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Efficient near-telomere-to-telomere assembly of nanopore simplex reads

Haoyu Cheng, Han Qu, Sean K. McKenzie, Katherine R. Lawrence, Rhydian Windsor, Mike Vella, Peter J. Park, Heng Li

2026Nature19 citationsDOIOpen Access PDF

Abstract

Telomere-to-telomere (T2T) assembly is the ultimate goal for de novo genome assembly. Existing algorithms1,2 capable of near-T2T assembly all require Oxford Nanopore Technologies (ONT) ultra-long reads, which are costly and experimentally challenging to obtain and are thus often unavailable for samples without established cell lines3. Here we introduce hifiasm (ONT), an algorithm that can produce near-T2T assemblies from standard ONT simplex reads, eliminating the need for ultra-long sequencing. Compared with existing methods, hifiasm (ONT) reduces computational demands by an order of magnitude and reconstructs more chromosomes from telomere to telomere on the same datasets. This advance substantially broadens the feasibility of T2T assembly for applications previously limited by the high cost and experimental requirement of ultra-long reads. A genome assembly method called hifiasm (ONT) allows the assembly of chromosomes from telomere to telomere without the need for ultra-long reads, and outperforms conventional methods on most evaluation metrics.

Topics & Concepts

NanoporeNanopore sequencingComputer scienceSimplexTelomereSequence assemblyComputational biologySimplex algorithmGenomeNanotechnologyAlgorithmOrder (exchange)BiologySynthetic biologyTelomeres, Telomerase, and SenescenceAdvanced biosensing and bioanalysis techniquesNuclear Structure and Function
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