Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig

PCAWG Evolution and Heterogeneity Working Group; PCAWG Consortium; Yulia Rubanova; Ruian Shi; Caitlin F. Harrigan; Roujia Li; Jeff Wintersinger; Nil Sahin; Amit G. Deshwar; Stefan C. Dentro; Ignaty Leshchiner; Moritz Gerstung; Clemency Jolly; Kerstin Haase; Maxime Tarabichi; Jeff Wintersinger; Amit G. Deshwar; Kaixian Yu; Santiago Gonzalez; Yulia Rubanova; Geoff Macintyre; David J. Adams; Pavana Anur; Rameen Beroukhim; Paul C. Boutros; David D. Bowtell; Peter J. Campbell; Shaolong Cao; Elizabeth L. Christie; Marek Cmero; Yupeng Cun; Kevin J. Dawson; Jonas Demeulemeester; Nilgun Donmez; Ruben M. Drews; Roland Eils; Yu Fan; Matthew Fittall; Dale W. Garsed; Gad Getz; Gavin Ha; Marcin Imielinski; Lara Jerman; Yuan Ji; Kortine Kleinheinz; Juhee Lee; Henry Lee-Six; Dimitri G. Livitz; Salem Malikic; Florian Markowetz; Inigo Martincorena; Thomas J. Mitchell; Ville Mustonen; Layla Oesper; Martin Peifer; Myron Peto; Benjamin J. Raphael; Daniel Rosebrock; S. Cenk Sahinalp; Adriana Salcedo; Matthias Schlesner; Steven Schumacher; Subhajit Sengupta; Ruian Shi; Seung Jun Shin; Oliver Spiro; Lincoln D. Stein; Ignacio Vázquez-García; Shankar Vembu; David A. Wheeler; Tsun Po Yang; Xiaotong Yao; Ke Yuan; Hongtu Zhu; Wenyi Wang; Quaid D. Morris; Paul T. Spellman; David C. Wedge; Peter Van Loo; Quaid D. Morris; 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; Li Ding; Lucinda A. Fulton; Ramaswamy Govindan; Reyka Jayasinghe; Tim Ley; Christopher A. Miller; David Mutch; Michael C. Wendl

doi:10.1038/s41467-020-14352-7

Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig

PCAWG Evolution and Heterogeneity Working Group, PCAWG Consortium, Yulia Rubanova, Ruian Shi, Caitlin F. Harrigan, Roujia Li, Jeff Wintersinger, Nil Sahin, Amit G. Deshwar, Stefan C. Dentro, Ignaty Leshchiner, Moritz Gerstung, Clemency Jolly, Kerstin Haase, Maxime Tarabichi, Jeff Wintersinger, Amit G. Deshwar, Kaixian Yu, Santiago Gonzalez, Yulia RubanovaGeoff Macintyre, David J. Adams, Pavana Anur, Rameen Beroukhim, Paul C. Boutros, David D. Bowtell, Peter J. Campbell, Shaolong Cao, Elizabeth L. Christie, Marek Cmero, Yupeng Cun, Kevin J. Dawson, Jonas Demeulemeester, Nilgun Donmez, Ruben M. Drews, Roland Eils, Yu Fan, Matthew Fittall, Dale W. Garsed, Gad Getz, Gavin Ha, Marcin Imielinski, Lara Jerman, Yuan Ji, Kortine Kleinheinz, Juhee Lee, Henry Lee-Six, Dimitri G. Livitz, Salem Malikic, Florian Markowetz, Inigo Martincorena, Thomas J. Mitchell, Ville Mustonen, Layla Oesper, Martin Peifer, Myron Peto, Benjamin J. Raphael, Daniel Rosebrock, S. Cenk Sahinalp, Adriana Salcedo, Matthias Schlesner, Steven Schumacher, Subhajit Sengupta, Ruian Shi, Seung Jun Shin, Oliver Spiro, Lincoln D. Stein, Ignacio Vázquez-García, Shankar Vembu, David A. Wheeler, Tsun Po Yang, Xiaotong Yao, Ke Yuan, Hongtu Zhu, Wenyi Wang, Quaid D. Morris, Paul T. Spellman, David C. Wedge, Peter Van Loo, Quaid D. Morris, 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, Li Ding, Lucinda A. 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

The type and genomic context of cancer mutations depend on their causes. These causes have been characterized using signatures that represent mutation types that co-occur in the same tumours. However, it remains unclear how mutation processes change during cancer evolution due to the lack of reliable methods to reconstruct evolutionary trajectories of mutational signature activity. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we present TrackSig, a new method that reconstructs these trajectories using optimal, joint segmentation and deconvolution of mutation type and allele frequencies from a single tumour sample. In simulations, we find TrackSig has a 3–5% activity reconstruction error, and 12% false detection rate. It outperforms an aggressive baseline in situations with branching evolution, CNA gain, and neutral mutations. Applied to data from 2658 tumours and 38 cancer types, TrackSig permits pan-cancer insight into evolutionary changes in mutational processes.

Original language	English
Article number	731
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-14352-7
State	Published - Dec 1 2020

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10.1038/s41467-020-14352-7

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PCAWG Evolution and Heterogeneity Working Group, PCAWG Consortium, Rubanova, Y., Shi, R., Harrigan, C. F., Li, R., Wintersinger, J., Sahin, N., Deshwar, A. G., Dentro, S. C., Leshchiner, I., Gerstung, M., Jolly, C., Haase, K., Tarabichi, M., Wintersinger, J., Deshwar, A. G., Yu, K., Gonzalez, S., ... Wendl, M. C. (2020). Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig. Nature communications, 11(1), Article 731. https://doi.org/10.1038/s41467-020-14352-7

@article{2b8e2ecf391b49199b2cd062ea29c35b,

title = "Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig",

abstract = "The type and genomic context of cancer mutations depend on their causes. These causes have been characterized using signatures that represent mutation types that co-occur in the same tumours. However, it remains unclear how mutation processes change during cancer evolution due to the lack of reliable methods to reconstruct evolutionary trajectories of mutational signature activity. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we present TrackSig, a new method that reconstructs these trajectories using optimal, joint segmentation and deconvolution of mutation type and allele frequencies from a single tumour sample. In simulations, we find TrackSig has a 3–5% activity reconstruction error, and 12% false detection rate. It outperforms an aggressive baseline in situations with branching evolution, CNA gain, and neutral mutations. Applied to data from 2658 tumours and 38 cancer types, TrackSig permits pan-cancer insight into evolutionary changes in mutational processes.",

author = "{PCAWG Evolution and Heterogeneity Working Group} and {PCAWG Consortium} and Yulia Rubanova and Ruian Shi and Harrigan, {Caitlin F.} and Roujia Li and Jeff Wintersinger and Nil Sahin and Deshwar, {Amit G.} and Dentro, {Stefan C.} and Ignaty Leshchiner and Moritz Gerstung and Clemency Jolly and Kerstin Haase and Maxime Tarabichi and Jeff Wintersinger and Deshwar, {Amit G.} and Kaixian Yu and Santiago Gonzalez and Yulia Rubanova and Geoff Macintyre and Adams, {David J.} and Pavana Anur and Rameen Beroukhim and Boutros, {Paul C.} and Bowtell, {David D.} and Campbell, {Peter J.} and Shaolong Cao and Christie, {Elizabeth L.} and Marek Cmero and Yupeng Cun and Dawson, {Kevin J.} and Jonas Demeulemeester and Nilgun Donmez and Drews, {Ruben M.} and Roland Eils and Yu Fan and Matthew Fittall and Garsed, {Dale W.} and Gad Getz and Gavin Ha and Marcin Imielinski and Lara Jerman and Yuan Ji and Kortine Kleinheinz and Juhee Lee and Henry Lee-Six and Livitz, {Dimitri G.} and Salem Malikic and Florian Markowetz and Inigo Martincorena and Mitchell, {Thomas J.} and Ville Mustonen and Layla Oesper and Martin Peifer and Myron Peto and Raphael, {Benjamin J.} and Daniel Rosebrock and Sahinalp, {S. Cenk} and Adriana Salcedo and Matthias Schlesner and Steven Schumacher and Subhajit Sengupta and Ruian Shi and Shin, {Seung Jun} and Oliver Spiro and Stein, {Lincoln D.} and Ignacio V{\'a}zquez-Garc{\'i}a and Shankar Vembu and Wheeler, {David A.} and Yang, {Tsun Po} and Xiaotong Yao and Ke Yuan and Hongtu Zhu and Wenyi Wang and Morris, {Quaid D.} and Spellman, {Paul T.} and Wedge, {David C.} and {Van Loo}, Peter and Morris, {Quaid D.} 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 Li Ding and Fulton, {Lucinda A.} 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/s41467-020-14352-7",

language = "English",

volume = "11",

journal = "Nature communications",

issn = "2041-1723",

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PCAWG Evolution and Heterogeneity Working Group, PCAWG Consortium, Rubanova, Y, Shi, R, Harrigan, CF, Li, R, Wintersinger, J, Sahin, N, Deshwar, AG, Dentro, SC, Leshchiner, I, Gerstung, M, Jolly, C, Haase, K, Tarabichi, M, Wintersinger, J, Deshwar, AG, Yu, K, Gonzalez, S, Rubanova, Y, Macintyre, G, Adams, DJ, Anur, P, Beroukhim, R, Boutros, PC, Bowtell, DD, Campbell, PJ, Cao, S, Christie, EL, Cmero, M, Cun, Y, Dawson, KJ, Demeulemeester, J, Donmez, N, Drews, RM, Eils, R, Fan, Y, Fittall, M, Garsed, DW, Getz, G, Ha, G, Imielinski, M, Jerman, L, Ji, Y, Kleinheinz, K, Lee, J, Lee-Six, H, Livitz, DG, Malikic, S, Markowetz, F, Martincorena, I, Mitchell, TJ, Mustonen, V, Oesper, L, Peifer, M, Peto, M, Raphael, BJ, Rosebrock, D, Sahinalp, SC, Salcedo, A, Schlesner, M, Schumacher, S, Sengupta, S, Shi, R, Shin, SJ, Spiro, O, Stein, LD, Vázquez-García, I, Vembu, S, Wheeler, DA, Yang, TP, Yao, X, Yuan, K, Zhu, H, Wang, W, Morris, QD, Spellman, PT, Wedge, DC, Van Loo, P, Morris, QD, 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 , Ding, L , Fulton, LA , Govindan, R , Jayasinghe, R , Ley, T , Miller, CA , Mutch, D & Wendl, MC 2020, 'Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig', Nature communications, vol. 11, no. 1, 731. https://doi.org/10.1038/s41467-020-14352-7

TY - JOUR

T1 - Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig

AU - PCAWG Evolution and Heterogeneity Working Group

AU - PCAWG Consortium

AU - Rubanova, Yulia

AU - Shi, Ruian

AU - Harrigan, Caitlin F.

AU - Li, Roujia

AU - Wintersinger, Jeff

AU - Sahin, Nil

AU - Deshwar, Amit G.

AU - Dentro, Stefan C.

AU - Leshchiner, Ignaty

AU - Gerstung, Moritz

AU - Jolly, Clemency

AU - Haase, Kerstin

AU - Tarabichi, Maxime

AU - Wintersinger, Jeff

AU - Deshwar, Amit G.

AU - Yu, Kaixian

AU - Gonzalez, Santiago

AU - Rubanova, Yulia

AU - Macintyre, Geoff

AU - Adams, David J.

AU - Anur, Pavana

AU - Beroukhim, Rameen

AU - Boutros, Paul C.

AU - Bowtell, David D.

AU - Campbell, Peter J.

AU - Cao, Shaolong

AU - Christie, Elizabeth L.

AU - Cmero, Marek

AU - Cun, Yupeng

AU - Dawson, Kevin J.

AU - Demeulemeester, Jonas

AU - Donmez, Nilgun

AU - Drews, Ruben M.

AU - Eils, Roland

AU - Fan, Yu

AU - Fittall, Matthew

AU - Garsed, Dale W.

AU - Getz, Gad

AU - Ha, Gavin

AU - Imielinski, Marcin

AU - Jerman, Lara

AU - Ji, Yuan

AU - Kleinheinz, Kortine

AU - Lee, Juhee

AU - Lee-Six, Henry

AU - Livitz, Dimitri G.

AU - Malikic, Salem

AU - Markowetz, Florian

AU - Martincorena, Inigo

AU - Mitchell, Thomas J.

AU - Mustonen, Ville

AU - Oesper, Layla

AU - Peifer, Martin

AU - Peto, Myron

AU - Raphael, Benjamin J.

AU - Rosebrock, Daniel

AU - Sahinalp, S. Cenk

AU - Salcedo, Adriana

AU - Schlesner, Matthias

AU - Schumacher, Steven

AU - Sengupta, Subhajit

AU - Shi, Ruian

AU - Shin, Seung Jun

AU - Spiro, Oliver

AU - Stein, Lincoln D.

AU - Vázquez-García, Ignacio

AU - Vembu, Shankar

AU - Wheeler, David A.

AU - Yang, Tsun Po

AU - Yao, Xiaotong

AU - Yuan, Ke

AU - Zhu, Hongtu

AU - Wang, Wenyi

AU - Morris, Quaid D.

AU - Spellman, Paul T.

AU - Wedge, David C.

AU - Van Loo, Peter

AU - Morris, Quaid D.

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 - Ding, Li

AU - Fulton, Lucinda A.

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 - The type and genomic context of cancer mutations depend on their causes. These causes have been characterized using signatures that represent mutation types that co-occur in the same tumours. However, it remains unclear how mutation processes change during cancer evolution due to the lack of reliable methods to reconstruct evolutionary trajectories of mutational signature activity. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we present TrackSig, a new method that reconstructs these trajectories using optimal, joint segmentation and deconvolution of mutation type and allele frequencies from a single tumour sample. In simulations, we find TrackSig has a 3–5% activity reconstruction error, and 12% false detection rate. It outperforms an aggressive baseline in situations with branching evolution, CNA gain, and neutral mutations. Applied to data from 2658 tumours and 38 cancer types, TrackSig permits pan-cancer insight into evolutionary changes in mutational processes.

AB - The type and genomic context of cancer mutations depend on their causes. These causes have been characterized using signatures that represent mutation types that co-occur in the same tumours. However, it remains unclear how mutation processes change during cancer evolution due to the lack of reliable methods to reconstruct evolutionary trajectories of mutational signature activity. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we present TrackSig, a new method that reconstructs these trajectories using optimal, joint segmentation and deconvolution of mutation type and allele frequencies from a single tumour sample. In simulations, we find TrackSig has a 3–5% activity reconstruction error, and 12% false detection rate. It outperforms an aggressive baseline in situations with branching evolution, CNA gain, and neutral mutations. Applied to data from 2658 tumours and 38 cancer types, TrackSig permits pan-cancer insight into evolutionary changes in mutational processes.

UR - http://www.scopus.com/inward/record.url?scp=85079071600&partnerID=8YFLogxK

U2 - 10.1038/s41467-020-14352-7

DO - 10.1038/s41467-020-14352-7

M3 - Article

C2 - 32024834

AN - SCOPUS:85079071600

SN - 2041-1723

VL - 11

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 731

ER -

Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig

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