Title
RIP: the regulatory interaction predictor--a machine learning-based approach for predicting target genes of transcription factors.
Abstract
Motivation: Understanding transcriptional gene regulation is essential for studying cellular systems. Identifying genome-wide targets of transcription factors (TFs) provides the basis to discover the involvement of TFs and TF cooperativeness in cellular systems and pathogenesis. Results: We present the regulatory interaction predictor (RIP), a machine learning approach that inferred 73 923 regulatory interactions (RIs) for 301 human TFs and 11 263 target genes with considerably good quality and 4516 RIs with very high quality. The inference of RIs is independent of any specific condition. Our approach employs support vector machines (SVMs) trained on a set of experimentally proven RIs from a public repository (TRANSFAC). Features of RIs for the learning process are based on a correlation meta-analysis of 4064 gene expression profiles from 76 studies, in silico predictions of transcription factor binding sites (TFBSs) and combinations of these employing knowledge about co-regulation of genes by a common TF (TF-module). The trained SVMs were applied to infer new RIs for a large set of TFs and genes. In a case study, we employed the inferred RIs to analyze an independent microarray dataset. We identified key TFs regulating the transcriptional response upon interferon alpha stimulation of monocytes, most prominently interferon-stimulated gene factor 3 (ISGF3). Furthermore, predicted TF-modules were highly associated to their functionally related pathways. Conclusion: Descriptors of gene expression, TFBS predictions, experimentally verified binding information and statistical combination of this enabled inferring RIs on a genome-wide scale for human genes with considerably good precision serving as a good basis for expression profiling studies.
Year
DOI
Venue
2011
10.1093/bioinformatics/btr366
BIOINFORMATICS
Field
DocType
Volume
Data mining,Gene,Computer science,Artificial intelligence,Transcription factor,In silico,Interferon-Stimulated Gene Factor 3,DNA binding site,Regulation of gene expression,Bioinformatics,TRANSFAC,Gene expression profiling,Machine learning
Journal
27
Issue
ISSN
Citations 
16
1367-4803
3
PageRank 
References 
Authors
0.44
10
3
Name
Order
Citations
PageRank
Tobias Bauer130.44
Roland Eils264470.09
Rainer König330.44