Peak calling

Peak calling is a computational method used to identify areas in a genome that have been enriched with aligned reads as a consequence of performing a ChIP-sequencing or MeDIP-seq experiment. These areas are those where a protein interacts with DNA.[1] When the protein is a transcription factor, the enriched area is its transcription factor binding site (TFBS). Popular software programs include MACS.[2] Wilbanks and colleagues[3] is a survey of the ChIP-seq peak callers, and Bailey et al.[4] is a description of practical guidelines for peak calling in ChIP-seq data.

Peak calling may be conducted on transcriptome/exome as well to RNA epigenome sequencing data from MeRIPseq[5] or m6Aseq[6] for detection of post-transcriptional RNA modification sites with software programs, such as exomePeak.[7] Many of the peak calling tools are optimised for only some kind of assays such as only for transcription-factor ChIP-seq or only for DNase-seq.[8] However new generation of peak callers such as DFilter[9] are based on generalised optimal theory of detection and has been shown to work for nearly all kinds for tag profile signals from next-gen sequencing data. It is also possible to do more complex analysis using such tools like combining multiple ChIP-seq signal to detect regulatory sites. [10]

In the context of ChIP-exo, this process is known as 'peak-pair calling'.[11]

Differential peak calling is about identifying significant differences in two ChIP-seq signals. One can distinguish between one-stage and two-stage differential peak callers. One stage differential peak callers work in two phases: first, call peaks on individual ChIP-seq signals and second, combine individual signals and apply statistical tests to estimate differential peaks. DBChIP[12] and MAnorm[13] are examples for one stage differential peak callers.

Two stage differential peak callers segment two ChIP-seq signals and identify differential peaks in one step. They take advantage of signal segmentation approaches such as Hidden Markov Models. Examples for two-stage differential peak callers are ChIPDiff,[14] ODIN.[15] and THOR. Differential peak calling can also be applied in the context of analyzing RNA-binding protein binding sites.[16]