Journal Article

Regulatory impact factors: unraveling the transcriptional regulation of complex traits from expression data

Antonio Reverter, Nicholas J. Hudson, Shivashankar H. Nagaraj, Miguel Pérez-Enciso and Brian P. Dalrymple

in Bioinformatics

Volume 26, issue 7, pages 896-904
Published in print April 2010 | ISSN: 1367-4803
Published online February 2010 | e-ISSN: 1460-2059 | DOI:
Regulatory impact factors: unraveling the transcriptional regulation of complex traits from expression data

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Motivation: Although transcription factors (TF) play a central regulatory role, their detection from expression data is limited due to their low, and often sparse, expression. In order to fill this gap, we propose a regulatory impact factor (RIF) metric to identify critical TF from gene expression data.

Results: To substantiate the generality of RIF, we explore a set of experiments spanning a wide range of scenarios including breast cancer survival, fat, gonads and sex differentiation. We show that the strength of RIF lies in its ability to simultaneously integrate three sources of information into a single measure: (i) the change in correlation existing between the TF and the differentially expressed (DE) genes; (ii) the amount of differential expression of DE genes; and (iii) the abundance of DE genes. As a result, RIF analysis assigns an extreme score to those TF that are consistently most differentially co-expressed with the highly abundant and highly DE genes (RIF1), and to those TF with the most altered ability to predict the abundance of DE genes (RIF2). We show that RIF analysis alone recovers well-known experimentally validated TF for the processes studied. The TF identified confirm the importance of PPAR signaling in adipose development and the importance of transduction of estrogen signals in breast cancer survival and sexual differentiation. We argue that RIF has universal applicability, and advocate its use as a promising hypotheses generating tool for the systematic identification of novel TF not yet documented as critical.


Supplementary information: Supplementary data are available at Bioinformatics online.

Journal Article.  7454 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology

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