ChIP-BIT2: a software tool to detect weak binding events using a Bayesian integration approach

Xi Chen,Leena Hilakivi-Clarke,Jianhua Xuan,Andrew F Neuwald,Robert Clarke,Xu Shi

doi:10.1186/s12859-021-04108-5

Abstract

BackgroundChIP-seq combines chromatin immunoprecipitation assays with sequencing and identifies genome-wide binding sites for DNA binding proteins. While many binding sites have strong ChIP-seq ‘peak’ observations and are well captured, there are still regions bound by proteins weakly, with a relatively low ChIP-seq signal enrichment. These weak binding sites, especially those at promoters and enhancers, are functionally important because they also regulate nearby gene expression. Yet, it remains a challenge to accurately identify weak binding sites in ChIP-seq data due to the ambiguity in differentiating these weak binding sites from the amplified background DNAs.ResultsChIP-BIT2 (http://sourceforge.net/projects/chipbitc/) is a software package for ChIP-seq peak detection. ChIP-BIT2 employs a mixture model integrating protein and control ChIP-seq data and predicts strong or weak protein binding sites at promoters, enhancers, or other genomic locations. For binding sites at gene promoters, ChIP-BIT2 simultaneously predicts their target genes. ChIP-BIT2 has been validated on benchmark regions and tested using large-scale ENCODE ChIP-seq data, demonstrating its high accuracy and wide applicability.ConclusionChIP-BIT2 is an efficient ChIP-seq peak caller. It provides a better lens to examine weak binding sites and can refine or extend the existing binding site collection, providing additional regulatory regions for decoding the mechanism of gene expression regulation.

Highlights

ChIP-seq technique combines chromatin immunoprecipitation (ChIP) assays with massively parallel sequencing (Seq) and delivers genome-wide profiling of DNA sites bound by a specific protein [1, 2]
ChIP‐BIT algorithm The challenge in weak peak detection of ChIP-seq data lies in the ambiguity in differentiating weak signals of protein binding sites from noise signals produced by the background regions
Histone modification benchmark analysis The ChIP-BIT algorithm has been benchmarked on narrow Transcription factor binding site (TFBS) and demonstrated to perform better than conventional peak callers [8, 20]

Summary

Introduction

ChIP-seq technique combines chromatin immunoprecipitation (ChIP) assays with massively parallel sequencing (Seq) and delivers genome-wide profiling of DNA sites bound by a specific protein [1, 2]. Partner TFs and most HMs bind at more diverse loci and some of them have weak ChIP-seq signal enrichment at long DNA segments [5,6,7]. ChIP-seq combines chromatin immunoprecipitation assays with sequencing and identifies genome-wide binding sites for DNA binding proteins. While many binding sites have strong ChIP-seq ‘peak’ observations and are well captured, there are still regions bound by proteins weakly, with a relatively low ChIP-seq signal enrichment. These weak binding sites, especially those at promoters and enhancers, are functionally important because they regulate nearby gene expression.

Methods

Results

Discussion

Conclusion