Tandem-genotypes: robust detection of tandem repeat expansions from long DNA reads

Tandemly repeated DNA is highly mutable and causes at least 31 diseases, but it is hard to detect pathogenic repeat expansions genome-wide. Here, we report robust detection of human repeat expansions from careful alignments of long but error-prone (PacBio and nanopore) reads to a reference genome. O...

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Autores principales: Mitsuhashi, Satomi, Frith, Martin C., Mizuguchi, Takeshi, Miyatake, Satoko, Toyota, Tomoko, Adachi, Hiroaki, Oma, Yoko, Kino, Yoshihiro, Mitsuhashi, Hiroaki, Matsumoto, Naomichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Method
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425644/
https://www.ncbi.nlm.nih.gov/pubmed/30890163
http://dx.doi.org/10.1186/s13059-019-1667-6
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author Mitsuhashi, Satomi
Frith, Martin C.
Mizuguchi, Takeshi
Miyatake, Satoko
Toyota, Tomoko
Adachi, Hiroaki
Oma, Yoko
Kino, Yoshihiro
Mitsuhashi, Hiroaki
Matsumoto, Naomichi
author_facet Mitsuhashi, Satomi
Frith, Martin C.
Mizuguchi, Takeshi
Miyatake, Satoko
Toyota, Tomoko
Adachi, Hiroaki
Oma, Yoko
Kino, Yoshihiro
Mitsuhashi, Hiroaki
Matsumoto, Naomichi
author_sort Mitsuhashi, Satomi
collection PubMed
description Tandemly repeated DNA is highly mutable and causes at least 31 diseases, but it is hard to detect pathogenic repeat expansions genome-wide. Here, we report robust detection of human repeat expansions from careful alignments of long but error-prone (PacBio and nanopore) reads to a reference genome. Our method is robust to systematic sequencing errors, inexact repeats with fuzzy boundaries, and low sequencing coverage. By comparing to healthy controls, we prioritize pathogenic expansions within the top 10 out of 700,000 tandem repeats in whole genome sequencing data. This may help to elucidate the many genetic diseases whose causes remain unknown. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13059-019-1667-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-64256442019-04-01 Tandem-genotypes: robust detection of tandem repeat expansions from long DNA reads Mitsuhashi, Satomi Frith, Martin C. Mizuguchi, Takeshi Miyatake, Satoko Toyota, Tomoko Adachi, Hiroaki Oma, Yoko Kino, Yoshihiro Mitsuhashi, Hiroaki Matsumoto, Naomichi Genome Biol Method Tandemly repeated DNA is highly mutable and causes at least 31 diseases, but it is hard to detect pathogenic repeat expansions genome-wide. Here, we report robust detection of human repeat expansions from careful alignments of long but error-prone (PacBio and nanopore) reads to a reference genome. Our method is robust to systematic sequencing errors, inexact repeats with fuzzy boundaries, and low sequencing coverage. By comparing to healthy controls, we prioritize pathogenic expansions within the top 10 out of 700,000 tandem repeats in whole genome sequencing data. This may help to elucidate the many genetic diseases whose causes remain unknown. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13059-019-1667-6) contains supplementary material, which is available to authorized users. BioMed Central 2019-03-19 /pmc/articles/PMC6425644/ /pubmed/30890163 http://dx.doi.org/10.1186/s13059-019-1667-6 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Method
Mitsuhashi, Satomi
Frith, Martin C.
Mizuguchi, Takeshi
Miyatake, Satoko
Toyota, Tomoko
Adachi, Hiroaki
Oma, Yoko
Kino, Yoshihiro
Mitsuhashi, Hiroaki
Matsumoto, Naomichi
Tandem-genotypes: robust detection of tandem repeat expansions from long DNA reads
title Tandem-genotypes: robust detection of tandem repeat expansions from long DNA reads
title_full Tandem-genotypes: robust detection of tandem repeat expansions from long DNA reads
title_fullStr Tandem-genotypes: robust detection of tandem repeat expansions from long DNA reads
title_full_unstemmed Tandem-genotypes: robust detection of tandem repeat expansions from long DNA reads
title_short Tandem-genotypes: robust detection of tandem repeat expansions from long DNA reads
title_sort tandem-genotypes: robust detection of tandem repeat expansions from long dna reads
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425644/
https://www.ncbi.nlm.nih.gov/pubmed/30890163
http://dx.doi.org/10.1186/s13059-019-1667-6
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