Combined burden and functional impact tests for cancer driver discovery using DriverPower

PCAWG Drivers and Functional Interpretation Working Group; PCAWG Consortium; Shimin Shuai; Federico Abascal; Samirkumar B. Amin; Gary D. Bader; Pratiti Bandopadhayay; Jonathan Barenboim; Rameen Beroukhim; Johanna Bertl; Keith A. Boroevich; Søren Brunak; Peter J. Campbell; Joana Carlevaro-Fita; Dimple Chakravarty; Calvin Wing Yiu Chan; Ken Chen; Jung Kyoon Choi; Jordi Deu-Pons; Priyanka Dhingra; Klev Diamanti; Lars Feuerbach; J. Lynn Fink; Nuno A. Fonseca; Joan Frigola; Carlo Gambacorti-Passerini; Dale W. Garsed; Mark Gerstein; Gad Getz; Qianyun Guo; Ivo G. Gut; David Haan; Mark P. Hamilton; Nicholas J. Haradhvala; Arif O. Harmanci; Mohamed Helmy; Carl Herrmann; Julian M. Hess; Asger Hobolth; Ermin Hodzic; Chen Hong; Henrik Hornshøj; Keren Isaev; Jose M.G. Izarzugaza; Rory Johnson; Todd A. Johnson; Malene Juul; Randi Istrup Juul; Andre Kahles; Abdullah Kahraman; Manolis Kellis; Ekta Khurana; Jaegil Kim; Jong K. Kim; Youngwook Kim; Jan Komorowski; Jan O. Korbel; Sushant Kumar; Andrés Lanzós; Erik Larsson; Michael S. Lawrence; Donghoon Lee; Kjong Van Lehmann; Shantao Li; Xiaotong Li; Ziao Lin; Eric Minwei Liu; Lucas Lochovsky; Shaoke Lou; Tobias Madsen; Kathleen Marchal; Iñigo Martincorena; Alexander Martinez-Fundichely; Yosef E. Maruvka; Patrick D. McGillivray; William Meyerson; Ferran Muiños; Loris Mularoni; Hidewaki Nakagawa; Morten Muhlig Nielsen; Marta Paczkowska; Keunchil Park; Kiejung Park; Jakob Skou Pedersen; Tirso Pons; Sergio Pulido-Tamayo; Benjamin J. Raphael; Jüri Reimand; Iker Reyes-Salazar; Matthew A. Reyna; Esther Rheinbay; Mark A. Rubin; Carlota Rubio-Perez; S. Cenk Sahinalp; Gordon Saksena; Leonidas Salichos; Chris Sander; Steven E. Schumacher; Mark Shackleton; Ofer Shapira; Ciyue Shen; Raunak Shrestha; Shimin Shuai; Nikos Sidiropoulos; Lina Sieverling; Nasa Sinnott-Armstrong; Lincoln D. Stein; Joshua M. Stuart; David Tamborero; Grace Tiao; Tatsuhiko Tsunoda; Husen M. Umer; Liis Uusküla-Reimand; Alfonso Valencia; Miguel Vazquez; Lieven P.C. Verbeke; Claes Wadelius; Lina Wadi; Jiayin Wang; Jonathan Warrell; Sebastian M. Waszak; Joachim Weischenfeldt; David A. Wheeler; Guanming Wu; Jun Yu; Jing Zhang; Xuanping Zhang; Yan Zhang; Zhongming Zhao; Lihua Zou; Christian von Mering; Steven Gallinger; 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; 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; 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/s41467-019-13929-1

Combined burden and functional impact tests for cancer driver discovery using DriverPower

PCAWG Drivers and Functional Interpretation Working Group, PCAWG Consortium, Shimin Shuai, Federico Abascal, Samirkumar B. Amin, Gary D. Bader, Pratiti Bandopadhayay, Jonathan Barenboim, Rameen Beroukhim, Johanna Bertl, Keith A. Boroevich, Søren Brunak, Peter J. Campbell, Joana Carlevaro-Fita, Dimple Chakravarty, Calvin Wing Yiu Chan, Ken Chen, Jung Kyoon Choi, Jordi Deu-Pons, Priyanka DhingraKlev Diamanti, Lars Feuerbach, J. Lynn Fink, Nuno A. Fonseca, Joan Frigola, Carlo Gambacorti-Passerini, Dale W. Garsed, Mark Gerstein, Gad Getz, Qianyun Guo, Ivo G. Gut, David Haan, Mark P. Hamilton, Nicholas J. Haradhvala, Arif O. Harmanci, Mohamed Helmy, Carl Herrmann, Julian M. Hess, Asger Hobolth, Ermin Hodzic, Chen Hong, Henrik Hornshøj, Keren Isaev, Jose M.G. Izarzugaza, Rory Johnson, Todd A. Johnson, Malene Juul, Randi Istrup Juul, Andre Kahles, Abdullah Kahraman, Manolis Kellis, Ekta Khurana, Jaegil Kim, Jong K. Kim, Youngwook Kim, Jan Komorowski, Jan O. Korbel, Sushant Kumar, Andrés Lanzós, Erik Larsson, Michael S. Lawrence, Donghoon Lee, Kjong Van Lehmann, Shantao Li, Xiaotong Li, Ziao Lin, Eric Minwei Liu, Lucas Lochovsky, Shaoke Lou, Tobias Madsen, Kathleen Marchal, Iñigo Martincorena, Alexander Martinez-Fundichely, Yosef E. Maruvka, Patrick D. McGillivray, William Meyerson, Ferran Muiños, Loris Mularoni, Hidewaki Nakagawa, Morten Muhlig Nielsen, Marta Paczkowska, Keunchil Park, Kiejung Park, Jakob Skou Pedersen, Tirso Pons, Sergio Pulido-Tamayo, Benjamin J. Raphael, Jüri Reimand, Iker Reyes-Salazar, Matthew A. Reyna, Esther Rheinbay, Mark A. Rubin, Carlota Rubio-Perez, S. Cenk Sahinalp, Gordon Saksena, Leonidas Salichos, Chris Sander, Steven E. Schumacher, Mark Shackleton, Ofer Shapira, Ciyue Shen, Raunak Shrestha, Shimin Shuai, Nikos Sidiropoulos, Lina Sieverling, Nasa Sinnott-Armstrong, Lincoln D. Stein, Joshua M. Stuart, David Tamborero, Grace Tiao, Tatsuhiko Tsunoda, Husen M. Umer, Liis Uusküla-Reimand, Alfonso Valencia, Miguel Vazquez, Lieven P.C. Verbeke, Claes Wadelius, Lina Wadi, Jiayin Wang, Jonathan Warrell, Sebastian M. Waszak, Joachim Weischenfeldt, David A. Wheeler, Guanming Wu, Jun Yu, Jing Zhang, Xuanping Zhang, Yan Zhang, Zhongming Zhao, Lihua Zou, Christian von Mering, Steven Gallinger, 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, 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, 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

25 Scopus citations

Abstract

The discovery of driver mutations is one of the key motivations for cancer genome sequencing. 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 describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features derived from public sources, DriverPower’s background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.

Original language	English
Article number	734
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-13929-1
State	Published - Dec 1 2020

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10.1038/s41467-019-13929-1

Cite this

PCAWG Drivers and Functional Interpretation Working Group, PCAWG Consortium, Shuai, S., Abascal, F., Amin, S. B., Bader, G. D., Bandopadhayay, P., Barenboim, J., Beroukhim, R., Bertl, J., Boroevich, K. A., Brunak, S., Campbell, P. J., Carlevaro-Fita, J., Chakravarty, D., Chan, C. W. Y., Chen, K., Choi, J. K., Deu-Pons, J., ... Wendl, M. C. (2020). Combined burden and functional impact tests for cancer driver discovery using DriverPower. Nature communications, 11(1), Article 734. https://doi.org/10.1038/s41467-019-13929-1

@article{6b9f57c36cc14175b4feea1e1e1a1897,

title = "Combined burden and functional impact tests for cancer driver discovery using DriverPower",

abstract = "The discovery of driver mutations is one of the key motivations for cancer genome sequencing. 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 describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features derived from public sources, DriverPower{\textquoteright}s background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.",

author = "{PCAWG Drivers and Functional Interpretation Working Group} and {PCAWG Consortium} and Shimin Shuai and Federico Abascal and Amin, {Samirkumar B.} and Bader, {Gary D.} and Pratiti Bandopadhayay and Jonathan Barenboim and Rameen Beroukhim and Johanna Bertl and Boroevich, {Keith A.} and S{\o}ren Brunak and Campbell, {Peter J.} and Joana Carlevaro-Fita and Dimple Chakravarty and Chan, {Calvin Wing Yiu} and Ken Chen and Choi, {Jung Kyoon} and Jordi Deu-Pons and Priyanka Dhingra and Klev Diamanti and Lars Feuerbach and Fink, {J. Lynn} and Fonseca, {Nuno A.} and Joan Frigola and Carlo Gambacorti-Passerini and Garsed, {Dale W.} and Mark Gerstein and Gad Getz and Qianyun Guo and Gut, {Ivo G.} and David Haan and Hamilton, {Mark P.} and Haradhvala, {Nicholas J.} and Harmanci, {Arif O.} and Mohamed Helmy and Carl Herrmann and Hess, {Julian M.} and Asger Hobolth and Ermin Hodzic and Chen Hong and Henrik Hornsh{\o}j and Keren Isaev and Izarzugaza, {Jose M.G.} and Rory Johnson and Johnson, {Todd A.} and Malene Juul and Juul, {Randi Istrup} and Andre Kahles and Abdullah Kahraman and Manolis Kellis and Ekta Khurana and Jaegil Kim and Kim, {Jong K.} and Youngwook Kim and Jan Komorowski and Korbel, {Jan O.} and Sushant Kumar and Andr{\'e}s Lanz{\'o}s and Erik Larsson and Lawrence, {Michael S.} and Donghoon Lee and Lehmann, {Kjong Van} and Shantao Li and Xiaotong Li and Ziao Lin and Liu, {Eric Minwei} and Lucas Lochovsky and Shaoke Lou and Tobias Madsen and Kathleen Marchal and I{\~n}igo Martincorena and Alexander Martinez-Fundichely and Maruvka, {Yosef E.} and McGillivray, {Patrick D.} and William Meyerson and Ferran Mui{\~n}os and Loris Mularoni and Hidewaki Nakagawa and Nielsen, {Morten Muhlig} and Marta Paczkowska and Keunchil Park and Kiejung Park and Pedersen, {Jakob Skou} and Tirso Pons and Sergio Pulido-Tamayo and Raphael, {Benjamin J.} and J{\"u}ri Reimand and Iker Reyes-Salazar and Reyna, {Matthew A.} and Esther Rheinbay and Rubin, {Mark A.} and Carlota Rubio-Perez and Sahinalp, {S. Cenk} and Gordon Saksena and Leonidas Salichos and Chris Sander and Schumacher, {Steven E.} and Mark Shackleton and Ofer Shapira and Ciyue Shen and Raunak Shrestha and Shimin Shuai and Nikos Sidiropoulos and Lina Sieverling and Nasa Sinnott-Armstrong and Stein, {Lincoln D.} and Stuart, {Joshua M.} and David Tamborero and Grace Tiao and Tatsuhiko Tsunoda and Umer, {Husen M.} and Liis Uusk{\"u}la-Reimand and Alfonso Valencia and Miguel Vazquez and Verbeke, {Lieven P.C.} and Claes Wadelius and Lina Wadi and Jiayin Wang and Jonathan Warrell and Waszak, {Sebastian M.} and Joachim Weischenfeldt and Wheeler, {David A.} and Guanming Wu and Jun Yu and Jing Zhang and Xuanping Zhang and Yan Zhang and Zhongming Zhao and Lihua Zou and {von Mering}, Christian and Steven Gallinger 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 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 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,

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doi = "10.1038/s41467-019-13929-1",

language = "English",

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PCAWG Drivers and Functional Interpretation Working Group, PCAWG Consortium, Shuai, S, Abascal, F, Amin, SB, Bader, GD, Bandopadhayay, P, Barenboim, J, Beroukhim, R, Bertl, J, Boroevich, KA, Brunak, S, Campbell, PJ, Carlevaro-Fita, J, Chakravarty, D, Chan, CWY, Chen, K, Choi, JK, Deu-Pons, J, Dhingra, P, Diamanti, K, Feuerbach, L, Fink, JL, Fonseca, NA, Frigola, J, Gambacorti-Passerini, C, Garsed, DW, Gerstein, M, Getz, G, Guo, Q, Gut, IG, Haan, D, Hamilton, MP, Haradhvala, NJ, Harmanci, AO, Helmy, M, Herrmann, C, Hess, JM, Hobolth, A, Hodzic, E, Hong, C, Hornshøj, H, Isaev, K, Izarzugaza, JMG, Johnson, R, Johnson, TA, Juul, M, Juul, RI, Kahles, A, Kahraman, A, Kellis, M, Khurana, E, Kim, J, Kim, JK, Kim, Y, Komorowski, J, Korbel, JO, Kumar, S, Lanzós, A, Larsson, E, Lawrence, MS, Lee, D, Lehmann, KV, Li, S, Li, X, Lin, Z, Liu, EM, Lochovsky, L, Lou, S, Madsen, T, Marchal, K, Martincorena, I, Martinez-Fundichely, A, Maruvka, YE, McGillivray, PD, Meyerson, W, Muiños, F, Mularoni, L, Nakagawa, H, Nielsen, MM, Paczkowska, M, Park, K, Park, K, Pedersen, JS, Pons, T, Pulido-Tamayo, S, Raphael, BJ, Reimand, J, Reyes-Salazar, I, Reyna, MA, Rheinbay, E, Rubin, MA, Rubio-Perez, C, Sahinalp, SC, Saksena, G, Salichos, L, Sander, C, Schumacher, SE, Shackleton, M, Shapira, O, Shen, C, Shrestha, R, Shuai, S, Sidiropoulos, N, Sieverling, L, Sinnott-Armstrong, N, Stein, LD, Stuart, JM, Tamborero, D, Tiao, G, Tsunoda, T, Umer, HM, Uusküla-Reimand, L, Valencia, A, Vazquez, M, Verbeke, LPC, Wadelius, C, Wadi, L, Wang, J, Warrell, J, Waszak, SM, Weischenfeldt, J, Wheeler, DA, Wu, G, Yu, J, Zhang, J, Zhang, X, Zhang, Y, Zhao, Z, Zou, L, von Mering, C, Gallinger, S, 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, 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, Ding, L , Fulton, LA , Fulton, RS , Govindan, R , Jayasinghe, R , Ley, T , Miller, CA , Mutch, D & Wendl, MC 2020, 'Combined burden and functional impact tests for cancer driver discovery using DriverPower', Nature communications, vol. 11, no. 1, 734. https://doi.org/10.1038/s41467-019-13929-1

TY - JOUR

T1 - Combined burden and functional impact tests for cancer driver discovery using DriverPower

AU - PCAWG Drivers and Functional Interpretation Working Group

AU - PCAWG Consortium

AU - Shuai, Shimin

AU - Abascal, Federico

AU - Amin, Samirkumar B.

AU - Bader, Gary D.

AU - Bandopadhayay, Pratiti

AU - Barenboim, Jonathan

AU - Beroukhim, Rameen

AU - Bertl, Johanna

AU - Boroevich, Keith A.

AU - Brunak, Søren

AU - Campbell, Peter J.

AU - Carlevaro-Fita, Joana

AU - Chakravarty, Dimple

AU - Chan, Calvin Wing Yiu

AU - Chen, Ken

AU - Choi, Jung Kyoon

AU - Deu-Pons, Jordi

AU - Dhingra, Priyanka

AU - Diamanti, Klev

AU - Feuerbach, Lars

AU - Fink, J. Lynn

AU - Fonseca, Nuno A.

AU - Frigola, Joan

AU - Gambacorti-Passerini, Carlo

AU - Garsed, Dale W.

AU - Gerstein, Mark

AU - Getz, Gad

AU - Guo, Qianyun

AU - Gut, Ivo G.

AU - Haan, David

AU - Hamilton, Mark P.

AU - Haradhvala, Nicholas J.

AU - Harmanci, Arif O.

AU - Helmy, Mohamed

AU - Herrmann, Carl

AU - Hess, Julian M.

AU - Hobolth, Asger

AU - Hodzic, Ermin

AU - Hong, Chen

AU - Hornshøj, Henrik

AU - Isaev, Keren

AU - Izarzugaza, Jose M.G.

AU - Johnson, Rory

AU - Johnson, Todd A.

AU - Juul, Malene

AU - Juul, Randi Istrup

AU - Kahles, Andre

AU - Kahraman, Abdullah

AU - Kellis, Manolis

AU - Khurana, Ekta

AU - Kim, Jaegil

AU - Kim, Jong K.

AU - Kim, Youngwook

AU - Komorowski, Jan

AU - Korbel, Jan O.

AU - Kumar, Sushant

AU - Lanzós, Andrés

AU - Larsson, Erik

AU - Lawrence, Michael S.

AU - Lee, Donghoon

AU - Lehmann, Kjong Van

AU - Li, Shantao

AU - Li, Xiaotong

AU - Lin, Ziao

AU - Liu, Eric Minwei

AU - Lochovsky, Lucas

AU - Lou, Shaoke

AU - Madsen, Tobias

AU - Marchal, Kathleen

AU - Martincorena, Iñigo

AU - Martinez-Fundichely, Alexander

AU - Maruvka, Yosef E.

AU - McGillivray, Patrick D.

AU - Meyerson, William

AU - Muiños, Ferran

AU - Mularoni, Loris

AU - Nakagawa, Hidewaki

AU - Nielsen, Morten Muhlig

AU - Paczkowska, Marta

AU - Park, Keunchil

AU - Park, Kiejung

AU - Pedersen, Jakob Skou

AU - Pons, Tirso

AU - Pulido-Tamayo, Sergio

AU - Raphael, Benjamin J.

AU - Reimand, Jüri

AU - Reyes-Salazar, Iker

AU - Reyna, Matthew A.

AU - Rheinbay, Esther

AU - Rubin, Mark A.

AU - Rubio-Perez, Carlota

AU - Sahinalp, S. Cenk

AU - Saksena, Gordon

AU - Salichos, Leonidas

AU - Sander, Chris

AU - Schumacher, Steven E.

AU - Shackleton, Mark

AU - Shapira, Ofer

AU - Shen, Ciyue

AU - Shrestha, Raunak

AU - Shuai, Shimin

AU - Sidiropoulos, Nikos

AU - Sieverling, Lina

AU - Sinnott-Armstrong, Nasa

AU - Stein, Lincoln D.

AU - Stuart, Joshua M.

AU - Tamborero, David

AU - Tiao, Grace

AU - Tsunoda, Tatsuhiko

AU - Umer, Husen M.

AU - Uusküla-Reimand, Liis

AU - Valencia, Alfonso

AU - Vazquez, Miguel

AU - Verbeke, Lieven P.C.

AU - Wadelius, Claes

AU - Wadi, Lina

AU - Wang, Jiayin

AU - Warrell, Jonathan

AU - Waszak, Sebastian M.

AU - Weischenfeldt, Joachim

AU - Wheeler, David A.

AU - Wu, Guanming

AU - Yu, Jun

AU - Zhang, Jing

AU - Zhang, Xuanping

AU - Zhang, Yan

AU - Zhao, Zhongming

AU - Zou, Lihua

AU - von Mering, Christian

AU - Gallinger, Steven

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 - 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 - 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 - The discovery of driver mutations is one of the key motivations for cancer genome sequencing. 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 describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features derived from public sources, DriverPower’s background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.

AB - The discovery of driver mutations is one of the key motivations for cancer genome sequencing. 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 describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features derived from public sources, DriverPower’s background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.

UR - http://www.scopus.com/inward/record.url?scp=85079072523&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-13929-1

DO - 10.1038/s41467-019-13929-1

M3 - Article

C2 - 32024818

AN - SCOPUS:85079072523

SN - 2041-1723

VL - 11

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 734

ER -

Combined burden and functional impact tests for cancer driver discovery using DriverPower

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