Inferring structural variant cancer cell fraction

PCAWG Evolution and Heterogeneity Working Group; PCAWG Consortium; Marek Cmero; Ke Yuan; Cheng Soon Ong; Jan Schröder; David J. Adams; Pavana Anur; Rameen Beroukhim; Paul C. Boutros; David D.L. Bowtell; Peter J. Campbell; Shaolong Cao; Elizabeth L. Christie; Yupeng Cun; Kevin J. Dawson; Jonas Demeulemeester; Stefan C. Dentro; Amit G. Deshwar; Nilgun Donmez; Ruben M. Drews; Roland Eils; Yu Fan; Matthew W. Fittall; Dale W. Garsed; Moritz Gerstung; Gad Getz; Santiago Gonzalez; Gavin Ha; Kerstin Haase; Marcin Imielinski; Lara Jerman; Yuan Ji; Clemency Jolly; Kortine Kleinheinz; Juhee Lee; Henry Lee-Six; Ignaty Leshchiner; Dimitri Livitz; Salem Malikic; Iñigo Martincorena; Thomas J. Mitchell; Quaid D. Morris; Ville Mustonen; Layla Oesper; Martin Peifer; Myron Peto; Benjamin J. Raphael; Daniel Rosebrock; Yulia Rubanova; S. Cenk Sahinalp; Adriana Salcedo; Matthias Schlesner; Steven E. Schumacher; Subhajit Sengupta; Ruian Shi; Seung Jun Shin; Paul T. Spellman; Oliver Spiro; Lincoln D. Stein; Maxime Tarabichi; Peter Van Loo; Shankar Vembu; Ignacio Vázquez-García; Wenyi Wang; David C. Wedge; David A. Wheeler; Jeffrey A. Wintersinger; Tsun Po Yang; Xiaotong Yao; Kaixian Yu; Hongtu Zhu; Niall M. Corcoran; Tony Papenfuss; Christopher M. Hovens; Florian Markowetz; Geoff Macintyre; Lauri A. Aaltonen; Federico Abascal; Adam Abeshouse; Hiroyuki Aburatani; David J. Adams; Nishant Agrawal; Keun Soo Ahn; Sung Min Ahn; Hiroshi Aikata; Rehan Akbani; Kadir C. Akdemir; Hikmat Al-Ahmadie; Sultan T. Al-Sedairy; Fatima Al-Shahrour; Malik Alawi; Monique Albert; Kenneth Aldape; Ludmil B. Alexandrov; Adrian Ally; Kathryn Alsop; Eva G. Alvarez; Fernanda Amary; Samirkumar B. Amin; Brice Aminou; Ole Ammerpohl; Matthew J. Anderson; Yeng Ang; Davide Antonello; Pavana Anur; Samuel Aparicio; Elizabeth L. Appelbaum; Yasuhito Arai; Axel Aretz; Koji Arihiro; Shun ichi Ariizumi; Joshua Armenia; Laurent Arnould; Sylvia Asa; Yassen Assenov; Gurnit Atwal; Sietse Aukema; J. Todd Auman; Miriam R.R. Aure; Philip Awadalla; Marta Aymerich; Gary D. Bader; Adrian Baez-Ortega; Matthew H. Bailey; Peter J. Bailey; Miruna Balasundaram; Saianand Balu; Pratiti Bandopadhayay; Rosamonde E. Banks; Stefano Barbi; Andrew P. Barbour; Jonathan Barenboim; Jill Barnholtz-Sloan; Hugh Barr; Elisabet Barrera; John Bartlett; Javier Bartolome; Claudio Bassi; Oliver F. Bathe; Daniel Baumhoer; Prashant Bavi; Stephen B. Baylin; Wojciech Bazant; Duncan Beardsmore; Timothy A. Beck; Sam Behjati; Andreas Behren; Beifang Niu; Cindy Bell; Sergi Beltran; Christopher Benz; Andrew Berchuck; Anke K. Bergmann; Erik N. Bergstrom; Benjamin P. Berman; Daniel M. Berney; Stephan H. Bernhart; Mario Berrios; Samantha Bersani; Johanna Bertl; Miguel Betancourt; Vinayak Bhandari; Shriram G. Bhosle; Andrew V. Biankin; Matthias Bieg; Darell Bigner; Hans Binder; Ewan Birney; Michael Birrer; Nidhan K. Biswas; Bodil Bjerkehagen; Tom Bodenheimer; Lori Boice; Giada Bonizzato; Johann S. De Bono; Arnoud Boot; Moiz S. Bootwalla; Ake Borg; Arndt Borkhardt; Keith A. Boroevich; Ivan Borozan; Christoph Borst; Marcus Bosenberg; Mattia Bosio; Jacqueline Boultwood; Guillaume Bourque; Paul C. Boutros; G. Steven Bova; David T. Bowen; Reanne Bowlby; Sandrine Boyault; Rich Boyce; Li Ding; Lucinda A. Fulton; Robert S. Fulton; Ramaswamy Govindan; Reyka Jayasinghe; Tim Ley; Christopher A. Miller; David Mutch; Michael C. Wendl

doi:10.1038/s41467-020-14351-8

Inferring structural variant cancer cell fraction

PCAWG Evolution and Heterogeneity Working Group, PCAWG Consortium, Marek Cmero, Ke Yuan, Cheng Soon Ong, Jan Schröder, David J. Adams, Pavana Anur, Rameen Beroukhim, Paul C. Boutros, David D.L. Bowtell, Peter J. Campbell, Shaolong Cao, Elizabeth L. Christie, Yupeng Cun, Kevin J. Dawson, Jonas Demeulemeester, Stefan C. Dentro, Amit G. Deshwar, Nilgun DonmezRuben M. Drews, Roland Eils, Yu Fan, Matthew W. Fittall, Dale W. Garsed, Moritz Gerstung, Gad Getz, Santiago Gonzalez, Gavin Ha, Kerstin Haase, Marcin Imielinski, Lara Jerman, Yuan Ji, Clemency Jolly, Kortine Kleinheinz, Juhee Lee, Henry Lee-Six, Ignaty Leshchiner, Dimitri Livitz, Salem Malikic, Iñigo Martincorena, Thomas J. Mitchell, Quaid D. Morris, Ville Mustonen, Layla Oesper, Martin Peifer, Myron Peto, Benjamin J. Raphael, Daniel Rosebrock, Yulia Rubanova, S. Cenk Sahinalp, Adriana Salcedo, Matthias Schlesner, Steven E. Schumacher, Subhajit Sengupta, Ruian Shi, Seung Jun Shin, Paul T. Spellman, Oliver Spiro, Lincoln D. Stein, Maxime Tarabichi, Peter Van Loo, Shankar Vembu, Ignacio Vázquez-García, Wenyi Wang, David C. Wedge, David A. Wheeler, Jeffrey A. Wintersinger, Tsun Po Yang, Xiaotong Yao, Kaixian Yu, Hongtu Zhu, Niall M. Corcoran, Tony Papenfuss, Christopher M. Hovens, Florian Markowetz, Geoff Macintyre, Lauri A. Aaltonen, Federico Abascal, Adam Abeshouse, Hiroyuki Aburatani, David J. Adams, Nishant Agrawal, Keun Soo Ahn, Sung Min Ahn, Hiroshi Aikata, Rehan Akbani, Kadir C. Akdemir, Hikmat Al-Ahmadie, Sultan T. Al-Sedairy, Fatima Al-Shahrour, Malik Alawi, Monique Albert, Kenneth Aldape, Ludmil B. Alexandrov, Adrian Ally, Kathryn Alsop, Eva G. Alvarez, Fernanda Amary, Samirkumar B. Amin, Brice Aminou, Ole Ammerpohl, Matthew J. Anderson, Yeng Ang, Davide Antonello, Pavana Anur, Samuel Aparicio, Elizabeth L. Appelbaum, Yasuhito Arai, Axel Aretz, Koji Arihiro, Shun ichi Ariizumi, Joshua Armenia, Laurent Arnould, Sylvia Asa, Yassen Assenov, Gurnit Atwal, Sietse Aukema, J. Todd Auman, Miriam R.R. Aure, Philip Awadalla, Marta Aymerich, Gary D. Bader, Adrian Baez-Ortega, Matthew H. Bailey, Peter J. Bailey, Miruna Balasundaram, Saianand Balu, Pratiti Bandopadhayay, Rosamonde E. Banks, Stefano Barbi, Andrew P. Barbour, Jonathan Barenboim, Jill Barnholtz-Sloan, Hugh Barr, Elisabet Barrera, John Bartlett, Javier Bartolome, Claudio Bassi, Oliver F. Bathe, Daniel Baumhoer, Prashant Bavi, Stephen B. Baylin, Wojciech Bazant, Duncan Beardsmore, Timothy A. Beck, Sam Behjati, Andreas Behren, Beifang Niu, Cindy Bell, Sergi Beltran, Christopher Benz, Andrew Berchuck, Anke K. Bergmann, Erik N. Bergstrom, Benjamin P. Berman, Daniel M. Berney, Stephan H. Bernhart, Mario Berrios, Samantha Bersani, Johanna Bertl, Miguel Betancourt, Vinayak Bhandari, Shriram G. Bhosle, Andrew V. Biankin, Matthias Bieg, Darell Bigner, Hans Binder, Ewan Birney, Michael Birrer, Nidhan K. Biswas, Bodil Bjerkehagen, Tom Bodenheimer, Lori Boice, Giada Bonizzato, Johann S. De Bono, Arnoud Boot, Moiz S. Bootwalla, Ake Borg, Arndt Borkhardt, Keith A. Boroevich, Ivan Borozan, Christoph Borst, Marcus Bosenberg, Mattia Bosio, Jacqueline Boultwood, Guillaume Bourque, Paul C. Boutros, G. Steven Bova, David T. Bowen, Reanne Bowlby, Sandrine Boyault, Rich Boyce, Li Ding, Lucinda A. Fulton, Robert S. Fulton, Ramaswamy Govindan, Reyka Jayasinghe, Tim Ley, Christopher A. Miller, David Mutch, Michael C. Wendl

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

30 Scopus citations

Abstract

We present SVclone, a computational method for inferring the cancer cell fraction of structural variant (SV) breakpoints from whole-genome sequencing data. SVclone accurately determines the variant allele frequencies of both SV breakends, then simultaneously estimates the cancer cell fraction and SV copy number. We assess performance using in silico mixtures of real samples, at known proportions, created from two clonal metastases from the same patient. We find that SVclone’s performance is comparable to single-nucleotide variant-based methods, despite having an order of magnitude fewer data points. As part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we use SVclone to reveal a subset of liver, ovarian and pancreatic cancers with subclonally enriched copy-number neutral rearrangements that show decreased overall survival. SVclone enables improved characterisation of SV intra-tumour heterogeneity.

Original language	English
Article number	730
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-14351-8
State	Published - Dec 1 2020

Access to Document

10.1038/s41467-020-14351-8

Cite this

PCAWG Evolution and Heterogeneity Working Group, PCAWG Consortium, Cmero, M., Yuan, K., Ong, C. S., Schröder, J., Adams, D. J., Anur, P., Beroukhim, R., Boutros, P. C., Bowtell, D. D. L., Campbell, P. J., Cao, S., Christie, E. L., Cun, Y., Dawson, K. J., Demeulemeester, J., Dentro, S. C., Deshwar, A. G., ... Wendl, M. C. (2020). Inferring structural variant cancer cell fraction. Nature communications, 11(1), Article 730. https://doi.org/10.1038/s41467-020-14351-8

@article{7776d500bc974ab5aadbdc9cef135660,

title = "Inferring structural variant cancer cell fraction",

abstract = "We present SVclone, a computational method for inferring the cancer cell fraction of structural variant (SV) breakpoints from whole-genome sequencing data. SVclone accurately determines the variant allele frequencies of both SV breakends, then simultaneously estimates the cancer cell fraction and SV copy number. We assess performance using in silico mixtures of real samples, at known proportions, created from two clonal metastases from the same patient. We find that SVclone{\textquoteright}s performance is comparable to single-nucleotide variant-based methods, despite having an order of magnitude fewer data points. As part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we use SVclone to reveal a subset of liver, ovarian and pancreatic cancers with subclonally enriched copy-number neutral rearrangements that show decreased overall survival. SVclone enables improved characterisation of SV intra-tumour heterogeneity.",

author = "{PCAWG Evolution and Heterogeneity Working Group} and {PCAWG Consortium} and Marek Cmero and Ke Yuan and Ong, {Cheng Soon} and Jan Schr{\"o}der and Adams, {David J.} and Pavana Anur and Rameen Beroukhim and Boutros, {Paul C.} and Bowtell, {David D.L.} and Campbell, {Peter J.} and Shaolong Cao and Christie, {Elizabeth L.} and Yupeng Cun and Dawson, {Kevin J.} and Jonas Demeulemeester and Dentro, {Stefan C.} and Deshwar, {Amit G.} and Nilgun Donmez and Drews, {Ruben M.} and Roland Eils and Yu Fan and Fittall, {Matthew W.} and Garsed, {Dale W.} and Moritz Gerstung and Gad Getz and Santiago Gonzalez and Gavin Ha and Kerstin Haase and Marcin Imielinski and Lara Jerman and Yuan Ji and Clemency Jolly and Kortine Kleinheinz and Juhee Lee and Henry Lee-Six and Ignaty Leshchiner and Dimitri Livitz and Salem Malikic and I{\~n}igo Martincorena and Mitchell, {Thomas J.} and Morris, {Quaid D.} and Ville Mustonen and Layla Oesper and Martin Peifer and Myron Peto and Raphael, {Benjamin J.} and Daniel Rosebrock and Yulia Rubanova and Sahinalp, {S. Cenk} and Adriana Salcedo and Matthias Schlesner and Schumacher, {Steven E.} and Subhajit Sengupta and Ruian Shi and Shin, {Seung Jun} and Spellman, {Paul T.} and Oliver Spiro and Stein, {Lincoln D.} and Maxime Tarabichi and {Van Loo}, Peter and Shankar Vembu and Ignacio V{\'a}zquez-Garc{\'i}a and Wenyi Wang and Wedge, {David C.} and Wheeler, {David A.} and Wintersinger, {Jeffrey A.} and Yang, {Tsun Po} and Xiaotong Yao and Kaixian Yu and Hongtu Zhu and Corcoran, {Niall M.} and Tony Papenfuss and Hovens, {Christopher M.} and Florian Markowetz and Geoff Macintyre and Aaltonen, {Lauri A.} and Federico Abascal and Adam Abeshouse and Hiroyuki Aburatani and Adams, {David J.} and Nishant Agrawal and Ahn, {Keun Soo} and Ahn, {Sung Min} and Hiroshi Aikata and Rehan Akbani and Akdemir, {Kadir C.} and Hikmat Al-Ahmadie and Al-Sedairy, {Sultan T.} and Fatima Al-Shahrour and Malik Alawi and Monique Albert and Kenneth Aldape and Alexandrov, {Ludmil B.} and Adrian Ally and Kathryn Alsop and Alvarez, {Eva G.} and Fernanda Amary and Amin, {Samirkumar B.} and Brice Aminou and Ole Ammerpohl and Anderson, {Matthew J.} and Yeng Ang and Davide Antonello and Pavana Anur and Samuel Aparicio and Appelbaum, {Elizabeth L.} and Yasuhito Arai and Axel Aretz and Koji Arihiro and Ariizumi, {Shun ichi} and Joshua Armenia and Laurent Arnould and Sylvia Asa and Yassen Assenov and Gurnit Atwal and Sietse Aukema and Auman, {J. Todd} and Aure, {Miriam R.R.} and Philip Awadalla and Marta Aymerich and Bader, {Gary D.} and Adrian Baez-Ortega and Bailey, {Matthew H.} and Bailey, {Peter J.} and Miruna Balasundaram and Saianand Balu and Pratiti Bandopadhayay and Banks, {Rosamonde E.} and Stefano Barbi and Barbour, {Andrew P.} and Jonathan Barenboim and Jill Barnholtz-Sloan and Hugh Barr and Elisabet Barrera and John Bartlett and Javier Bartolome and Claudio Bassi and Bathe, {Oliver F.} and Daniel Baumhoer and Prashant Bavi and Baylin, {Stephen B.} and Wojciech Bazant and Duncan Beardsmore and Beck, {Timothy A.} and Sam Behjati and Andreas Behren and Beifang Niu and Cindy Bell and Sergi Beltran and Christopher Benz and Andrew Berchuck and Bergmann, {Anke K.} and Bergstrom, {Erik N.} and Berman, {Benjamin P.} and Berney, {Daniel M.} and Bernhart, {Stephan H.} and Mario Berrios and Samantha Bersani and Johanna Bertl and Miguel Betancourt and Vinayak Bhandari and Bhosle, {Shriram G.} and Biankin, {Andrew V.} and Matthias Bieg and Darell Bigner and Hans Binder and Ewan Birney and Michael Birrer and Biswas, {Nidhan K.} and Bodil Bjerkehagen and Tom Bodenheimer and Lori Boice and Giada Bonizzato and {De Bono}, {Johann S.} and Arnoud Boot and Bootwalla, {Moiz S.} and Ake Borg and Arndt Borkhardt and Boroevich, {Keith A.} and Ivan Borozan and Christoph Borst and Marcus Bosenberg and Mattia Bosio and Jacqueline Boultwood and Guillaume Bourque and Boutros, {Paul C.} and Bova, {G. Steven} and Bowen, {David T.} and Reanne Bowlby and Sandrine Boyault and Rich Boyce and Li Ding and Fulton, {Lucinda A.} and Fulton, {Robert S.} and Ramaswamy Govindan and Reyka Jayasinghe and Tim Ley and Miller, {Christopher A.} and David Mutch and Wendl, {Michael C.}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41467-020-14351-8",

language = "English",

volume = "11",

journal = "Nature communications",

issn = "2041-1723",

number = "1",

}

PCAWG Evolution and Heterogeneity Working Group, PCAWG Consortium, Cmero, M, Yuan, K, Ong, CS, Schröder, J, Adams, DJ, Anur, P, Beroukhim, R, Boutros, PC, Bowtell, DDL, Campbell, PJ, Cao, S, Christie, EL, Cun, Y, Dawson, KJ, Demeulemeester, J, Dentro, SC, Deshwar, AG, Donmez, N, Drews, RM, Eils, R, Fan, Y, Fittall, MW, Garsed, DW, Gerstung, M, Getz, G, Gonzalez, S, Ha, G, Haase, K, Imielinski, M, Jerman, L, Ji, Y, Jolly, C, Kleinheinz, K, Lee, J, Lee-Six, H, Leshchiner, I, Livitz, D, Malikic, S, Martincorena, I, Mitchell, TJ, Morris, QD, Mustonen, V, Oesper, L, Peifer, M, Peto, M, Raphael, BJ, Rosebrock, D, Rubanova, Y, Sahinalp, SC, Salcedo, A, Schlesner, M, Schumacher, SE, Sengupta, S, Shi, R, Shin, SJ, Spellman, PT, Spiro, O, Stein, LD, Tarabichi, M, Van Loo, P, Vembu, S, Vázquez-García, I, Wang, W, Wedge, DC, Wheeler, DA, Wintersinger, JA, Yang, TP, Yao, X, Yu, K, Zhu, H, Corcoran, NM, Papenfuss, T, Hovens, CM, Markowetz, F, Macintyre, G, Aaltonen, LA, Abascal, F, Abeshouse, A, Aburatani, H, Adams, DJ, Agrawal, N, Ahn, KS, Ahn, SM, Aikata, H, Akbani, R, Akdemir, KC, Al-Ahmadie, H, Al-Sedairy, ST, Al-Shahrour, F, Alawi, M, Albert, M, Aldape, K, Alexandrov, LB, Ally, A, Alsop, K, Alvarez, EG, Amary, F, Amin, SB, Aminou, B, Ammerpohl, O, Anderson, MJ, Ang, Y, Antonello, D, Anur, P, Aparicio, S, Appelbaum, EL, Arai, Y, Aretz, A, Arihiro, K, Ariizumi, SI, Armenia, J, Arnould, L, Asa, S, Assenov, Y, Atwal, G, Aukema, S, Auman, JT, Aure, MRR, Awadalla, P, Aymerich, M, Bader, GD, Baez-Ortega, A, Bailey, MH, Bailey, PJ, Balasundaram, M, Balu, S, Bandopadhayay, P, Banks, RE, Barbi, S, Barbour, AP, Barenboim, J, Barnholtz-Sloan, J, Barr, H, Barrera, E, Bartlett, J, Bartolome, J, Bassi, C, Bathe, OF, Baumhoer, D, Bavi, P, Baylin, SB, Bazant, W, Beardsmore, D, Beck, TA, Behjati, S, Behren, A, Niu, B, Bell, C, Beltran, S, Benz, C, Berchuck, A, Bergmann, AK, Bergstrom, EN, Berman, BP, Berney, DM, Bernhart, SH, Berrios, M, Bersani, S, Bertl, J, Betancourt, M, Bhandari, V, Bhosle, SG, Biankin, AV, Bieg, M, Bigner, D, Binder, H, Birney, E, Birrer, M, Biswas, NK, Bjerkehagen, B, Bodenheimer, T, Boice, L, Bonizzato, G, De Bono, JS, Boot, A, Bootwalla, MS, Borg, A, Borkhardt, A, Boroevich, KA, Borozan, I, Borst, C, Bosenberg, M, Bosio, M, Boultwood, J, Bourque, G, Boutros, PC, Bova, GS, Bowen, DT, Bowlby, R, Boyault, S, Boyce, R, Ding, L , Fulton, LA , Fulton, RS , Govindan, R , Jayasinghe, R , Ley, T , Miller, CA , Mutch, D & Wendl, MC 2020, 'Inferring structural variant cancer cell fraction', Nature communications, vol. 11, no. 1, 730. https://doi.org/10.1038/s41467-020-14351-8

TY - JOUR

T1 - Inferring structural variant cancer cell fraction

AU - PCAWG Evolution and Heterogeneity Working Group

AU - PCAWG Consortium

AU - Cmero, Marek

AU - Yuan, Ke

AU - Ong, Cheng Soon

AU - Schröder, Jan

AU - Adams, David J.

AU - Anur, Pavana

AU - Beroukhim, Rameen

AU - Boutros, Paul C.

AU - Bowtell, David D.L.

AU - Campbell, Peter J.

AU - Cao, Shaolong

AU - Christie, Elizabeth L.

AU - Cun, Yupeng

AU - Dawson, Kevin J.

AU - Demeulemeester, Jonas

AU - Dentro, Stefan C.

AU - Deshwar, Amit G.

AU - Donmez, Nilgun

AU - Drews, Ruben M.

AU - Eils, Roland

AU - Fan, Yu

AU - Fittall, Matthew W.

AU - Garsed, Dale W.

AU - Gerstung, Moritz

AU - Getz, Gad

AU - Gonzalez, Santiago

AU - Ha, Gavin

AU - Haase, Kerstin

AU - Imielinski, Marcin

AU - Jerman, Lara

AU - Ji, Yuan

AU - Jolly, Clemency

AU - Kleinheinz, Kortine

AU - Lee, Juhee

AU - Lee-Six, Henry

AU - Leshchiner, Ignaty

AU - Livitz, Dimitri

AU - Malikic, Salem

AU - Martincorena, Iñigo

AU - Mitchell, Thomas J.

AU - Morris, Quaid D.

AU - Mustonen, Ville

AU - Oesper, Layla

AU - Peifer, Martin

AU - Peto, Myron

AU - Raphael, Benjamin J.

AU - Rosebrock, Daniel

AU - Rubanova, Yulia

AU - Sahinalp, S. Cenk

AU - Salcedo, Adriana

AU - Schlesner, Matthias

AU - Schumacher, Steven E.

AU - Sengupta, Subhajit

AU - Shi, Ruian

AU - Shin, Seung Jun

AU - Spellman, Paul T.

AU - Spiro, Oliver

AU - Stein, Lincoln D.

AU - Tarabichi, Maxime

AU - Van Loo, Peter

AU - Vembu, Shankar

AU - Vázquez-García, Ignacio

AU - Wang, Wenyi

AU - Wedge, David C.

AU - Wheeler, David A.

AU - Wintersinger, Jeffrey A.

AU - Yang, Tsun Po

AU - Yao, Xiaotong

AU - Yu, Kaixian

AU - Zhu, Hongtu

AU - Corcoran, Niall M.

AU - Papenfuss, Tony

AU - Hovens, Christopher M.

AU - Markowetz, Florian

AU - Macintyre, Geoff

AU - Aaltonen, Lauri A.

AU - Abascal, Federico

AU - Abeshouse, Adam

AU - Aburatani, Hiroyuki

AU - Adams, David J.

AU - Agrawal, Nishant

AU - Ahn, Keun Soo

AU - Ahn, Sung Min

AU - Aikata, Hiroshi

AU - Akbani, Rehan

AU - Akdemir, Kadir C.

AU - Al-Ahmadie, Hikmat

AU - Al-Sedairy, Sultan T.

AU - Al-Shahrour, Fatima

AU - Alawi, Malik

AU - Albert, Monique

AU - Aldape, Kenneth

AU - Alexandrov, Ludmil B.

AU - Ally, Adrian

AU - Alsop, Kathryn

AU - Alvarez, Eva G.

AU - Amary, Fernanda

AU - Amin, Samirkumar B.

AU - Aminou, Brice

AU - Ammerpohl, Ole

AU - Anderson, Matthew J.

AU - Ang, Yeng

AU - Antonello, Davide

AU - Anur, Pavana

AU - Aparicio, Samuel

AU - Appelbaum, Elizabeth L.

AU - Arai, Yasuhito

AU - Aretz, Axel

AU - Arihiro, Koji

AU - Ariizumi, Shun ichi

AU - Armenia, Joshua

AU - Arnould, Laurent

AU - Asa, Sylvia

AU - Assenov, Yassen

AU - Atwal, Gurnit

AU - Aukema, Sietse

AU - Auman, J. Todd

AU - Aure, Miriam R.R.

AU - Awadalla, Philip

AU - Aymerich, Marta

AU - Bader, Gary D.

AU - Baez-Ortega, Adrian

AU - Bailey, Matthew H.

AU - Bailey, Peter J.

AU - Balasundaram, Miruna

AU - Balu, Saianand

AU - Bandopadhayay, Pratiti

AU - Banks, Rosamonde E.

AU - Barbi, Stefano

AU - Barbour, Andrew P.

AU - Barenboim, Jonathan

AU - Barnholtz-Sloan, Jill

AU - Barr, Hugh

AU - Barrera, Elisabet

AU - Bartlett, John

AU - Bartolome, Javier

AU - Bassi, Claudio

AU - Bathe, Oliver F.

AU - Baumhoer, Daniel

AU - Bavi, Prashant

AU - Baylin, Stephen B.

AU - Bazant, Wojciech

AU - Beardsmore, Duncan

AU - Beck, Timothy A.

AU - Behjati, Sam

AU - Behren, Andreas

AU - Niu, Beifang

AU - Bell, Cindy

AU - Beltran, Sergi

AU - Benz, Christopher

AU - Berchuck, Andrew

AU - Bergmann, Anke K.

AU - Bergstrom, Erik N.

AU - Berman, Benjamin P.

AU - Berney, Daniel M.

AU - Bernhart, Stephan H.

AU - Berrios, Mario

AU - Bersani, Samantha

AU - Bertl, Johanna

AU - Betancourt, Miguel

AU - Bhandari, Vinayak

AU - Bhosle, Shriram G.

AU - Biankin, Andrew V.

AU - Bieg, Matthias

AU - Bigner, Darell

AU - Binder, Hans

AU - Birney, Ewan

AU - Birrer, Michael

AU - Biswas, Nidhan K.

AU - Bjerkehagen, Bodil

AU - Bodenheimer, Tom

AU - Boice, Lori

AU - Bonizzato, Giada

AU - De Bono, Johann S.

AU - Boot, Arnoud

AU - Bootwalla, Moiz S.

AU - Borg, Ake

AU - Borkhardt, Arndt

AU - Boroevich, Keith A.

AU - Borozan, Ivan

AU - Borst, Christoph

AU - Bosenberg, Marcus

AU - Bosio, Mattia

AU - Boultwood, Jacqueline

AU - Bourque, Guillaume

AU - Boutros, Paul C.

AU - Bova, G. Steven

AU - Bowen, David T.

AU - Bowlby, Reanne

AU - Boyault, Sandrine

AU - Boyce, Rich

AU - Ding, Li

AU - Fulton, Lucinda A.

AU - Fulton, Robert S.

AU - Govindan, Ramaswamy

AU - Jayasinghe, Reyka

AU - Ley, Tim

AU - Miller, Christopher A.

AU - Mutch, David

AU - Wendl, Michael C.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - We present SVclone, a computational method for inferring the cancer cell fraction of structural variant (SV) breakpoints from whole-genome sequencing data. SVclone accurately determines the variant allele frequencies of both SV breakends, then simultaneously estimates the cancer cell fraction and SV copy number. We assess performance using in silico mixtures of real samples, at known proportions, created from two clonal metastases from the same patient. We find that SVclone’s performance is comparable to single-nucleotide variant-based methods, despite having an order of magnitude fewer data points. As part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we use SVclone to reveal a subset of liver, ovarian and pancreatic cancers with subclonally enriched copy-number neutral rearrangements that show decreased overall survival. SVclone enables improved characterisation of SV intra-tumour heterogeneity.

AB - We present SVclone, a computational method for inferring the cancer cell fraction of structural variant (SV) breakpoints from whole-genome sequencing data. SVclone accurately determines the variant allele frequencies of both SV breakends, then simultaneously estimates the cancer cell fraction and SV copy number. We assess performance using in silico mixtures of real samples, at known proportions, created from two clonal metastases from the same patient. We find that SVclone’s performance is comparable to single-nucleotide variant-based methods, despite having an order of magnitude fewer data points. As part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we use SVclone to reveal a subset of liver, ovarian and pancreatic cancers with subclonally enriched copy-number neutral rearrangements that show decreased overall survival. SVclone enables improved characterisation of SV intra-tumour heterogeneity.

UR - http://www.scopus.com/inward/record.url?scp=85079039901&partnerID=8YFLogxK

U2 - 10.1038/s41467-020-14351-8

DO - 10.1038/s41467-020-14351-8

M3 - Article

C2 - 32024845

AN - SCOPUS:85079039901

SN - 2041-1723

VL - 11

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 730

ER -

Inferring structural variant cancer cell fraction

Abstract

Access to Document

Other files and links

Fingerprint

Cite this