High-resolution diploid 3D genome reconstruction using Pore-C data

Chen, Y.; Lin, Z.-B.; Wang, S.; Wu, B.; Niu, L.-J.; Zhong, J.-Y.; Sun, Y.-M.; Bai, X.; Liu, L.-R.; Xie, W.; Luo, R.; Hou, C.; Luo, F.; Xiao, C.-L.

doi:10.1101/2023.08.29.555243

bioRxiv · 10.1101/2023.08.29.555243

High-resolution diploid 3D genome reconstruction using Pore-C data

Chen, Y.·Lin, Z.-B.·Wang, S.·Wu, B.·Niu, L.-J.·Zhong, J.-Y.·Sun, Y.-M.·Bai, X.·Liu, L.-R.·Xie, W.·Luo, R.·Hou, C.·Luo, F.·Xiao, C.-L.

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Abstract

In diploid organisms, spatial variations between homologous chromosomes are essential to many biological phenomena. Currently, it is still challenging to efficiently reconstruct a high-quality diploid 3D human genome. Here, we introduce Dip3D, reconstructing the diploid 3D human genome using Pore-C data of one sample. Dip3D has solved multiple problems in genome-wide SNV calling and haplo-tagging caused by the high sequencing error rates in Pore-C type data. Dip3D capitalizes on the high-order chromosomal interaction characteristics, enabling robust haplotype imputation and intricate haplotype-specific 3D structure discovery. Dip3D outperforms previous methods in data utilization rate, contact matrix resolution, and completeness by one order of magnitude. Moreover, Dip3D allows capturing haplotype high-order interactions that are unseen in Hi-C type data. We demonstrated the identified haplotype substructures such as Topologically Associating Domains (TADs) in the constructed 3D human genome, and unraveled connections between genic haplotype-specific high-order interactions and imbalanced allelic expression.

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Chen, Y., Lin, Z.-B., Wang, S., Wu, B., Niu, L.-J., Zhong, J.-Y., Sun, Y.-M., Bai, X., Liu, L.-R., Xie, W., Luo, R., Hou, C., Luo, F., Xiao, C.-L.. 2023-08-31. High-resolution diploid 3D genome reconstruction using Pore-C data. https://doi.org/10.1101/2023.08.29.555243

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