Characterizing protein-DNA binding event subtypes in ChIP-exo data

Bioinformatics
Naomi YamadaShaun Mahony

Abstract

Regulatory proteins associate with the genome either by directly binding cognate DNA motifs or via protein-protein interactions with other regulators. Each recruitment mechanism may be associated with distinct motifs and may also result in distinct characteristic patterns in high-resolution protein-DNA binding assays. For example, the ChIP-exo protocol precisely characterizes protein-DNA crosslinking patterns by combining chromatin immunoprecipitation (ChIP) with 5' → 3' exonuclease digestion. Since different regulatory complexes will result in different protein-DNA crosslinking signatures, analysis of ChIP-exo tag enrichment patterns should enable detection of multiple protein-DNA binding modes for a given regulatory protein. However, current ChIP-exo analysis methods either treat all binding events as being of a uniform type or rely on motifs to cluster binding events into subtypes. To systematically detect multiple protein-DNA interaction modes in a single ChIP-exo experiment, we introduce the ChIP-exo mixture model (ChExMix). ChExMix probabilistically models the genomic locations and subtype memberships of binding events using both ChIP-exo tag distribution patterns and DNA motifs. We demonstrate that ChExMix achieves accur...Continue Reading

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Citations

Dec 6, 2018·Nucleic Acids Research·Marius GheorgheAnthony Mathelier
Feb 6, 2020·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Naomi YamadaShaun Mahony
May 1, 2020·NPJ Breast Cancer·Hanan S ElsarrajFariba Behbod
Feb 20, 2021·Nature Genetics·Žiga AvsecJulia Zeitlinger
Feb 13, 2021·NPJ Breast Cancer·Hanan S ElsarrajFariba Behbod
Mar 12, 2021·Nature·Matthew J RossiB Franklin Pugh
Jun 28, 2021·BMC Genomics·Rafael Riudavets PuigAnthony Mathelier
Jul 13, 2021·Bioinformatics·Anushua Biswas, Leelavati Narlikar

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