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Cell Syst DOI:10.1016/j.cels.2017.08.002

Decomposing Oncogenic Transcriptional Signatures to Generate Maps of Divergent Cellular States.

Publication TypeJournal Article
Year of Publication2017
AuthorsKim, JWook, Abudayyeh, OO, Yeerna, H, Yeang, C-H, Stewart, M, Jenkins, RW, Kitajima, S, Konieczkowski, DJ, Medetgul-Ernar, K, Cavazos, T, Mah, C, Ting, S, Van Allen, EM, Cohen, O, Mcdermott, J, Damato, E, Aguirre, AJ, Liang, J, Liberzon, A, Alexe, G, Doench, J, Ghandi, M, Vazquez, F, Weir, BA, Tsherniak, A, Subramanian, A, Meneses-Cime, K, Park, J, Clemons, P, Garraway, LA, Thomas, D, Boehm, JS, Barbie, DA, Hahn, WC, Mesirov, JP, Tamayo, P
JournalCell Syst
Date Published2017 Aug 23

The systematic sequencing of the cancer genome has led to the identification of numerous genetic alterations in cancer. However, a deeper understanding of the functional consequences of these alterations is necessary to guide appropriate therapeutic strategies. Here, we describe Onco-GPS (OncoGenic Positioning System), a data-driven analysis framework to organize individual tumor samples with shared oncogenic alterations onto a reference map defined by their underlying cellular states. We applied the methodology to the RAS pathway and identified nine distinct components that reflect transcriptional activities downstream of RAS and defined several functional states associated with patterns of transcriptional component activation that associates with genomic hallmarks and response to genetic and pharmacological perturbations. These results show that the Onco-GPS is an effective approach to explore the complex landscape of oncogenic cellular states across cancers, and an analytic framework to summarize knowledge, establish relationships, and generate more effective disease models for research or as part of individualized precision medicine paradigms.


Alternate JournalCell Syst
PubMed ID28837809
PubMed Central IDPMC5639711
Grant ListR01 GM074024 / GM / NIGMS NIH HHS / United States
U01 CA199253 / CA / NCI NIH HHS / United States
U24 CA194107 / CA / NCI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
R01 CA130988 / CA / NCI NIH HHS / United States
U01 HG008699 / HG / NHGRI NIH HHS / United States
U01 CA176058 / CA / NCI NIH HHS / United States
R01 CA109467 / CA / NCI NIH HHS / United States
R01 CA154480 / CA / NCI NIH HHS / United States
UL1 TR001102 / TR / NCATS NIH HHS / United States
R01 CA121941 / CA / NCI NIH HHS / United States