Assembly and diploid architecture of an individual human genome via single-molecule technologies

Matthew Pendleton; Robert Sebra; Andy Wing Chun Pang; Ajay Ummat; Oscar Franzen; Tobias Rausch; Adrian M. Stütz; William Stedman; Thomas Anantharaman; Alex Hastie; Heng Dai; Markus Hsi Yang Fritz; Han Cao; Ariella Cohain; Gintaras Deikus; Russell E. Durrett; Scott C. Blanchard; Roger Altman; Chen Shan Chin; Yan Guo; Ellen E. Paxinos; Jan O. Korbel; Robert B. Darnell; W. Richard McCombie; Pui Yan Kwok; Christopher E. Mason; Eric E. Schadt; Ali Bashir

doi:10.1038/nmeth.3454

Assembly and diploid architecture of an individual human genome via single-molecule technologies

Matthew Pendleton, Robert Sebra, Andy Wing Chun Pang, Ajay Ummat, Oscar Franzen, Tobias Rausch, Adrian M. Stütz, William Stedman, Thomas Anantharaman, Alex Hastie, Heng Dai, Markus Hsi Yang Fritz, Han Cao, Ariella Cohain, Gintaras Deikus, Russell E. Durrett, Scott C. Blanchard, Roger Altman, Chen Shan Chin, Yan GuoEllen E. Paxinos, Jan O. Korbel, Robert B. Darnell, W. Richard McCombie, Pui Yan Kwok, Christopher E. Mason, Eric E. Schadt, Ali Bashir

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368 Scopus citations

Abstract

We present the first comprehensive analysis of a diploid human genome that combines single-molecule sequencing with single-molecule genome maps. Our hybrid assembly markedly improves upon the contiguity observed from traditional shotgun sequencing approaches, with scaffold N50 values approaching 30 Mb, and we identified complex structural variants (SVs) missed by other high-throughput approaches. Furthermore, by combining Illumina short-read data with long reads, we phased both single-nucleotide variants and SVs, generating haplotypes with over 99% consistency with previous trio-based studies. Our work shows that it is now possible to integrate single-molecule and high-throughput sequence data to generate de novo assembled genomes that approach reference quality.

Original language	English
Pages (from-to)	780-786
Number of pages	7
Journal	Nature Methods
Volume	12
Issue number	8
DOIs	https://doi.org/10.1038/nmeth.3454
State	Published - 30 Jul 2015

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Pendleton, M., Sebra, R., Pang, A. W. C., Ummat, A., Franzen, O., Rausch, T., Stütz, A. M., Stedman, W., Anantharaman, T., Hastie, A., Dai, H., Fritz, M. H. Y., Cao, H., Cohain, A., Deikus, G., Durrett, R. E., Blanchard, S. C., Altman, R., Chin, C. S., ... Bashir, A. (2015). Assembly and diploid architecture of an individual human genome via single-molecule technologies. Nature Methods, 12(8), 780-786. https://doi.org/10.1038/nmeth.3454

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title = "Assembly and diploid architecture of an individual human genome via single-molecule technologies",

abstract = "We present the first comprehensive analysis of a diploid human genome that combines single-molecule sequencing with single-molecule genome maps. Our hybrid assembly markedly improves upon the contiguity observed from traditional shotgun sequencing approaches, with scaffold N50 values approaching 30 Mb, and we identified complex structural variants (SVs) missed by other high-throughput approaches. Furthermore, by combining Illumina short-read data with long reads, we phased both single-nucleotide variants and SVs, generating haplotypes with over 99% consistency with previous trio-based studies. Our work shows that it is now possible to integrate single-molecule and high-throughput sequence data to generate de novo assembled genomes that approach reference quality.",

author = "Matthew Pendleton and Robert Sebra and Pang, {Andy Wing Chun} and Ajay Ummat and Oscar Franzen and Tobias Rausch and St{\"u}tz, {Adrian M.} and William Stedman and Thomas Anantharaman and Alex Hastie and Heng Dai and Fritz, {Markus Hsi Yang} and Han Cao and Ariella Cohain and Gintaras Deikus and Durrett, {Russell E.} and Blanchard, {Scott C.} and Roger Altman and Chin, {Chen Shan} and Yan Guo and Paxinos, {Ellen E.} and Korbel, {Jan O.} and Darnell, {Robert B.} and McCombie, {W. Richard} and Kwok, {Pui Yan} and Mason, {Christopher E.} and Schadt, {Eric E.} and Ali Bashir",

year = "2015",

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day = "30",

doi = "10.1038/nmeth.3454",

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Pendleton, M, Sebra, R, Pang, AWC, Ummat, A, Franzen, O, Rausch, T, Stütz, AM, Stedman, W, Anantharaman, T, Hastie, A, Dai, H, Fritz, MHY, Cao, H, Cohain, A, Deikus, G, Durrett, RE, Blanchard, SC, Altman, R, Chin, CS, Guo, Y, Paxinos, EE, Korbel, JO, Darnell, RB, McCombie, WR, Kwok, PY, Mason, CE, Schadt, EE & Bashir, A 2015, 'Assembly and diploid architecture of an individual human genome via single-molecule technologies', Nature Methods, vol. 12, no. 8, pp. 780-786. https://doi.org/10.1038/nmeth.3454

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T1 - Assembly and diploid architecture of an individual human genome via single-molecule technologies

AU - Pendleton, Matthew

AU - Sebra, Robert

AU - Pang, Andy Wing Chun

AU - Ummat, Ajay

AU - Franzen, Oscar

AU - Rausch, Tobias

AU - Stütz, Adrian M.

AU - Stedman, William

AU - Anantharaman, Thomas

AU - Hastie, Alex

AU - Dai, Heng

AU - Fritz, Markus Hsi Yang

AU - Cao, Han

AU - Cohain, Ariella

AU - Deikus, Gintaras

AU - Durrett, Russell E.

AU - Blanchard, Scott C.

AU - Altman, Roger

AU - Chin, Chen Shan

AU - Guo, Yan

AU - Paxinos, Ellen E.

AU - Korbel, Jan O.

AU - Darnell, Robert B.

AU - McCombie, W. Richard

AU - Kwok, Pui Yan

AU - Mason, Christopher E.

AU - Schadt, Eric E.

AU - Bashir, Ali

PY - 2015/7/30

Y1 - 2015/7/30

N2 - We present the first comprehensive analysis of a diploid human genome that combines single-molecule sequencing with single-molecule genome maps. Our hybrid assembly markedly improves upon the contiguity observed from traditional shotgun sequencing approaches, with scaffold N50 values approaching 30 Mb, and we identified complex structural variants (SVs) missed by other high-throughput approaches. Furthermore, by combining Illumina short-read data with long reads, we phased both single-nucleotide variants and SVs, generating haplotypes with over 99% consistency with previous trio-based studies. Our work shows that it is now possible to integrate single-molecule and high-throughput sequence data to generate de novo assembled genomes that approach reference quality.

AB - We present the first comprehensive analysis of a diploid human genome that combines single-molecule sequencing with single-molecule genome maps. Our hybrid assembly markedly improves upon the contiguity observed from traditional shotgun sequencing approaches, with scaffold N50 values approaching 30 Mb, and we identified complex structural variants (SVs) missed by other high-throughput approaches. Furthermore, by combining Illumina short-read data with long reads, we phased both single-nucleotide variants and SVs, generating haplotypes with over 99% consistency with previous trio-based studies. Our work shows that it is now possible to integrate single-molecule and high-throughput sequence data to generate de novo assembled genomes that approach reference quality.

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VL - 12

SP - 780

EP - 786

JO - Nature Methods

JF - Nature Methods

IS - 8

ER -

Assembly and diploid architecture of an individual human genome via single-molecule technologies

Abstract

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