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Bioinformatics
Article . 2023 . Peer-reviewed
License: CC BY
Data sources: Crossref
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Bioinformatics
Article . 2023
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JTK: targeted diploid genome assembler

Authors: Bansho Masutani; Yoshihiko Suzuki; Yuta Suzuki; Shinichi Morishita;

JTK: targeted diploid genome assembler

Abstract

Abstract Motivation Diploid assembly, or determining sequences of homologous chromosomes separately, is essential to elucidate genetic differences between haplotypes. One approach is to call and phase single nucleotide variants (SNVs) on a reference sequence. However, this approach becomes unstable on large segmental duplications (SDs) or structural variations (SVs) because the alignments of reads deriving from these regions tend to be unreliable. Another approach is to use highly accurate PacBio HiFi reads to output diploid assembly directly. Nonetheless, HiFi reads cannot phase homozygous regions longer than their length and require oxford nanopore technology (ONT) reads or Hi-C to produce a fully phased assembly. Is a single long-read sequencing technology sufficient to create an accurate diploid assembly? Results Here, we present JTK, a megabase-scale diploid genome assembler. It first randomly samples kilobase-scale sequences (called ‘chunks’) from the long reads, phases variants found on them, and produces two haplotypes. The novel idea of JTK is to utilize chunks to capture SNVs and SVs simultaneously. From 60-fold ONT reads on the HG002 and a Japanese sample, it fully assembled two haplotypes with approximately 99.9% accuracy on the histocompatibility complex (MHC) and the leukocyte receptor complex (LRC) regions, which was impossible by the reference-based approach. In addition, in the LRC region on a Japanese sample, JTK output an assembly of better contiguity than those built from high-coverage HiFi+Hi-C. In the coming age of pan-genomics, JTK would complement the reference-based phasing method to assemble the difficult-to-assemble but medically important regions. Availability and implementation JTK is available at https://github.com/ban-m/jtk, and the datasets are available at https://doi.org/10.5281/zenodo.7790310 or JGAS000580 in DDBJ.

Related Organizations
Keywords

Original Paper, Genome, Haplotypes, High-Throughput Nucleotide Sequencing, Sequence Analysis, DNA, Genomics, Diploidy

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
2
Average
Average
Average
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