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New! Pore- C: the complete solution for investigating chromosome conformation

Tue 12th November 2019

Nanopore sequencing can now be used for investigating chromatin contacts, to identify genome-wide contacts directly, without amplification.

Weill Cornell Medicine and Oxford Nanopore have published a pre-print describing this new technique, and an end-to-end workflow and analysis tools are now available online.

Investigating genome architecture

Chromatin structure relies on the physical interaction of many genomic loci and investigating the architecture of the genome is relevant and important for understanding how genomic elements interact, and therefore how gene expression is regulated.

Most traditional methods of chromatin conformation capture and sequencing can only find pairwise interactions between two genomic loci. Coupling chromatin conformation capture with nanopore long reads means multiple contacts can be spanned in a single read, giving multi-way, higher order information.

More in-depth interrogation

This technique — Pore-C — is consistent with gold-standard pairwise contact maps at the compartment, topologically-associated domain, and loop levels, and more efficient than existing multi-way methods. The long-range information encoded in Pore-C reads can be used to scaffold and correct genome assemblies and aid the reconstruction of complex rearrangements spanning multiple megabases and chromosomes.

As well as providing a more in-depth interrogation of the 3D genome and its impact on regulation of gene expression, it is possible to access interactions among repeat regions, and across structural variants. By omitting PCR, the technique also minimises sequencing bias, enabling further insights in those regions with high or low GC-content.

Finally, as each nanopore long read contains more interactions compared to a short read, fewer sequencing reads are needed to build a complete picture.

Sissel Juul, Director, Genomic Applications, Oxford Nanopore commented:

“Our results establish Pore-C as the most simple and scalable assay for the genome-wide assessment of combinatorial chromatin interactions. We look forward to seeing how users of nanopore devices utilise this technique to gain new insights across a broad range of research applications.”

Read the full publication.

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