Interrogating the “unsequenceable” genomic trinucleotide repeat disorders by long-read sequencing

Microsatellite expansion, such as trinucleotide repeat expansion (TRE), is known to cause a number of genetic diseases. Sanger sequencing and next-generation short-read sequencing are unable to interrogate TRE reliably. We developed a novel algorithm called RepeatHMM to estimate repeat counts from l...

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Detalles Bibliográficos
Autores principales: Liu, Qian, Zhang, Peng, Wang, Depeng, Gu, Weihong, Wang, Kai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Method
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514472/
https://www.ncbi.nlm.nih.gov/pubmed/28720120
http://dx.doi.org/10.1186/s13073-017-0456-7
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author Liu, Qian
Zhang, Peng
Wang, Depeng
Gu, Weihong
Wang, Kai
author_facet Liu, Qian
Zhang, Peng
Wang, Depeng
Gu, Weihong
Wang, Kai
author_sort Liu, Qian
collection PubMed
description Microsatellite expansion, such as trinucleotide repeat expansion (TRE), is known to cause a number of genetic diseases. Sanger sequencing and next-generation short-read sequencing are unable to interrogate TRE reliably. We developed a novel algorithm called RepeatHMM to estimate repeat counts from long-read sequencing data. Evaluation on simulation data, real amplicon sequencing data on two repeat expansion disorders, and whole-genome sequencing data generated by PacBio and Oxford Nanopore technologies showed superior performance over competing approaches. We concluded that long-read sequencing coupled with RepeatHMM can estimate repeat counts on microsatellites and can interrogate the “unsequenceable” genomic trinucleotide repeat disorders. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-017-0456-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-55144722017-07-19 Interrogating the “unsequenceable” genomic trinucleotide repeat disorders by long-read sequencing Liu, Qian Zhang, Peng Wang, Depeng Gu, Weihong Wang, Kai Genome Med Method Microsatellite expansion, such as trinucleotide repeat expansion (TRE), is known to cause a number of genetic diseases. Sanger sequencing and next-generation short-read sequencing are unable to interrogate TRE reliably. We developed a novel algorithm called RepeatHMM to estimate repeat counts from long-read sequencing data. Evaluation on simulation data, real amplicon sequencing data on two repeat expansion disorders, and whole-genome sequencing data generated by PacBio and Oxford Nanopore technologies showed superior performance over competing approaches. We concluded that long-read sequencing coupled with RepeatHMM can estimate repeat counts on microsatellites and can interrogate the “unsequenceable” genomic trinucleotide repeat disorders. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-017-0456-7) contains supplementary material, which is available to authorized users. BioMed Central 2017-07-18 /pmc/articles/PMC5514472/ /pubmed/28720120 http://dx.doi.org/10.1186/s13073-017-0456-7 Text en © The Author(s). 2017 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
Liu, Qian
Zhang, Peng
Wang, Depeng
Gu, Weihong
Wang, Kai
Interrogating the “unsequenceable” genomic trinucleotide repeat disorders by long-read sequencing
title Interrogating the “unsequenceable” genomic trinucleotide repeat disorders by long-read sequencing
title_full Interrogating the “unsequenceable” genomic trinucleotide repeat disorders by long-read sequencing
title_fullStr Interrogating the “unsequenceable” genomic trinucleotide repeat disorders by long-read sequencing
title_full_unstemmed Interrogating the “unsequenceable” genomic trinucleotide repeat disorders by long-read sequencing
title_short Interrogating the “unsequenceable” genomic trinucleotide repeat disorders by long-read sequencing
title_sort interrogating the “unsequenceable” genomic trinucleotide repeat disorders by long-read sequencing
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514472/
https://www.ncbi.nlm.nih.gov/pubmed/28720120
http://dx.doi.org/10.1186/s13073-017-0456-7
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