Malta, Tathiane M; Sokolov, Artem; Gentles, Andrew J; Burzykowski, Tomasz; Poisson, Laila; Weinstein, John N; Kamińska, Bożena; Huelsken, Joerg; Omberg, Larsson; Gevaert, Olivier; Colaprico, Antonio; Czerwińska, Patrycja; Mazurek, Sylwia; Mishra, Lopa; Heyn, Holger; Krasnitz, Alex; Godwin, Andrew K; Lazar, Alexander J; Stuart, Joshua M; Hoadley, Katherine A; ... (2018). Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation. Cell, 173(2), 338-354.e15. Cell Press 10.1016/j.cell.2018.03.034
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0092-8674 |
Publisher: |
Cell Press |
Language: |
English |
Submitter: |
Marla Rittiner |
Date Deposited: |
09 Oct 2019 16:16 |
Last Modified: |
23 Oct 2019 17:12 |
Publisher DOI: |
10.1016/j.cell.2018.03.034 |
PubMed ID: |
29625051 |
Additional Information: |
Mark Rubin (Direktor DBMR), Precision Medicine, DBMR, ist Collaborator für diese Publikation. |
Uncontrolled Keywords: |
The Cancer Genome Atlas cancer stem cells dedifferentiation epigenomic genomic machine learning pan-cancer stemness |
BORIS DOI: |
10.7892/boris.126375 |
URI: |
https://boris.unibe.ch/id/eprint/126375 |
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