美国加州太平洋生物科学Michael A. Eberle研究组实现基因组尺度上串联重复序列的特征描述与可视化。2024年1月2日，《自然—生物技术》杂志在线发表了这项成果。

研究人员介绍了串联重复基因分型工具（TRGT）和配套的串联重复（TR）数据库。TRGT可从PacBio HiFi测序数据中确定特定TR的共识序列和甲基化水平。它还能报告支持每个重复等位基因的读数。这些读数随后可通过配套的TR可视化工具进行可视化。在评估了937122个TR后，TRGT显示出98.38%的孟德尔一致性，并允许存在单个重复单位差异。

在六个已知重复扩增的样本中，TRGT检测到了所有的扩增，同时还识别出了甲基化信号和嵌套，并提供了比现有方法更精细的重复长度分辨率。此外，研究人员还发布了一个数据库，其中包含100个基因组中937122个TR的等位基因序列和甲基化水平。

研究人员表示，TR变异与基因表达变化和许多罕见的单基因疾病有关。虽然长线程测序能提供准确的全长序列和TR的甲基化，但仍需要计算方法来分析整个基因组中的 TR。

附：英文原文

Title: Characterization and visualization of tandem repeats at genome scale

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

Issue&Volume: 2024-01-02

Abstract: 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.

DOI: 10.1038/s41587-023-02057-3

Source: https://www.nature.com/articles/s41587-023-02057-3