A graphical model approach visualizes regulatory relationships between genome-wide transcription factor binding profiles
Publication Date
2016-10-25Journal Title
Briefings in Bioinformatics
ISSN
1467-5463
Publisher
Oxford University Press
Language
English
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Ng, F. S., Ruau, D., Wernisch, L., & Gottgens, B. (2016). A graphical model approach visualizes regulatory relationships between genome-wide transcription factor binding profiles. Briefings in Bioinformatics https://doi.org/10.1093/bib/bbw102
Abstract
Integrated analysis of multiple genome-wide transcription factor (TF)-binding profiles will be vital to advance our understanding of the global impact of TF binding. However, existing methods for measuring similarity in large numbers of chromatin immunoprecipitation assays with sequencing (ChIP-seq), such as correlation, mutual information or enrichment analysis, are limited in their ability to display functionally relevant TF relationships. In this study, we propose the use of graphical models to determine conditional independence between TFs and showed that network visualization provides a promising alternative to distinguish ‘direct’ versus ‘indirect’ TF interactions. We applied four algorithms to measure ‘direct’ dependence to a compendium of 367 mouse haematopoietic TF ChIP-seq samples and obtained a consensus network known as a ‘TF association network’ where edges in the network corresponded to likely causal pairwise relationships between TFs. The ‘TF association network’ illustrates the role of TFs in developmental pathways, is reminiscent of combinatorial TF regulation, corresponds to known protein–protein interactions and indicates substantial TF-binding reorganization in leukemic cell types. With the rapid increase in TF ChIP-Seq data sets, the approach presented here will be a powerful tool to study transcriptional programmes across a wide range of biological systems.
Keywords
ChIP-seq, network, transcriptional regulation, haematopoiesis
Sponsorship
Bloodwise, the Biotechnology and Biological Sciences Research Council, the Leukaemia and Lymphoma Society, Cancer Research UK, the National Institute for Health Research Cambridge Biomedical Research Centre, and the Wellcome Trust and MRC Cambridge Institute for Medical Research and Wellcome Trust—Medical Research Council Cambridge Stem Cell Institute; Yousef Jameel scholarship awarded by the Cambridge Commonwealth, European and International Trust (to F.S.L.N.).
Funder references
Leukaemia & Lymphoma Research (12029)
BBSRC (BB/I00050X/1)
Cancer Research UK (12765)
Wellcome Trust (097922/Z/11/Z)
MRC (MC_PC_12009)
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.1093/bib/bbw102
This record's URL: https://www.repository.cam.ac.uk/handle/1810/261213
Rights
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International
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