Abstract

Hi-C data is important for studying chromatin three-dimensional structure. However, the resolution of most existing Hi-C data is generally coarse due to sequencing cost. Therefore, it will be helpful if we can predict high-resolution Hi-C data from low-coverage sequencing data. Here we developed a novel and simple computational method based on deep learning named super-resolution Hi-C (SRHiC) to enhance the resolution of Hi-C data. We verified SRHiC on Hi-C data in human cell line. We also evaluated the generalization power of SRHiC by enhancing Hi-C data resolution in other human and mouse cell types. Results showed that SRHiC outperforms the state-of-the-art methods in accuracy of prediction.

Highlights

  • Chromatin three-dimensional (3D) structure is vital to biological processes (Cremer and Cremer, 2001; Bonev and Cavalli, 2016), such as genome replication, DNA mutation and repair, transcription and so on

  • We found that HiCNN showed much longer time for training than super-resolution high-throughput chromosome conformation capture (Hi-C) (SRHiC) and HiCPlus (Supplementary Table S1)

  • The training time required by HiCNN was nearly 17.6 times that of HiCPlus, and the time required by SRHiC was 2.9 times that of HiCPlus

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Summary

Introduction

Chromatin three-dimensional (3D) structure is vital to biological processes (Cremer and Cremer, 2001; Bonev and Cavalli, 2016), such as genome replication, DNA mutation and repair, transcription and so on. The advent of the high-throughput chromosome conformation capture (Hi-C) technique makes it possible to measure all pair-wise interactions across the entire genome (Lieberman-Aiden et al, 2009). High-throughput chromosome conformation capture data is usually represented as a contact matrix Mn × n, where Mi,j indicates the number of observed interactions (read pair count) between genomic regions i and j. The size (e.g., 10 Kb) of each bin is called the resolution of Hi-C contact matrix. The linear increase of resolution requires a quadratic increase in the total number of sequencing reads. To address this issue, it is necessary to develop a computational method to predict high-resolution Hi-C contact maps from low-resolution Hi-C data

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