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Scalable Open Science Approach for Mutation Calling of Tumor Exomes Using Multiple Genomic Pipelines
Kyle Ellrott, Matthew H. Bailey, Gordon Saksena, Kyle R. Covington, Cyriac Kandoth, Chip Stewart, Julian M. Hess, Singer Ma, Kami Chiotti, Michael D. McLellan, Heidi J. Sofia, Carolyn Hutter, Gad Getz, David A. Wheeler, Li Ding, Rory Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy Defreitas, Scott Frazer, Nils Gehlenborg, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Michael S. Noble, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael I. Miller, Sheila M. Reynolds, Ilya Shmulevich, Vésteinn Thórsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michaël Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Galen F. Gao, Benjamin E. Gross, Zachary Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah Phillips, Ed Reznik, Francisco Sánchez-Vega, Chris Sander, Nikolaus Schultz, Robert P. Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul T. Spellman, Christopher C. Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert A. Holt, Steven J.M. Jones, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Andrew D. Cherniack, Carrie Cibulskis, Stacey Gabriel, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju Kucherlapati, Stephen B. Baylin, Leslie Cope, Ludmila Danilova, Phillip H. Lai, Dennis T. Maglinte, David Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Katherine A. Hoadley, Alan P. Hoyle, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Chad J. Creighton, Huyen N. Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Hai Hu, Viktoriya Korchina, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna M. Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, Liu Xi, Fengmei Zhao, Elizabeth L. Appelbaum, Matthew G. Cordes, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Elaine R. Mardis, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark E. Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier‐Foster, Mark Gerken, Kristen Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall M. Corcoran, Tony Costello, Christopher M. Hovens, André Lopes Carvalho, Ana Carolina de Carvalho, José Humberto Tavares Guerreiro Fregnani, Adhemar Longatto‐Filho, Rui Manuel Reis, Cristovam Scapulatempo‐Neto, Henrique C.S. Silveira, Daniel Onofre Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David G. Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Shabunin Av, Mikhail Tavobilov, Christopher McPherson, Ronald E. Warnick, Ross S. Berkowitz, Daniel Cramer, Colleen M. Feltmate, Neil S. Horowitz, Adam S. Kibel, Michael G. Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz‐Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino Maria De Rose, Felice Giuliante, Marc T. Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Leonid Kvecher, Caroline Larson, Richard Mural, Stella Somiari, Aleš Vícha, Tomáš Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John A. Chabot, Hanina Hibshoosh, Antonia R. Sepulveda, Tao Su, Timothy C. Wang, Olga Potapova, Olga L. Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman‐Roman, Xavier Sastre, Marc‐Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell D. Bigner, Eric Lipp, Jeffrey R. Marks, Shannon J. McCall, Roger E. McLendon, Angeles Alvarez Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith A. Delman, Seth Force, Fadlo R. Khuri, Kelly R. Magliocca, Shishir K. Maithel, Jeffrey J. Olson, Taofeek K. Owonikoko, Alan Pickens, Suresh Ramalingam, Dong Min Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert H. J. Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, J. C. Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Robert Stoehr, Helge Täubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Wung Chung, W. Jeffrey Edenfield, Julie Martin, Éric Baudin, Glenn J. Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven N. Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elı́as Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bùi Đức Phú, Yufang Tang, Howard Colman, Kimberley Evason, Peter Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave S.�B. Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh J. Borad, Alan H. Bryce, Erik P. Castle, Vishal S. Chandan, John C. Cheville, John A. Copland, Michael B. Farnell, Thomas J. Flotte, Nasra H. Giama, Thai H. Ho, Michael L. Kendrick, Jean‐Pierre Kocher, Karla Kopp, Catherine D. Moser, David M. Nagorney, Daniel R. O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia G. Que, Michael Rivera, Lewis R. Roberts, Robert C. Smallridge, Thomas C. Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell R. Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Charles Guo, Alexander J. Lazar, Christopher J. Logothetis, Funda Meric‐Bernstam, César A. Moran, Lois M. Ramondetta, David Rice, Anil K. Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne S. Tsao, Ignacio Wistuba, Candace Carter, Lauren E. Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina V. Long, Graham J. Mann, Michael Quinn, Robyn P.M. Saw, Richard A. Scolyer, Kerwin F. Shannon, Andrew J. Spillane, Jonathan R. Stretch, Maria Synott, John F. Thompson, James S. Wilmott, Hikmat Al‐Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor E. Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer R. Smith, Howard Zaren, Joong‐Won Park, Nguyễn Phi Hùng, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacák, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey I. Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John M.S. Bartlett, Jay Engel, Sébastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter J. Urba, Nicholas K. Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gian Luca Grazi, Mirella Marino, Roberta Merola, Ronald R. de Krijger, Anne‐Paule Gimenez‐Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kıvanç Birsoy, Gene H. Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Quaid Morris, Jeffrey A. Borgia, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl‐Friedrich Becker, Klaus‐Peter Janssen, Julia Slotta‐Huspenina, Mohamed H. Abdel‐Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James C. Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul E. Wakely, Paul Hansen, Ronald M. Lechan, James Powers, Arthur S. Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima P. Porten, Jens Waldmann, Martin Faßnacht, L. Sylvia, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark A. Nelson, Oliver F. Bathe, Peter R. Carroll, June M. Chan, Philip J. DiSaia, Pat Glenn, Robin Kate Kelley, Charles N. Landen, Joanna Phillips, Michael D. Prados, Jeffry Simko, Karen Smith‐McCune, Scott Vandenberg, Kevin K. Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis A. Carey, Ian Forgie, Massimo Mannelli, Michael E. Carney, Brenda Hernandez, Benito Campos, Christel Herold‐Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David G. Beer, Thomas J. Giordano, Anne‐Marie Mes‐Masson, Fred Saad, Thèrése Bocklage, Lisa M. Landrum, Robert S. Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan L. Walker, Rosemary E. Zuna, Michael B. Feldman, Federico Valdivieso, Rajiv Dhir, James D. Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, José Sebastião dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Pretti da Cunha Tirapelli, James W.F. Catto, Kathy Agnew, Elizabeth M. Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol R. Bradford, Thomas E. Carey, Jeffey Moyer, Lisa A. Peterson, Mark E. Prince, Laura S. Rozek, Gregory T. Wolf, Rayleen Bowman, Kwun M. Fong, Ian A. Yang, Robert J. Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John F. DiPersio, Bettina F. Drake, Ramaswamy Govindan, Sharon E. Heath, Timothy J. Ley, Brian A. Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, Armaz Mariamidze
Bibliographic record
VenueCell Systems · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsnot available
FundersNational Cancer InstituteNational Institutes of HealthBC Cancer FoundationInstituto Tecnológico de Costa RicaBroad InstituteUniversity of California, Santa CruzNational Human Genome Research InstituteMemorial Sloan-Kettering Cancer CenterNational Cancer Institute, Cairo UniversityVan Andel Research InstituteCancer Prevention and Research Institute of Texas
KeywordsGenomicsExome sequencingExomeComputational biologyComputer scienceScalabilityMetagenomicsGenomeDNA sequencingBiologyMutationData miningGeneticsDatabaseGene
Abstract
The Cancer Genome Atlas (TCGA) cancer genomics dataset includes over 10,000 tumor-normal exome pairs across 33 different cancer types, in total >400 TB of raw data files requiring analysis. Here we describe the Multi-Center Mutation Calling in Multiple Cancers project, our effort to generate a comprehensive encyclopedia of somatic mutation calls for the TCGA data to enable robust cross-tumor-type analyses. Our approach accounts for variance and batch effects introduced by the rapid advancement of DNA extraction, hybridization-capture, sequencing, and analysis methods over time. We present best practices for applying an ensemble of seven mutation-calling algorithms with scoring and artifact filtering. The dataset created by this analysis includes 3.5 million somatic variants and forms the basis for PanCan Atlas papers. The results have been made available to the research community along with the methods used to generate them. This project is the result of collaboration from a number of institutes and demonstrates how team science drives extremely large genomics projects.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
metaresearch head score (Codex)0.008
metaresearch head score (Gemma)0.017
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesOpen science
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.995
Threshold uncertainty score0.040
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.008 | 0.017 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.004 | 0.004 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.004 | 0.004 |
| Open science | 0.005 | 0.008 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
Opus teacher head0.032
GPT teacher head0.281
Teacher spread0.249 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
Study designSimulation or modeling
Domainnot available
GenreMethods
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".
Quick stats
Citations942
Published2018
Admission routes1
Has abstractyes