Abstract
Chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-Seq) is a powerful technology to profile the location of proteins of interest on a whole-genome scale. To identify the enrichment location of proteins, many programs and algorithms have been proposed. However, none of the commonly used peak calling programs could accurately explain the binding features of target proteins detected by ChIP-Seq. Here, publicly available data on 12 histone modifications, including H3K4ac/me1/me2/me3, H3K9ac/me3, H3K27ac/me3, H3K36me3, H3K56ac, and H3K79me1/me2, generated from a human embryonic stem cell line (H1), were profiled with five peak callers (CisGenome, MACS1, MACS2, PeakSeq, and SISSRs). The performance of the peak calling programs was compared in terms of reproducibility between replicates, examination of enriched regions to variable sequencing depths, the specificity-to-noise signal, and sensitivity of peak prediction. There were no major differences among peak callers when analyzing point source histone modifications. The peak calling results from histone modifications with low fidelity, such as H3K4ac, H3K56ac, and H3K79me1/me2, showed low performance in all parameters, which indicates that their peak positions might not be located accurately. Our comparative results could provide a helpful guide to choose a suitable peak calling program for specific histone modifications.
Highlights
Protein-binding regions in the context of chromatin have been detected by the chromatin immunoprecipitation (ChIP) method
Overview of ChIP-Seq data analysis For the comparative analysis of ChIP-Seq peak calling programs, data on 12 types of histone modifications were initially filtered and only high-quality mappable reads were used for further analysis (Supplementary Table 3)
The peak counts of H3K4me3, H3K9ac, H3K27me3, and H3K56ac were similar in most peak calling programs except SISSRs
Summary
Protein-binding regions in the context of chromatin have been detected by the chromatin immunoprecipitation (ChIP) method. Post-translational modifications of histone tails play an important role in the epigenetic regulation of genome activity. These modifications include acetylation, methylation, Jeon HG et al Comparison of ChIP-Seq peak calling programs phosphorylation, and ubiquitination. Acetylated histones provide a chromatin environment accessible to the transcriptional machinery by changing the chromatin conformation. Some histone methylations, such as H3K4me and H3K4me, are mostly located on promoters, whereas H3K36me is predominantly found on the gene bodies of transcriptionally active genes [4,5]
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