Get ready for short tandem repeats analysis using long reads-the challenges and the state of the art

Short tandem repeats (STRs) are repetitive DNA sequences that contribute to genetic diversity and play a significant role in disease susceptibility. The human genome contains approximately 1.5 million STR loci, collectively covering around 3% of the total sequence. Certain repeat expansions can sign...

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Main Authors: Marija Chaushevska, Karmele Alapont-Celaya, Anne Kristine Schack, Lukasz Krych, M. Carmen Garrido Navas, Anastasia Krithara, Gjorgji Madjarov
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Genetics
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Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2025.1610026/full
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author Marija Chaushevska
Marija Chaushevska
Karmele Alapont-Celaya
Anne Kristine Schack
Anne Kristine Schack
Lukasz Krych
M. Carmen Garrido Navas
M. Carmen Garrido Navas
M. Carmen Garrido Navas
Anastasia Krithara
Gjorgji Madjarov
Gjorgji Madjarov
author_facet Marija Chaushevska
Marija Chaushevska
Karmele Alapont-Celaya
Anne Kristine Schack
Anne Kristine Schack
Lukasz Krych
M. Carmen Garrido Navas
M. Carmen Garrido Navas
M. Carmen Garrido Navas
Anastasia Krithara
Gjorgji Madjarov
Gjorgji Madjarov
author_sort Marija Chaushevska
collection DOAJ
description Short tandem repeats (STRs) are repetitive DNA sequences that contribute to genetic diversity and play a significant role in disease susceptibility. The human genome contains approximately 1.5 million STR loci, collectively covering around 3% of the total sequence. Certain repeat expansions can significantly impact cellular function by altering protein synthesis, impairing DNA repair, and leading to neurodegenerative and neuromuscular diseases. Traditional short-read sequencing struggles to accurately characterize STRs due to its limited read length, which limits the ability to resolve repeat expansions, increases mapping errors, and reduces sensitivity for detecting large insertions or interruptions. This review examines how long-read sequencing technologies, particularly Oxford Nanopore and PacBio, overcome these limitations by enabling direct sequencing of full STR regions with improved accuracy. We discuss challenges in sequencing, bioinformatics workflows, and the latest computational tools for STR detection. Additionally, we highlight the strengths and limitations of different methods, providing deeper insight into the future of STR genotyping.
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institution Kabale University
issn 1664-8021
language English
publishDate 2025-07-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Genetics
spelling doaj-art-7cc58943663d4f83881eea67eb789f102025-08-20T03:33:02ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-07-011610.3389/fgene.2025.16100261610026Get ready for short tandem repeats analysis using long reads-the challenges and the state of the artMarija Chaushevska0Marija Chaushevska1Karmele Alapont-Celaya2Anne Kristine Schack3Anne Kristine Schack4Lukasz Krych5M. Carmen Garrido Navas6M. Carmen Garrido Navas7M. Carmen Garrido Navas8Anastasia Krithara9Gjorgji Madjarov10Gjorgji Madjarov11Faculty of Computer Science and Engineering, University Saints Cyril and Methodius, Skopje, North MacedoniagMendel ApS, Copenhagen, DenmarkgMendel ApS, Copenhagen, DenmarkgMendel ApS, Copenhagen, DenmarkFood Microbiology and Fermentation, Department of Food Science, University of Copenhagen, Copenhagen, DenmarkFood Microbiology and Fermentation, Department of Food Science, University of Copenhagen, Copenhagen, DenmarkgMendel ApS, Copenhagen, DenmarkCardiovascular Development Group, Department of Experimental Biology, University of Jaen, Jaen, SpainGENetic COUNselling (CONGEN), Genetic Counselling Services, Granada, SpainInstitute of Informatics and Telecommunications, National Centre of Scientific Research “Demokritos”, Athens, GreeceFaculty of Computer Science and Engineering, University Saints Cyril and Methodius, Skopje, North MacedoniagMendel ApS, Copenhagen, DenmarkShort tandem repeats (STRs) are repetitive DNA sequences that contribute to genetic diversity and play a significant role in disease susceptibility. The human genome contains approximately 1.5 million STR loci, collectively covering around 3% of the total sequence. Certain repeat expansions can significantly impact cellular function by altering protein synthesis, impairing DNA repair, and leading to neurodegenerative and neuromuscular diseases. Traditional short-read sequencing struggles to accurately characterize STRs due to its limited read length, which limits the ability to resolve repeat expansions, increases mapping errors, and reduces sensitivity for detecting large insertions or interruptions. This review examines how long-read sequencing technologies, particularly Oxford Nanopore and PacBio, overcome these limitations by enabling direct sequencing of full STR regions with improved accuracy. We discuss challenges in sequencing, bioinformatics workflows, and the latest computational tools for STR detection. Additionally, we highlight the strengths and limitations of different methods, providing deeper insight into the future of STR genotyping.https://www.frontiersin.org/articles/10.3389/fgene.2025.1610026/fullshort tandem repeatslong readssequencing technologiesstructural variantsvariant detectionbioinformatics tools
spellingShingle Marija Chaushevska
Marija Chaushevska
Karmele Alapont-Celaya
Anne Kristine Schack
Anne Kristine Schack
Lukasz Krych
M. Carmen Garrido Navas
M. Carmen Garrido Navas
M. Carmen Garrido Navas
Anastasia Krithara
Gjorgji Madjarov
Gjorgji Madjarov
Get ready for short tandem repeats analysis using long reads-the challenges and the state of the art
Frontiers in Genetics
short tandem repeats
long reads
sequencing technologies
structural variants
variant detection
bioinformatics tools
title Get ready for short tandem repeats analysis using long reads-the challenges and the state of the art
title_full Get ready for short tandem repeats analysis using long reads-the challenges and the state of the art
title_fullStr Get ready for short tandem repeats analysis using long reads-the challenges and the state of the art
title_full_unstemmed Get ready for short tandem repeats analysis using long reads-the challenges and the state of the art
title_short Get ready for short tandem repeats analysis using long reads-the challenges and the state of the art
title_sort get ready for short tandem repeats analysis using long reads the challenges and the state of the art
topic short tandem repeats
long reads
sequencing technologies
structural variants
variant detection
bioinformatics tools
url https://www.frontiersin.org/articles/10.3389/fgene.2025.1610026/full
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