Visualization and analysis of medically relevant tandem repeats in nanopore sequencing of control cohorts with pathSTR.

IF 6.2 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genome research Pub Date : 2024-11-20 DOI:10.1101/gr.279265.124

Wouter De Coster, Ida Höijer, Inge Bruggeman, Svenn D'Hert, Malin Melin, Adam Ameur, Rosa Rademakers

{"title":"Visualization and analysis of medically relevant tandem repeats in nanopore sequencing of control cohorts with pathSTR.","authors":"Wouter De Coster, Ida Höijer, Inge Bruggeman, Svenn D'Hert, Malin Melin, Adam Ameur, Rosa Rademakers","doi":"10.1101/gr.279265.124","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":"2074-2080"},"PeriodicalIF":6.2000,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genome research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1101/gr.279265.124","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

纳米孔测序中与医学相关的串联重复序列的可视化和分析，以及病理序列对照组。

缺乏人群规模的数据库阻碍了与医学相关的串联重复序列和重复扩增的研究和诊断。我们试图利用我们的 pathSTR 网络工具填补这一空白，该工具利用大型队列的长读程测序来确定健康人群的重复序列长度和序列组成。当前版本包括在牛津纳米孔技术公司的 PromethION 上测序的 1000 基因组计划队列中的 1040 个个体。利用 STRdust 和 LongTR 对一组全面的医学相关串联重复序列进行了基因分型，以确定串联重复序列的长度和序列组成。PathSTR 为该数据集提供了丰富的可视化功能，并提供了上传个人数据以便与对照组数据进行比较的功能。我们利用一名 1 型肌张力营养不良症患者的定向纳米孔测序数据演示了这一应用的实施。这一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，从而更好地评估在患者身上观察到的罕见串联重复等位基因。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Genome research 生物-生化与分子生物学

CiteScore

12.40

自引率

1.40%

发文量

140

审稿时长

6 months

期刊介绍： Launched in 1995, Genome Research is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies. New data in these areas are published as research papers, or methods and resource reports that provide novel information on technologies or tools that will be of interest to a broad readership. Complete data sets are presented electronically on the journal''s web site where appropriate. The journal also provides Reviews, Perspectives, and Insight/Outlook articles, which present commentary on the latest advances published both here and elsewhere, placing such progress in its broader biological context.