Removing unwanted variation between samples in Hi-C experiments

K Fletez-Brant, Y Qiu, DU Gorkin, M Hu… - Briefings in …, 2024 - academic.oup.com
Briefings in Bioinformatics, 2024academic.oup.com
Hi-C data are commonly normalized using single sample processing methods, with focus on
comparisons between regions within a given contact map. Here, we aim to compare contact
maps across different samples. We demonstrate that unwanted variation, of likely technical
origin, is present in Hi-C data with replicates from different individuals, and that properties of
this unwanted variation change across the contact map. We present band-wise
normalization and batch correction, a method for normalization and batch correction of Hi-C …
Abstract
Hi-C data are commonly normalized using single sample processing methods, with focus on comparisons between regions within a given contact map. Here, we aim to compare contact maps across different samples. We demonstrate that unwanted variation, of likely technical origin, is present in Hi-C data with replicates from different individuals, and that properties of this unwanted variation change across the contact map. We present band-wise normalization and batch correction, a method for normalization and batch correction of Hi-C data and show that it substantially improves comparisons across samples, including in a quantitative trait loci analysis as well as differential enrichment across cell types.
Oxford University Press
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