January 2, 2024  |  Human genetics research

Characterization and visualization of tandem repeats at genome scale

Authors: Egor Dolzhenko, Adam English, Harriet Dashnow, Guilherme De Sena Brandine, Tom Mokveld, William J. Rowell, Caitlin Karniski, Zev Kronenberg, Matt C. Danzi, Warren A. Cheung, Chengpeng Bi, Emily Farrow, Aaron Wenger, Khi Pin Chua, Verónica Martínez-Cerdeño, Trevor D. Bartley, Peng Jin, David L. Nelson, Stephan Zuchner, Tomi Pastinen, Aaron R. Quinlan, Fritz J. Sedlazeck & Michael A. Eberle

Tandem repeat (TR) variation is associated with gene expression changes and numerous rare monogenic diseases. Although long-read sequencing provides accurate full-length sequences and methylation of TRs, there is still a need for computational methods to profile TRs across the genome. Here we introduce the Tandem Repeat Genotyping Tool (TRGT) and an accompanying TR database. TRGT determines the consensus sequences and methylation levels of specified TRs from PacBio HiFi sequencing data. It also reports reads that support each repeat allele. These reads can be subsequently visualized with a companion TR visualization tool. Assessing 937,122 TRs, TRGT showed a Mendelian concordance of 98.38%, allowing a single repeat unit difference. In six samples with known repeat expansions, TRGT detected all expansions while also identifying methylation signals and mosaicism and providing finer repeat length resolution than existing methods. Additionally, we released a database with allele sequences and methylation levels for 937,122 TRs across 100 genomes.

Journal: Nature Biotechnology
DOI: 10.1038/s41587-023-02057-3
Year: 2024

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