Reconstruction of diploid higher-order human 3D genome interactions from noisy Pore-C data using Dip3D
- PMID: 40038455
- DOI: 10.1038/s41594-025-01512-w
Reconstruction of diploid higher-order human 3D genome interactions from noisy Pore-C data using Dip3D
Erratum in
-
Author Correction: Reconstruction of diploid higher-order human 3D genome interactions from noisy Pore-C data using Dip3D.Nat Struct Mol Biol. 2025 Jul;32(7):1318. doi: 10.1038/s41594-025-01571-z. Nat Struct Mol Biol. 2025. PMID: 40295772 No abstract available.
Abstract
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.
© 2025. The Author(s), under exclusive licence to Springer Nature America, Inc.
Conflict of interest statement
Competing interests: The authors declare no competing interests.
References
-
- Zheng, H. & Xie, W. The role of 3D genome organization in development and cell differentiation. Nat. Rev. Mol. Cell Biol. 20, 535–550 (2019). - PubMed
-
- Bonev, B. & Cavalli, G. Organization and function of the 3D genome. Nat. Rev. Genet. 17, 661–678 (2016). - PubMed
-
- Quinodoz, S. A. et al. Higher-order inter-chromosomal hubs shape 3D genome organization in the nucleus. Cell 174, 744–757.e24 (2018).
-
- Deshpande, A. S. et al. Identifying synergistic high-order 3D chromatin conformations from genome-scale nanopore concatemer sequencing. Nat. Biotechnol. 40, 1488–1499 (2022). - PubMed
MeSH terms
Substances
LinkOut - more resources
Full Text Sources