Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation.
- Authors
- Mohamed H. Abdel-Rahman
- Adam Abeshouse
- Clement Adebamowo
- Sally N. Adebamowo
- Kathy Agnew
- Keunsoo Ahn
- Jaffer A. Ajani
- Rehan Akbani
- Teniola Akeredolu
- Hikmat Al-Ahmadie
- Monique Albert
- Iakovina Alexopoulou
- Adrian Ally
- Domenico Alvaro
- Matthew L. Anderson
- Chris Andry
- Anna Antenucci
- Pavana Anur
- Elizabeth L. Appelbaum
- Natália D. Aredes
- Joshua Armenia
- Angel Arnaout
- Sylvia L. Asa
- J. Todd Auman
- Marta Aymerich
- Dina Aziz
- Matthew Bailey
- Miruna Balasundaram
- Saianand Balu
- Gene Barnett
- Jill S. Barnholtz-Sloan
- Wendi Barrett
- John Bartlett
- Oliver Bathe
- Eric Baudin
- Stephen Baylin
- Karl-Friedrich Becker
- David Beer
- Madhusmita Behera
- Carmen Behrens
- Debra Bell
- Sue Bell
- Michelle Bellair
- Joseph Bennett
- Christopher Benz
- Andrew Berchuck
- Ashton C. Berger
- Alain Bergeron
- Ross Berkowitz
- Brady Bernard
- Rameen Beroukhim
- Felix Beuschlein
- Carlo Bifulco
- Darell Bigner
- Michael Birrer
- Kivanc Birsoy
- Therese Bocklage
- Tom Bodenheimer
- Jolanta Bondaruk
- Moiz S. Bootwalla
- Mitesh Borad
- Jeffrey A. Borgia
- Aaron Bossler
- Natalia Botnariuc
- Alex Boussioutas
- Jay Bowen
- Reanne Bowlby
- Rayleen Bowman
- Carol Bradford
- Maria Consiglia Bragazzi
- Daniel J. Brat
- Anne Breggia
- Cathy Brewer
- Fadi Brimo
- Russell Broaddus
- Denise Brooks
- Bradley M. Broom
- Thomas Broudy
- Alan H. Bryce
- Glenn Bubley
- Raphael Bueno
- Andrew Burnette
- Tomasz Burzykowski
- Samantha J. Caesar-Johnson
- Chiara Calatozzolo
- Elias Campo
- Benito Campos
- Irina Caraman
- Vincenzo Cardinale
- Francis Carey
- Thomas Carey
- Carlos Gilberto Carlotti
- Rebecca Carlsen
- Michael Carney
- Guido Carpino
- Peter R. Carroll
- Candace Carter
- Andre L. Carvalho
- Erik Castle
- Patricia D. Castro
- James Catto
- Colleen M. Cebulla
- Mircea Cernat
- John Chabot
- Debyani Chakravarty
- Nyasha Chambwe
- June M. Chan
- Timothy A. Chan
- Vishal Chandan
- Kyle Chang
- Walid K. Chatila
- Inga Chemencedji
- Amy Chen
- Chu Chen
- Feixiong Cheng
- Andrew D. Cherniack
- David Chesla
- Simone Chevalier
- John Cheville
- Juok Cho
- Eric Chuah
- Sudha Chudamani
- Ki Chung
- Carrie Cibulskis
- Adrian Clipca
- Antonio Colaprico
- Howard Colman
- Leslie Cope
- John A. Copland
- Niall Corcoran
- Matthew G. Cordes
- Tony Costello
- Sandra Cottingham
- Marta Couce
- Kyle Covington
- Daniel Crain
- Daniel Cramer
- Jenette Creaney
- Chad J. Creighton
- Lucia Cuppini
- Erin Curley
- Stefania Cuzzubbo
- Bogdan Czerniak
- Patrycja Czerwińska
- Ludmila Danilova
- Amy Davis
- Ino de Bruijn
- Ana C. de Carvalho
- Ronald de Krijger
- Assunta De Rienzo
- Agostino De Rose
- Timothy DeFreitas
- Keith Delman
- John A. Demchok
- Laurence Desjardins
- Karen Devine
- Brenda Deyarmin
- Noreen Dhalla
- Renumathy Dhanasekaran
- Varsha Dhankani
- Rajiv Dhir
- Francesco DiMeco
- Li Ding
- Huyen Dinh
- Mikhail Dinkin
- John DiPersio
- Philip Disaia
- HarshaVardhan Doddapaneni
- Lawrence A. Donehower
- Serghei Doruc
- Jose Sebastião Dos Santos
- Peter R. Dottino
- Bettina Drake
- Jennifer Drummond
- Paul Drwiega
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- Rebecca Duell
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- John Eckman
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- J. Bradley Elder
- Jay Engel
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- Bita Esmaeli
- Kimberley Evason
- Francesco Facciolo
- Cheng Fan
- Huihui Fan
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- Ina Felau
- Michael Feldman
- Colleen Feltmate
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- Jianjiong Gao
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- Julie M. Gastier-Foster
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- Nils Gehlenborg
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- Mark Gerken
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- Nasra Giama
- Richard A. Gibbs
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- Karla Kopp
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- Anil Korkut
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- Shiyun Ling
- Eric Lipp
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- Xiuping Liu
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- Kelinda Tucker
- Bernard Têtu
- Andreas Unterberg
- Walter Urba
- Federico Valdivieso
- Nguyen Van Bang
- David J. Van Den Berg
- Kim E. van Kessel
- Erwin G. Van Meir
- Brian Van Tine
- Scott VandenBerg
- Umadevi Veluvolu
- Ales Vicha
- Daniel O. Vidal
- Cathy D. Vocke
- Doug Voet
- Andreas von Deimling
- Olga Voronina
- Sven Wach
- Paul Wakely
- Jens Waldmann
- Joan Walker
- Yunhu Wan
- Jing Wang
- Jioajiao Wang
- Linghua Wang
- Min Wang
- Timothy Wang
- Zhining Wang
- Ronald Warnick
- John N. Weinstein
- Daniel J. Weisenberger
- Nicolas Wentzensen
- Peter Westervelt
- David A. Wheeler
- Matthew D. Wilkerson
- Felicia Williams
- James Wilmott
- Richard K. Wilson
- Lisa Wise
- Ignacio Wistuba
- Maciej Wiznerowicz
- Gregory Wolf
- Yingli Wolinsky
- Christopher K. Wong
- Tina Wong
- Robert Worrell
- Ye Wu
- Bernd Wullich
- Liu Xi
- Hannah Yang
- Ian Yang
- Ju Dong Yang
- Liming Yang
- Christina Yau
- Peggy Yena
- Leigh Anne Zach
- Howard Zaren
- Tomas Zelinka
- Jean C. Zenklusen
- Hailei Zhang
- Hongxin Zhang
- Hongzheng Zhang
- Jiashan (Julia) Zhang
- Jiexin Zhang
- Lizhi Zhang
- Wei Zhang
- Fengmei Zhao
- Wanding Zhou
- Erik Zmuda
- Rosemary Zuna
- Ellen C. Zwarthoff
- Publication date
- 1 January 2018
- Publisher
- 'Elsevier BV'
- Doi
Abstract
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 differentiationSimilar works
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