ExpansionHunter Denovo: A computational method for locating known and novel repeat expansions in short-read sequencing data

Egor Dolzhenko; Mark F. Bennett; Phillip A. Richmond; Brett Trost; Sai Chen; Joke J.F.A. Van Vugt; Charlotte Nguyen; Giuseppe Narzisi; Vladimir G. Gainullin; Andrew M. Gross; Bryan R. Lajoie; Ryan J. Taft; Wyeth W. Wasserman; Stephen W. Scherer; Jan H. Veldink; David R. Bentley; Ryan K.C. Yuen; Melanie Bahlo; Michael A. Eberle

doi:10.1186/s13059-020-02017-z

ExpansionHunter Denovo: A computational method for locating known and novel repeat expansions in short-read sequencing data

Egor Dolzhenko, Mark F. Bennett, Phillip A. Richmond, Brett Trost, Sai Chen, Joke J.F.A. Van Vugt, Charlotte Nguyen, Giuseppe Narzisi, Vladimir G. Gainullin, Andrew M. Gross, Bryan R. Lajoie, Ryan J. Taft, Wyeth W. Wasserman, Stephen W. Scherer, Jan H. Veldink, David R. Bentley, Ryan K.C. Yuen, Melanie Bahlo, Michael A. Eberle^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Repeat expansions are responsible for over 40 monogenic disorders, and undoubtedly more pathogenic repeat expansions remain to be discovered. Existing methods for detecting repeat expansions in short-read sequencing data require predefined repeat catalogs. Recent discoveries emphasize the need for methods that do not require pre-specified candidate repeats. To address this need, we introduce ExpansionHunter Denovo, an efficient catalog-free method for genome-wide repeat expansion detection. Analysis of real and simulated data shows that our method can identify large expansions of 41 out of 44 pathogenic repeats, including nine recently reported non-reference repeat expansions not discoverable via existing methods.

Original language	English
Article number	102
Number of pages	14
Journal	Genome Biology
Volume	21
Issue number	1
DOIs	https://doi.org/10.1186/s13059-020-02017-z
Publication status	Published - 28 Apr 2020

Keywords

Fragile X syndrome
Friedreich ataxia
Genome-wide analysis
Huntington disease
Myotonic dystrophy type 1
Repeat expansions
Short tandem repeats
Whole-genome sequencing data
Fragile X Syndrome/genetics
Humans
Myotonic Dystrophy/genetics
Case-Control Studies
Whole Genome Sequencing
DNA Repeat Expansion
Huntington Disease/genetics
High-Throughput Nucleotide Sequencing
Software
Friedreich Ataxia/genetics
Microsatellite Repeats

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Dolzhenko, E., Bennett, M. F., Richmond, P. A., Trost, B., Chen, S., Van Vugt, J. J. F. A., Nguyen, C., Narzisi, G., Gainullin, V. G., Gross, A. M., Lajoie, B. R., Taft, R. J., Wasserman, W. W., Scherer, S. W., Veldink, J. H., Bentley, D. R., Yuen, R. K. C., Bahlo, M., & Eberle, M. A. (2020). ExpansionHunter Denovo: A computational method for locating known and novel repeat expansions in short-read sequencing data. Genome Biology, 21(1), Article 102. https://doi.org/10.1186/s13059-020-02017-z

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title = "ExpansionHunter Denovo: A computational method for locating known and novel repeat expansions in short-read sequencing data",

abstract = "Repeat expansions are responsible for over 40 monogenic disorders, and undoubtedly more pathogenic repeat expansions remain to be discovered. Existing methods for detecting repeat expansions in short-read sequencing data require predefined repeat catalogs. Recent discoveries emphasize the need for methods that do not require pre-specified candidate repeats. To address this need, we introduce ExpansionHunter Denovo, an efficient catalog-free method for genome-wide repeat expansion detection. Analysis of real and simulated data shows that our method can identify large expansions of 41 out of 44 pathogenic repeats, including nine recently reported non-reference repeat expansions not discoverable via existing methods.",

keywords = "Fragile X syndrome, Friedreich ataxia, Genome-wide analysis, Huntington disease, Myotonic dystrophy type 1, Repeat expansions, Short tandem repeats, Whole-genome sequencing data, Fragile X Syndrome/genetics, Humans, Myotonic Dystrophy/genetics, Case-Control Studies, Whole Genome Sequencing, DNA Repeat Expansion, Huntington Disease/genetics, High-Throughput Nucleotide Sequencing, Software, Friedreich Ataxia/genetics, Microsatellite Repeats",

author = "Egor Dolzhenko and Bennett, {Mark F.} and Richmond, {Phillip A.} and Brett Trost and Sai Chen and {Van Vugt}, {Joke J.F.A.} and Charlotte Nguyen and Giuseppe Narzisi and Gainullin, {Vladimir G.} and Gross, {Andrew M.} and Lajoie, {Bryan R.} and Taft, {Ryan J.} and Wasserman, {Wyeth W.} and Scherer, {Stephen W.} and Veldink, {Jan H.} and Bentley, {David R.} and Yuen, {Ryan K.C.} and Melanie Bahlo and Eberle, {Michael A.}",

year = "2020",

month = apr,

day = "28",

doi = "10.1186/s13059-020-02017-z",

language = "English",

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journal = "Genome Biology",

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Dolzhenko, E, Bennett, MF, Richmond, PA, Trost, B, Chen, S, Van Vugt, JJFA, Nguyen, C, Narzisi, G, Gainullin, VG, Gross, AM, Lajoie, BR, Taft, RJ, Wasserman, WW, Scherer, SW, Veldink, JH, Bentley, DR, Yuen, RKC, Bahlo, M & Eberle, MA 2020, 'ExpansionHunter Denovo: A computational method for locating known and novel repeat expansions in short-read sequencing data', Genome Biology, vol. 21, no. 1, 102. https://doi.org/10.1186/s13059-020-02017-z

TY - JOUR

T1 - ExpansionHunter Denovo

T2 - A computational method for locating known and novel repeat expansions in short-read sequencing data

AU - Dolzhenko, Egor

AU - Bennett, Mark F.

AU - Richmond, Phillip A.

AU - Trost, Brett

AU - Chen, Sai

AU - Van Vugt, Joke J.F.A.

AU - Nguyen, Charlotte

AU - Narzisi, Giuseppe

AU - Gainullin, Vladimir G.

AU - Gross, Andrew M.

AU - Lajoie, Bryan R.

AU - Taft, Ryan J.

AU - Wasserman, Wyeth W.

AU - Scherer, Stephen W.

AU - Veldink, Jan H.

AU - Bentley, David R.

AU - Yuen, Ryan K.C.

AU - Bahlo, Melanie

AU - Eberle, Michael A.

PY - 2020/4/28

Y1 - 2020/4/28

N2 - Repeat expansions are responsible for over 40 monogenic disorders, and undoubtedly more pathogenic repeat expansions remain to be discovered. Existing methods for detecting repeat expansions in short-read sequencing data require predefined repeat catalogs. Recent discoveries emphasize the need for methods that do not require pre-specified candidate repeats. To address this need, we introduce ExpansionHunter Denovo, an efficient catalog-free method for genome-wide repeat expansion detection. Analysis of real and simulated data shows that our method can identify large expansions of 41 out of 44 pathogenic repeats, including nine recently reported non-reference repeat expansions not discoverable via existing methods.

AB - Repeat expansions are responsible for over 40 monogenic disorders, and undoubtedly more pathogenic repeat expansions remain to be discovered. Existing methods for detecting repeat expansions in short-read sequencing data require predefined repeat catalogs. Recent discoveries emphasize the need for methods that do not require pre-specified candidate repeats. To address this need, we introduce ExpansionHunter Denovo, an efficient catalog-free method for genome-wide repeat expansion detection. Analysis of real and simulated data shows that our method can identify large expansions of 41 out of 44 pathogenic repeats, including nine recently reported non-reference repeat expansions not discoverable via existing methods.

KW - Fragile X syndrome

KW - Friedreich ataxia

KW - Genome-wide analysis

KW - Huntington disease

KW - Myotonic dystrophy type 1

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KW - Short tandem repeats

KW - Whole-genome sequencing data

KW - Fragile X Syndrome/genetics

KW - Humans

KW - Myotonic Dystrophy/genetics

KW - Case-Control Studies

KW - Whole Genome Sequencing

KW - DNA Repeat Expansion

KW - Huntington Disease/genetics

KW - High-Throughput Nucleotide Sequencing

KW - Software

KW - Friedreich Ataxia/genetics

KW - Microsatellite Repeats

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U2 - 10.1186/s13059-020-02017-z

DO - 10.1186/s13059-020-02017-z

M3 - Article

C2 - 32345345

AN - SCOPUS:85084107188

SN - 1474-7596

VL - 21

JO - Genome Biology

JF - Genome Biology

IS - 1

M1 - 102

ER -

ExpansionHunter Denovo: A computational method for locating known and novel repeat expansions in short-read sequencing data

Abstract

Keywords

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