ChExMix: A Method for Identifying and Classifying Protein–DNA Interaction Subtypes

Abstract

Regulatory proteins can employ multiple direct and indirect modes of interaction with the genome. The ChIP-exo mixture model (ChExMix) provides a principled approach to detecting multiple protein–DNA interaction modes in a single ChIP-exo experiment. ChExMix discovers and characterizes binding event subtypes in ChIP-exo data by leveraging both protein–DNA cross-linking signatures and DNA motifs. In this study, we present a summary of the major features and applications of ChExMix. We demonstrate that ChExMix does not require high-resolution protein–DNA binding assay data to detect binding event subtypes. Specifically, we apply ChExMix to analyze 393 ChIP-seq data profiles in K562 cells. Similar binding event subtypes are discovered across multiple proteins, suggesting the existence of colocalized regulatory protein modules that are recruited to DNA through a particular sequence-specific transcription factor. Our results thus suggest that ChExMix can characterize protein–DNA binding interaction modes using data from multiple types of protein–DNA interaction assays.