283 results on '"Lynch, Andy G."'
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2. Unravelling patient pathways in the context of antibacterial resistance in East Africa
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Keenan, Katherine, Fredricks, Kathryn J., Al Ahad, Mary Abed, Neema, Stella, Mwanga, Joseph R., Kesby, Mike, Mushi, Martha F., Aduda, Annette, Green, Dominique L., Lynch, Andy G., Huque, Sarah I., Mmbaga, Blandina T., Worthington, Hannah, Kansiime, Catherine, Olamijuwon, Emmanuel, Ntinginya, Nyanda E., Loza, Olga, Bazira, Joel, Maldonado-Barragán, Antonio, Smith, VAnne, Decano, Arun Gonzales, Njeru, John Mwaniki, Sandeman, Alison, Stelling, John, Elliott, Alison, Aanensen, David, Gillespie, Stephen H., Kibiki, Gibson, Sabiiti, Wilber, Sloan, Derek J., Asiimwe, Benon B., Kiiru, John, Mshana, Stephen E., and Holden, Matthew T. G.
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- 2023
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3. Genomic evolution shapes prostate cancer disease type
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Woodcock, Dan J., Sahli, Atef, Teslo, Ruxandra, Bhandari, Vinayak, Gruber, Andreas J., Ziubroniewicz, Aleksandra, Gundem, Gunes, Xu, Yaobo, Butler, Adam, Anokian, Ezequiel, Pope, Bernard J., Jung, Chol-Hee, Tarabichi, Maxime, Dentro, Stefan C., Farmery, J. Henry R., Van Loo, Peter, Warren, Anne Y., Gnanapragasam, Vincent, Hamdy, Freddie C., Bova, G. Steven, Foster, Christopher S., Neal, David E., Lu, Yong-Jie, Kote-Jarai, Zsofia, Fraser, Michael, Bristow, Robert G., Boutros, Paul C., Costello, Anthony J., Corcoran, Niall M., Hovens, Christopher M., Massie, Charlie E., Lynch, Andy G., Brewer, Daniel S., Eeles, Rosalind A., Cooper, Colin S., and Wedge, David C.
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- 2024
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4. PCR Duplicate Proportion Estimation and Consequences for DNA Copy Number Calculations
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Lynch, Andy G., Smith, Mike L., Eldridge, Matthew D., Tavaré, Simon, Bispo, Regina, editor, Henriques-Rodrigues, Lígia, editor, Alpizar-Jara, Russell, editor, and de Carvalho, Miguel, editor
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- 2022
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5. Statistical Challenges in Mutational Signature Analyses of Cancer Sequencing Data
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Velasco-Pardo, Víctor, Papathomas, Michail, Lynch, Andy G., Bispo, Regina, editor, Henriques-Rodrigues, Lígia, editor, Alpizar-Jara, Russell, editor, and de Carvalho, Miguel, editor
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- 2022
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6. The role of multidimensional poverty in antibiotic misuse: a mixed-methods study of self-medication and non-adherence in Kenya, Tanzania, and Uganda
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Green, Dominique L, Keenan, Katherine, Fredricks, Kathryn J, Huque, Sarah I, Mushi, Martha F, Kansiime, Catherine, Asiimwe, Benon, Kiiru, John, Mshana, Stephen E, Neema, Stella, Mwanga, Joseph R, Kesby, Mike, Lynch, Andy G, Worthington, Hannah, Olamijuwon, Emmanuel, Abed Al Ahad, Mary, Aduda, Annette, Njeru, John Mwaniki, Mmbaga, Blandina T, Bazira, Joel, Sandeman, Alison, Stelling, John, Gillespie, Stephen H, Kibiki, Gibson, Sabiiti, Wilber, Sloan, Derek J, Holden, Matthew T G, Smith, V Anne, Decano, Arun Gonzales, Maldonado-Barragán, Antonio, Aanensen, David, Ntinginya, Nyanda E, Elliott, Alison, and Clarkson, Madeleine
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- 2023
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7. Microbiomes of Urine and the Prostate Are Linked to Human Prostate Cancer Risk Groups
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Hurst, Rachel, Meader, Emma, Gihawi, Abraham, Rallapalli, Ghanasyam, Clark, Jeremy, Kay, Gemma L., Webb, Martyn, Manley, Kate, Curley, Helen, Walker, Helen, Kumar, Ravi, Schmidt, Katarzyna, Crossman, Lisa, Eeles, Rosalind A., Wedge, David C., Lynch, Andy G., Massie, Charlie E., Yazbek-Hanna, Marcelino, Rochester, Mark, Mills, Robert D., Mithen, Richard F., Traka, Maria H., Ball, Richard Y., O'Grady, Justin, Brewer, Daniel S., Wain, John, and Cooper, Colin S.
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- 2022
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8. Rare Germline Variants Are Associated with Rapid Biochemical Recurrence After Radical Prostate Cancer Treatment: A Pan Prostate Cancer Group Study
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Burns, Daniel, Anokian, Ezequiel, Saunders, Edward J., Bristow, Robert G., Fraser, Michael, Reimand, Jüri, Schlomm, Thorsten, Sauter, Guido, Brors, Benedikt, Korbel, Jan, Weischenfeldt, Joachim, Waszak, Sebastian M., Corcoran, Niall M., Jung, Chol-Hee, Pope, Bernard J., Hovens, Chris M., Cancel-Tassin, Géraldine, Cussenot, Olivier, Loda, Massimo, Sander, Chris, Hayes, Vanessa M., Dalsgaard Sorensen, Karina, Lu, Yong-Jie, Hamdy, Freddie C., Foster, Christopher S., Gnanapragasam, Vincent, Butler, Adam, Lynch, Andy G., Massie, Charlie E., Woodcock, Dan J., Cooper, Colin S., Wedge, David C., Brewer, Daniel S., Kote-Jarai, Zsofia, and Eeles, Rosalind A.
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- 2022
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9. Low-cost and clinically applicable copy number profiling using repeat DNA
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Abujudeh, Sam, Zeki, Sebastian S., van Lanschot, Meta C.J., Pusung, Mark, Weaver, Jamie M.J., Li, Xiaodun, Noorani, Ayesha, Metz, Andrew J., Bornschein, Jan, Bower, Lawrence, Miremadi, Ahmad, Fitzgerald, Rebecca C., Morrissey, Edward R., and Lynch, Andy G.
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- 2022
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10. The architecture of clonal expansions in morphologically normal tissue from cancerous and non-cancerous prostates
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Buhigas, Claudia, Warren, Anne Y., Leung, Wing-Kit, Whitaker, Hayley C., Luxton, Hayley J., Hawkins, Steve, Kay, Jonathan, Butler, Adam, Xu, Yaobo, Woodcock, Dan J., Merson, Sue, Frame, Fiona M., Sahli, Atef, Abascal, Federico, Martincorena, Iñigo, Bova, G. Steven, Foster, Christopher S., Campbell, Peter, Maitland, Norman J., Neal, David E., Massie, Charlie E., Lynch, Andy G., Eeles, Rosalind A., Cooper, Colin S., Wedge, David C., and Brewer, Daniel S.
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- 2022
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11. Evidencing the Intersection of Environmental, Socioeconomic, Behavioural and Demographic Drivers of Antibacterial Resistance in East Africa
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Keenan, Katherine, primary, Papathomas, Michail, additional, Mshana, Stephen E., additional, Asiimwe, Benon, additional, Kiiru, John, additional, Lynch, Andy G., additional, Kesby, Mike, additional, Neema, Stella, additional, Mwanga, Joseph R., additional, Mushi, Martha F., additional, Green, Dominique L., additional, Jing, Wei, additional, Olamijuwon, Emmanuel, additional, Zhang, Qing, additional, Sippy, Rachel, additional, Fredricks, Kathryn J., additional, Gillespie, Stephen Henry, additional, Sabiti, Wilber, additional, Bazira, Joel, additional, Sloan, Derek J., additional, Mmbaga, Blandina T., additional, Kibiki, Gibson, additional, Stelling, John, additional, Smith, V. Anne, additional, Sandeman, Alison, additional, Holden, Matthew T. G., additional, and Consortium, HATUA, additional
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- 2024
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12. Predominance of multidrug-resistant bacteria causing urinary tract infections among symptomatic patients in East Africa: a call for action
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Maldonado-Barragán, Antonio, primary, Mshana, Stephen E, additional, Keenan, Katherine, additional, Ke, Xuejia, additional, Gillespie, Stephen H, additional, Stelling, John, additional, Maina, John, additional, Bazira, Joel, additional, Muhwezi, Ivan, additional, Mushi, Martha F, additional, Green, Dominique L, additional, Kesby, Mike, additional, Lynch, Andy G, additional, Sabiiti, Wilber, additional, Sloan, Derek J, additional, Sandeman, Alison, additional, Kiiru, John, additional, Asiimwe, Benon, additional, and Holden, Matthew T G, additional
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- 2023
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13. DESNT: A Poor Prognosis Category of Human Prostate Cancer
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Luca, Bogdan-Alexandru, Brewer, Daniel S., Edwards, Dylan R., Edwards, Sandra, Whitaker, Hayley C., Merson, Sue, Dennis, Nening, Cooper, Rosalin A., Hazell, Steven, Warren, Anne Y., Eeles, Rosalind, Lynch, Andy G., Ross-Adams, Helen, Lamb, Alastair D., Neal, David E., Sethia, Krishna, Mills, Robert D., Ball, Richard Y., Curley, Helen, Clark, Jeremy, Moulton, Vincent, and Cooper, Colin S.
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- 2018
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14. Identification of Prognostic Phenotypes of Esophageal Adenocarcinoma in 2 Independent Cohorts
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Noorani, Ayesha, Edwards, Paul A.W., Grehan, Nicola, Nutzinger, Barbara, Hughes, Caitriona, Fidziukiewicz, Elwira, Bornschein, Jan, MacRae, Shona, Crawte, Jason, Contino, Gianmarco, Li, Xiaodun, Rue, Rachel de la, O’Donovan, Maria, Miremad, Ahmad, Malhotra, Shalini, Tripathi, Monika, Tavaré, Simon, Lynch, Andy G., Eldridge, Matthew, Secrier, Maria, Bower, Lawrence, Devonshire, Ginny, Perner, Juliane, Jammula, Sriganesh, Davies, Jim, Crichton, Charles, Carroll, Nick, Safranek, Peter, Hindmarsh, Andrew, Sujendran, Vijayendran, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O’Neill, J. Robert, Tucker, Olga, Beggs, Andrew, Taniere, Philippe, Puig, Sonia, Underwood, Timothy J., Noble, Fergus, Owsley, Jack, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Mahadeva, Ula, Goh, Vicky, Ciccarelli, Francesca D., Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Saunders, John, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Igali, Laszlo, Scott, Michael, Sothi, Sharmila, Suortamo, Sari, Lishman, Suzy, Hanna, George B., Peters, Christopher J., Grabowska, Anna, Turkington, Richard, Sawas, Tarek, Killcoyne, Sarah, Iyer, Prasad G., Wang, Kenneth K., Smyrk, Thomas C., Kisiel, John B., Qin, Yi, Ahlquist, David A., Rustgi, Anil K., Costa, Rui J., Gerstung, Moritz, Fitzgerald, Rebecca C., and Katzka, David A.
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- 2018
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15. Predominance of multidrug-resistant bacteria causing urinary tract infections among symptomatic patients in East Africa: a call for action.
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Maldonado-Barragán, Antonio, Mshana, Stephen E, Keenan, Katherine, Ke, Xuejia, Gillespie, Stephen H, Stelling, John, Maina, John, Bazira, Joel, Muhwezi, Ivan, Mushi, Martha F, Green, Dominique L, Kesby, Mike, Lynch, Andy G, Sabiiti, Wilber, Sloan, Derek J, Sandeman, Alison, Kiiru, John, Asiimwe, Benon, and Holden, Matthew T G
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- 2024
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16. Ultrasensitive Detection of Circulating Tumour DNA enriches for Patients with a Greater Risk of Recurrence of Clinically Localised Prostate Cancer
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Pope, Bernard, Park, Gahee, Lau, Edmund, Belic, Jelena, Lach, Radoslaw, George, Anne, McCoy, Patrick, Nguyen, Anne, Grima, Corrina, Campbell, Bethany, Jung, Chol-hee, Ditter, Emma-Jane, Zhao, Hui, Wedge, David C., Brewer, Daniel S., Lynch, Andy G., Dev, Harveer, Gnanpragasam, Vincent J., Rosenfeld, Nitzan, Hovens, Christopher M., Corcoran, Niall M., and Massie, Charles E.
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- 2024
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17. Supplementary Data from CamGFR v2: A New Model for Estimating the Glomerular Filtration Rate from Standardized or Non-standardized Creatinine in Patients with Cancer
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Williams, Edward H., primary, Flint, Thomas R., primary, Connell, Claire M., primary, Giglio, Daniel, primary, Lee, Hassal, primary, Ha, Taehoon, primary, Gablenz, Eva, primary, Bird, Nicholas J., primary, Weaver, James M.J., primary, Potts, Harry, primary, Whitley, Cameron T., primary, Bookman, Michael A., primary, Lynch, Andy G., primary, Meyer, Hannah V., primary, Tavaré, Simon, primary, and Janowitz, Tobias, primary
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- 2023
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18. Identifying Prostate Cancer-Specific Signatures Through Unbiased Capture of Methylated Cell-Free DNA
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Lleshi, Ermira, primary, Milne-Clark, Toby, additional, Lee Yu, Henson, additional, Martin, Henno, additional, Hanson, Robert, additional, Lach, Radoslaw, additional, Rossi, Sabrina, additional, Flewitt, Andrew, additional, Lynch, Andy G., additional, Gnanapragasam, Vincent, additional, Massie, Charlie, additional, and Dev, Harveer, additional
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- 2023
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19. A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns
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Jiao, Wei, Atwal, Gurnit, Polak, Paz, Karlic, Rosa, Cuppen, Edwin, Al-Shahrour, Fatima, Bailey, Peter J, Biankin, Andrew V, Boutros, Paul C, Campbell, Peter J, Chang, David K, Cooke, Susanna L, Deshpande, Vikram, Faltas, Bishoy M, Faquin, William C, Garraway, Levi, Getz, Gad, Grimmond, Sean M, Haider, Syed, Hoadley, Katherine A, Kaiser, Vera B, Kato, Mamoru, Kübler, Kirsten, Lazar, Alexander J, Li, Constance H, Louis, David N, Margolin, Adam, Martin, Sancha, Nahal-Bose, Hardeep K, Nielsen, G Petur, Nik-Zainal, Serena, Omberg, Larsson, P’ng, Christine, Perry, Marc D, Rheinbay, Esther, Rubin, Mark A, Semple, Colin A, Sgroi, Dennis C, Shibata, Tatsuhiro, Siebert, Reiner, Smith, Jaclyn, Stein, Lincoln D, Stobbe, Miranda D, Sun, Ren X, Thai, Kevin, Wright, Derek W, Wu, Chin-Lee, Yuan, Ke, Zhang, Junjun, Danyi, Alexandra, de Ridder, Jeroen, van Herpen, Carla, Lolkema, Martijn P, Steeghs, Neeltje, Morris, Quaid D, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barenboim, Jonathan, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, Prashant, Baylin, Stephen B, Bazant, Wojciech, Beardsmore, Duncan, Beck, Timothy A, Behjati, Sam, Behren, Andreas, Niu, Beifang, Bell, Cindy, Beltran, Sergi, Benz, Christopher, Berchuck, Andrew, Bergmann, Anke K, Bergstrom, Erik N, Berman, Benjamin P, Berney, Daniel M, Bernhart, Stephan H, Beroukhim, Rameen, Berrios, Mario, Bersani, Samantha, Bertl, Johanna, Betancourt, Miguel, Bhandari, Vinayak, Bhosle, Shriram G, Bieg, Matthias, Bigner, Darell, Binder, Hans, Birney, Ewan, Birrer, Michael, Biswas, Nidhan K, Bjerkehagen, Bodil, Bodenheimer, Tom, Boice, Lori, Bonizzato, Giada, De Bono, Johann S, Boot, Arnoud, Bootwalla, Moiz S, Borg, Ake, Borkhardt, Arndt, Boroevich, Keith A, Borozan, Ivan, Borst, Christoph, Bosenberg, Marcus, Bosio, Mattia, Boultwood, Jacqueline, Bourque, Guillaume, Bova, G Steven, Bowen, David T, Bowlby, Reanne, Bowtell, David DL, Boyault, Sandrine, Boyce, Rich, Boyd, Jeffrey, Brazma, Alvis, Brennan, Paul, Brewer, Daniel S, Brinkman, Arie B, Bristow, Robert G, Broaddus, Russell R, Brock, Jane E, Brock, Malcolm, Broeks, Annegien, Brooks, Angela N, Brooks, Denise, Brors, Benedikt, Brunak, Søren, Bruxner, Timothy JC, Bruzos, Alicia L, Buchanan, Alex, Buchhalter, Ivo, Buchholz, Christiane, Bullman, Susan, Burke, Hazel, Burkhardt, Birgit, Burns, Kathleen H, Busanovich, John, Bustamante, Carlos D, Butler, Adam P, Butte, Atul J, Byrne, Niall J, Børresen-Dale, Anne-Lise, Caesar-Johnson, Samantha J, Cafferkey, Andy, Cahill, Declan, Calabrese, Claudia, Caldas, Carlos, Calvo, Fabien, Camacho, Niedzica, Campo, Elias, Cantù, Cinzia, Cao, Shaolong, Carey, Thomas E, Carlevaro-Fita, Joana, Carlsen, Rebecca, Cataldo, Ivana, Cazzola, Mario, Cebon, Jonathan, Cerfolio, Robert, Chadwick, Dianne E, Chakravarty, Dimple, Chalmers, Don, Chan, Calvin Wing Yiu, Chan, Kin, Chan-Seng-Yue, Michelle, Chandan, Vishal S, Chanock, Stephen J, Chantrill, Lorraine A, Chateigner, Aurélien, Chatterjee, Nilanjan, Chayama, Kazuaki, Chen, Hsiao-Wei, Chen, Jieming, Chen, Ken, Chen, Yiwen, Chen, Zhaohong, Cherniack, Andrew D, Chien, Jeremy, Chiew, Yoke-Eng, Chin, Suet-Feung, Cho, Juok, Cho, Sunghoon, Choi, Jung Kyoon, Choi, Wan, Chomienne, Christine, Chong, Zechen, Choo, Su Pin, Chou, Angela, Christ, Angelika N, Christie, Elizabeth L, Chuah, Eric, Cibulskis, Carrie, Cibulskis, Kristian, Cingarlini, Sara, Clapham, Peter, Claviez, Alexander, Cleary, Sean, Cloonan, Nicole, Cmero, Marek, Collins, Colin C, Connor, Ashton A, Cooper, Colin S, Cope, Leslie, Corbo, Vincenzo, Cordes, Matthew G, Cordner, Stephen M, Cortés-Ciriano, Isidro, Covington, Kyle, Cowin, Prue A, Craft, Brian, Craft, David, Creighton, Chad J, Cun, Yupeng, Curley, Erin, Cutcutache, Ioana, Czajka, Karolina, Czerniak, Bogdan, Dagg, Rebecca A, Danilova, Ludmila, Davi, Maria Vittoria, Davidson, Natalie R, Davies, Helen, Davis, Ian J, Davis-Dusenbery, Brandi N, Dawson, Kevin J, De La Vega, Francisco M, De Paoli-Iseppi, Ricardo, Defreitas, Timothy, Dei Tos, Angelo P, Delaneau, Olivier, Demchok, John A, Demeulemeester, Jonas, Demidov, German M, Demircioğlu, Deniz, Dennis, Nening M, Denroche, Robert E, Dentro, Stefan C, Desai, Nikita, Deshwar, Amit G, Desmedt, Christine, Deu-Pons, Jordi, Dhalla, Noreen, Dhani, Neesha C, Dhingra, Priyanka, Dhir, Rajiv, DiBiase, Anthony, Diamanti, Klev, Ding, Li, Ding, Shuai, Dinh, Huy Q, Dirix, Luc, Doddapaneni, HarshaVardhan, Donmez, Nilgun, Dow, Michelle T, Drapkin, Ronny, Drechsel, Oliver, Drews, Ruben M, Serge, Serge, Dudderidge, Tim, Dueso-Barroso, Ana, Dunford, Andrew J, Dunn, Michael, Dursi, Lewis Jonathan, Duthie, Fraser R, Dutton-Regester, Ken, Eagles, Jenna, Easton, Douglas F, Edmonds, Stuart, Edwards, Paul A, Edwards, Sandra E, Eeles, Rosalind A, Ehinger, Anna, Eils, Juergen, Eils, Roland, El-Naggar, Adel, Eldridge, Matthew, Ellrott, Kyle, Erkek, Serap, Escaramis, Georgia, Espiritu, Shadrielle MG, Estivill, Xavier, Etemadmoghadam, Dariush, Eyfjord, Jorunn E, Fan, Daiming, Fan, Yu, Farcas, Claudiu, Fassan, Matteo, Fatima, Aquila, Favero, Francesco, Fayzullaev, Nodirjon, Felau, Ina, Fereday, Sian, Ferguson, Martin L, Ferretti, Vincent, Feuerbach, Lars, Field, Matthew A, Fink, J Lynn, Finocchiaro, Gaetano, Fisher, Cyril, Fittall, Matthew W, Fitzgerald, Anna, Fitzgerald, Rebecca C, Flanagan, Adrienne M, Fleshner, Neil E, Flicek, Paul, Foekens, John A, Fong, Kwun M, Fonseca, Nuno A, Foster, Christopher S, Fox, Natalie S, Fraser, Michael, Frazer, Scott, Frenkel-Morgenstern, Milana, Friedman, William, Frigola, Joan, Fronick, Catrina C, Fujimoto, Akihiro, Fujita, Masashi, Fukayama, Masashi, Fulton, Lucinda A, Fulton, Robert S, Furuta, Mayuko, Futreal, P Andrew, Füllgrabe, Anja, Gabriel, Stacey B, Gallinger, Steven, Gambacorti-Passerini, Carlo, Gao, Jianjiong, Gao, Shengjie, Garred, Øystein, Garrison, Erik, Garsed, Dale W, Gehlenborg, Nils, Gelpi, Josep LL, George, Joshy, Gerhard, Daniela S, Gerhauser, Clarissa, Gershenwald, Jeffrey E, Gerstein, Mark, Gerstung, Moritz, Ghori, Mohammed, Ghossein, Ronald, Giama, Nasra H, Gibbs, Richard A, Gibson, Bob, Gill, Anthony J, Gill, Pelvender, Giri, Dilip D, Glodzik, Dominik, Gnanapragasam, Vincent J, Goebler, Maria Elisabeth, Goldman, Mary J, Gomez, Carmen, Gonzalez, Santiago, Gonzalez-Perez, Abel, Gordenin, Dmitry A, Gossage, James, Gotoh, Kunihito, Govindan, Ramaswamy, Grabau, Dorthe, Graham, Janet S, Grant, Robert C, Green, Anthony R, Green, Eric, Greger, Liliana, Grehan, Nicola, Grimaldi, Sonia, Grossman, Robert L, Grundhoff, Adam, Gundem, Gunes, Guo, Qianyun, Gupta, Manaswi, Gupta, Shailja, Gut, Ivo G, Gut, Marta, Göke, Jonathan, Ha, Gavin, Haake, Andrea, Haan, David, Haas, Siegfried, Haase, Kerstin, Haber, James E, Habermann, Nina, Hach, Faraz, Hama, Natsuko, Hamdy, Freddie C, Hamilton, Anne, Hamilton, Mark P, Han, Leng, Hanna, George B, Hansmann, Martin, Haradhvala, Nicholas J, Harismendy, Olivier, Harliwong, Ivon, Harmanci, Arif O, Harrington, Eoghan, Hasegawa, Takanori, Haussler, David, Hawkins, Steve, Hayami, Shinya, Hayashi, Shuto, Hayes, D Neil, Hayes, Stephen J, Hayward, Nicholas K, Hazell, Steven, He, Yao, Heath, Allison P, Heath, Simon C, Hedley, David, Hegde, Apurva M, Heiman, David I, Heinold, Michael C, Heins, Zachary, Heisler, Lawrence E, Hellstrom-Lindberg, Eva, Helmy, Mohamed, Heo, Seong Gu, Hepperla, Austin J, Heredia-Genestar, José María, Herrmann, Carl, Hersey, Peter, Hess, Julian M, Hilmarsdottir, Holmfridur, Hinton, Jonathan, Hirano, Satoshi, Hiraoka, Nobuyoshi, Hobolth, Asger, Hodzic, Ermin, Hoell, Jessica I, Hoffmann, Steve, Hofmann, Oliver, Holbrook, Andrea, Holik, Aliaksei Z, Hollingsworth, Michael A, Holmes, Oliver, Holt, Robert A, Hong, Chen, Hong, Eun Pyo, Hong, Jongwhi H, Hooijer, Gerrit K, Hornshøj, Henrik, Hosoda, Fumie, Hou, Yong, Hovestadt, Volker, Howat, William, Hoyle, Alan P, Hruban, Ralph H, Hu, Jianhong, Hu, Taobo, Hua, Xing, Huang, Kuan-lin, Huang, Mei, Huang, Mi Ni, Huang, Vincent, Huang, Yi, Huber, Wolfgang, Hudson, Thomas J, Hummel, Michael, Hung, Jillian A, Huntsman, David, Hupp, Ted R, Huse, Jason, Huska, Matthew R, Hutter, Barbara, Hutter, Carolyn M, Hübschmann, Daniel, Iacobuzio-Donahue, Christine A, Imbusch, Charles David, Imielinski, Marcin, Imoto, Seiya, Isaacs, William B, Isaev, Keren, Ishikawa, Shumpei, Iskar, Murat, Islam, SM Ashiqul, Ittmann, Michael, Ivkovic, Sinisa, Izarzugaza, Jose MG, Jacquemier, Jocelyne, Jakrot, Valerie, Jamieson, Nigel B, Jang, Gun Ho, Jang, Se Jin, Jayaseelan, Joy C, Jayasinghe, Reyka, Jefferys, Stuart R, Jegalian, Karine, Jennings, Jennifer L, Jeon, Seung-Hyup, Jerman, Lara, Ji, Yuan, Johansson, Peter A, Johns, Amber L, Johns, Jeremy, Johnson, Rory, Johnson, Todd A, Jolly, Clemency, Joly, Yann, Jonasson, Jon G, Jones, Corbin D, Jones, David R, Jones, David TW, Jones, Nic, Jones, Steven JM, Jonkers, Jos, Ju, Young Seok, Juhl, Hartmut, Jung, Jongsun, Juul, Malene, Juul, Randi Istrup, Juul, Sissel, Jäger, Natalie, Kabbe, Rolf, Kahles, Andre, Kahraman, Abdullah, Kakavand, Hojabr, Kalimuthu, Sangeetha, von Kalle, Christof, Kang, Koo Jeong, 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Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
In cancer, the primary tumour’s organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24 common cancer types produced by the PCAWG Consortium. Our classifier achieves an accuracy of 91% on held-out tumor samples and 88% and 83% respectively on independent primary and metastatic samples, roughly double the accuracy of trained pathologists when presented with a metastatic tumour without knowledge of the primary. Surprisingly, adding information on driver mutations reduced accuracy. Our results have clinical applicability, underscore how patterns of somatic passenger mutations encode the state of the cell of origin, and can inform future strategies to detect the source of circulating tumour DNA.
- Published
- 2023
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20. Combined burden and functional impact tests for cancer driver discovery using DriverPower
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - 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.
- Published
- 2023
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21. Integrative pathway enrichment analysis of multivariate omics data
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Paczkowska, Marta, Barenboim, Jonathan, Sintupisut, Nardnisa, Fox, Natalie S, Zhu, Helen, Abd-Rabbo, Diala, Mee, Miles W, Boutros, Paul C, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Brunak, Søren, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Getz, Gad, Gonzalez-Perez, Abel, Guo, Qianyun, Gut, Ivo G, Haan, David, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Izarzugaza, Jose MG, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kahraman, Abdullah, Kellis, Manolis, Khurana, Ekta, Kim, Jaegil, Kim, Jong K, Kim, Youngwook, Komorowski, Jan, Korbel, Jan O, Kumar, Sushant, Lanzós, Andrés, Lawrence, Michael S, Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, McGillivray, Patrick D, Meyerson, William, Muiños, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Park, Keunchil, Park, Kiejung, Pedersen, Jakob Skou, Pich, Oriol, Pons, Tirso, Pulido-Tamayo, Sergio, Raphael, Benjamin J, Reyes-Salazar, Iker, Reyna, Matthew A, Rheinbay, Esther, Rubin, Mark A, Rubio-Perez, Carlota, Sabarinathan, Radhakrishnan, Sahinalp, S Cenk, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E, Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D, Stuart, Joshua M, Tamborero, David, Tiao, Grace, Tsunoda, Tatsuhiko, Umer, Husen M, Uusküla-Reimand, Liis, Valencia, Alfonso, Vazquez, Miguel, Verbeke, Lieven PC, Wadelius, Claes, Wadi, Lina, Wang, Jiayin, Warrell, Jonathan, Waszak, Sebastian M, Weischenfeldt, Joachim, Wheeler, David A, Wu, Guanming, Yu, Jun, Zhang, Jing, Zhang, Xuanping, Zhang, Yan, Zhao, Zhongming, Zou, Lihua, von Mering, Christian, Reimand, Jüri, Aaltonen, Lauri A, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Al-Shahrour, Fatima, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Atwal, Gurnit, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Baez-Ortega, Adrian, Bailey, Matthew H, Bailey, Peter J, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, Prashant, Baylin, Stephen B, Bazant, Wojciech, Beardsmore, Duncan, Beck, Timothy A, Behjati, Sam, Behren, Andreas, Niu, Beifang, Bell, Cindy, Beltran, Sergi, Benz, Christopher, Berchuck, Andrew, Bergmann, Anke K, Bergstrom, Erik N, Berman, Benjamin P, Berney, Daniel M, Bernhart, Stephan H, Berrios, Mario, Bersani, Samantha, Betancourt, Miguel, Bhandari, Vinayak, Bhosle, Shriram G, Biankin, Andrew V, Bieg, Matthias, Bigner, Darell, Binder, Hans, Birney, Ewan, Birrer, Michael, Biswas, Nidhan K, Bjerkehagen, Bodil, Bodenheimer, Tom, Boice, Lori, Bonizzato, Giada, De Bono, Johann S, Boot, Arnoud, Bootwalla, Moiz S, Borg, Ake, Borkhardt, Arndt, Borozan, Ivan, Borst, Christoph, Bosenberg, Marcus, Bosio, Mattia, Boultwood, Jacqueline, Bourque, Guillaume, Bova, G Steven, Bowen, David T, Bowlby, Reanne, Bowtell, David DL, Boyault, Sandrine, Boyce, Rich, Boyd, Jeffrey, Brazma, Alvis, Brennan, Paul, Brewer, Daniel S, Brinkman, Arie B, Bristow, Robert G, Broaddus, Russell R, Brock, Jane E, Brock, Malcolm, Broeks, Annegien, Brooks, Angela N, Brooks, Denise, Brors, Benedikt, Bruxner, Timothy JC, Bruzos, Alicia L, Buchanan, Alex, Buchhalter, Ivo, Buchholz, Christiane, Bullman, Susan, Burke, Hazel, Burkhardt, Birgit, Burns, Kathleen H, Busanovich, John, Bustamante, Carlos D, Butler, Adam P, Butte, Atul J, Byrne, Niall J, Børresen-Dale, Anne-Lise, Caesar-Johnson, Samantha J, Cafferkey, Andy, Cahill, Declan, Calabrese, Claudia, Caldas, Carlos, Calvo, Fabien, Camacho, Niedzica, Campo, Elias, Cantù, Cinzia, Cao, Shaolong, Carey, Thomas E, Carlsen, Rebecca, Cataldo, Ivana, Cazzola, Mario, Cebon, Jonathan, Cerfolio, Robert, Chadwick, Dianne E, Chalmers, Don, Chan, Kin, Chan-Seng-Yue, Michelle, Chandan, Vishal S, Chang, David K, Chanock, Stephen J, Chantrill, Lorraine A, Chateigner, Aurélien, Chatterjee, Nilanjan, Chayama, Kazuaki, Chen, Hsiao-Wei, Chen, Jieming, Chen, Yiwen, Chen, Zhaohong, Cherniack, Andrew D, Chien, Jeremy, Chiew, Yoke-Eng, Chin, Suet-Feung, Cho, Juok, Cho, Sunghoon, Choi, Wan, Chomienne, Christine, Chong, Zechen, Choo, Su Pin, Chou, Angela, Christ, Angelika N, Christie, Elizabeth L, Chuah, Eric, Cibulskis, Carrie, Cibulskis, Kristian, Cingarlini, Sara, Clapham, Peter, Claviez, Alexander, Cleary, Sean, Cloonan, Nicole, Cmero, Marek, Collins, Colin C, Connor, Ashton A, Cooke, Susanna L, Cooper, Colin S, Cope, Leslie, Corbo, Vincenzo, Cordes, Matthew G, Cordner, Stephen M, Cortés-Ciriano, Isidro, Covington, Kyle, Cowin, Prue A, Craft, Brian, Craft, David, Creighton, Chad J, Cun, Yupeng, Curley, Erin, Cutcutache, Ioana, Czajka, Karolina, Czerniak, Bogdan, Dagg, Rebecca A, Danilova, Ludmila, Davi, Maria Vittoria, Davidson, Natalie R, Davies, Helen, Davis, Ian J, Davis-Dusenbery, Brandi N, Dawson, Kevin J, De La Vega, Francisco M, De Paoli-Iseppi, Ricardo, Defreitas, Timothy, Dei Tos, Angelo P, Delaneau, Olivier, Demchok, John A, Demeulemeester, Jonas, Demidov, German M, Demircioğlu, Deniz, Dennis, Nening M, Denroche, Robert E, Dentro, Stefan C, Desai, Nikita, Deshpande, Vikram, Deshwar, Amit G, Desmedt, Christine, Dhalla, Noreen, Dhani, Neesha C, Dhir, Rajiv, DiBiase, Anthony, Ding, Li, Ding, Shuai, Dinh, Huy Q, Dirix, Luc, Doddapaneni, HarshaVardhan, Donmez, Nilgun, Dow, Michelle T, Drapkin, Ronny, Drechsel, Oliver, Drews, Ruben M, Serge, Serge, Dudderidge, Tim, Dueso-Barroso, Ana, Dunford, Andrew J, Dunn, Michael, Dursi, Lewis Jonathan, Duthie, Fraser R, Dutton-Regester, Ken, Eagles, Jenna, Easton, Douglas F, Edmonds, Stuart, Edwards, Paul A, Edwards, Sandra E, Eeles, Rosalind A, Ehinger, Anna, Eils, Juergen, Eils, Roland, El-Naggar, Adel, Eldridge, Matthew, Ellrott, Kyle, Erkek, Serap, Escaramis, Georgia, Espiritu, Shadrielle MG, Estivill, Xavier, Etemadmoghadam, Dariush, Eyfjord, Jorunn E, Faltas, Bishoy M, Fan, Daiming, Fan, Yu, Faquin, William C, Farcas, Claudiu, Fassan, Matteo, Fatima, Aquila, Favero, Francesco, Fayzullaev, Nodirjon, Felau, Ina, Fereday, Sian, Ferguson, Martin L, Ferretti, Vincent, Field, Matthew A, Finocchiaro, Gaetano, Fisher, Cyril, Fittall, Matthew W, Fitzgerald, Anna, Fitzgerald, Rebecca C, Flanagan, Adrienne M, Fleshner, Neil E, Flicek, Paul, Foekens, John A, Fong, Kwun M, Foster, Christopher S, Fraser, Michael, Frazer, Scott, Frenkel-Morgenstern, Milana, Friedman, William, Fronick, Catrina C, Fujimoto, Akihiro, Fujita, Masashi, Fukayama, Masashi, Fulton, Lucinda A, Fulton, Robert S, Furuta, Mayuko, Futreal, P Andrew, Füllgrabe, Anja, Gabriel, Stacey B, Gallinger, Steven, Gao, Jianjiong, Gao, Shengjie, Garraway, Levi, Garred, Øystein, Garrison, Erik, Gehlenborg, Nils, Gelpi, Josep LL, George, Joshy, Gerhard, Daniela S, Gerhauser, Clarissa, Gershenwald, Jeffrey E, Gerstung, Moritz, Ghori, Mohammed, Ghossein, Ronald, Giama, Nasra H, Gibbs, Richard A, Gibson, Bob, Gill, Anthony J, Gill, Pelvender, Giri, Dilip D, Glodzik, Dominik, Gnanapragasam, Vincent J, Goebler, Maria Elisabeth, Goldman, Mary J, Gomez, Carmen, Gonzalez, Santiago, Gordenin, Dmitry A, Gossage, James, Gotoh, Kunihito, Govindan, Ramaswamy, Grabau, Dorthe, Graham, Janet S, Grant, Robert C, Green, Anthony R, Green, Eric, Greger, Liliana, Grehan, Nicola, Grimaldi, Sonia, Grimmond, Sean M, Grossman, Robert L, Grundhoff, Adam, Gundem, Gunes, Gupta, Manaswi, Gupta, Shailja, Gut, Marta, Göke, Jonathan, Ha, Gavin, Haake, Andrea, Haas, Siegfried, Haase, Kerstin, Haber, James E, Habermann, Nina, Hach, Faraz, Haider, Syed, Hama, Natsuko, Hamdy, Freddie C, Hamilton, Anne, Han, Leng, Hanna, George B, Hansmann, Martin, Harismendy, Olivier, Harliwong, Ivon, Harrington, Eoghan, Hasegawa, Takanori, Haussler, David, Hawkins, Steve, Hayami, Shinya, Hayashi, Shuto, Hayes, D Neil, Hayes, Stephen J, Hayward, Nicholas K, Hazell, Steven, He, Yao, Heath, Allison P, Heath, Simon C, Hedley, David, Hegde, Apurva M, Heiman, David I, Heinold, Michael C, Heins, Zachary, Heisler, Lawrence E, Hellstrom-Lindberg, Eva, Heo, Seong Gu, Hepperla, Austin J, Heredia-Genestar, José María, Hersey, Peter, Hilmarsdottir, Holmfridur, Hinton, Jonathan, Hirano, Satoshi, Hiraoka, Nobuyoshi, Hoadley, Katherine A, Hoell, Jessica I, Hoffmann, Steve, Hofmann, Oliver, Holbrook, Andrea, Holik, Aliaksei Z, Hollingsworth, Michael A, Holmes, Oliver, Holt, Robert A, Hong, Eun Pyo, Hong, Jongwhi H, Hooijer, Gerrit K, Hosoda, Fumie, Hou, Yong, Hovestadt, Volker, Howat, William, Hoyle, Alan P, Hruban, Ralph H, Hu, Jianhong, Hu, Taobo, Hua, Xing, Huang, Kuan-lin, Huang, Mei, Huang, Mi Ni, Huang, Vincent, Huang, Yi, Huber, Wolfgang, Hudson, Thomas J, Hummel, Michael, Hung, Jillian A, Huntsman, David, Hupp, Ted R, Huse, Jason, Huska, Matthew R, Hutter, Barbara, Hutter, Carolyn M, Hübschmann, Daniel, Iacobuzio-Donahue, Christine A, Imbusch, Charles David, Imielinski, Marcin, Imoto, Seiya, Isaacs, William B, Ishikawa, Shumpei, Iskar, Murat, Islam, SM Ashiqul, Ittmann, Michael, Ivkovic, Sinisa, Jacquemier, Jocelyne, Jakrot, Valerie, Jamieson, Nigel B, Jang, Gun Ho, Jang, Se Jin, Jayaseelan, Joy C, Jayasinghe, Reyka, Jefferys, Stuart R, Jegalian, Karine, Jennings, Jennifer L, Jeon, Seung-Hyup, Jerman, Lara, Ji, Yuan, Jiao, Wei, Johansson, Peter A, Johns, Amber L, Johns, Jeremy, Jolly, Clemency, Joly, Yann, Jonasson, Jon G, Jones, Corbin D, Jones, David R, Jones, David TW, Jones, Nic, Jones, Steven JM, Jonkers, Jos, Ju, Young Seok, Juhl, Hartmut, Jung, Jongsun, Juul, Sissel, Jäger, Natalie, Kabbe, Rolf, Kaiser, Vera B, Kakavand, Hojabr, Kalimuthu, Sangeetha, von Kalle, Christof, Kang, Koo Jeong, Karaszi, Katalin, Karlan, Beth, Karlić, Rosa, Karsch, Dennis, Kasaian, Katayoon, Kassahn, Karin S, Katai, Hitoshi, Kato, Mamoru, Katoh, Hiroto, Kawakami, Yoshiiku, Kay, Jonathan D, Kazakoff, Stephen H, Kazanov, Marat D, Keays, Maria, Kebebew, Electron, Kefford, Richard F, Kench, James G, Kennedy, Catherine J, Kerssemakers, Jules NA, Khoo, David, Khoo, Vincent, Khuntikeo, Narong, Kilpinen, Helena, Kim, Hark Kyun, Kim, Hyung-Lae, Kim, Hyung-Yong, Kim, Hyunghwan, Kim, Jihoon, King, Tari A, Klapper, Wolfram, Kleinheinz, Kortine, Klimczak, Leszek J, Knappskog, Stian, Kneba, Michael, Knoppers, Bartha M, Koh, Youngil, Komura, Daisuke, Komura, Mitsuhiro, Kong, Gu, Kool, Marcel, Korchina, Viktoriya, Korshunov, Andrey, Koscher, Michael, Koster, Roelof, Kote-Jarai, Zsofia, Koures, Antonios, Kovacevic, Milena, Kremeyer, Barbara, Kretzmer, Helene, Kreuz, Markus, Krishnamurthy, Savitri, Kube, Dieter, Kumar, Kiran, Kumar, Pardeep, Kumar, Yogesh, Kundra, Ritika, Kübler, Kirsten, Küppers, Ralf, Lagergren, Jesper, Lai, Phillip H, Laird, Peter W, Lakhani, Sunil R, Lalansingh, Christopher M, Lalonde, Emilie, Lamaze, Fabien C, Lambert, Adam, Lander, Eric, Landgraf, Pablo, Landoni, Luca, Langerød, Anita, Larsimont, Denis, Larsson, Erik, Lathrop, Mark, Lau, Loretta MS, Lawerenz, Chris, Lawlor, Rita T, Lazar, Alexander J, Lazic, Ana Mijalkovic, Le, Xuan, Lee, Darlene, Lee, Eunjung Alice, Lee, Hee Jin, Lee, Jake June-Koo, Lee, Jeong-Yeon, Lee, Juhee, Lee, Ming Ta Michael, Lee-Six, Henry, Lehrach, Hans, Lenze, Dido, Leonard, Conrad R, Leongamornlert, Daniel A, Leshchiner, Ignaty, Letourneau, Louis, Letunic, Ivica, Levine, Douglas A, Lewis, Lora, Ley, Tim, Li, Chang, Li, Constance H, Li, Haiyan Irene, Li, Jun, Li, Lin, Li, Siliang, Li, Xiaobo, Li, Xinyue, Li, Yilong, Liang, Han, Liang, Sheng-Ben, Lichter, Peter, Lin, Pei, Linehan, WM, Lingjærde, Ole Christian, Liu, Dongbing, Liu, Fei-Fei Fei, Liu, Fenglin, Liu, Jia, Liu, Xingmin, Livingstone, Julie, Livitz, Dimitri, Livni, Naomi, Loeffler, Markus, Long, Georgina V, Lopez-Guillermo, Armando, Louis, David N, Lovat, Laurence B, Lu, Yiling, Lu, Yong-Jie, Lu, Youyong, Luchini, Claudio, Lungu, Ilinca, Luo, Xuemei, Luxton, Hayley J, Lynch, Andy G, Lype, Lisa, López, Cristina, López-Otín, Carlos, Z, Eric, Ma, Yussanne, MacGrogan, Gaetan, MacRae, Shona, Macintyre, Geoff, Maejima, Kazuhiro, Mafficini, Andrea, Maglinte, Dennis T, Maitra, Arindam, Majumder, Partha P, Malcovati, Luca, Malikic, Salem, Malleo, Giuseppe, Mann, Graham J, Mantovani-Löffler, Luisa, Marchegiani, Giovanni, Mardis, Elaine R, Margolin, Adam A, Marin, Maximillian G, Markowetz, Florian, Markowski, Julia, Marks, Jeffrey, Marques-Bonet, Tomas, Marra, Marco A, Marsden, Luke, Martens, John WM, Martin, Sancha, Martin-Subero, Jose I, Mashl, R Jay, Massie, Charlie E, Matthew, Thomas J, Matthews, Lucy, Mayer, Erik, Mayes, Simon, Mayo, Michael, Mbabaali, Faridah, McCune, Karen, McDermott, Ultan, McLellan, Michael D, McPherson, John D, McPherson, John R, McPherson, Treasa A, Meier, Samuel R, Meng, Alice, Meng, Shaowu, Menzies, Andrew, Merrett, Neil D, Merson, Sue, Meyerson, Matthew, Mieczkowski, Piotr A, Mihaiescu, George L, Mijalkovic, Sanja, Mikkelsen, Tom, Milella, Michele, Mileshkin, Linda, Miller, Christopher A, Miller, David K, Miller, Jessica K, Mills, Gordon B, Milovanovic, Ana, Minner, Sarah, Miotto, Marco, Arnau, Gisela Mir, Mirabello, Lisa, Mitchell, Chris, Mitchell, Thomas J, Miyano, Satoru, Miyoshi, Naoki, Mizuno, Shinichi, Molnár-Gábor, Fruzsina, Moore, Malcolm J, Moore, Richard A, Morganella, Sandro, Morris, Quaid D, Morrison, Carl, Mose, Lisle E, Moser, Catherine D, Mungall, Andrew J, Mungall, Karen, Musgrove, Elizabeth A, Mustonen, Ville, Mutch, David, Muyas, Francesc, Muzny, Donna M, Muñoz, Alfonso, Myers, Jerome, Myklebost, Ola, Möller, Peter, Nagae, Genta, Nagrial, Adnan M, Nahal-Bose, Hardeep K, Nakagama, Hitoshi, Nakamura, Hiromi, Nakamura, Toru, Nakano, Kaoru, Nandi, Tannistha, Nangalia, Jyoti, Nastic, Mia, Navarro, Arcadi, Navarro, Fabio CP, Neal, David E, Nettekoven, Gerd, Newell, Felicity, Newhouse, Steven J, Newton, Yulia, Ng, Alvin Wei Tian, Ng, Anthony, Nicholson, Jonathan, Nicol, David, Nie, Yongzhan, Nielsen, G Petur, Nik-Zainal, Serena, Noble, Michael S, Nones, Katia, Northcott, Paul A, Notta, Faiyaz, O’Connor, Brian D, O’Donnell, Peter, O’Donovan, Maria, O’Meara, Sarah, O’Neill, Brian Patrick, O’Neill, J Robert, Ocana, David, Ochoa, Angelica, Oesper, Layla, Ogden, Christopher, Ohdan, Hideki, Ohi, Kazuhiro, Ohno-Machado, Lucila, Oien, Karin A, Ojesina, Akinyemi I, Ojima, Hidenori, Okusaka, Takuji, Omberg, Larsson, Ong, Choon Kiat, Ossowski, Stephan, Ott, German, Ouellette, BF Francis, P’ng, Christine, Paiella, Salvatore, Pairojkul, Chawalit, Pajic, Marina, Pan-Hammarström, Qiang, Papaemmanuil, Elli, Papatheodorou, Irene, Paramasivam, Nagarajan, Park, Ji Wan, Park, Joong-Won, Park, Peter J, Parker, Joel S, Parsons, Simon L, Pass, Harvey, Pasternack, Danielle, Pastore, Alessandro, Patch, Ann-Marie, Pauporté, Iris, Pea, Antonio, Pearson, John V, Pedamallu, Chandra Sekhar, Pederzoli, Paolo, Peifer, Martin, Pennell, Nathan A, Perou, Charles M, Perry, Marc D, Petersen, Gloria M, Peto, Myron, Petrelli, Nicholas, Petryszak, Robert, Pfister, Stefan M, Phillips, Mark, Pickett, Hilda A, Pihl, Todd D, Pillay, Nischalan, Pinder, Sarah, Pinese, Mark, Pinho, Andreia V, Pitkänen, Esa, Pivot, Xavier, Piñeiro-Yáñez, Elena, Planko, Laura, Plass, Christoph, Polak, Paz, Popescu, Irinel, Potapova, Olga, Prasad, Aparna, Preston, Shaun R, Prinz, Manuel, Pritchard, Antonia L, Prokopec, Stephenie D, Provenzano, Elena, Puente, Xose S, Puig, Sonia, Puiggròs, Montserrat, Pupo, Gulietta M, Purdie, Colin A, Quinn, Michael C, Rabionet, Raquel, Rader, Janet S, Radlwimmer, Bernhard, Radovic, Petar, Raeder, Benjamin, Raine, Keiran M, Ramakrishna, Manasa, Ramakrishnan, Kamna, Ramalingam, Suresh, Rathmell, W Kimryn, Rausch, Tobias, Reifenberger, Guido, Reis-Filho, Jorge, Reuter, Victor, Reynolds, Sheila M, Riazalhosseini, Yasser, Richardson, Andrea L, Richter, Julia, Ringel, Matthew, Ringnér, Markus, Rino, Yasushi, Rippe, Karsten, Roach, Jeffrey, Roberts, Lewis R, Roberts, Nicola D, Roberts, Steven A, Robertson, A Gordon, Robertson, Alan J, Rodriguez, Javier Bartolomé, Rodriguez-Martin, Bernardo, Rodríguez-González, F Germán, Roehrl, Michael HA, Rohde, Marius, Rokutan, Hirofumi, Romieu, Gilles, Rooman, Ilse, Roques, Tom, Rosebrock, Daniel, Rosenberg, Mara, Rosenstiel, Philip C, Rosenwald, Andreas, Rowe, Edward W, Royo, Romina, Rozen, Steven G, Rubanova, Yulia, Rudneva, Vasilisa A, Rusev, Borislav C, Ruzzenente, Andrea, Rätsch, Gunnar, Sabelnykova, Veronica Y, Sadeghi, Sara, Saini, Natalie, Saito-Adachi, Mihoko, Salcedo, Adriana, Salgado, Roberto, Sallari, Richard, Saller, Charles, Salvia, Roberto, Sam, Michelle, Samra, Jaswinder S, Sanchez-Vega, Francisco, Sanders, Grant, Sarin, Rajiv, Sarrafi, Iman, Sasaki-Oku, Aya, Sauer, Torill, Sauter, Guido, Saw, Robyn PM, Scardoni, Maria, Scarlett, Christopher J, Scarpa, Aldo, Scelo, Ghislaine, Schadendorf, Dirk, Schein, Jacqueline E, Schilhabel, Markus B, Schlesner, Matthias, Schlomm, Thorsten, Schmidt, Heather K, Schramm, Sarah-Jane, Schreiber, Stefan, Schultz, Nikolaus, Schwarz, Roland F, Scolyer, Richard A, Scott, David, Scully, Ralph, Seethala, Raja, Segre, Ayellet V, Selander, Iris, Semple, Colin A, Senbabaoglu, Yasin, Sengupta, Subhajit, Sereni, Elisabetta, Serra, Stefano, Sgroi, Dennis C, Shah, Nimish C, Shahabi, Sagedeh, Shang, Catherine A, Shang, Ping, Shelton, Troy, Shen, Hui, Shepherd, Rebecca, Shi, Ruian, Shi, Yan, Shiah, Yu-Jia, Shibata, Tatsuhiro, Shih, Juliann, Shimizu, Eigo, Shimizu, Kiyo, Shin, Seung Jun, Shiraishi, Yuichi, Shmaya, Tal, Shmulevich, Ilya, Shorser, Solomon I, Short, Charles, Shringarpure, Suyash S, Shriver, Craig, Siebert, Reiner, Sieuwerts, Anieta M, Signoretti, Sabina, Sikora, Katarzyna O, Simbolo, Michele, Simon, Ronald, Simons, Janae V, Simpson, Jared T, Simpson, Peter T, Singer, Samuel, Sipahimalani, Payal, Skelly, Tara J, Smid, Marcel, Smith, Jaclyn, Smith-McCune, Karen, Socci, Nicholas D, Sofia, Heidi J, Soloway, Matthew G, Song, Lei, Sood, Anil K, Sothi, Sharmila, Sotiriou, Christos, Soulette, Cameron M, Span, Paul N, Spellman, Paul T, Sperandio, Nicola, Spillane, Andrew J, Spiro, Oliver, Spring, Jonathan, Staaf, Johan, Stadler, Peter F, Staib, Peter, Stark, Stefan G, Stebbings, Lucy, Stefánsson, Ólafur Andri, Stegle, Oliver, Stenhouse, Alasdair, Stewart, Chip, Stilgenbauer, Stephan, Stobbe, Miranda D, Stratton, Michael R, Stretch, Jonathan R, Struck, Adam J, Stunnenberg, Henk G, Su, Hong, Su, Xiaoping, Sun, Ren X, Sungalee, Stephanie, Susak, Hana, Suzuki, Akihiro, Sweep, Fred, Szczepanowski, Monika, Sültmann, Holger, Yugawa, Takashi, Tam, Angela, Tan, Benita Kiat Tee, Tan, Donghui, Tan, Patrick, Tanaka, Hiroko, Taniguchi, Hirokazu, Tanskanen, Tomas J, Tarabichi, Maxime, Tarnuzzer, Roy, Tarpey, Patrick, Taschuk, Morgan L, Tatsuno, Kenji, Tavaré, Simon, Taylor, Darrin F, Taylor-Weiner, Amaro, Teague, Jon W, Teh, Bin Tean, Tembe, Varsha, Temes, Javier, Thai, Kevin, Thayer, Sarah P, Thiessen, Nina, Thomas, Gilles, Thomas, Sarah, Thompson, Alan, Thompson, Alastair M, Thompson, John FF, Thompson, R Houston, Thorne, Heather, Thorne, Leigh B, Thorogood, Adrian, Tijanic, Nebojsa, Timms, Lee E, Tirabosco, Roberto, Tojo, Marta, Tommasi, Stefania, Toon, Christopher W, Toprak, Umut H, Torrents, David, Tortora, Giampaolo, Tost, Jörg, Totoki, Yasushi, Townend, David, Traficante, Nadia, Treilleux, Isabelle, Trotta, Jean-Rémi, Trümper, Lorenz HP, Tsao, Ming, MC Tubio, Jose, Tucker, Olga, Turkington, Richard, Turner, Daniel J, Tutt, Andrew, Ueno, Masaki, Ueno, Naoto T, Umbricht, Christopher, Underwood, Timothy J, Urban, Lara, Urushidate, Tomoko, Ushiku, Tetsuo, Van Den Berg, David J, Van Laere, Steven, Van Loo, Peter, Van Meir, Erwin G, Van den Eynden, Gert G, Van der Kwast, Theodorus, Vasudev, Naveen, Vedururu, Ravikiran, Veluvolu, Umadevi, Vembu, Shankar, Vermeulen, Peter, Verrill, Clare, Viari, Alain, Vicente, David, Vicentini, Caterina, 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Vijver, Marc J, and Veer, L van’t
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. 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 tumor types, we integrated genes with coding and non-coding mutations and revealed frequently mutated pathways and additional cancer genes with infrequent mutations. We also analyzed prognostic molecular pathways by integrating genomic and transcriptomic features of 1780 breast cancers and highlighted associations with immune response and anti-apoptotic signaling. Integration of ChIP-seq and RNA-seq data for master regulators of the Hippo pathway across normal human tissues identified processes of tissue regeneration and stem cell regulation. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations.
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- 2023
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22. Pathway and network analysis of more than 2500 whole cancer genomes
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
- Published
- 2023
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23. Divergent mutational processes distinguish hypoxic and normoxic tumours
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. 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 quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations in TP53, MYC and PTEN are enriched in hypoxic tumours, and mutations in PTEN interact with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer.
- Published
- 2023
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24. Genomic footprints of activated telomere maintenance mechanisms in cancer
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Okusaka, Takuji, Omberg, Larsson, Ong, Choon Kiat, Ott, German, Ouellette, BF Francis, P’ng, Christine, Paczkowska, Marta, Paiella, Salvatore, Pairojkul, Chawalit, Pajic, Marina, Pan-Hammarström, Qiang, Papaemmanuil, Elli, Papatheodorou, Irene, Paramasivam, Nagarajan, Park, Ji Wan, Park, Joong-Won, Park, Keunchil, Park, Kiejung, Parker, Joel S, Parsons, Simon L, Pass, Harvey, Pasternack, Danielle, Pastore, Alessandro, Patch, Ann-Marie, Pauporté, Iris, Pea, Antonio, Pedamallu, Chandra Sekhar, Pedersen, Jakob Skou, Pederzoli, Paolo, Peifer, Martin, Pennell, Nathan A, Perou, Charles M, Perry, Marc D, Petersen, Gloria M, Peto, Myron, Petrelli, Nicholas, Petryszak, Robert, Pfister, Stefan M, Phillips, Mark, Pich, Oriol, Pickett, Hilda A, Pihl, Todd D, Pillay, Nischalan, Pinder, Sarah, Pinese, Mark, Pinho, Andreia V, Pitkänen, Esa, Pivot, Xavier, Piñeiro-Yáñez, Elena, Planko, Laura, Plass, Christoph, Polak, Paz, Pons, Tirso, Popescu, Irinel, Potapova, Olga, Prasad, Aparna, Preston, Shaun R, 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Christian
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer.
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- 2023
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25. Unravelling patient pathways in the context of antibacterial resistance in East Africa
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Keenan, Katherine, primary, Fredricks, Kathryn J., additional, Ahad, Mary Abed Al, additional, Neema, Stella, additional, Mwanga, Joseph R., additional, Kesby, Mike, additional, Mushi, Martha F., additional, Aduda, Annette, additional, Green, Dominique L., additional, Lynch, Andy G., additional, Huque, Sarah I., additional, Mmbaga, Blandina T., additional, Worthington, Hannah, additional, Kansiime, Catherine, additional, Olamijuwon, Emmanuel, additional, Ntinginya, Nyanda E., additional, Loza, Olga, additional, Bazira, Joel, additional, Maldonado-Barragán, Antonio, additional, Smith, V Anne, additional, Decano, Arun Gonzales, additional, Mwaniki, John Njeru, additional, Sandeman, Alison, additional, Stelling, John, additional, Elliott, Alison, additional, Aanensen, David, additional, Gillespie, Stephen H., additional, Kibiki, Gibson, additional, Sabiiti, Wilber, additional, Sloan, Derek J., additional, Asiimwe, Benon B., additional, Kiiru, John, additional, Mshana, Stephen E., additional, Holden, Matthew T. G., additional, and Consortium, HATUA, additional
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- 2022
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26. Identification of plasma proteins associated with oesophageal cancer chemotherapeutic treatment outcomes using SWATH-MS
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Guo, Naici, primary, Minas, Giorgos, additional, Synowsky, Silvia A., additional, Dunne, Margaret R., additional, Ahmed, Hasnain, additional, McShane, Rhiannon, additional, Bhardwaj, Anshul, additional, Donlon, Noel E., additional, Lorton, Cliona, additional, O'Sullivan, Jacintha, additional, Reynolds, John V., additional, Caie, Peter D., additional, Shirran, Sally L., additional, Lynch, Andy G., additional, Stewart, Alan J., additional, and Arya, Swati, additional
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- 2022
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27. Publisher Correction: Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data
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Farmery, James H. R., Smith, Mike L., NIHR BioResource - Rare Diseases, and Lynch, Andy G.
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- 2018
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28. Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data
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Farmery, James H. R., Smith, Mike L., NIHR BioResource - Rare Diseases, and Lynch, Andy G.
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- 2018
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29. Choline Kinase Alpha as an Androgen Receptor Chaperone and Prostate Cancer Therapeutic Target
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Asim, Mohammad, Massie, Charles E., Orafidiya, Folake, Pértega-Gomes, Nelma, Warren, Anne Y., Esmaeili, Mohsen, Selth, Luke A., Zecchini, Heather I., Luko, Katarina, Qureshi, Arham, Baridi, Ajoeb, Menon, Suraj, Madhu, Basetti, Escriu, Carlos, Lyons, Scott, Vowler, Sarah L., Zecchini, Vincent R., Shaw, Greg, Hessenkemper, Wiebke, Russell, Roslin, Mohammed, Hisham, Stefanos, Niki, Lynch, Andy G., Grigorenko, Elena, D’Santos, Clive, Taylor, Chris, Lamb, Alastair, Sriranjan, Rouchelle, Yang, Jiali, Stark, Rory, Dehm, Scott M., Rennie, Paul S., Carroll, Jason S., Griffiths, John R., Tavaré, Simon, Mills, Ian G., McEwan, Iain J., Baniahmad, Aria, Tilley, Wayne D., and Neal, David E.
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- 2016
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30. Additional file 1 of Low-cost and clinically applicable copy number profiling using repeat DNA
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Abujudeh, Sam, Zeki, Sebastian S., van Lanschot, Meta C.J., Pusung, Mark, Weaver, Jamie M.J., Li, Xiaodun, Noorani, Ayesha, Metz, Andrew J., Bornschein, Jan, Bower, Lawrence, Miremadi, Ahmad, Fitzgerald, Rebecca C., Morrissey, Edward R., and Lynch, Andy G.
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Additional file 1 Supplementary materials (Supplementary Notes 1, 2, 3, 4 and 5. Supplementary Table S1. Supplementary Fig. S1. Supplementary Fig. S2).
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- 2022
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31. Additional file 2 of The architecture of clonal expansions in morphologically normal tissue from cancerous and non-cancerous prostates
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Buhigas, Claudia, Warren, Anne Y., Leung, Wing-Kit, Whitaker, Hayley C., Luxton, Hayley J., Hawkins, Steve, Kay, Jonathan, Butler, Adam, Xu, Yaobo, Woodcock, Dan J., Merson, Sue, Frame, Fiona M., Sahli, Atef, Abascal, Federico, Martincorena, Iñigo, Bova, G. Steven, Foster, Christopher S., Campbell, Peter, Maitland, Norman J., Neal, David E., Massie, Charlie E., Lynch, Andy G., Eeles, Rosalind A., Cooper, Colin S., Wedge, David C., and Brewer, Daniel S.
- Abstract
Additional file 2: Supplementary Figure 1. Age vs number of SNVs detected for normal tissue from Prostate cancer patients and non-prostate cancer donors. For the non-cancer donors, the number of SNVs detected is remarkably consistent (range: 104 to 159), apart from one outlier from a cystoprostatectomy with an exceptionally high number of mutations (1202) that is uniquely classified as BPH. There is no significant correlation in the non-cancer donors between age and SNVs (ρ = -0.015, P = 0.98, Spearman’s correlation; this is retained even when the outlier is included: ρ = 0.49, P = 0.27). The number of SNVs detected for non-cancer patients is over 100 SNVs lower than all prostate cancer patients except for one prostate cancer outlier, even in the three samples which are of similar age to the prostate cancer cohort. Looking at only samples in the range 50-73 there is a statistically significant difference in the number of SNVs in prostate cancer vs non-prostate cancer donors (P = 0.0093; Wilcoxon rank sum test; excluding the normal outlier). Supplementary Figure 2. Example density plots of cell cultured fibroblasts and morphologically normal samples from patients where phylogenies could not be reconstructed due to only having one sample per patient or no detected clonal expansions under positive selection. They show the posterior distribution of the fraction of cells bearing a mutation, modelled by a one-dimensional Bayesian Dirichlet process [43]. The median density is indicated by the purple line and 95% confidence intervals by the blue region. The grey histogram shows the observed frequency density of mutations as a function of the fraction of cells bearing the mutation. Supplementary Figure 3. Subclonal architecture of patients with morphologically normal and matched tumour (N-T). Phylogenies revealing the relationships between clones for each case. Each coloured line represents a clone/subclone detected in a particular sample. When two or more coloured lines are together, they represent a clone that is found in all the samples represented. The length of the line is proportional to the weighted number of single nucleotide variants present in each clone; the thickness represents the clonal cell fraction associated with that clone (more detail in Additional file 3). Dotted lines are associated with samples that have no evidence of a unique sample specific clone. Supplementary Figure 4. The relationship between the clonal cell fraction (CCF) and the type of normal samples. Boxplots showing the distribution of estimated CCF for each clone detected and the type of normal sample (non-BPH normal tissue, normal tissue with BPH and BPH fibroblasts). Supplementary Table 1. Summary of patients with multiple normal samples. Patients 0006, 0007 and 0008 have multiple samples from non-BPH normal and tumour tissue and patients 0065, 0073 and 0077 have a sample from non-BPH and BPH normal tissue. Supplementary Table 2. The number of mutations in common between normal samples from the same donor. Supplementary Table 3. The mutation characteristics of three groups of samples defined by the proportion of genome affected by copy number alterations. Group 1: Tumour samples examined by Wedge et al. [30] with less than 6% of the genome affected by CNAs; Group 2: Tumour samples examined by Wedge et al. [30] with more than 6% of the genome affected by CNAs; and Group 3: normal samples examined in our study where no CNAs were detected. The median number of SNVs and indels are shown for each group.
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- 2022
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32. Whole-genome sequencing provides new insights into the clonal architecture of Barrett's esophagus and esophageal adenocarcinoma
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Ross-Innes, Caryn S, Becq, Jennifer, Warren, Andrew, Cheetham, R Keira, Northen, Helen, O'Donovan, Maria, Malhotra, Shalini, di Pietro, Massimiliano, Ivakhno, Sergii, He, Miao, Weaver, Jamie M J, Lynch, Andy G, Kingsbury, Zoya, Ross, Mark, Humphray, Sean, Bentley, David, and Fitzgerald, Rebecca C
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- 2015
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33. Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer
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Asim, Mohammad, Tarish, Firas, Zecchini, Heather I., Sanjiv, Kumar, Gelali, Eleni, Massie, Charles E., Baridi, Ajoeb, Warren, Anne Y., Zhao, Wanfeng, Ogris, Christoph, McDuffus, Leigh-Anne, Mascalchi, Patrice, Shaw, Greg, Dev, Harveer, Wadhwa, Karan, Wijnhoven, Paul, Forment, Josep V., Lyons, Scott R., Lynch, Andy G., O’Neill, Cormac, Zecchini, Vincent R., Rennie, Paul S., Baniahmad, Aria, Tavaré, Simon, Mills, Ian G., Galanty, Yaron, Crosetto, Nicola, Schultz, Niklas, Neal, David, and Helleday, Thomas
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- 2017
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34. Resolving the immune landscape of human prostate at a single-cell level in health and cancer
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Tuong, Zewen Kelvin, primary, Loudon, Kevin W., additional, Berry, Brendan, additional, Richoz, Nathan, additional, Jones, Julia, additional, Tan, Xiao, additional, Nguyen, Quan, additional, George, Anne, additional, Hori, Satoshi, additional, Field, Sarah, additional, Lynch, Andy G., additional, Kania, Katarzyna, additional, Coupland, Paul, additional, Babbage, Anne, additional, Grenfell, Richard, additional, Barrett, Tristan, additional, Warren, Anne Y., additional, Gnanapragasam, Vincent, additional, Massie, Charlie, additional, and Clatworthy, Menna R., additional
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- 2021
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35. Protocol for an interdisciplinary cross-sectional study investigating the social, biological and community-level drivers of antimicrobial resistance (AMR): Holistic Approach to Unravel Antibacterial Resistance in East Africa (HATUA)
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Asiimwe, Benon B, Kiiru, John, Mshana, Stephen E, Neema, Stella, Keenan, Katherine, Kesby, Mike, Mwanga, Joseph R, Sloan, Derek J, Mmbaga, Blandina T, Smith, V Anne, Gillespie, Stephen H, Lynch, Andy G, Sandeman, Alison, Stelling, John, Elliott, Alison, Aanensen, David M, Kibiki, Gibson E, Sabiiti, Wilber, Holden, Matthew TG, and HATUA Consortium
- Abstract
INTRODUCTION: Antimicrobial resistance (AMR) is a global health threat that requires urgent research using a multidisciplinary approach. The biological drivers of AMR are well understood, but factors related to treatment seeking and the social contexts of antibiotic (AB) use behaviours are less understood. Here we describe the Holistic Approach to Unravel Antibacterial Resistance in East Africa, a multicentre consortium that investigates the diverse drivers of drug resistance in urinary tract infections (UTIs) in East Africa. METHODS AND ANALYSIS: This study will take place in Uganda, Kenya and Tanzania. We will conduct geospatial mapping of AB sellers, and conduct mystery client studies and in-depth interviews (IDIs) with drug sellers to investigate AB provision practices. In parallel, we will conduct IDIs with doctors, alongside community focus groups. Clinically diagnosed patients with UTI will be recruited from healthcare centres, provide urine samples and complete a questionnaire capturing retrospective treatment pathways, sociodemographic characteristics, attitudes and knowledge. Bacterial isolates from urine and stool samples will be subject to culture and antibiotic sensitivity testing. Genomic DNA from bacterial isolates will be extracted with a subset being sequenced. A follow-up household interview will be conducted with 1800 UTI-positive patients, where further environmental samples will be collected. A subsample of patients will be interviewed using qualitative tools. Questionnaire data, microbiological analysis and qualitative data will be linked at the individual level. Quantitative data will be analysed using statistical modelling, including Bayesian network analysis, and all forms of qualitative data analysed through iterative thematic content analysis. ETHICS AND DISSEMINATION: Approvals have been obtained from all national and local ethical review bodies in East Africa and the UK. Results will be disseminated in communities, with local and global policy stakeholders, and in academic circles. They will have great potential to inform policy, improve clinical practice and build regional pathogen surveillance capacity.
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- 2021
36. Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
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Xi, Ruibin, Jain, Dhawal, Jung, Youngsook L., Yang, Lixing, Gordenin, Dmitry, Pellman, David S., Akdemir, Kadir C., Alvarez, Eva G., Baez-Ortega, Adrian, Beroukhim, Rameen, Boutros, Paul C., Bowtell, David D. L., Brors, Benedikt, Burns, Kathleen H., Campbell, Peter J., Chan, Kin, Chen, Ken, Cortés-Ciriano, Isidro, Dueso-Barroso, Ana, Dunford, Andrew J., Edwards, Paul A., Estivill, Xavier, Etemadmoghadam, Dariush, Feuerbach, Lars, Fink, J. Lynn, Frenkel-Morgenstern, Milana, Garsed, Dale W., Gerstein, Mark, Gordenin, Dmitry A., Haan, David, Haber, James E., Hess, Julian M., Hutter, Barbara, Imielinski, Marcin, Jones, David T. W., Ju, Young Seok, Kazanov, Marat D., Klimczak, Leszek J., Koh, Youngil, Korbel, Jan O., Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Li, Yilong, Lynch, Andy G., Macintyre, Geoff, Markowetz, Florian, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Miyano, Satoru, Nakagawa, Hidewaki, Navarro, Fabio C. P., Ossowski, Stephan, Park, Peter J., Pearson, John V., Puiggròs, Montserrat, Rippe, Karsten, Roberts, Nicola D., Roberts, Steven A., Rodriguez-Martin, Bernardo, Schumacher, Steven E., Scully, Ralph, Shackleton, Mark, Sidiropoulos, Nikos, Sieverling, Lina, Stewart, Chip, Torrents, David, Tubio, Jose M. C., Villasante, Izar, Waddell, Nicola, Wala, Jeremiah A., Weischenfeldt, Joachim, Yao, Xiaotong, Yoon, Sung-Soo, Zamora, Jorge, Zhang, Cheng-Zhong, Cortés-Ciriano, Isidro [0000-0002-2036-494X], Lee, Jake June-Koo [0000-0003-1348-4094], Xi, Ruibin [0000-0001-7545-7361], Gordenin, Dmitry [0000-0002-8399-1836], Klimczak, Leszek J. [0000-0003-3048-2576], Zhang, Cheng-Zhong [0000-0001-8825-7158], Park, Peter J. [0000-0001-9378-960X], and Apollo - University of Cambridge Repository
- Subjects
631/67 ,45 ,analysis ,631/208/212 ,45/23 ,631/114 - Abstract
Funder: Ludwig Center at Harvard, Funder: National Cancer Institute: K22CA193848, Funder: US National Institutes of Health Intramural Research Program Project Z1AES103266, Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer.
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- 2021
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37. Additional file of The cost of reducing starting RNA quantity for Illumina BeadArrays: A bead-level dilution experiment
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Lynch, Andy G, Hadfield, James, Dunning, Mark J, Osborne, Michelle, Thorne, Natalie P, and Tavaré, Simon
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mental disorders - Abstract
Additional file of The cost of reducing starting RNA quantity for Illumina BeadArrays: A bead-level dilution experiment
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- 2021
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38. Additional file 1 of The cost of reducing starting RNA quantity for Illumina BeadArrays: A bead-level dilution experiment
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Lynch, Andy G, Hadfield, James, Dunning, Mark J, Osborne, Michelle, Thorne, Natalie P, and Tavaré, Simon
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Additional file 1: Supplementary material. File giving details of 1) Experimental Design: Array Layout, 2) Lab Methods: Obtaining bead-level data, 3) Lab Methods: Quality assessment metrics, 4) Lab Methods: Quality assessment - comparison with MAQC, 5) Lab Methods: Quality assessment - Association between starting RNA quantity and intensity, 6) Criteria for including bead-types, 7) Results: Detection, 8) Results: Negative controls, 9) Results: Differential expression but no expression, and 10) Results: Differential expression - detection of small changes. (PDF 475 KB)
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- 2021
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39. CamGFR v2: A New Model for Estimating the Glomerular Filtration Rate from Standardized or Non-standardized Creatinine in Patients with Cancer
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Williams, Edward H., primary, Flint, Thomas R., additional, Connell, Claire M., additional, Giglio, Daniel, additional, Lee, Hassal, additional, Ha, Taehoon, additional, Gablenz, Eva, additional, Bird, Nicholas J., additional, Weaver, James M.J., additional, Potts, Harry, additional, Whitley, Cameron T., additional, Bookman, Michael A., additional, Lynch, Andy G., additional, Meyer, Hannah V., additional, Tavaré, Simon, additional, and Janowitz, Tobias, additional
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- 2021
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40. The Role of Multidimensional Poverty in Antibiotic Misuse: A Study of Self-Medication and Non-Adherence in Kenya, Tanzania, and Uganda
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Green, Dominique L., primary, Keenan, Katherine, additional, Huque, Sarah I., additional, Kesby, Mike, additional, Mushi, Martha F., additional, Kansiime, Catherine, additional, Asiimwe, Benon, additional, Kiiru, John, additional, Mshana, Stephen E., additional, Neema, Stella, additional, Mwanga, Joseph R., additional, Fredricks, Kathryn J., additional, Lynch, Andy G., additional, Worthington, Hannah, additional, Olamijuwon, Emmanuel, additional, Ahad, Mary Abed Al, additional, Aduda, Annette, additional, Mmbaga, Blandina T., additional, Bazira, Joel, additional, Sandeman, Alison, additional, Stelling, John, additional, Gillespie, Stephen Henry, additional, Kibiki, Gibson, additional, Sabiti, Wilber, additional, Sloan, Derek J., additional, Holden, Matthew T. G., additional, and Consortium, HATUA, additional
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- 2021
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41. Publisher Correction:Whole-genome sequencing of a sporadic primary immunodeficiency cohort (Nature, (2020), 583, 7814, (90-95), 10.1038/s41586-020-2265-1)
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Thaventhiran, James E.D., Lango Allen, Hana, Burren, Oliver S., Rae, William, Greene, Daniel, Staples, Emily, Zhang, Zinan, Farmery, James H.R., Simeoni, Ilenia, Rivers, Elizabeth, Maimaris, Jesmeen, Penkett, Christopher J., Stephens, Jonathan, Deevi, Sri V.V., Sanchis-Juan, Alba, Gleadall, Nicholas S., Thomas, Moira J., Sargur, Ravishankar B., Gordins, Pavels, Baxendale, Helen E., Brown, Matthew, Tuijnenburg, Paul, Worth, Austen, Hanson, Steven, Linger, Rachel J., Buckland, Matthew S., Rayner-Matthews, Paula J., Gilmour, Kimberly C., Samarghitean, Crina, Seneviratne, Suranjith L., Sansom, David M., Lynch, Andy G., Megy, Karyn, Ellinghaus, Eva, Ellinghaus, David, Jorgensen, Silje F., Karlsen, Tom H., Stirrups, Kathleen E., Cutler, Antony J., Kumararatne, Dinakantha S., Chandra, Anita, Edgar, J. David M., Herwadkar, Archana, Cooper, Nichola, Grigoriadou, Sofia, Huissoon, Aarnoud P., Goddard, Sarah, Jolles, Stephen, Schuetz, Catharina, Boschann, Felix, Abbs, Stephen, Adhya, Zoe, Adlard, Julian, Afzal, Maryam, Ahmed, Irshad, Ahmed, Munaza, Ahmed, Saeed, Aitman, Timothy J., Alachkar, Hana, Alamelu, Jayanthi, Alikhan, Raza, Allen, Carl E., Allen, Louise, Allsup, David J., Alvi, Arif, Ambegaonkar, Gautam, Anantharachagan, Ariharan, Ancliff, Philip, Anderson, Julie, Antrobus, Richard, Armstrong, Ruth, Arno, Gavin, Arumugakani, Gururaj, Arya, Rita, Ashford, Sofie, Astle, William J., Attwood, Anthony, Austin, Steve, Aydinok, Yesim, Ayub, Waqar, Babbs, Christian, Bacchelli, Chiara, Baglin, Trevor, Bakchoul, Tamam, Bariana, Tadbir K., Barratt, Jonathan, Barwell, Julian, Baski, John, Bates, Rachel W., Batista, Joana, Baynam, Gareth, Bennett, David L., Bethune, Claire, Bhatnagar, Neha, Bibi, Shahnaz, Bierzynska, Agnieszka, Biss, Tina, Bitner-Glindzicz, Maria A.K., Bleda, Marta, Blesneac, Iulia, Boardman, Barbara, Boddana, Preetham, Bogaard, Harm J., Booth, Claire, Boyce, Sara, Bradley, John R., Brady, Angela, Breen, Gerome, Brennan, Paul, Brewer, Carole, Briley, Annette, Brown, Richard, Browning, Michael J., Brownlie, Mary, Bryson, Christine J., Buchan, Rachel J., Buck, Jackie, Bueser, Teofila, Diz, Carmen Bugarin, Burns, Siobhan O., Calleja, Paul, Carmichael, Jenny, Carr-White, Gerald, Carss, Keren J., Casey, Ruth, Chalmers, Elizabeth, Chambers, Jenny, Chambers, John, Chan, Melanie M.Y., Chan, Melissa V., Cheng, Floria, Chinn, Ivan K., Chinnery, Patrick F., Chitre, Manali, Chong, Sam, Christian, Martin T., Church, Colin, Clement, Emma M., Brod, Naomi Clements, Clifford, Hayley, Clowes, Virginia E., Coghlan, Gerry, Colby, Elizabeth, Cole, Trevor R.P., Collins, Janine H., Collins, Peter W., Condliffe, Robin, Cook, H. Terence, Cook, Stuart, Cookson, Victoria, Corris, Paul A., Creaser-Myers, Amanda, Crisp-Hihn, Abigail, Curry, Nicola S., Da Costa, Rosa, Danesino, Cesare, Daniels, Matthew J., Darby, Damaris, Daugherty, Louise C., Davies, E. G., Davies, Sophie, Davis, John, de Bree, Godelieve J., Deacock, Sarah, Deegan, Patrick B., Dempster, John, Dent, Timothy, Deshpande, Charu, Devlin, Lisa A., Dewhurst, Eleanor F., Dixit, Anand K., Dixon, Peter H., Doffinger, Rainer, Dolling, Helen, Dormand, Natalie, Downes, Kate, Drazyk, Anna M., Drewe, Elizabeth, Duarte, Daniel, Dutt, Tina, Edwards, Karen E., Egner, William, Ekani, Melanie N., El-Shanawany, Tariq, Elkhalifa, Shuayb, Elston, Tony, Emmerson, Ingrid, Erber, Wendy N., Erwood, Marie, Estiu, Maria C., Evans, Dafydd Gareth, Evans, Gillian, Everington, Tamara, Eyries, Mélanie, Favier, Remi, Firth, Helen V., Fitzpatrick, Maggie M., Fletcher, Debra, Flinter, Frances A., Fox, James C., Frary, Amy J., French, Courtney E., Freson, Kathleen, Frontini, Mattia, Furie, Bruce, Gale, Daniel P., Gall, Henning J., Gardham, Alice, Gaspar, H. Bobby, Gattens, Michael, Ghali, Neeti, Ghataorhe, Pavandeep K., Ghio, Stefano, Ghofrani, Hossein Ardeschir, Ghurye, Rohit, Gibbs, J. Simon R., Gilbert, Rodney D., Girerd, Barbara, Girling, Joanna C., Gissen, Paul, Gorman, Kathleen M., Gosal, David, Graf, Stefan, Grassi, Luigi, Greenhalgh, Alan J., Greenhalgh, Lynn, Greinacher, Andreas, Gresele, Paolo, Griffiths, Philip G., Griffiths, Sian, Grozeva, Detelina, Hackett, Scott J., Hadden, Robert D.M., Hadinnapola, Charaka, Hague, Rosie, Hague, William M., Haimel, Matthias, Hall, Matthew, Halmagyi, Csaba, Hammerton, Tracey, Hanson, Helen L., Harkness, Kirsty, Harper, Andrew R., Harper, Lorraine, Harris, Claire, Harrison, Claire, Hart, Daniel, Hassan, Ahamad, Hayman, Grant, Heemskerk, Johan W.M., Hegde, Shivaram, Henderson, Alex, Henderson, Robert H., Hensiek, Anke, Henskens, Yvonne M.C., Hodgson, Joshua, Hoffman, Jonathan, Holden, Simon, Holder, Muriel, Horvath, Rita, Houlden, Henry, Houweling, Arjan C., Howard, Luke S., Hu, Fengyuan, Hudson, Gavin, Hughes, Sean, Hughes, Stephen, Huis in ‘t Veld, Anna E., Humbert, Marc, Hurles, Matthew E., Hurst, Jane A., Irvine, Val, Izatt, Louise, James, Roger, Jeevaratnam, Praveen, Johnson, Mark, Johnson, Sally A., Jolley, Jennifer D., Jones, Bryony, Jones, Julie, Josifova, Dragana, Jurkute, Neringa, Karim, Yousuf M., Karoshi, Mahantesh A., Kasanicki, Mary A., Kazkaz, Hanadi, Kazmi, Rashid, Keeling, David, Kelleher, Peter, Kelly, Anne M., Kempster, Carly, Kennedy, Fiona, Kiani, Sorena, Kiely, David G., Kingston, Nathalie, Kinsey, Sally, Klein, Nigel, Klima, Robert, Knox, Ellen, Kostadima, Myrto A., Kovacs, Gabor, Koziell, Ania B., Kreuzhuber, Roman, Krishnakumar, Deepa, Kuijpers, Taco W., Kumar, Ajith, Kurian, Manju A., Laffan, James, Laffan, Michael A., Lalloo, Fiona, Lambert, Michele P., Lawman, Sarah H.A., Lawrie, Allan, Layton, D. Mark, Lear, Sara E., Lees, Melissa M., Lentaigne, Claire, Levine, Adam P., Lewington, Andrew J.P., Li, Wei, Liesner, Ri, Liu, Bin, Longhurst, Hilary, Lorenzo, Lorena E., Louka, Eleni, Hadeler, Silvia Lucato, Lyons, Paul A., Macdougall, Malcolm, Machado, Rajiv D., MacKenzie Ross, Robert V., Mackillop, Lucy H., MacLaren, Robert, Madan, Bella, Magee, Laura, Mahdi-Rogers, Mohamed, Maher, Eamonn R., Makris, Mike, Mangles, Sarah, Manson, Ania, Manzur, Adnan, Mapeta, Rutendo, Marchbank, Kevin J., Mark, Patrick B., Marks, Stephen, Markus, Hugh S., Marschall, Hanns Ulrich, Marshall, Andrew, Martin, Jennifer M., Masati, Larahmie, Mathias, Mary, Matser, Vera, Matthews, Emma L., Maw, Anna, Maxwell, Heather, McAlinden, Paul, McCarthy, Mark I., McDermott, Elizabeth M., McGowan, Simon J., McJannet, Coleen, McKinney, Harriet, Meacham, Stuart, Mead, Adam J., Castello, Ignacio Medina, Meehan, Sharon, Mehta, Sarju, Mercer, Catherine L., Michaelides, Michel, Michell, Anna C., Milford, David, Millar, Carolyn M., Millar, Hazel, Mistry, Anoop, Moenen, Floor, Moledina, Shahin, Montani, David, Moore, Anthony T., Moore, Jason, Morrell, Nicholas W., Morrisson, Valerie, Mozere, Monika, Muir, Keith W., Mumford, Andrew D., Murng, Sai H.K., Nasir, Iman, Nejentsev, Sergey, Newnham, Michael, Ng, Joanne, Ngoh, Adeline, Noorani, Sadia, Noori, Muna, Nurden, Paquita, O’Sullivan, Jennifer M., Obaji, Samya, Okoli, Steven, Oksenhendler, Eric, Olschewski, Andrea, Olschewski, Horst, Ong, Albert C.M., Ong, Kai Ren, Oram, Helen, Ormondroyd, Elizabeth, Othman, Shokri, Ouwehand, Willem H., Pantazis, Antonis, Papadia, Sofia, Papandreou, Apostolos, Park, Soo Mi, Parker, Alasdair P.J., Parry, David, Parsons, Georgina, Pasi, K. John, Paterson, Joan, Payne, Jeanette H., Peacock, Andrew J., Peerlinck, Kathelijne, Pepke-Zaba, Joanna, Perry, David, Petersen, Romina, Piechowski-Jozwiak, Bartlomiej, Pinto, Fernando, Polwarth, Gary J., Ponsford, Mark J., Prasad, Sanjay, Prokopenko, Inga, Psaila, Beth, Pyle, Angela, Qasim, Waseem, Quinn, Ellen, Quinti, Isabella, Raina, Sanjay, Ranganathan, Lavanya, Rankin, Julia, Rankin, Stuart, Rao, Anupama, Raymond, F. Lucy, Rehnstrom, Karola, Reid, Evan, Reilly, Mary M., Renton, Tara, Revel-Vilk, Shoshana, Rhodes, Christopher J., Rice, Andrew S.C., Richards, Emma E., Richards, Mike, Richardson, Sylvia, Richter, Alex, Robert, Leema, Roberts, Irene, Rondina, Matthew T., Rosser, Elisabeth, Rothwell, Peter, Roughley, Catherine, Roy, Noemi B., Rue-Albrecht, Kevin, Sadeghi-Alavijeh, Omid, Saleem, Moin A., Salmon, Richard M., Samani, Nilesh J., Sambrook, Jennifer G., Sandford, Richard, Santra, Saikat, Satchell, Simon C., Savic, Sinisa, Scelsi, Laura, Schotte, Gwen, Schulman, Sol, Schulze, Harald, Scott, Richard, Scully, Marie, Searle, Claire, Seeger, Werner, Sewell, W. A.Carrock, Seyres, Denis, Shackley, Fiona, Shamardina, Olga, Shapiro, Susan E., Sharma, Pankaj, Shehata, Hassan A., Shipley, Deborah, Shtoyerman, Rakefet, Sibson, Keith, Side, Lucy, Simpson, Michael, Sims, Matthew C., Sinha, Manish D., Sivapalaratnam, Suthesh, Skytte, Anne Bine, Smith, Kenneth G.C., Snape, Katie, Sneddon, Linda, Sohal, Aman, Soubrier, Florent, Southgate, Laura, Southwood, Mark, Splitt, Miranda, Staines, Simon, Stark, Hannah, Stauss, Hans, Steele, Cathal L., Stein, Daniel, Stein, Penelope E., Stock, Sophie, Stubbs, Matthew J., Suntharalingam, Jay, Swietlik, Emilia M., Symington, Emily, Tait, R. Campbell, Talks, Kate, Tan, Rhea Y.Y., Taylor, Gordon B., Thachil, Jecko, Themistocleous, Andreas C., Thomas, David C., Thomas, Ellen, Thomas, Patrick, Thompson, Dorothy A., Thomson, Kate, Thrasher, Adrian J., Thys, Chantal, Tilly, Tobias, Tischkowitz, Marc, Titterton, Catherine, Todd, John A., Toh, Cheng Hock, Tool, Anton T.J., Toshner, Mark R., Traylor, Matthew, Treacy, Carmen M., Treadaway, Paul, Trembath, Richard C., Trippier, Sarah, Tuna, Salih, Turek, Wojciech, Turro, Ernest, Upton, Paul D., Urniaz, Rafal, Vale, Tom, Van Geet, Chris, van Zuydam, Natalie, Vandersteen, Anthony M., Vazquez-Lopez, Marta, Veltman, Marijcke W.M., Vogt, Julie, von Ziegenweidt, Julie, Noordegraaf, Anton Vonk, Vora, Ajay, Vries, Minka J.A., Wakeling, Emma L., Walker, Neil, Walker, Suellen M., Walsh, Roddy, Wanjiku, Ivy, Ware, James S., Warner, Timothy Q., Wassmer, Evangeline, Watkins, Hugh, Watson, Henry G., Watt, Christopher, Waugh, Dean, Webb, Nick, Webster, Andrew R., Wei, Wei, Welch, Angela, Welch, Steven B., Werring, David, Wessels, Julie, Westbury, Sarah K., Westwood, John Paul W., Wharton, John, Whitehorn, Deborah, Whitworth, James, Wilkins, Martin R., Willcocks, Lisa, Williams, David J., Williamson, Catherine, Wong, Edwin K.S., Wood, Nicholas, Wood, Yvette, Woods, Christopher Geoffrey, Woodward, Emma R., Workman, Sarita, Wort, Stephen J., Yates, Katherine, Yeatman, Nigel, Yong, Patrick F.K., Young, Timothy, Yu, Ping, Yu-Wai-Man, Patrick, Zlamalova, Eliska, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, and ACS - Atherosclerosis & ischemic syndromes
- Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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- 2020
42. Whole-genome sequencing of a sporadic primary immunodeficiency cohort
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Thaventhiran, James E. D., Lango Allen, Hana, Burren, Oliver S., Rae, William, Greene, Daniel, Staples, Emily, Zhang, Zinan, Farmery, James H. R., Simeoni, Ilenia, Rivers, Elizabeth, Maimaris, Jesmeen, Penkett, Christopher J., Stephens, Jonathan, Deevi, Sri V. V., Sanchis-Juan, Alba, Gleadall, Nicholas S., Thomas, Moira J., Sargur, Ravishankar B., Gordins, Pavels, Baxendale, Helen E., Brown, Matthew, Tuijnenburg, Paul, Worth, Austen, Hanson, Steven, Linger, Rachel J., Buckland, Matthew S., Rayner-Matthews, Paula J., Gilmour, Kimberly C., Samarghitean, Crina, Seneviratne, Suranjith L., Sansom, David M., Lynch, Andy G., Megy, Karyn, Ellinghaus, Eva, Ellinghaus, David, Jorgensen, Silje F., Karlsen, Tom H., Stirrups, Kathleen E., Cutler, Antony J., Kumararatne, Dinakantha S., Chandra, Anita, Edgar, J. David M., Herwadkar, Archana, Cooper, Nichola, Grigoriadou, Sofia, Huissoon, Aarnoud P., Goddard, Sarah, Jolles, Stephen, Schuetz, Catharina, Boschann, Felix, Lyons, Paul A., Hurles, Matthew E., Savic, Sinisa, Burns, Siobhan O., Kuijpers, Taco W., Turro, Ernest, Ouwehand, Willem H., Thrasher, Adrian J., Smith, Kenneth G. C., Tait, R. Campbell, Chalmers, Elizabeth, Hague, Rosie, Maxwell, Heather, Peacock, Andrew J., Mark, Patrick B., and Muir, Keith W.
- Abstract
Primary immunodeficiency (PID) is characterized by recurrent and often life-threatening infections, autoimmunity and cancer, and it poses major diagnostic and therapeutic challenges. Although the most severe forms of PID are identified in early childhood, most patients present in adulthood, typically with no apparent family history and a variable clinical phenotype of widespread immune dysregulation: about 25% of patients have autoimmune disease, allergy is prevalent and up to 10% develop lymphoid malignancies1,2,3. Consequently, in sporadic (or non-familial) PID genetic diagnosis is difficult and the role of genetics is not well defined. Here we address these challenges by performing whole-genome sequencing in a large PID cohort of 1,318 participants. An analysis of the coding regions of the genome in 886 index cases of PID found that disease-causing mutations in known genes that are implicated in monogenic PID occurred in 10.3% of these patients, and a Bayesian approach (BeviMed4) identified multiple new candidate PID-associated genes, including IVNS1ABP. We also examined the noncoding genome, and found deletions in regulatory regions that contribute to disease causation. In addition, we used a genome-wide association study to identify loci that are associated with PID, and found evidence for the colocalization of—and interplay between—novel high-penetrance monogenic variants and common variants (at the PTPN2 and SOCS1 loci). This begins to explain the contribution of common variants to the variable penetrance and phenotypic complexity that are observed in PID. Thus, using a cohort-based whole-genome-sequencing approach in the diagnosis of PID can increase diagnostic yield and further our understanding of the key pathways that influence immune responsiveness in humans.
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- 2020
43. Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis
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Weaver, Jamie MJ, Ross-Innes, Caryn S, Shannon, Nicholas, Lynch, Andy G, Forshew, Tim, Barbera, Mariagnese, Murtaza, Muhammed, Ong, Chin-Ann J, Lao-Sirieix, Pierre, Dunning, Mark J, Smith, Laura, Smith, Mike L, Anderson, Charlotte L, Carvalho, Benilton, O'Donovan, Maria, Underwood, Timothy J, May, Andrew P, Grehan, Nicola, Hardwick, Richard, Davies, Jim, Oloumi, Arusha, Aparicio, Sam, Caldas, Carlos, Eldridge, Matthew D, Edwards, Paul AW, Rosenfeld, Nitzan, Tavaré, Simon, Fitzgerald, Rebecca C, OCCAMS Consortium, Lynch, Andy [0000-0002-7876-7338], Dunning, Mark [0000-0002-8853-9435], Caldas, Carlos [0000-0003-3547-1489], Eldridge, Matthew [0000-0002-5799-8911], Edwards, Paul [0000-0002-4789-3374], Rosenfeld, Nitzan [0000-0002-2825-4788], Fitzgerald, Rebecca [0000-0002-3434-3568], and Apollo - University of Cambridge Repository
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Cancer genome sequencing ,Adult ,Male ,Esophageal Neoplasms ,Carcinogenesis ,ICGC ,Biology ,Adenocarcinoma ,medicine.disease_cause ,Malignancy ,Somatic evolution in cancer ,Article ,Barrett Esophagus ,Genetics ,medicine ,Barrett’s esophagus ,Humans ,esophageal cancer ,Barretts esophagus ,Aged ,Aged, 80 and over ,whole genome sequencing ,Mutation ,Sequence Analysis, DNA ,Middle Aged ,medicine.disease ,digestive system diseases ,3. Good health ,Dysplasia ,Cancer research ,Female ,Precancerous Conditions ,Genome-Wide Association Study - Abstract
Cancer genome sequencing studies have identified numerous driver genes, but the relative timing of mutations in carcinogenesis remains unclear. The gradual progression from premalignant Barrett's esophagus to esophageal adenocarcinoma (EAC) provides an ideal model to study the ordering of somatic mutations. We identified recurrently mutated genes and assessed clonal structure using whole-genome sequencing and amplicon resequencing of 112 EACs. We next screened a cohort of 109 biopsies from 2 key transition points in the development of malignancy: benign metaplastic never-dysplastic Barrett's esophagus (NDBE; n=66) and high-grade dysplasia (HGD; n=43). Unexpectedly, the majority of recurrently mutated genes in EAC were also mutated in NDBE. Only TP53 and SMAD4 mutations occurred in a stage-specific manner, confined to HGD and EAC, respectively. Finally, we applied this knowledge to identify high-risk Barrett's esophagus in a new non-endoscopic test. In conclusion, mutations in EAC driver genes generally occur exceptionally early in disease development with profound implications for diagnostic and therapeutic strategies.
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- 2020
- Full Text
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44. High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations
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Zhang, Yiqun, Chen, Fengju, Fonseca, Nuno A., He, Yao, Fujita, Masashi, Nakagawa, Hidewaki, Zhang, Zemin, Brazma, Alvis, Creighton, Chad J., Amin, Samirkumar B., Awadalla, Philip, Bailey, Peter J., Brooks, Angela N., Calabrese, Claudia, Chateigner, Aurélien, Cortés-Ciriano, Isidro, Craft, Brian, Craft, David, Davidson, Natalie R., Demircioğlu, Deniz, Erkek, Serap, Frenkel-Morgenstern, Milana, Goldman, Mary J., Greger, Liliana, Göke, Jonathan, Hoadley, Katherine A., Hou, Yong, Huska, Matthew R., Kahles, Andre, Khurana, Ekta, Kilpinen, Helena, Korbel, Jan O., Lamaze, Fabien C., Lehmann, Kjong-Van, Li, Chang, Li, Siliang, Li, Xiaobo, Li, Xinyue, Liu, Dongbing, Liu, Fenglin, Liu, Xingmin, Marin, Maximillian G., Markowski, Julia, Meyerson, Matthew, Nandi, Tannistha, Nielsen, Morten Muhlig, Ojesina, Akinyemi I., Ouellette, B. F. Francis, Pan-Hammarström, Qiang, Park, Peter J., Pedamallu, Chandra Sekhar, Pedersen, Jakob Skou, Perry, Marc D., Rätsch, Gunnar, Schwarz, Roland F., Shiraishi, Yuichi, Siebert, Reiner, Soulette, Cameron M., Stark, Stefan G., Stegle, Oliver, Su, Hong, Tan, Patrick, Teh, Bin Tean, Urban, Lara, Wang, Jian, Waszak, Sebastian M., Wu, Kui, Xiang, Qian, Xiong, Heng, Yakneen, Sergei, Yang, Huanming, Ye, Chen, Yung, Christina K., Zhang, Fan, Zhang, Junjun, Zhang, Xiuqing, Zheng, Liangtao, Zhu, Jingchun, Zhu, Shida, Akdemir, Kadir C., Alvarez, Eva G., Baez-Ortega, Adrian, Beroukhim, Rameen, Boutros, Paul C., Bowtell, David D. L., Brors, Benedikt, Burns, Kathleen H., Campbell, Peter J., Chan, Kin, Chen, Ken, Dueso-Barroso, Ana, Dunford, Andrew J., Edwards, Paul A., Estivill, Xavier, Etemadmoghadam, Dariush, Feuerbach, Lars, Fink, J. Lynn, Garsed, Dale W., Gerstein, Mark, Gordenin, Dmitry A., Haan, David, Haber, James E., Hess, Julian M., Hutter, Barbara, Imielinski, Marcin, Jones, David T. W., Ju, Young Seok, Kazanov, Marat D., Klimczak, Leszek J., Koh, Youngil, Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Li, Yilong, Lynch, Andy G., Macintyre, Geoff, Markowetz, Florian, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Miyano, Satoru, Navarro, Fabio C. P., Ossowski, Stephan, Pearson, John V., Puiggròs, Montserrat, Rippe, Karsten, Roberts, Nicola D., Roberts, Steven A., Rodriguez-Martin, Bernardo, Schumacher, Steven E., Scully, Ralph, Shackleton, Mark, Sidiropoulos, Nikos, Sieverling, Lina, Stewart, Chip, Torrents, David, Tubio, Jose M. C., Villasante, Izar, Waddell, Nicola, Wala, Jeremiah A., Weischenfeldt, Joachim, Yang, Lixing, Yao, Xiaotong, Yoon, Sung-Soo, Zamora, Jorge, and Zhang, Cheng-Zhong
- Abstract
The impact of somatic structural variants (SVs) on gene expression in cancer is largely unknown. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data and RNA sequencing from a common set of 1220 cancer cases, we report hundreds of genes for which the presence within 100 kb of an SV breakpoint associates with altered expression. For the majority of these genes, expression increases rather than decreases with corresponding breakpoint events. Up-regulated cancer-associated genes impacted by this phenomenon include TERT, MDM2, CDK4, ERBB2, CD274, PDCD1LG2, and IGF2. TERT-associated breakpoints involve ~3% of cases, most frequently in liver biliary, melanoma, sarcoma, stomach, and kidney cancers. SVs associated with up-regulation of PD1 and PDL1 genes involve ~1% of non-amplified cases. For many genes, SVs are significantly associated with increased numbers or greater proximity of enhancer regulatory elements near the gene. DNA methylation near the promoter is often increased with nearby SV breakpoint, which may involve inactivation of repressor elements.
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- 2020
45. Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition
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Alvarez, Eva G., Baez-Ortega, Adrian, Zamora, Jorge, Supek, Fran, Demeulemeester, Jonas, Santamarina, Martin, Temes, Javier, Garcia-Souto, Daniel, Detering, Harald, Li, Yilong, Rodriguez-Castro, Jorge, Dueso-Barroso, Ana, Bruzos, Alicia L., Dentro, Stefan C., Blanco, Miguel G., Contino, Gianmarco, Ardeljan, Daniel, Tojo, Marta, Zumalave, Sonia, Edwards, Paul A. W., Puiggròs, Montserrat, Chong, Zechen, Lee, Eunjung Alice, Raine, Keiran, Butler, Adam, Waszak, Sebastian M., Schumacher, Steven E., Monlong, Jean, Maura, Francesco, Bolli, Niccolo, Bourque, Guillaume, Gerstein, Mark, Wedge, David C., Beroukhim, Rameen, Torrents, David, Martincorena, Inigo, Fitzgerald, Rebecca C., Van Loo, Peter, Kazazian, Haig H., Tubio, Jose M. C., Akdemir, Kadir C., Boutros, Paul C., Bowtell, David D. L., Brors, Benedikt, Burns, Kathleen H., Campbell, Peter J., Chan, Kin, Chen, Ken, Cortés-Ciriano, Isidro, Dunford, Andrew J., Edwards, Paul A., Estivill, Xavier, Etemadmoghadam, Dariush, Feuerbach, Lars, Fink, J. Lynn, Frenkel-Morgenstern, Milana, Garsed, Dale W., Gordenin, Dmitry A., Haan, David, Haber, James E., Hess, Julian M., Hutter, Barbara, Imielinski, Marcin, Jones, David T. W., Ju, Young Seok, Kazanov, Marat D., Klimczak, Leszek J., Koh, Youngil, Korbel, Jan O., Kumar, Kiran, Lee, Jake June-Koo, Lynch, Andy G., Macintyre, Geoff, Markowetz, Florian, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Meyerson, Matthew, Miyano, Satoru, Nakagawa, Hidewaki, Navarro, Fabio C. P., Ossowski, Stephan, Park, Peter J., Pearson, John V., Rippe, Karsten, Roberts, Nicola D., Roberts, Steven A., Rodriguez-Martin, Bernardo, Scully, Ralph, Shackleton, Mark, Sidiropoulos, Nikos, Sieverling, Lina, Stewart, Chip, Villasante, Izar, Waddell, Nicola, Wala, Jeremiah A., Weischenfeldt, Joachim, Yang, Lixing, Yao, Xiaotong, Yoon, Sung-Soo, Zhang, Cheng-Zhong, Rodriguez-Martin, Bernardo [0000-0003-4693-3140], Supek, Fran [0000-0002-7811-6711], Demeulemeester, Jonas [0000-0002-2660-2478], Ju, Young Seok [0000-0002-5514-4189], Temes, Javier [0000-0003-3370-4728], Garcia-Souto, Daniel [0000-0002-0997-8799], Blanco, Miguel G. [0000-0002-2883-7326], Ardeljan, Daniel [0000-0002-5593-421X], Roberts, Nicola D. [0000-0002-0469-1043], Zumalave, Sonia [0000-0002-2108-1861], Edwards, Paul A. W. [0000-0002-4789-3374], Weischenfeldt, Joachim [0000-0002-3917-5524], Chen, Ken [0000-0003-4013-5279], Wala, Jeremiah A. [0000-0001-6591-1620], Raine, Keiran [0000-0002-5634-1539], Waszak, Sebastian M. [0000-0003-3042-9521], Navarro, Fabio C. P. [0000-0002-5640-9070], Monlong, Jean [0000-0002-9737-5516], Bourque, Guillaume [0000-0002-3933-9656], Park, Peter J. [0000-0001-9378-960X], Korbel, Jan O. [0000-0002-2798-3794], Fitzgerald, Rebecca C. [0000-0002-3434-3568], Van Loo, Peter [0000-0003-0292-1949], Burns, Kathleen H. [0000-0003-1620-3761], Campbell, Peter J. [0000-0002-3921-0510], Tubio, Jose M. C. [0000-0003-3540-2459], and Apollo - University of Cambridge Repository
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692/699/67 ,45 ,631/208/212 ,article ,45/23 ,humanities - Abstract
Funder: Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia (Ministry of Culture, Education and University Planning, Government of Galicia); doi: https://doi.org/10.13039/501100008425, Funder: Ministerio de Educación, Cultura y Deporte (Ministry of Education, Culture and Sports, Spain); doi: https://doi.org/10.13039/501100003176, Funder: EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council); doi: https://doi.org/10.13039/100010663, Funder: Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness); doi: https://doi.org/10.13039/501100003329, Funder: Korea Health Industry Development Institute (KHIDI); doi: https://doi.org/10.13039/501100003710, Funder: Danish Medical Research Council, Funder: NIH, Funder: Associazione Italiana Contro le Leucemie-Linfomi e Mieloma, Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289, About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage–fusion–bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors.
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- 2020
46. Genomic footprints of activated telomere maintenance mechanisms in cancer
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Hong, Chen, Koser, Sandra D., Ginsbach, Philip, Kleinheinz, Kortine, Braun, Delia M., Xi, Ruibin, Kabbe, Rolf, Eils, Roland, Schlesner, Matthias, Brors, Benedikt, Jones, David T. W., Akdemir, Kadir C., Alvarez, Eva G., Baez-Ortega, Adrian, Beroukhim, Rameen, Boutros, Paul C., Bowtell, David D. L., Burns, Kathleen H., Campbell, Peter J., Chan, Kin, Chen, Ken, Cortés-Ciriano, Isidro, Dueso-Barroso, Ana, Dunford, Andrew J., Edwards, Paul A., Estivill, Xavier, Etemadmoghadam, Dariush, Feuerbach, Lars, Fink, J. Lynn, Frenkel-Morgenstern, Milana, Garsed, Dale W., Gerstein, Mark, Gordenin, Dmitry A., Haan, David, Haber, James E., Hess, Julian M., Hutter, Barbara, Imielinski, Marcin, Ju, Young Seok, Kazanov, Marat D., Klimczak, Leszek J., Koh, Youngil, Korbel, Jan O., Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Li, Yilong, Lynch, Andy G., Macintyre, Geoff, Markowetz, Florian, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Meyerson, Matthew, Miyano, Satoru, Nakagawa, Hidewaki, Navarro, Fabio C. P., Ossowski, Stephan, Park, Peter J., Pearson, John V., Puiggròs, Montserrat, Rippe, Karsten, Roberts, Nicola D., Roberts, Steven A., Rodriguez-Martin, Bernardo, Schumacher, Steven E., Scully, Ralph, Shackleton, Mark, Sidiropoulos, Nikos, Sieverling, Lina, Stewart, Chip, Torrents, David, Tubio, Jose M. C., Villasante, Izar, Waddell, Nicola, Wala, Jeremiah A., Weischenfeldt, Joachim, Yang, Lixing, Yao, Xiaotong, Yoon, Sung-Soo, Zamora, Jorge, Zhang, Cheng-Zhong, Sieverling, Lina [0000-0002-0595-4976], Hong, Chen [0000-0003-1244-3506], Hutter, Barbara [0000-0002-9034-0329], Braun, Delia M. [0000-0002-6059-7588], Cortés-Ciriano, Isidro [0000-0002-2036-494X], Xi, Ruibin [0000-0001-7545-7361], Park, Peter J. [0000-0001-9378-960X], Schlesner, Matthias [0000-0002-5896-4086], Rippe, Karsten [0000-0001-9951-9395], and Apollo - University of Cambridge Repository
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45 ,article ,631/67/69 ,631/114 ,692/4028/67 - Abstract
Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer.
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- 2020
47. Multicentre validation of the CamGFR model for estimated glomerular filtration rate
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Williams, Edward H., Connell, Claire M., Weaver, James M.J., Beh, Ian, Potts, Harry, Whitley, Cameron T., Bird, Nicholas, Al-Sayed, Tamer, Monaghan, Phillip, Fehr, Martin, Cathomas, Richard, Bertelli, Gianfilippo, Quinton, Amy, Lewis, Paul, Shamash, Jonathan, Wilson, Peter, Dooley, Michael, Poole, Susan, Mark, Patrick B., Bookman, Michael A., Earl, Helena, Jodrell, Duncan, Tavaré, Simon, Lynch, Andy G., and Janowitz, Tobias
- Abstract
Important oncological management decisions rely on kidney function assessed by serum creatinine-based estimated glomerular filtration rate (eGFR). However, no large-scale multicentre comparison of methods to determine eGFR in patients with cancer are available.\ud \ud To compare the performance of formulas for eGFR based on routine clinical parameters and serum creatinine not calibrated with isotope dilution mass spectrometry (non-IDMS), we studied 3,620 patients with cancer and 166 without cancer who had their GFR measured with an exogenous nuclear tracer at one of seven clinical centres. The mean measured GFR was 86 ml/min. Accuracy of all models was centre-dependent, reflecting inter-centre variability of non-IDMS creatinine measurements. CamGFR was the most accurate model for eGFR (root-mean-squared-error (RMSE) 17.3 ml/min) followed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) model (RMSE 18.2 ml/min).
- Published
- 2019
48. Statistical Aspects of ChIP-Seq Analysis
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Cairns, Jonathan, primary, Lynch, Andy G., additional, and Tavaré, Simon, additional
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- 2013
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49. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups
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Curtis, Christina, Shah, Sohrab P., Chin, Suet-Feung, Turashvili, Gulisa, Rueda, Oscar M., Dunning, Mark J., Speed, Doug, Lynch, Andy G., Samarajiwa, Shamith, Yuan, Yinyin, Gräf, Stefan, Ha, Gavin, Haffari, Gholamreza, Bashashati, Ali, Russell, Roslin, McKinney, Steven, Aparicio, Samuel, Brenton, James D., Ellis, Ian, Huntsman, David, Pinder, Sarah, Purushotham, Arnie, Murphy, Leigh, Caldas, Carlos, Bardwell, Helen, Ding, Zhihao, Jones, Linda, Liu, Bin, Papatheodorou, Irene, Sammut, Stephen J., Wishart, Gordon, Chia, Steven, Gelmon, Karen, Speers, Caroline, Watson, Peter, Blamey, Roger, Green, Andrew, Macmillan, Douglas, Rakha, Emad, Gillett, Cheryl, Grigoriadis, Anita, de Rinaldis, Emanuele, Tutt, Andy, Parisien, Michelle, Troup, Sandra, Chan, Derek, Fielding, Claire, Maia, Ana-Teresa, McGuire, Sarah, Osborne, Michelle, Sayalero, Sara M., Spiteri, Inmaculada, Hadfield, James, Bell, Lynda, Chow, Katie, Gale, Nadia, Kovalik, Maria, Ng, Ying, Prentice, Leah, Tavaré, Simon, Markowetz, Florian, Langerød, Anita, Provenzano, Elena, and Børresen-Dale, Anne-Lise
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- 2012
- Full Text
- View/download PDF
50. BayesPeak—an R package for analysing ChIP-seq data
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Cairns, Jonathan, Spyrou, Christiana, Stark, Rory, Smith, Mike L., Lynch, Andy G., and Tavaré, Simon
- Published
- 2011
- Full Text
- View/download PDF
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