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Reconstruction of Diploid Higher-order Human 3D Genome Interactions from Noisy Pore-C Data Using Dip3D
论文题目: Reconstruction of Diploid Higher-order Human 3D Genome Interactions from Noisy Pore-C Data Using Dip3D
作者: Ying Chen, Zhuo-Bin Lin, Shao-Kai Wang, Bo Wu, Longjian Niu, Jia-Yong Zhong, Yi-Meng Sun, Zhenxian Zheng, Xin Bai, Luo-Ran Liu, Wei Xie, Wei Chi, Titantian Ye, Ruibang Luo, Chunhui Hou, Feng Luo, Chuan-Le Xiao
联系作者: yetiantian@xhlab.ac.cn; rbluo@cs.hku.hk; houchunhui@mail.kiz.ac.cn; luofeng@clemson.edu; xiaochuanle@126.com
发表年度: 2025
DOI: DOI: 10.1038/s41594-025-01512-w
摘要:

Differential high-order chromatin interactions between homologous chromosomes affect many biological processes. Traditional chromatin conformation capture genome analysis methods mainly identify two-way interactions and cannot provide comprehensive haplotype information, especially for low-heterozygosity organisms such as human. Here, we present a pipeline of methods to delineate diploid high-order chromatin interactions from noisy Pore-C outputs. We trained a previously published single-nucleotide variant (SNV)-calling deep learning model, Clair3, on Pore-C data to achieve superior SNV calling, applied a filtering strategy to tag reads for haplotypes and established a haplotype imputation strategy for high-order concatemers. Learning the haplotype characteristics of high-order concatemers from high-heterozygosity mouse allowed us to devise a progressive haplotype imputation strategy, which improved the haplotype-informative Pore-C contact rate 14.1-fold to 76% in the HG001 cell line. Overall, the diploid three-dimensional (3D) genome interactions we derived using Dip3D surpassed conventional methods in noise reduction and contact distribution uniformity, with better haplotype-informative contact density and genomic coverage rates. Dip3D identified previously unresolved haplotype high-order interactions, in addition to an understanding of their relationship with allele-specific expression, such as in X-chromosome inactivation. These results lead us to conclude that Dip3D is a robust pipeline for the high-quality reconstruction of diploid high-order 3D genome interactions.

刊物名称: Nature Structural & Molecular Biology
论文出处: https://www.nature.com/articles/s41594-025-01512-w
影响因子: 12.5(2023IF)
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