DeepChIA-PET: Accurately predicting ChIA-PET from Hi-C and ChIP-seq with deep dilated networks.

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Abstract

Chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) can capture genome-wide chromatin interactions mediated by a specific DNA-associated protein. The ChIA-PET experiments have been applied to explore the key roles of different protein factors in chromatin folding and transcription regulation. However, compared with widely available Hi-C and ChIP-seq data, there are not many ChIA-PET datasets available in the literature. A computational method for accurately predicting ChIA-PET interactions from Hi-C and ChIP-seq data is needed that can save the efforts of performing wet-lab experiments. Here we present DeepChIA-PET, a supervised deep learning approach that can accurately predict ChIA-PET interactions by learning the latent relationships between ChIA-PET and two widely used data types: Hi-C and ChIP-seq. We trained our deep models with CTCF-mediated ChIA-PET of GM12878 as ground truth, and the deep network contains 40 dilated residual convolutional blocks. We first showed that DeepChIA-PET with only Hi-C as input significantly outperforms Peakachu, another computational method for predicting ChIA-PET from Hi-C but using random forests. We next proved that adding ChIP-seq as one extra input does improve the classification performance of DeepChIA-PET, but Hi-C plays a more prominent role in DeepChIA-PET than ChIP-seq. Our evaluation results indicate that our learned models can accurately predict not only CTCF-mediated ChIA-ET in GM12878 and HeLa but also non-CTCF ChIA-PET interactions, including RNA polymerase II (RNAPII) ChIA-PET of GM12878, RAD21 ChIA-PET of GM12878, and RAD21 ChIA-PET of K562. In total, DeepChIA-PET is an accurate tool for predicting the ChIA-PET interactions mediated by various chromatin-associated proteins from different cell types.Copyright: © 2023 Liu, Wang. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.