Accelerated identification of disease-causing variants with ultra-rapid nanopore genome sequencing

Sneha D. Goenka; John E. Gorzynski; Kishwar Shafin; Dianna G. Fisk; Trevor Pesout; Tanner D. Jensen; Jean Monlong; Pi Chuan Chang; Gunjan Baid; Jonathan A. Bernstein; Jeffrey W. Christle; Karen P. Dalton; Daniel R. Garalde; Megan E. Grove; Joseph Guillory; Alexey Kolesnikov; Maria Nattestad; Maura R.Z. Ruzhnikov; Mehrzad Samadi; Ankit Sethia; Elizabeth Spiteri; Christopher J. Wright; Katherine Xiong; Tong Zhu; Miten Jain; Fritz J. Sedlazeck; Andrew Carroll; Benedict Paten; Euan A. Ashley

doi:10.1038/s41587-022-01221-5

Accelerated identification of disease-causing variants with ultra-rapid nanopore genome sequencing

Sneha D. Goenka, John E. Gorzynski, Kishwar Shafin, Dianna G. Fisk, Trevor Pesout, Tanner D. Jensen, Jean Monlong, Pi Chuan Chang, Gunjan Baid, Jonathan A. Bernstein, Jeffrey W. Christle, Karen P. Dalton, Daniel R. Garalde, Megan E. Grove, Joseph Guillory, Alexey Kolesnikov, Maria Nattestad, Maura R.Z. Ruzhnikov, Mehrzad Samadi, Ankit SethiaElizabeth Spiteri, Christopher J. Wright, Katherine Xiong, Tong Zhu, Miten Jain, Fritz J. Sedlazeck, Andrew Carroll, Benedict Paten, Euan A. Ashley

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

69 Scopus citations

Abstract

Whole-genome sequencing (WGS) can identify variants that cause genetic disease, but the time required for sequencing and analysis has been a barrier to its use in acutely ill patients. In the present study, we develop an approach for ultra-rapid nanopore WGS that combines an optimized sample preparation protocol, distributing sequencing over 48 flow cells, near real-time base calling and alignment, accelerated variant calling and fast variant filtration for efficient manual review. Application to two example clinical cases identified a candidate variant in <8 h from sample preparation to variant identification. We show that this framework provides accurate variant calls and efficient prioritization, and accelerates diagnostic clinical genome sequencing twofold compared with previous approaches.

Original language	English (US)
Pages (from-to)	1035-1041
Number of pages	7
Journal	Nature biotechnology
Volume	40
Issue number	7
DOIs	https://doi.org/10.1038/s41587-022-01221-5
State	Published - Jul 2022
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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10.1038/s41587-022-01221-5

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Goenka, S. D., Gorzynski, J. E., Shafin, K., Fisk, D. G., Pesout, T., Jensen, T. D., Monlong, J., Chang, P. C., Baid, G., Bernstein, J. A., Christle, J. W., Dalton, K. P., Garalde, D. R., Grove, M. E., Guillory, J., Kolesnikov, A., Nattestad, M., Ruzhnikov, M. R. Z., Samadi, M., ... Ashley, E. A. (2022). Accelerated identification of disease-causing variants with ultra-rapid nanopore genome sequencing. Nature biotechnology, 40(7), 1035-1041. https://doi.org/10.1038/s41587-022-01221-5

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title = "Accelerated identification of disease-causing variants with ultra-rapid nanopore genome sequencing",

abstract = "Whole-genome sequencing (WGS) can identify variants that cause genetic disease, but the time required for sequencing and analysis has been a barrier to its use in acutely ill patients. In the present study, we develop an approach for ultra-rapid nanopore WGS that combines an optimized sample preparation protocol, distributing sequencing over 48 flow cells, near real-time base calling and alignment, accelerated variant calling and fast variant filtration for efficient manual review. Application to two example clinical cases identified a candidate variant in <8 h from sample preparation to variant identification. We show that this framework provides accurate variant calls and efficient prioritization, and accelerates diagnostic clinical genome sequencing twofold compared with previous approaches.",

author = "Goenka, {Sneha D.} and Gorzynski, {John E.} and Kishwar Shafin and Fisk, {Dianna G.} and Trevor Pesout and Jensen, {Tanner D.} and Jean Monlong and Chang, {Pi Chuan} and Gunjan Baid and Bernstein, {Jonathan A.} and Christle, {Jeffrey W.} and Dalton, {Karen P.} and Garalde, {Daniel R.} and Grove, {Megan E.} and Joseph Guillory and Alexey Kolesnikov and Maria Nattestad and Ruzhnikov, {Maura R.Z.} and Mehrzad Samadi and Ankit Sethia and Elizabeth Spiteri and Wright, {Christopher J.} and Katherine Xiong and Tong Zhu and Miten Jain and Sedlazeck, {Fritz J.} and Andrew Carroll and Benedict Paten and Ashley, {Euan A.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = jul,

doi = "10.1038/s41587-022-01221-5",

language = "English (US)",

volume = "40",

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Goenka, SD, Gorzynski, JE, Shafin, K, Fisk, DG, Pesout, T, Jensen, TD, Monlong, J, Chang, PC, Baid, G, Bernstein, JA, Christle, JW, Dalton, KP, Garalde, DR, Grove, ME, Guillory, J, Kolesnikov, A, Nattestad, M, Ruzhnikov, MRZ, Samadi, M, Sethia, A, Spiteri, E, Wright, CJ, Xiong, K, Zhu, T, Jain, M, Sedlazeck, FJ, Carroll, A, Paten, B & Ashley, EA 2022, 'Accelerated identification of disease-causing variants with ultra-rapid nanopore genome sequencing', Nature biotechnology, vol. 40, no. 7, pp. 1035-1041. https://doi.org/10.1038/s41587-022-01221-5

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AU - Goenka, Sneha D.

AU - Gorzynski, John E.

AU - Shafin, Kishwar

AU - Fisk, Dianna G.

AU - Pesout, Trevor

AU - Jensen, Tanner D.

AU - Monlong, Jean

AU - Chang, Pi Chuan

AU - Baid, Gunjan

AU - Bernstein, Jonathan A.

AU - Christle, Jeffrey W.

AU - Dalton, Karen P.

AU - Garalde, Daniel R.

AU - Grove, Megan E.

AU - Guillory, Joseph

AU - Kolesnikov, Alexey

AU - Nattestad, Maria

AU - Ruzhnikov, Maura R.Z.

AU - Samadi, Mehrzad

AU - Sethia, Ankit

AU - Spiteri, Elizabeth

AU - Wright, Christopher J.

AU - Xiong, Katherine

AU - Zhu, Tong

AU - Jain, Miten

AU - Sedlazeck, Fritz J.

AU - Carroll, Andrew

AU - Paten, Benedict

AU - Ashley, Euan A.

PY - 2022/7

Y1 - 2022/7

N2 - Whole-genome sequencing (WGS) can identify variants that cause genetic disease, but the time required for sequencing and analysis has been a barrier to its use in acutely ill patients. In the present study, we develop an approach for ultra-rapid nanopore WGS that combines an optimized sample preparation protocol, distributing sequencing over 48 flow cells, near real-time base calling and alignment, accelerated variant calling and fast variant filtration for efficient manual review. Application to two example clinical cases identified a candidate variant in <8 h from sample preparation to variant identification. We show that this framework provides accurate variant calls and efficient prioritization, and accelerates diagnostic clinical genome sequencing twofold compared with previous approaches.

AB - Whole-genome sequencing (WGS) can identify variants that cause genetic disease, but the time required for sequencing and analysis has been a barrier to its use in acutely ill patients. In the present study, we develop an approach for ultra-rapid nanopore WGS that combines an optimized sample preparation protocol, distributing sequencing over 48 flow cells, near real-time base calling and alignment, accelerated variant calling and fast variant filtration for efficient manual review. Application to two example clinical cases identified a candidate variant in <8 h from sample preparation to variant identification. We show that this framework provides accurate variant calls and efficient prioritization, and accelerates diagnostic clinical genome sequencing twofold compared with previous approaches.

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JO - Nature biotechnology

JF - Nature biotechnology

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ER -

Accelerated identification of disease-causing variants with ultra-rapid nanopore genome sequencing

Abstract

All Science Journal Classification (ASJC) codes

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