HiChIP-Peaks: a HiChIP peak calling algorithm.

Chenfu Shi,Gisela Orozco,Magnus Rattray,Inanc Birol

doi:10.1093/bioinformatics/btaa202

Abstract

MotivationHiChIP is a powerful tool to interrogate 3D chromatin organization. Current tools to analyse chromatin looping mechanisms using HiChIP data require the identification of loop anchors to work properly. However, current approaches to discover these anchors from HiChIP data are not satisfactory, having either a very high false discovery rate or strong dependence on sequencing depth. Moreover, these tools do not allow quantitative comparison of peaks across different samples, failing to fully exploit the information available from HiChIP datasets.ResultsWe develop a new tool based on a representation of HiChIP data centred on the re-ligation sites to identify peaks from HiChIP datasets, which can subsequently be used in other tools for loop discovery. This increases the reliability of these tools and improves recall rate as sequencing depth is reduced. We also provide a method to count reads mapping to peaks across samples, which can be used for differential peak analysis using HiChIP data.Availability and implementationHiChIP-Peaks is freely available at https://github.com/ChenfuShi/HiChIP_peaks.Supplementary information Supplementary data are available at Bioinformatics online.

Highlights

The three-dimensional conformation of the chromatin is fundamental in the regulation of gene expression; regulatory elements such as enhancers have been shown to act by physically interacting with their target promoters (Yao et al, 2015; Shlyueva et al, 2014; Bulger and Groudine, 2011; Nolis et al, 2009)
HiChIP is a recently developed technique to analyse chromatin conformation which consists of an in-situ Hi-C library preparation followed by a chromatin immunoprecipitation (ChIP) step, usually targeting the histone modification H3K27ac or cohesin
We note that our algorithm is able to produce a higher recall rate compared to Hichipper and we see that using peaks called with our algorithm yields significantly better stability in recall of loops for both cell types as the datasets size is reduced (Fig. 4 B, D)

Summary

Introduction

The three-dimensional conformation of the chromatin is fundamental in the regulation of gene expression; regulatory elements such as enhancers have been shown to act by physically interacting with their target promoters (Yao et al, 2015; Shlyueva et al, 2014; Bulger and Groudine, 2011; Nolis et al, 2009) These regulatory elements are highly regulated and context specific (Simeonov et al, 2017; Kundaje et al, 2015; Alasoo et al, 2018). HiChIP provides a new set of computational challenges because it combines biases introduced by two independent techniques: ChIP and in-situ Hi-C library preparation. This phenomenon is evidenced by libraries enriched for H3K27ac because this histone modification has a significantly more specific enrichment compared to cohesin

Methods

Results

Conclusion