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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation
Cell, Volume 173, No. 2, Year 2018
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Description
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. Stemness features extracted from transcriptomic and epigenetic data from TCGA tumors reveal novel biological and clinical insight, as well as potential drug targets for anti-cancer therapies. © 2018 The Authors
Authors & Co-Authors
Sokolov, Artem
United States, Boston
Harvard Medical School
Burzykowski, Tomasz
Belgium, Hasselt
Universiteit Hasselt
Omberg, Larsson
United States, Seattle
Sage Bionetworks
Gevaert, A. Olivier
United States, Palo Alto
Stanford University
Godwin, Andrew K.
United States, Kansas City
University of Kansas Medical Center
Lazar, A. J.
United States, Houston
The University of Texas Md Anderson Cancer Center
Caesar-Johnson, Samantha J.
Unknown Affiliation
Demchok, John A.
Unknown Affiliation
Felau, Ina
Unknown Affiliation
Kasapi, Melpomeni
Unknown Affiliation
Ferguson, Martin L.
Unknown Affiliation
Hutter, Carolyn M.
Unknown Affiliation
Sofia, Heidi J.
Unknown Affiliation
Tarnuzzer, Roy W.
Unknown Affiliation
Zenklusen, Jean Claude
Unknown Affiliation
Chudamani, Sudha
Unknown Affiliation
Liu, Jia
Unknown Affiliation
Lolla, Laxmi
Unknown Affiliation
Naresh, Rashi
Unknown Affiliation
Pihl, Todd D.
Unknown Affiliation
Sun, Qiang
Unknown Affiliation
Wan, Yunhu
Unknown Affiliation
Wu, Ye
Unknown Affiliation
Cho, Juok
Unknown Affiliation
DeFreitas, Timothy
Unknown Affiliation
Frazer, Scott
Unknown Affiliation
Gehlenborg, Nils
Unknown Affiliation
Getz, Gad A.
Unknown Affiliation
Heiman, David I.
Unknown Affiliation
Kim, Jaegil
Unknown Affiliation
Lawrence, Michael S.
Unknown Affiliation
Lin, Pei
Unknown Affiliation
Meier, Samuel R.
Unknown Affiliation
Noble, Michael S.
Unknown Affiliation
Saksena, Gordon
Unknown Affiliation
Voet, Doug
Unknown Affiliation
Zhang, Hailei
Unknown Affiliation
Bernard, Brady M.
Unknown Affiliation
Chambwe, Nyasha
Unknown Affiliation
Dhankani, Varsha
Unknown Affiliation
Knijnenburg, Theo A.
Unknown Affiliation
Kramer, Roger W.
Unknown Affiliation
Leinonen, Kalle
Unknown Affiliation
Liu, Yuexin
Unknown Affiliation
Miller, Michael B.
Unknown Affiliation
Reynolds, Sheila M.
Unknown Affiliation
Shmulevich, Ilya
Unknown Affiliation
Thorsson, Vesteinn
Unknown Affiliation
Zhang, Wei
Unknown Affiliation
Akbani, Rehan
Unknown Affiliation
Broom, Bradley M.
Unknown Affiliation
Hegde, Apurva M.
Unknown Affiliation
Ju, Zhenlin
Unknown Affiliation
Kanchi, Rupa S.
Unknown Affiliation
Korkut, Anil
Unknown Affiliation
Li, Jun
Unknown Affiliation
Liang, Han
Unknown Affiliation
Ling, Shiyun
Unknown Affiliation
Liu, Wenbin
Unknown Affiliation
Lu, Yiling
Unknown Affiliation
Mills, Gordon B.
Unknown Affiliation
Ng, Kwokshing
Unknown Affiliation
Rao, Arvind U.K.
Unknown Affiliation
Ryan, Michael C.
Unknown Affiliation
Wang, Jing
Unknown Affiliation
Armenia, Joshua
Unknown Affiliation
Chatila, Walid K.
Unknown Affiliation
de Bruijn, Ino
Unknown Affiliation
Schultz, Nikolaus D.
Unknown Affiliation
Yau, Christina
Unknown Affiliation
Parker, Joel S.
Unknown Affiliation
Wilkerson, Matthew D.
Unknown Affiliation
Bowlby, Reanne
Unknown Affiliation
Brooks, Denise B.
Unknown Affiliation
Jones, Steven J.M.
Unknown Affiliation
Ma, Yussanne P.
Unknown Affiliation
Marra, Marco A.
Unknown Affiliation
Moore, Richard A.
Unknown Affiliation
Mungall, Andrew J.
Unknown Affiliation
Mungall, Karen L.
Unknown Affiliation
Robertson, Andrew Gordon
Unknown Affiliation
Schein, Jacqueline E.
Unknown Affiliation
Berger, Ashton C.
Unknown Affiliation
Beroukhim, Rameen
Unknown Affiliation
Gabriel, Stacey Bolk
Unknown Affiliation
Ha, Gavin
Unknown Affiliation
Schumacher, Steven E.
Unknown Affiliation
Xu, Jian M.
Unknown Affiliation
van den Berg, David J.
Unknown Affiliation
Hoadley, Katherine A.
United States, Chapel Hill
The University of North Carolina at Chapel Hill
United States, Grand Rapids
Van Andel Research Institute
Jones, Corbin D.
Unknown Affiliation
Roach, Jeffrey M.
Unknown Affiliation
Fan, Huihui
Unknown Affiliation
Laird, Peter W.
Unknown Affiliation
Shen, Hui
Unknown Affiliation
Chang, Kyle
Unknown Affiliation
Creighton, Chad J.
Unknown Affiliation
Dinh, Huyen H.
Unknown Affiliation
Doddapaneni, Harshavardhan
Unknown Affiliation
Drummond, Jennifer A.
Unknown Affiliation
Gibbs, Richard A.L.
Unknown Affiliation
Hale, Walker
Unknown Affiliation
Han, Yi
Unknown Affiliation
Korchina, Viktoriya
Unknown Affiliation
Lee, Sandra L.
Unknown Affiliation
Lewis, Lora R.
Unknown Affiliation
Li, Wei
Unknown Affiliation
Morgan, Margaret B.
Unknown Affiliation
Muzny, Donna Marie
Unknown Affiliation
Wang, Linghua
Unknown Affiliation
Wheeler, David A.
Unknown Affiliation
Fronick, Catrina C.
Unknown Affiliation
Fulton, Robert S.
Unknown Affiliation
Mardis, Elaine R.
Unknown Affiliation
Wilson, Richard K.
Unknown Affiliation
Paulauskis, Joseph D.
Unknown Affiliation
Bowen, Jay
Unknown Affiliation
Gastier-Foster, Julie M.
Unknown Affiliation
Lichtenberg, Tara M.
Unknown Affiliation
Ramirez, Nilsa C.
Unknown Affiliation
Zmuda, Erik J.
Unknown Affiliation
Corcoran, Niall M.
Unknown Affiliation
Hovens, Christopher M.
Unknown Affiliation
Carvalho, André Lopes
Unknown Affiliation
Humberto Fregnani, Jose
Unknown Affiliation
Longatto-Filho, Adhemar
Unknown Affiliation
Reis, Rui Manuel Vieira
Unknown Affiliation
Castro, Patricia D.
Unknown Affiliation
Ittmann, Michael M.
Unknown Affiliation
Huntsman, David G.
Unknown Affiliation
Warnick, Ronald E.
Unknown Affiliation
Cramer, Daniel William
Unknown Affiliation
Kibel, Adam S.
Unknown Affiliation
Barnholtz-Sloan, Jill S.
Unknown Affiliation
De Rose, Agostino Maria
Unknown Affiliation
Giuliante, Felice
Unknown Affiliation
Goodman, Marc T.
Unknown Affiliation
Karlan, Beth Y.
Unknown Affiliation
Somiari, Stella B.
Unknown Affiliation
Lacombe, Louis
Unknown Affiliation
Chabot, John A.
Unknown Affiliation
Desjardins, Laurence C.
Unknown Affiliation
Sastre-Garau, Xavier X.
Unknown Affiliation
Stern, Marc Henri
Unknown Affiliation
Signoretti, Sabina
Unknown Affiliation
Berchuck, Andrew
Unknown Affiliation
Brat, Daniel J.
Unknown Affiliation
Delman, Keith A.
Unknown Affiliation
Khuri, Fadlo R.
Unknown Affiliation
Magliocca, Kelly R.
Unknown Affiliation
Owonikoko, Taofeek Kunle
Unknown Affiliation
Ramalingam, Suresh S.
Unknown Affiliation
Shin, Dongmoon
Unknown Affiliation
Looijenga, Leendert H.J.
Unknown Affiliation
Oosterhuis, Wolter J.W.
Unknown Affiliation
Chen, Chu
Unknown Affiliation
Houck, John
Unknown Affiliation
Hartmann, Arndt
Unknown Affiliation
Stoehr, Robert
Unknown Affiliation
Wullich, Bernd
Unknown Affiliation
Noushmehr, Houtan
United States, Detroit
Henry Ford Health System
Brazil, Sao Paulo
Universidade de São Paulo
Poland, Poznan
Poznan University of Medical Sciences
Girard, Nicolas
Unknown Affiliation
Campo, Elías
Unknown Affiliation
Colman, Howard
Unknown Affiliation
Martignetti, John A.
Unknown Affiliation
Gabra, H.
Unknown Affiliation
Akeredolu, Teniola
Unknown Affiliation
Birrer, Michael J.
Unknown Affiliation
Borad, Mitesh J.
Unknown Affiliation
Copland, John A.
Unknown Affiliation
Ho, Thai Huu
Unknown Affiliation
Patel, Tushar P.
Unknown Affiliation
Olson, Gloria Moy
Unknown Affiliation
Roberts, Lewis Rowland
Unknown Affiliation
Smallridge, Robert C.
Unknown Affiliation
Torbenson, Michael S.
Unknown Affiliation
Yang, Ju Dong
Unknown Affiliation
Brimo, Fadi
Unknown Affiliation
Fujimoto, Jyunya
Unknown Affiliation
Logothetis, Christopher J.
Unknown Affiliation
Meric-Bernstam, Funda
Unknown Affiliation
Moran, César A.
Unknown Affiliation
Rimner, Andreas C.
Unknown Affiliation
Sood, Anil K.
Unknown Affiliation
Tamboli, Pheroze
Unknown Affiliation
Tsao, Anne S.
Unknown Affiliation
Wistuba, Ignacio Ivans
Unknown Affiliation
Lee, Kenneth K.W.
Unknown Affiliation
Long, Georgina V.
Unknown Affiliation
Scolyer, Richard A.
Unknown Affiliation
Spillane, Andrew John
Unknown Affiliation
Wilmott, James S.
Unknown Affiliation
Chan, Timothy A.
Unknown Affiliation
Levine, Douglas A.
Unknown Affiliation
Smith, Jennifer Anne
Unknown Affiliation
Kebebew, Electron K.
Unknown Affiliation
Linehan, W. Marston
Unknown Affiliation
Pacak, Karel
Unknown Affiliation
Pinto, Peter A.
Unknown Affiliation
Schiffman, Mark H.
Unknown Affiliation
Wentzensen, Nicolas A.
Unknown Affiliation
Pass, Harvey Ira
Unknown Affiliation
Bartlett, John M.S.
Unknown Affiliation
Gilbert, Sebastien
Unknown Affiliation
Sekhon, Harman S.
Unknown Affiliation
Hayward, Nicholas K.
Unknown Affiliation
Marino, Mirella
Unknown Affiliation
Gimenez-Roqueplo, Anne Paule
Unknown Affiliation
Birsoy, Kivanç
Unknown Affiliation
Barnett, Gene H.
Unknown Affiliation
Brewer, Cathy J.
Unknown Affiliation
Farver, Carol F.
Unknown Affiliation
Pennell, Nathan A.
Unknown Affiliation
Morrison, Carl D.
Unknown Affiliation
Manikhas, Georgiy Moiseevich
Unknown Affiliation
Alvaro, Domenico
Unknown Affiliation
Dubina, Michael V.
Unknown Affiliation
Dhanasekaran, Renumathy
Unknown Affiliation
Slotta-Huspenina, Julia B.
Unknown Affiliation
Abdel-Rahman, Mohamed H.
Unknown Affiliation
Cebulla, Colleen M.
Unknown Affiliation
Pilarski, Robert T.
Unknown Affiliation
Rai, Karan
Unknown Affiliation
Schoenfield, Lynn R.
Unknown Affiliation
Grizzle, William E.
Unknown Affiliation
Porten, Sima P.
Unknown Affiliation
Asa, Sylvia L.
Unknown Affiliation
Schadendorf, Dirk
Unknown Affiliation
Graefen, Markus
Unknown Affiliation
Huland, Hartwig
Unknown Affiliation
Sauter, Guido
Unknown Affiliation
Schlomm, Thorsten
Unknown Affiliation
Simon, Ronald
Unknown Affiliation
Tennstedt, Pierre
Unknown Affiliation
Bathe, Oliver F.
Unknown Affiliation
Carroll, Peter R.
Unknown Affiliation
DiSaia, Philip John
Unknown Affiliation
Kelley, Robin Kate
Unknown Affiliation
Phillips, Joanna J.
Unknown Affiliation
Simko, Jeffry P.
Unknown Affiliation
Smith-McCune, Karen K.
Unknown Affiliation
Hernandez, Brenda Y.
Unknown Affiliation
Herold-Mende, Christel C.
Unknown Affiliation
Unterberg, Andreas Wilhelm
Unknown Affiliation
von Deimling, Andreas
Unknown Affiliation
Adebamowo, Clement
Unknown Affiliation
Adebamowo, Sally N.
Unknown Affiliation
Boussioutas, Alex
Unknown Affiliation
Mès-Masson, Anne Marie
Unknown Affiliation
Saad, Fred
Unknown Affiliation
Walker, Joan L.
Unknown Affiliation
Feldman, Michael D.
Unknown Affiliation
Dhir, Rajiv J.
Unknown Affiliation
Luketich, James D.
Unknown Affiliation
Agnew, Kathy J.
Unknown Affiliation
Creaney, Jenette
Unknown Affiliation
Robinson, Bruce Gregory
Unknown Affiliation
Shelley, Carl Simon
Unknown Affiliation
Bradford, Carol R.
Unknown Affiliation
Fong, Kwun Meng
Unknown Affiliation
Yang, Ian A.
Unknown Affiliation
Hooke, Jeffrey A.
Unknown Affiliation
Kovatich, Albert J.
Unknown Affiliation
Shriver, Craig D.
Unknown Affiliation
DIpersio, John F.
Unknown Affiliation
Drake, Bettina Fisher
Unknown Affiliation
Van Tine, Brian A.
Unknown Affiliation
Rubin, Mark A.
Unknown Affiliation
Statistics
Citations: 1,061
Authors: 268
Affiliations: 19
Identifiers
Doi:
10.1016/j.cell.2018.03.034
ISSN:
00928674
Research Areas
Cancer
Genetics And Genomics