Clinical cancer genomic profiling by three-platform sequencing of whole genome, whole exome and transcriptome

Michael Rusch; Joy Nakitandwe; Sheila Shurtleff; Scott Newman; Zhaojie Zhang; Michael N. Edmonson; Matthew Parker; Yuannian Jiao; Xiaotu Ma; Yanling Liu; Jiali Gu; Michael F. Walsh; Jared Becksfort; Andrew Thrasher; Yongjin Li; James McMurry; Erin Hedlund; Aman Patel; John Easton; Donald Yergeau; Bhavin Vadodaria; Ruth G. Tatevossian; Susana Raimondi; Dale Hedges; Xiang Chen; Kohei Hagiwara; Rose McGee; Giles W. Robinson; Jeffery M. Klco; Tanja A. Gruber; David W. Ellison; James R. Downing; Jinghui Zhang

doi:10.1038/s41467-018-06485-7

Clinical cancer genomic profiling by three-platform sequencing of whole genome, whole exome and transcriptome

Michael Rusch
, Joy Nakitandwe
, Sheila Shurtleff
, Scott Newman
, Zhaojie Zhang
, Michael N. Edmonson
, Matthew Parker
, Yuannian Jiao
, Xiaotu Ma
, Yanling Liu
, Jiali Gu
, Michael F. Walsh
, Jared Becksfort
, Andrew Thrasher
, Yongjin Li
, James McMurry
, Erin Hedlund
, Aman Patel
, John Easton
, Donald Yergeau

Bhavin Vadodaria, Ruth G. Tatevossian, Susana Raimondi, Dale Hedges, Xiang Chen, Kohei Hagiwara, Rose McGee, Giles W. Robinson, Jeffery M. Klco, Tanja A. Gruber, David W. Ellison, James R. Downing, Jinghui Zhang

Business and Entrepreneur Partnerships

St. Jude Children Research Hospital
University of Sheffield

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

182 Scopus citations

Abstract

To evaluate the potential of an integrated clinical test to detect diverse classes of somatic and germline mutations relevant to pediatric oncology, we performed three-platform whole-genome (WGS), whole exome (WES) and transcriptome (RNA-Seq) sequencing of tumors and normal tissue from 78 pediatric cancer patients in a CLIA-certified, CAP-accredited laboratory. Our analysis pipeline achieves high accuracy by cross-validating variants between sequencing types, thereby removing the need for confirmatory testing, and facilitates comprehensive reporting in a clinically-relevant timeframe. Three-platform sequencing has a positive predictive value of 97–99, 99, and 91% for somatic SNVs, indels and structural variations, respectively, based on independent experimental verification of 15,225 variants. We report 240 pathogenic variants across all cases, including 84 of 86 known from previous diagnostic testing (98% sensitivity). Combined WES and RNA-Seq, the current standard for precision oncology, achieved only 78% sensitivity. These results emphasize the critical need for incorporating WGS in pediatric oncology testing.

Original language	English
Article number	3962
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-06485-7
State	Published - Dec 1 2018

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Rusch, M., Nakitandwe, J., Shurtleff, S., Newman, S., Zhang, Z., Edmonson, M. N., Parker, M., Jiao, Y., Ma, X., Liu, Y., Gu, J., Walsh, M. F., Becksfort, J., Thrasher, A., Li, Y., McMurry, J., Hedlund, E., Patel, A., Easton, J., ... Zhang, J. (2018). Clinical cancer genomic profiling by three-platform sequencing of whole genome, whole exome and transcriptome. Nature Communications, 9(1), Article 3962. https://doi.org/10.1038/s41467-018-06485-7

@article{d645933025e244b2992397bff74414f9,

title = "Clinical cancer genomic profiling by three-platform sequencing of whole genome, whole exome and transcriptome",

abstract = "To evaluate the potential of an integrated clinical test to detect diverse classes of somatic and germline mutations relevant to pediatric oncology, we performed three-platform whole-genome (WGS), whole exome (WES) and transcriptome (RNA-Seq) sequencing of tumors and normal tissue from 78 pediatric cancer patients in a CLIA-certified, CAP-accredited laboratory. Our analysis pipeline achieves high accuracy by cross-validating variants between sequencing types, thereby removing the need for confirmatory testing, and facilitates comprehensive reporting in a clinically-relevant timeframe. Three-platform sequencing has a positive predictive value of 97–99, 99, and 91\% for somatic SNVs, indels and structural variations, respectively, based on independent experimental verification of 15,225 variants. We report 240 pathogenic variants across all cases, including 84 of 86 known from previous diagnostic testing (98\% sensitivity). Combined WES and RNA-Seq, the current standard for precision oncology, achieved only 78\% sensitivity. These results emphasize the critical need for incorporating WGS in pediatric oncology testing.",

author = "Michael Rusch and Joy Nakitandwe and Sheila Shurtleff and Scott Newman and Zhaojie Zhang and Edmonson, \{Michael N.\} and Matthew Parker and Yuannian Jiao and Xiaotu Ma and Yanling Liu and Jiali Gu and Walsh, \{Michael F.\} and Jared Becksfort and Andrew Thrasher and Yongjin Li and James McMurry and Erin Hedlund and Aman Patel and John Easton and Donald Yergeau and Bhavin Vadodaria and Tatevossian, \{Ruth G.\} and Susana Raimondi and Dale Hedges and Xiang Chen and Kohei Hagiwara and Rose McGee and Robinson, \{Giles W.\} and Klco, \{Jeffery M.\} and Gruber, \{Tanja A.\} and Ellison, \{David W.\} and Downing, \{James R.\} and Jinghui Zhang",

note = "Publisher Copyright: {\textcopyright} 2018, The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41467-018-06485-7",

language = "English",

volume = "9",

journal = "Nature Communications",

issn = "2041-1723",

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Rusch, M, Nakitandwe, J, Shurtleff, S, Newman, S, Zhang, Z, Edmonson, MN, Parker, M, Jiao, Y, Ma, X, Liu, Y, Gu, J, Walsh, MF, Becksfort, J, Thrasher, A, Li, Y, McMurry, J, Hedlund, E, Patel, A, Easton, J, Yergeau, D, Vadodaria, B, Tatevossian, RG, Raimondi, S, Hedges, D, Chen, X, Hagiwara, K, McGee, R, Robinson, GW, Klco, JM, Gruber, TA, Ellison, DW, Downing, JR & Zhang, J 2018, 'Clinical cancer genomic profiling by three-platform sequencing of whole genome, whole exome and transcriptome', Nature Communications, vol. 9, no. 1, 3962. https://doi.org/10.1038/s41467-018-06485-7

TY - JOUR

T1 - Clinical cancer genomic profiling by three-platform sequencing of whole genome, whole exome and transcriptome

AU - Rusch, Michael

AU - Nakitandwe, Joy

AU - Shurtleff, Sheila

AU - Newman, Scott

AU - Zhang, Zhaojie

AU - Edmonson, Michael N.

AU - Parker, Matthew

AU - Jiao, Yuannian

AU - Ma, Xiaotu

AU - Liu, Yanling

AU - Gu, Jiali

AU - Walsh, Michael F.

AU - Becksfort, Jared

AU - Thrasher, Andrew

AU - Li, Yongjin

AU - McMurry, James

AU - Hedlund, Erin

AU - Patel, Aman

AU - Easton, John

AU - Yergeau, Donald

AU - Vadodaria, Bhavin

AU - Tatevossian, Ruth G.

AU - Raimondi, Susana

AU - Hedges, Dale

AU - Chen, Xiang

AU - Hagiwara, Kohei

AU - McGee, Rose

AU - Robinson, Giles W.

AU - Klco, Jeffery M.

AU - Gruber, Tanja A.

AU - Ellison, David W.

AU - Downing, James R.

AU - Zhang, Jinghui

PY - 2018/12/1

Y1 - 2018/12/1

N2 - To evaluate the potential of an integrated clinical test to detect diverse classes of somatic and germline mutations relevant to pediatric oncology, we performed three-platform whole-genome (WGS), whole exome (WES) and transcriptome (RNA-Seq) sequencing of tumors and normal tissue from 78 pediatric cancer patients in a CLIA-certified, CAP-accredited laboratory. Our analysis pipeline achieves high accuracy by cross-validating variants between sequencing types, thereby removing the need for confirmatory testing, and facilitates comprehensive reporting in a clinically-relevant timeframe. Three-platform sequencing has a positive predictive value of 97–99, 99, and 91% for somatic SNVs, indels and structural variations, respectively, based on independent experimental verification of 15,225 variants. We report 240 pathogenic variants across all cases, including 84 of 86 known from previous diagnostic testing (98% sensitivity). Combined WES and RNA-Seq, the current standard for precision oncology, achieved only 78% sensitivity. These results emphasize the critical need for incorporating WGS in pediatric oncology testing.

AB - To evaluate the potential of an integrated clinical test to detect diverse classes of somatic and germline mutations relevant to pediatric oncology, we performed three-platform whole-genome (WGS), whole exome (WES) and transcriptome (RNA-Seq) sequencing of tumors and normal tissue from 78 pediatric cancer patients in a CLIA-certified, CAP-accredited laboratory. Our analysis pipeline achieves high accuracy by cross-validating variants between sequencing types, thereby removing the need for confirmatory testing, and facilitates comprehensive reporting in a clinically-relevant timeframe. Three-platform sequencing has a positive predictive value of 97–99, 99, and 91% for somatic SNVs, indels and structural variations, respectively, based on independent experimental verification of 15,225 variants. We report 240 pathogenic variants across all cases, including 84 of 86 known from previous diagnostic testing (98% sensitivity). Combined WES and RNA-Seq, the current standard for precision oncology, achieved only 78% sensitivity. These results emphasize the critical need for incorporating WGS in pediatric oncology testing.

UR - https://www.scopus.com/pages/publications/85054076893

U2 - 10.1038/s41467-018-06485-7

DO - 10.1038/s41467-018-06485-7

M3 - Article

C2 - 30262806

AN - SCOPUS:85054076893

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3962

ER -

Clinical cancer genomic profiling by three-platform sequencing of whole genome, whole exome and transcriptome

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