Characterization and visualization of tandem repeats at genome scale.

TitleCharacterization and visualization of tandem repeats at genome scale.
Publication TypeJournal Article
Year of Publication2024
AuthorsDolzhenko, E, English, A, Dashnow, H, Brandine, GDe Sena, Mokveld, T, Rowell, WJ, Karniski, C, Kronenberg, Z, Danzi, MC, Cheung, WA, Bi, C, Farrow, E, Wenger, A, Chua, KPin, Martínez-Cerdeño, V, Bartley, TD, Jin, P, Nelson, DL, Züchner, S, Pastinen, T, Quinlan, AR, Sedlazeck, FJ, Eberle, MA
JournalNat Biotechnol
Date Published2024 Jan 02

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.

Alternate JournalNat Biotechnol
PubMed ID38168995
PubMed Central ID6958913
Grant ListF31 HG011205 / HG / NHGRI NIH HHS / United States
K08 HG008986 / HG / NHGRI NIH HHS / United States
RC2 TR004391 / TR / NCATS NIH HHS / United States