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ImpuT2T: Pangenome-Based Patching for Human Genome Assemblies

Lin, M.-J.; Shivakumar, V. S.; Langmead, B.; Human Pangenome Reference Consortium,

2026-07-28 bioinformatics
10.64898/2026.07.27.741037 bioRxiv
Show abstract

With improvements in sequencing and assembly have come many high-quality telomere-to-telomere assemblies and reference pangenomes. However, the long-read sequencing recipes needed for high quality assemblies are expensive, and out of reach for many research groups. Here we propose ImpuT2T, a method that takes an assembly produced via inexpensive HiFi sequencing reads, and uses a panel of T2T (or near-T2T) assemblies to scaffold and fill ("patch") the gaps between the HiFi contigs. Benchmarking against reference assemblies demonstrates that ImpuT2T is highly effective at patching human HiFi assemblies, consistently outperforming existing patching approaches. Moreover, we show that including more haplotypes in the pangenome improves the quality of the patched assemblies, with the greatest gains achieved using the full HPRC Release 2 pangenome.

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