Chen, XiShi, XuNeuwald, Andrew F.Hilakivi-Clarke, LeenaClarke, RobertXuan, Jianhua2021-04-192021-04-192021-04-15BMC Bioinformatics. 2021 Apr 15;22(1):193http://hdl.handle.net/10919/103056Background 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.application/pdfenCreative Commons Attribution 4.0 InternationalArticle - Refereed2021-04-18The Author(s)https://doi.org/10.1186/s12859-021-04108-5