Applied and Translational Neurogenomics Group, VIB Center for Molecular Neurology, VIB, 2610 Antwerp, Belgium;
Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp, Belgium.
Genome Res. 2024 Nov 20;34(11):2074-2080. doi: 10.1101/gr.279265.124.
The lack of population-scale databases hampers research and diagnostics for medically relevant tandem repeats and repeat expansions. We attempt to fill this gap using our pathSTR web tool, which leverages long-read sequencing of large cohorts to determine repeat length and sequence composition in a healthy population. The current version includes 1040 individuals of The 1000 Genomes Project cohort sequenced on the Oxford Nanopore Technologies PromethION. A comprehensive set of medically relevant tandem repeats has been genotyped using STRdust and LongTR to determine the tandem repeat length and sequence composition. PathSTR provides rich visualizations of this data set and the feature to upload one's data for comparison along the control cohort. We demonstrate the implementation of this application using data from targeted nanopore sequencing of a patient with myotonic dystrophy type 1. This resource will empower the genetics community to get a more complete overview of normal variation in tandem repeat length and sequence composition and, as such, enable a better assessment of rare tandem repeat alleles observed in patients.
缺乏基于人群的数据库会阻碍与医学相关串联重复和重复扩展的研究和诊断。我们尝试使用我们的 pathSTR 网络工具来填补这一空白，该工具利用长读测序对大样本进行测序，以确定健康人群中的重复长度和序列组成。当前版本包括在牛津纳米孔技术 PromethION 上对 1000 基因组计划队列中的 1040 个人进行测序。使用 STRdust 和 LongTR 对一组全面的医学相关串联重复进行基因分型，以确定串联重复的长度和序列组成。PathSTR 提供了此数据集的丰富可视化效果，并提供了将自己的数据上传进行与对照队列比较的功能。我们使用来自 1 型肌强直性营养不良患者靶向纳米孔测序的数据展示了此应用程序的实现。该资源将使遗传学界能够更全面地了解串联重复长度和序列组成的正常变异，从而更好地评估患者中观察到的罕见串联重复等位基因。
