Abstract

SummaryCapture Hi-C is a powerful approach for detecting chromosomal interactions involving, at least on one end, DNA regions of interest, such as gene promoters. We present Chicdiff, an R package for robust detection of differential interactions in Capture Hi-C data. Chicdiff enhances a state-of-the-art differential testing approach for count data with bespoke normalization and multiple testing procedures that account for specific statistical properties of Capture Hi-C. We validate Chicdiff on published Promoter Capture Hi-C data in human Monocytes and CD4+ T cells, identifying multitudes of cell type-specific interactions, and confirming the overall positive association between promoter interactions and gene expression.Availability and implementationChicdiff is implemented as an R package that is publicly available at https://github.com/RegulatoryGenomicsGroup/chicdiff.Supplementary information Supplementary data are available at Bioinformatics online.

Highlights

  • Differential signal detection in sequencing data is one of the most common tasks in genomic analyses

  • Multiple tools have been developed for this purpose, many of which, including DESeq and EdgeR, are based on the negative binomial models for count data (Anders and Huber, 2010; Robinson et al, 2010)

  • In Capture Hi-C (CHi-C), the genome-wide pulldown of pairs of interacting genomic fragments by Hi-C is followed by sequence capture to selectively enrich Hi-C material for interactions involving fragments of interest, termed 'baits'

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Summary

Summary

Capture Hi-C is a powerful approach for detecting chromosomal interactions involving, at least on one end, DNA regions of interest, such as gene promoters. We present Chicdiff, an R package for robust detection of differential interactions in Capture Hi-C data. Chicdiff enhances a state-of-the-art differential testing approach for count data with bespoke normalisation and multiple testing procedures that account for specific statistical properties of Capture Hi-C. We validate Chicdiff on published Promoter Capture Hi-C data in human Monocytes and CD4+T cells, identifying multitudes of cell type-specific interactions, and confirming the overall positive association between promoter interactions and gene expression. Chicdiff is implemented as an R package that is publicly available at https://github.com/RegulatoryGenomicsGroup/chicdiff

Introduction
Feature selection
Data normalisation and significance testing
Weighted multiple testing treatment
Use example
Conclusions
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