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Cited by 347Genomics and Phylogenetic StudiesChromosomal and Genetic VariationsFractal and DNA sequence analysis

Tandem repeats lead to sequence assembly errors and impose multi-level challenges for genome and protein databases

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Tørresen, Ole K, Star, Bastiaan, Mier, Pablo, Andrade-Navarro, Miguel A, Bateman, Alex, Jarnot, Patryk, Gruca, Aleksandra, Grynberg, Marcin +5 more·2019·Nucleic Acids Research
DOI 10.1093/nar/gkz841PMC PMC6868369
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Abstract

The widespread occurrence of repetitive stretches of DNA in genomes of organisms across the tree of life imposes fundamental challenges for sequencing, genome assembly, and automated annotation of genes and proteins. This multi-level problem can lead to errors in genome and protein databases that are often not recognized or acknowledged. As a consequence, end users working with sequences with repetitive regions are faced with ‘ready-to-use’ deposited data whose trustworthiness is difficult to determine, let alone to quantify. Here, we provide a review of the problems associated with tandem repeat sequences that originate from different stages during the sequencing-assembly-annotation-deposition workflow, and that may proliferate in public database repositories affecting all downstream analyses. As a case study, we provide examples of the Atlantic cod genome, whose sequencing and assembly were hindered by a particularly high prevalence of tandem repeats. We complement this case study with examples from other species, where mis-annotations and sequencing errors have propagated into protein databases. With this review, we aim to raise the awareness level within the community of database users, and alert scientists working in the underlying workflow of database creation that the data they omit or improperly assemble may well contain important biological information valuable to others.

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  • Short reads have high precision but pose challenges in genome assembly and alignment due to their propensity for multiple mappings on the same genome.

    “Short reads, typically ranging from 100 to 600 base pairs, have been lauded for their high precision but pose challenges in genome assembly and alignment due to their propensity for multiple mappings on the same genome [5].”

    From Whole-Genome Alignment: Methods, Challenges, and Future Directions (2024) · cites this paper as [5]

    The ‘High-throughput sequencing technologies’ section reports a low error rate for short Illumina reads and says their length prevents them from resolving many repeats; ‘Repeat content and fragmented assemblies’ says assembly problems are greater with shorter reads (page numbers unavailable). The copy does not establish the claimed 100–600 bp range or specifically attribute alignment difficulties to reads mapping to multiple places in the same genome. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Authors
Tørresen, O. K., Star, B., Mier, P., Andrade-Navarro, M. A., Bateman, A., Jarnot, P., Gruca, A., Grynberg, M., Kajava, A. V., Promponas, V. J., Anisimova, M., Jakobsen, K. S., & Linke, D.
Affiliations
  • University of Oslo (NO)
  • Johannes Gutenberg University Mainz (DE)
  • European Bioinformatics Institute (GB)
  • Silesian University of Technology (PL)
  • Institute of Biochemistry and Biophysics, Polish Academy of Sciences (PL)
  • Centre National de la Recherche Scientifique (FR)
  • University of Cyprus (CY)
  • SIB Swiss Institute of Bioinformatics (CH)
Corresponding author
Linke, Dirk
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2019-10-04
Volume
47
Issue
21
Pages
10994-11006
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkz841
PMC
PMC6868369
OpenAlex
W2977428858
Cited by
347
References
7
Citations by year
2026: 37 · 2025: 50 · 2024: 54 · 2023: 51 · 2022: 64 · 2021: 58 · 2020: 31 · 2018: 1 · 2012: 1
FWCI
3.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • HAL (submittedVersion, other-oa)
  • Zürcher Hochschule für Angewandte Wissenschaften digital collection (Zurich University of Applied Sciences) (submittedVersion, cc-by-nc-nd)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
  • ZHAW Digital Collection (cc-by)
Funders
  • Research Council of Norway (251076)
  • University of Oslo
  • Institute of Informatics
  • European Union through the European Social Fund (POWR.03.02.00-00-I029)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fractal and DNA sequence analysis
Keywords
tandem repeats, repetitive DNA, genome assembly errors, sequence assembly, genome annotation, protein databases, genomic databases, sequencing errors, data quality
MeSH terms
Scientific Experimental Error, Animals, DNA, Sequence Analysis, DNA, Tandem Repeat Sequences, Databases, Nucleic Acid, Databases, Protein, Gadus morhua

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