Nanopore sequencing of DNA concatemers reveals higher-order features of chromatin structure [article]

Netha Ulahannan, Matthew Pendleton, Aditya S Deshpande, Stefan Schwenk, Julie M Behr, Xiaoguang Dai, Carly Tyer, Priyesh Rughani, Sarah Kudman, Emily Adney, Huasong Tian, David Wilkes (+6 others)
2019 bioRxiv   pre-print
Higher-order chromatin structure arises from the combinatorial physical interactions of many genomic loci. To investigate this aspect of genome architecture we developed Pore-C, which couples chromatin conformation capture with Oxford Nanopore Technologies (ONT) long reads to directly sequence multi-way chromatin contacts without amplification. In GM12878, we demonstrate that the pairwise interaction patterns implicit in Pore-C multi-way contacts are consistent with gold standard Hi-C pairwise
more » ... ontact maps at the compartment, TAD, and loop scales. In addition, Pore-C also detects higher-order chromatin structure at 18.5-fold higher efficiency and greater fidelity than SPRITE, a previously published higher-order chromatin profiling technology. We demonstrate Pore-C's ability to detect and visualize multi-locus hubs associated with histone locus bodies and active / inactive nuclear compartments in GM12878. In the breast cancer cell line HCC1954, Pore-C contacts enable the reconstruction of complex and aneuploid rearranged alleles spanning multiple megabases and chromosomes. Finally, we apply Pore-C to generate a chromosome scale de novo assembly of the HG002 genome. Our results establish Pore-C as the most simple and scalable assay for the genome-wide assessment of combinatorial chromatin interactions, with additional applications for cancer rearrangement reconstruction and de novo genome assembly.
doi:10.1101/833590 fatcat:aamus4z5gfagfiwtom3ujgneca