Identification of significant chromatin contacts from HiChIP data by FitHiChIP

Sourya Bhattacharyya, Vivek Chandra, Pandurangan Vijayanand and Ferhat Ay ()
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Sourya Bhattacharyya: La Jolla Institute for Immunology
Vivek Chandra: La Jolla Institute for Immunology
Pandurangan Vijayanand: La Jolla Institute for Immunology
Ferhat Ay: La Jolla Institute for Immunology

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract HiChIP/PLAC-seq is increasingly becoming popular for profiling 3D chromatin contacts among regulatory elements and for annotating functions of genetic variants. Here we describe FitHiChIP, a computational method for loop calling from HiChIP/PLAC-seq data, which jointly models the non-uniform coverage and genomic distance scaling of contact counts to compute statistical significance estimates. We also develop a technique to filter putative bystander loops that can be explained by stronger adjacent loops. Compared to existing methods, FitHiChIP performs better in recovering contacts reported by Hi-C, promoter capture Hi-C and ChIA-PET experiments and in capturing previously validated promoter-enhancer interactions. FitHiChIP loop calls are reproducible among replicates and are consistent across different experimental settings. Our work also provides a framework for differential HiChIP analysis with an option to utilize ChIP-seq data for further characterizing differential loops. Even though designed for HiChIP, FitHiChIP is also applicable to other conformation capture assays.

Date: 2019
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DOI: 10.1038/s41467-019-11950-y

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