Breakthrough algorithm enables partially phased, near telomere-to-telomere assembly using standard Oxford Nanopore Simplex reads

New hifiasm-ONT assembly method delivers high-quality, cost-efficient near T2T assemblies using standard Oxford Nanopore Simplex reads, broadening access to comprehensive genome assemblies across research and clinical applications

A new paper, released this week on bioRxiv, introduces hifiasm-ONT, a breakthrough genome assembly algorithm that enables partially phased, near telomere-to-telomere (T2T) assemblies¹, using Oxford Nanopore Simplex reads and standard sample prep.

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Developed by Haoyu Cheng, Han Qu, Heng Li, and Peter Park, with support from Oxford Nanopore’s machine learning and applications teams, this major algorithmic innovation unlocks the length advantage of Oxford Nanopore’s Simplex² reads (obtained with standard Ligation Sequencing Kit library preparation methods which can produce 30 kb N50 read lengths), while significantly reducing data input and computational requirements.

The method avoids reliance on ultra-long reads or complex protocols, expanding access to advanced near-T2T assemblies across a range of applications – from clinical research to biodiversity genomics. Furthermore, this method delivered results that exceed those from traditional high-accuracy technologies, with greater contiguity, lower cost, and streamlined preparation, broadening the reach of information-rich genomic insights.

"This is a significant moment in the accessibility of near-T2T genome assemblies. Researchers can now achieve high-quality assemblies using routine Oxford Nanopore workflows, without the need for ultra-long sequencing,” commented Gordon Sanghera, CEO of Oxford Nanopore Technologies. “In genomics, what you’re missing matters, and this advancement opens the door to information-rich insights across a wider range of applications."

More details about this method will be presented at London Calling 2025 by Haoyu Cheng, the lead algorithm designer and first author of the paper. His talk will explore how the advanced algorithm design is unlocking the full potential of Oxford Nanopore’s any-read length sequencing platform and pushing genome assembly into a new era of affordability, accessibility, and scalability.

1. Partially phased near telomere-to-telomere (T2T) assemblies represents a complete diploid genome, highly contiguous, but includes haplotype switches within contigs. For users seeking fully haplotype-resolved assemblies, the addition of Pore-C or Trio data enables fully phased contigs, derived exclusively from the maternal or paternal haplotype, eliminating haplotype switches.

2. Simplex involves the sequencing of a single strand. The template DNA strand passes through the nanopore and is basecalled.

Reference

Haoyu, C., Han, Q., Sean, M., et al. bioRxiv (2025). Efficient near telomere-to-telomere assembly of Nanopore Simplex reads. https://www.biorxiv.org/content/10.1101/2025.04.14.648685v1

About Oxford Nanopore Technologies

Oxford Nanopore Technologies’ goal is to bring the widest benefits to society through enabling the analysis of anything, by anyone, anywhere. The company has developed a new generation of nanopore-based sensing technology for faster, information rich, accessible and affordable molecular analysis. The first application is DNA/RNA sequencing, and the technology is in development for the analysis of other types of molecules including proteins. The technology is used in more than 125 countries to understand and characterise the biology of humans and diseases such as cancer, plants, animals, bacteria, viruses, and whole environments. Oxford Nanopore Technologies products are intended for molecular biology applications and are not intended for diagnostic purposes. For more, visit: https://nanoporetech.com/

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