{"title":"Estimating the size of long tandem repeat expansions from short reads with ScatTR","authors":"Rashid Al-Abri, Gamze Gursoy","doi":"10.1101/gr.280563.125","DOIUrl":null,"url":null,"abstract":"Tandem repeats (TRs) are sequences of DNA where two or more base pairs are repeated back-to-back at specific locations in the genome. TR expansions, where the number of repeat units exceeds the normal range, have been implicated in over 50 conditions. However, accurately measuring the copy number of TRs is challenging, especially when their expansions are larger than the fragment sizes used in standard short-read genome sequencing. Here, we introduce ScatTR, a novel computational method that leverages a maximum likelihood framework to estimate the copy number of large TR expansions from short-read sequencing data. ScatTR calculates the likelihood of different alignments between sequencing reads and reference sequences that represent various TR lengths and employs a Monte Carlo technique to find the best match. In simulated data, ScatTR outperforms state-of-the-art methods, particularly for TRs with longer motifs and those with lengths that greatly exceed typical sequencing fragment sizes. When applied to data from the 1000 Genomes Project, ScatTR detects potential large TR expansions that other methods missed, highlighting its ability to better characterize genome-wide TR variation.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"146 1","pages":""},"PeriodicalIF":5.5000,"publicationDate":"2025-08-21","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.280563.125","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
Tandem repeats (TRs) are sequences of DNA where two or more base pairs are repeated back-to-back at specific locations in the genome. TR expansions, where the number of repeat units exceeds the normal range, have been implicated in over 50 conditions. However, accurately measuring the copy number of TRs is challenging, especially when their expansions are larger than the fragment sizes used in standard short-read genome sequencing. Here, we introduce ScatTR, a novel computational method that leverages a maximum likelihood framework to estimate the copy number of large TR expansions from short-read sequencing data. ScatTR calculates the likelihood of different alignments between sequencing reads and reference sequences that represent various TR lengths and employs a Monte Carlo technique to find the best match. In simulated data, ScatTR outperforms state-of-the-art methods, particularly for TRs with longer motifs and those with lengths that greatly exceed typical sequencing fragment sizes. When applied to data from the 1000 Genomes Project, ScatTR detects potential large TR expansions that other methods missed, highlighting its ability to better characterize genome-wide TR variation.
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.