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

• Main Authors: Chen, X. (Author), Clarke, R. (Author), Hilakivi-Clarke, L. (Author), Neuwald, A.F (Author), Shi, X. (Author), Xuan, J. (Author)
• Format: Article
• Language: English
• Published: BioMed Central Ltd 2021
• Subjects: article; Bayes theorem; Bayes Theorem; Bayesian integration; binding site; Binding sites; Binding Sites; chromatin immunoprecipitation; Chromatin Immunoprecipitation; Chromatin immunoprecipitation assay; chromatin immunoprecipitation sequencing; Control chips; DNA microarray; DNA sequence; DNA-binding protein; enhancer region; Gene encoding; Gene expression; Gene expression regulation; Genomic locations; high throughput sequencing; High-Throughput Nucleotide Sequencing; Oligonucleotide Array Sequence Analysis; Peak detection; promoter region; protein binding; Protein-binding sites; Proteins; Regulatory regions; Sequence Analysis, DNA; software; Software
• Online Access: View Fulltext in Publisher

 Background: 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 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. Results: ChIP-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. Conclusion: ChIP-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. © 2021, The Author(s).