling pathway resource with multi-layered regulatory networks. BMC Syst Biol. 2013; 7:7. PMC: 3599410. DOI: 10.1186/1752-0509-7-7. View

4.
Harris A, Pinkert C, Crawford M, Langdon W, Brinster R, Adams J . The E mu-myc transgenic mouse. A model for high-incidence spontaneous lymphoma and leukemia of early B cells. J Exp Med. 1988; 167(2):353-71. PMC: 2188841. DOI: 10.1084/jem.167.2.353. View

5.
Subramanian A, Tamayo P, Mootha V, Mukherjee S, Ebert B, Gillette M . Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102(43):15545-50. PMC: 1239896. DOI: 10.1073/pnas.0506580102. View