Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK

Dhruva Biswas, Yun-Hsin Liu, David A. Moore, Takahiro Karasaki, Kristiana Grigoriadis, Selvaraju Veeriah, Cristina Naceur-Lombardelli, Neil Magno, Sophia Ward, Alexander M. Frankell, Ariana Huebner, Corentin Richard, Crispin T. Hiley, Emilia L. Lim, Francisco Gimeno-Valiente, Krupa Thakkar, Maise Al Bakir, Monica Sivakumar, Ieva Usaite, Sadegh Saghafinia, Sharon Vanloo, Sian Harries, Antonia Toncheva, Paulina Prymas, Bushra Mussa, Michalina Magala, Elizabeth Keene, Abigail Bunkum, Carlos Martínez-Ruiz, Clare Puttick, Despoina Karagianni, James R. M. Black, Kerstin Thol, Nicholas McGranahan, Olivia Lucas, Robert Bentham, Roberto Vendramin, Sergio A. Quezada, Simone Zaccaria, Sonya Hessey, Supreet Kaur Bola, Wing Kin Liu, Rija Zaidi, Lucrezia Patruno, Martin D. Forster, Siow Ming Lee, Mariam Jamal-Hanjani, Nnennaya Kanu, Nicolai J. Birkbak & Charles Swanton

Bill Lyons Informatics Centre, University College London Cancer Institute, London, UK

Dhruva Biswas & Javier Herrero

Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK

Dhruva Biswas, David A. Moore, Takahiro Karasaki, Kristiana Grigoriadis, Wei-Ting Lu, Sophia Ward, Alexander M. Frankell, Mark S. Hill, Emma Colliver, Ariana Huebner, Crispin T. Hiley, Emilia L. Lim, Maise Al Bakir, Sian Harries, Clare Puttick, James R. M. Black, Olivia Lucas, Roberto Vendramin, Gareth A. Wilson, Rachel Rosenthal, Andrew Rowan, Chris Bailey, Claudia Lee, Katey S. S. Enfield, Mihaela Angelova, Oriol Pich, Cian Murphy, Maria Zagorulya, Michelle M. Leung, Nicolai J. Birkbak & Charles Swanton

Centre for Inflammation Biology and Cancer Immunology, King’s College London, London, UK

Yin Wu

Department of Medical Oncology, Guy’s Hospital, London, UK

Yin Wu

Department of Cellular Pathology, University College London Hospitals, London, UK

David A. Moore, Teresa Marafioti, Elaine Borg, Mary Falzon & Reena Khiroya

Cancer Metastasis Lab, University College London Cancer Institute, London, UK

Takahiro Karasaki, Abigail Bunkum, Sonya Hessey, Wing Kin Liu & Mariam Jamal-Hanjani

Department of Thoracic Surgery, Respiratory Center, Toranomon Hospital, Tokyo, Japan

Takahiro Karasaki

Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK

Kristiana Grigoriadis, Ariana Huebner, Carlos Martínez-Ruiz, Clare Puttick, Kerstin Thol, Robert Bentham, Michelle M. Leung & Thomas Patrick Jones

Genomics Science Technology Platform, The Francis Crick Institute, London, UK

Sophia Ward, Daniel M. Snell, Olga O’Neill, Daniel Leonce, Jerome Nicod & Sian Harries

Oncogene Biology Laboratory, The Francis Crick Institute, London, UK

Sophie de Carné Trécesson & Julian Downward

Bioinformatics and Biostatistics, The Francis Crick Institute, London, UK

Philip East

Cancer Research UK and University College London Cancer Trials Centre, University College London, London, UK

Aman Malhi & Allan Hackshaw

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

Johanna Mattsson, Amanda Lindberg & Patrick Micke

1st Department of Pulmonology, National Koranyi Institute of Pulmonology, Budapest, Hungary

Judit Moldvay

Department of Pulmonology, University of Szeged Albert Szent-Gyorgyi Medical School, Szeged, Hungary

Judit Moldvay

National Koranyi Institute of Pulmonology, Budapest, Hungary

Zsolt Megyesfalvi, Balazs Dome & János Fillinger

Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary

Zsolt Megyesfalvi & Balazs Dome

Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria

Zsolt Megyesfalvi & Balazs Dome

Department of Translational Medicine, Lund University, Lund, Sweden

Balazs Dome

Computational Health Informatics Program, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

Zoltan Szallasi

Department of Oncology, University College London Hospitals, London, UK

Martin D. Forster, Siow Ming Lee, Sarah Benafif, Dionysis Papadatos-Pastos, James Wilson, Tanya Ahmad, Mariam Jamal-Hanjani & Charles Swanton

Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark

Nicolai J. Birkbak

Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

Nicolai J. Birkbak

Computational Cancer Genomics Research Group, University College London Cancer Institute, London, UK

Abigail Bunkum, Olivia Lucas, Simone Zaccaria, Sonya Hessey, Rija Zaidi & Lucrezia Patruno

Immune Regulation and Tumour Immunotherapy Group, Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK

Despoina Karagianni, Sergio A. Quezada & Supreet Kaur Bola

Cancer Genome Evolution Research Group, University College London Cancer Institute, London, UK

Nicholas McGranahan

University College London Hospitals, London, UK

Olivia Lucas, Emilie Martinoni Hoogenboom, Fleur Monk, James W. Holding, Junaid Choudhary, Kunal Bhakhri, Pat Gorman, Robert C. M. Stephens, Yien Ning Sophia Wong, Maria Chiara Pisciella & Steve Bandula

Tumour Immunogenomics and Immunosurveillance Laboratory, University College London Cancer Institute, London, UK

Roberto Vendramin

Cancer Research UK Lung Cancer Centre of Excellence, University College London, Cancer Institute, London, UK

Michelle M. Leung

The Whittington Hospital NHS Trust, London, UK

Sarah Benafif, Jack French & Kayleigh Gilbert

University College London Cancer Institute, London, UK

Angela Dwornik, Angeliki Karamani, Benny Chain, David R. Pearce, Georgia Stavrou, Gerasimos-Theodoros Mastrokalos, Helen L. Lowe, James L. Reading, John A. Hartley, Kayalvizhi Selvaraju, Leah Ensell, Mansi Shah, Maria Litovchenko, Piotr Pawlik, Samuel Gamble, Seng Kuong Anakin Ung & Victoria Spanswick

The Francis Crick Institute, London, UK

Clare E. Weeden, Eva Grönroos, Jacki Goldman, Mickael Escudero, Philip Hobson, Stefan Boeing, Tamara Denner, Vittorio Barbè, William Hill, Yutaka Naito, Erik Sahai, Zoe Ramsden, George Kassiotis & Imran Noorani

Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK

George Kassiotis

Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, London, UK

Imran Noorani

University College London, London, UK

Imran Noorani

Singleton Hospital, Swansea Bay University Health Board, Swansea, UK

Jason F. Lester

University Hospitals of Leicester NHS Trust, Leicester, UK

Amrita Bajaj, Apostolos Nakas, Azmina Sodha-Ramdeen, Mohamad Tufail, Molly Scotland, Rebecca Boyles, Sridhar Rathinam, Sean Dulloo & Dean A. Fennell

University of Leicester, Leicester, UK

Sean Dulloo & Dean A. Fennell

Leicester Medical School, University of Leicester, Leicester, UK

Claire Wilson

Cancer Research Centre, University of Leicester, Leicester, UK

Gurdeep Matharu & Jacqui A. Shaw

Royal Free London NHS Foundation Trust, London, UK

Ekaterini Boleti

Aberdeen Royal Infirmary NHS Grampian, Aberdeen, UK

Heather Cheyne, Mohammed Khalil, Shirley Richardson & Tracey Cruickshank

Department of Medical Oncology, Aberdeen Royal Infirmary NHS Grampian, Aberdeen, UK

Gillian Price

University of Aberdeen, Aberdeen, UK

Gillian Price & Keith M. Kerr

Department of Pathology, Aberdeen Royal Infirmary NHS Grampian, Aberdeen, UK

Keith M. Kerr

Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK

Babu Naidu

Guy’s and St Thomas’ NHS Foundation Trust, London, UK

Akshay J. Patel

University Hospital Birmingham NHS Foundation Trust, Birmingham, UK

Aya Osman, Mandeesh Sangha, Gerald Langman, Helen Shackleford, Madava Djearaman & Gary Middleton

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK

Gary Middleton

Manchester Cancer Research Centre Biobank, Manchester, UK

Angela Leek, Jack Davies Hodgkinson & Nicola Totton

Wythenshawe Hospital, Manchester University NHS Foundation Trust, Wythenshawe, UK

Eustace Fontaine, Felice Granato, Juliette Novasio, Kendadai Rammohan, Leena Joseph, Paul Bishop, Vijay Joshi, Sara Waplington & Adam Atkin

Manchester University NHS Foundation Trust, Manchester, UK

Antonio Paiva-Correia

Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK

Philip Crosbie

Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK

Philip Crosbie

Cancer Research UK Lung Cancer Centre of Excellence, University of Manchester, Manchester, UK

Philip Crosbie, Katherine D. Brown, Mathew Carter, Anshuman Chaturvedi, Pedro Oliveira, Colin R. Lindsay, Fiona H. Blackhall & Yvonne Summers

The Christie NHS Foundation Trust, Manchester, UK

Katherine D. Brown, Mathew Carter, Anshuman Chaturvedi & Pedro Oliveira

Division of Cancer Sciences, The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK

Colin R. Lindsay, Fiona H. Blackhall, Yvonne Summers & Matthew G. Krebs

CRUK Manchester Institute Cancer Biomarker Centre, University of Manchester, Manchester, UK

Jonathan Tugwood & Caroline Dive

CRUK Lung Cancer Centre of Excellence, University of Manchester, Manchester, UK

Jonathan Tugwood & Caroline Dive

Artificial Intelligence in MedicineAIM Program, Mass General Brigham, Harvard Medical School, Boston, MA, USA

Hugo J. W. L. Aerts

Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

Hugo J. W. L. Aerts

Radiology and Nuclear Medicine, CARIM and GROW, Maastricht University, Maastricht, The Netherlands

Hugo J. W. L. Aerts

Institute for Computational Cancer Biology, Center for Integrated OncologyCIO, Cancer Research Center Cologne EssenCCCE, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

Roland F. Schwarz

Berlin Institute for the Foundations of Learning and DataBIFOLD, Berlin, Germany

Roland F. Schwarz & Tom L. Kaufmann

Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany

Tom L. Kaufmann

Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Peter Van Loo

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Peter Van Loo

Cancer Genomics Laboratory, The Francis Crick Institute, London, UK

Peter Van Loo & Carla Castignani

Medical Genomics, University College London Cancer Institute, London, UK

Carla Castignani & Stephan Beck

Department of Pathology, ZAS Hospitals, Antwerp, Belgium

Roberto Salgado

Division of Research, Peter MacCallum Cancer Centre, Melbourne, Australia

Roberto Salgado

Danish Cancer Institute, Copenhagen, Denmark

Miklos Diossy

Computational Health Informatics Program, Boston Children’s Hospital, Boston, MA, USA

Miklos Diossy

Department of Physics of Complex Systems, ELTE Eötvös Loránd University, Budapest, Hungary

Miklos Diossy

Integrative Cancer Genomics Laboratory, VIB Center for Cancer Biology, Leuven, Belgium

Jonas Demeulemeester

VIB Center for AI & Computational Biology, Leuven, Belgium

Jonas Demeulemeester

Department of Oncology, KU Leuven, Leuven, Belgium

Jonas Demeulemeester

Experimental Histopathology, The Francis Crick Institute, London, UK

Emma Nye & Richard Kevin Stone

University College London Cancer Institute, London, UK and Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK

Jayant K. Rane

Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK

Jeanette Kittel, Kerstin Haase, Kexin Koh & Rachel Scott

Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London, UK

Jeanette Kittel, Kerstin Haase, Kexin Koh & Rachel Scott

Department of Haematology, University College London Hospitals, London, UK

Karl S. Peggs

Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK

Karl S. Peggs

National Cancer Centre, Singapore, Singapore

Yien Ning Sophia Wong

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA

Thomas B. K. Watkins

Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, London, UK

Catarina Veiga

Department of Medical Physics and Bioengineering, University College London Cancer Institute, London, UK

Gary Royle

Department of Medical Physics and Biomedical Engineering, University College London, London, UK

Charles-Antoine Collins-Fekete

Institute of Nuclear Medicine, Division of Medicine, University College London, London, UK

Francesco Fraioli

Institute of Structural and Molecular Biology, University College London, London, UK

Paul Ashford

Department of Radiology, University College London Hospitals, London, UK

Alexander James Procter, Asia Ahmed, Magali N. Taylor & Arjun Nair

UCL Respiratory, Department of Medicine, University College London, London, UK

Arjun Nair

Department of Thoracic Surgery, University College London Hospital NHS Trust, London, UK

David Lawrence & Davide Patrini

Lungs for Living Research Centre, UCL Respiratory, University College London, London, UK

Neal Navani & Ricky M. Thakrar

Department of Thoracic Medicine, University College London Hospitals, London, UK

Neal Navani & Ricky M. Thakrar

Lungs for Living Research Centre, UCL Respiratory, Department of Medicine, University College London, London, UK

Sam M. Janes

Integrated Radiology Department, North-Buda St John’s Central Hospital, Budapest, Hungary

Zoltan Kaplar

Institute of Nuclear Medicine, University College London Hospitals, London, UK

Zoltan Kaplar

Cancer Research UK and UCL Cancer Trials Centre, London, UK

Allan Hackshaw, Camilla Pilotti, Rachel Leslie, Anne-Marie Hacker, Sean Smith & Aoife Walker

The Institute of Cancer Research, London, UK

Anca Grapa

Garvan Institute of Medical Research, Sydeny, New South Wales, Australia

Hanyun Zhang

Case45, London, UK

Khalid AbdulJabbar

The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Xiaoxi Pan

The University of Texas MD Anderson Cancer Center, Houston, USA

Yinyin Yuan

Independent Cancer Patient’s voice, London, UK

David Chuter & Mairead MacKenzie

University Hospital Southampton NHS Foundation Trust, Southampton, UK

Serena Chee & Patricia Georg

The NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK

Aiman Alzetani

Department of Oncology, University Hospital Southampton NHS Foundation Trust, Southampton, UK

Judith Cave

Academic Division of Thoracic Surgery, Imperial College London, London, UK

Eric Lim

Royal Brompton and Harefield Hospitals, part of Guy’s and St Thomas’ NHS Foundation Trust, London, UK

Eric Lim, Paulo De Sousa, Simon Jordan, Alexandra Rice, Hilgardt Raubenheimer, Harshil Bhayani, Lyn Ambrose, Anand Devaraj, Hemangi Chavan, Sofina Begum, Silviu I. Buderi, Daniel Kaniu, Mpho Malima, Sarah Booth, Andrew G. Nicholson, Nadia Fernandes, Pratibha Shah & Chiara Proli

National Heart and Lung Institute, Imperial College, London, UK

Andrew G. Nicholson

Royal Surrey Hospital, Royal Surrey Hospitals NHS Foundation Trust, Guildford, UK

Madeleine Hewish

University of Surrey, Guildford, UK

Madeleine Hewish

University of Sheffield, Sheffield, UK

Sarah Danson

Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

Sarah Danson

Liverpool Heart and Chest Hospital, Liverpool, UK

Michael J. Shackcloth

Princess Alexandra Hospital, The Princess Alexandra Hospital NHS Trust, Harlow, UK

Lily Robinson & Peter Russell

School of Cancer Sciences, University of Glasgow, Glasgow, UK

Kevin G. Blyth

Beatson Institute for Cancer Research, University of Glasgow, Glasgow, UK

Kevin G. Blyth

Queen Elizabeth University Hospital, Glasgow, UK

Kevin G. Blyth

Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK

Andrew Kidd

NHS Greater Glasgow and Clyde, Glasgow, UK

Craig Dick

Cancer Research UK Scotland Institute, Glasgow, UK

John Le Quesne

Institute of Cancer Sciences, University of Glasgow, Glasgow, UK

John Le Quesne

NHS Greater Glasgow and Clyde Pathology Department, Queen Elizabeth University Hospital, Glasgow, UK

John Le Quesne

Golden Jubilee National Hospital, Clydebank, UK

Alan Kirk, Mo Asif, Rocco Bilancia, Nikos Kostoulas, Jennifer Whiteley & Mathew Thomas

The contact address for the TRACERx consortium is ctc.tracerx@ucl.ac.uk. D.B. and Y.-H.L. designed the experiments, performed the bioinformatics analyses and wrote the manuscript. N.J.B., J.H., Y.W., D.A.M., T.K., K.G. and W.L. provided early feedback and helped to direct the avenues of bioinformatics analysis. S.V., C.N.-L., N.M. and S.W. performed sample collection and RNA extraction and helped with data interpretation. A.M.F., M.H. and E.C. performed data processing and helped with data interpretation. S.d.C.T., P.E., A.M., D.M.S., O.O., D.L., J. Mattson, A.L., P.M., J. Moldvay, Z.M., B.D., J.F., J.N., J.D., Z.S. and N.K. provided access to additional datasets and helped with data interpretation. A.H. provided statistical advice. M.J.-H. designed the TRACERx study protocols and helped to analyze the clinical characteristics of the patients. D.B. and C.S. conceived the project, acquired funding, supervised the study and edited the manuscript. All authors reviewed and approved the manuscript.