Combined burden and functional impact tests for cancer driver discovery using DriverPower
Creators: name: Shuai, Shimin
name: Abascal, Federico
name: Amin, Samirkumar B
name: Bader, Gary D
name: Bandopadhayay, Pratiti
name: Barenboim, Jonathan
name: Beroukhim, Rameen
name: Bertl, Johanna
name: Boroevich, Keith A
name: Brunak, Søren
name: Campbell, Peter J
name: Carlevaro-Fita, Joana
name: Chakravarty, Dimple
name: Chan, Calvin Wing Yiu
name: Chen, Ken
name: Choi, Jung Kyoon
name: Deu-Pons, Jordi
name: Dhingra, Priyanka
name: Diamanti, Klev
name: Feuerbach, Lars
name: Fink, J Lynn
name: Fonseca, Nuno A
name: Frigola, Joan
name: Gambacorti-Passerini, Carlo
name: Garsed, Dale W
name: Gerstein, Mark
name: Getz, Gad
name: Guo, Qianyun
name: Gut, Ivo G
name: Haan, David
name: Hamilton, Mark P
name: Haradhvala, Nicholas J
name: Harmanci, Arif O
name: Helmy, Mohamed
name: Herrmann, Carl
name: Hess, Julian M
name: Hobolth, Asger
name: Hodzic, Ermin
name: Hong, Chen
name: Hornshøj, Henrik
name: Isaev, Keren
name: Izarzugaza, Jose MG
name: Johnson, Rory
name: Johnson, Todd A
name: Juul, Malene
name: Juul, Randi Istrup
name: Kahles, Andre
name: Kahraman, Abdullah
name: Kellis, Manolis
name: Khurana, Ekta
name: Kim, Jaegil
name: Kim, Jong K
name: Kim, Youngwook
name: Komorowski, Jan
name: Korbel, Jan O
name: Kumar, Sushant
name: Lanzós, Andrés
name: Larsson, Erik
name: Lawrence, Michael S
name: Lee, Donghoon
name: Lehmann, Kjong-Van
name: Li, Shantao
name: Li, Xiaotong
name: Lin, Ziao
name: Liu, Eric Minwei
name: Lochovsky, Lucas
name: Lou, Shaoke
name: Madsen, Tobias
name: Marchal, Kathleen
name: Martincorena, Iñigo
name: Martinez-Fundichely, Alexander
name: Maruvka, Yosef E
name: McGillivray, Patrick D
name: Meyerson, William
name: Muiños, Ferran
name: Mularoni, Loris
name: Nakagawa, Hidewaki
name: Nielsen, Morten Muhlig
name: Paczkowska, Marta
name: Park, Keunchil
name: Park, Kiejung
name: Pedersen, Jakob Skou
name: Pons, Tirso
name: Pulido-Tamayo, Sergio
name: Raphael, Benjamin J
name: Reimand, Jüri
name: Reyes-Salazar, Iker
name: Reyna, Matthew A
name: Rheinbay, Esther
name: Rubin, Mark A
name: Rubio-Perez, Carlota
name: Sahinalp, S Cenk
name: Saksena, Gordon
name: Salichos, Leonidas
name: Sander, Chris
name: Schumacher, Steven E
name: Shackleton, Mark
name: Shapira, Ofer
name: Shen, Ciyue
name: Shrestha, Raunak
name: Sidiropoulos, Nikos
name: Sieverling, Lina
name: Sinnott-Armstrong, Nasa
name: Stein, Lincoln D
name: Stuart, Joshua M
name: Tamborero, David
name: Tiao, Grace
name: Tsunoda, Tatsuhiko
name: Umer, Husen M
name: Uusküla-Reimand, Liis
name: Valencia, Alfonso
name: Vazquez, Miguel
name: Verbeke, Lieven PC
name: Wadelius, Claes
name: Wadi, Lina
name: Wang, Jiayin
name: Warrell, Jonathan
name: Waszak, Sebastian M
name: Weischenfeldt, Joachim
name: Wheeler, David A
name: Wu, Guanming
name: Yu, Jun
name: Zhang, Jing
name: Zhang, Xuanping
name: Zhang, Yan
name: Zhao, Zhongming
name: Zou, Lihua
name: von Mering, Christian
name: Gallinger, Steven
name: Aaltonen, Lauri A
name: Abeshouse, Adam
name: Aburatani, Hiroyuki
name: Adams, David J
name: Agrawal, Nishant
name: Ahn, Keun Soo
name: Ahn, Sung-Min
name: Aikata, Hiroshi
name: Akbani, Rehan
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name: Al-Ahmadie, Hikmat
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name: Chien, Jeremy
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name: Hinton, Jonathan
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name: Kaiser, Vera B
name: Kakavand, Hojabr
name: Kalimuthu, Sangeetha
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Publisher: name: The Francis Crick Institute
Year: 2023
Subjects: classificationCode: Tumour Biology
subject: Tumour Biology
classificationCode: Genetics & Genomics
subject: Genetics &amp; Genomics
classificationCode: Human Biology & Physiology
subject: Human Biology &amp; Physiology
classificationCode: Structural Biology & Biophysics
subject: Structural Biology &amp; Biophysics
classificationCode: Ecology,Evolution & Ethology
subject: Ecology,Evolution &amp; Ethology
classificationCode: Computational & Systems Biology
subject: Computational &amp; Systems Biology

description: 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.