Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiationстатья из журнала
Аннотация: Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation.
Год издания: 2018
Авторы: Tathiane M. Malta, Artem Sokolov, Andrew J. Gentles, Tomasz Burzykowski, Laila Poisson, John N. Weinstein, Bożena Kamińska, Joerg Huelsken, Larsson Omberg, Olivier Gevaert, Antonio Colaprico, Patrycja Czerwińska, Sylwia Mazurek, Lopa Mishra, Holger Heyn, A. Krasnitz, Andrew K. Godwin, Alexander J. Lazar, Joshua M. Stuart, Katherine A. Hoadley, Peter W. Laird, Houtan Noushmehr, Maciej Wiznerowicz, Rory Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, 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, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Thomas J. Giordano, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael B. 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, Michael T. Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Galen F. Gao, Benjamin 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 E. 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, Peter J. Park, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert A. Holt, Steven J.M. Jones, L. Sylvia, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, Lewis R. Roberts, 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, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Huihui Fan, Katherine A. Hoadley, Alan P. Hoyle, Joshua M. Stuart, 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, Kyle R. Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Hai Hu, Viktoriya Korchina, Charles Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna M. Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Xi Liu, Fengmei Zhao, Julian M. Hess, Elizabeth L. Appelbaum, Matthew H. Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, 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 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 K. Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, 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 Voronina, Laurence Desjardins, Odette Mariani, Sergio Román-Román, 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 M. 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, 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 R. 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 J. 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 M. Petersen, Florencia G. Que, Michael Rivera, Lewis R. Roberts, Robert C. Smallridge, Thomas C. Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Hui Shen, 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 C. Thompson, Patricia Troncoso, Anne S. Tsao, Ignacio I. Wistuba, Candace Carter, Lauren E. Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina V. Long, Graham J. Mann, Michael C. 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 Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, J. M. 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 G. Bartlett, Jay Engel, Sebastién 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, Cecilia Williams, Quaid Morris, Jeffrey A. Borgia, Jun Li, 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 L. 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 N. Moore, Katherine Moxley, Russel Postier, Joan L. Walker, Rosemary E. Zuna, Michaël 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, Robert I. Haddad, 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
Издательство: Cell Press
Источник: Cell
Ключевые слова: Cancer Genomics and Diagnostics, Single-cell and spatial transcriptomics, Ferroptosis and cancer prognosis
Другие ссылки: Cell (HTML)
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Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (PDF)
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Data Archiving and Networked Services (DANS) (PDF)
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Infoscience (Ecole Polytechnique Fédérale de Lausanne) (HTML)
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Infoscience (Ecole Polytechnique Fédérale de Lausanne) (PDF)
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Том: 173
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Страницы: 338–354.e15