ArticleCell systems2017
Decomposing Oncogenic Transcriptional Signatures to Generate Maps of Divergent Cellular States.
Open access · bronzeAbstract read
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Article in Cell systems, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 14% of its field
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
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Corrections and comments
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Authors and funding
36 authors at 5 institutions in 2 countries.
Jong Wook KimCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA.
Omar O AbudayyehCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Huwate YeernaMoores Cancer Center, University of California San Diego, La Jolla, CA 92103, USA.
Chen-Hsiang YeangCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Institute of Statistical Science, Academia Sinica, Taipei, 11529, Taiwan.
Michelle StewartCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Russell W JenkinsDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Shunsuke KitajimaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
David J KonieczkowskiCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, MA 02114, USA.
Kate Medetgul-ErnarMoores Cancer Center, University of California San Diego, La Jolla, CA 92103, USA.
Taylor CavazosMoores Cancer Center, University of California San Diego, La Jolla, CA 92103, USA.
Clarence MahSchool of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, University of California San Diego, La Jolla, CA 92103, USA.
Stephanie TingMoores Cancer Center, University of California San Diego, La Jolla, CA 92103, USA.
Eliezer M Van AllenCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Ofir CohenCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
John McdermottCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Emily DamatoCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Andrew J AguirreCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA.
Jonathan LiangCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Arthur LiberzonCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Gabriella AlexeCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Graduate Program in Bioinformatics, Boston University, Boston, MA 02215, USA.
John DoenchCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Mahmoud GhandiCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Francisca VazquezCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Barbara A WeirCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Aviad TsherniakCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Aravind SubramanianCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Karina Meneses-CimeMoores Cancer Center, University of California San Diego, La Jolla, CA 92103, USA.
Jason ParkMoores Cancer Center, University of California San Diego, La Jolla, CA 92103, USA.
Paul ClemonsCenter for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142, USA.
Levi A GarrawayCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA.
David ThomasCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Jesse S BoehmCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
David A BarbieCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
William C HahnCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA; Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Jill P MesirovCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; School of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, University of California San Diego, La Jolla, CA 92103, USA.
Pablo TamayoCancer Program, Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; School of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, University of California San Diego, La Jolla, CA 92103, USA. Electronic address: ptamayo@ucsd.edu.
Broad Institute · USUniversity of California, San Diego · USDana-Farber Cancer Institute · USBoston University · USBrigham and Women's Hospital · US
Funding
Harvard Clinical and Translational Science CenterUL1TR001102 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2013 to 2017
$106.2MMedical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0MThe Dana-Farber Cancer Institute Cancer Target Discovery and Development CenterU01CA176058 · NCI · DANA-FARBER CANCER INST · PI HAHN, WILLIAM C. · 2013 to 2021
$7.8MGENOMIC ANALYSIS OF MEDULLOBLASTOMASR01CA109467 · NCI · CHILDREN'S HOSPITAL BOSTON · PI MESIROV, JILL P., POMEROY, SCOTT LOREN · 2004 to 2015
$7.3MSupporting Integrative Genomic Analysis Users with GenePatternR01GM074024 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MESIROV, JILL P. · 2005 to 2019
$6.6MKnowledge-based Gene Expression Analysis for Biomedical and Cancer ResearchR01CA121941 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MESIROV, JILL P. · 2006 to 2016
$5.1MSystematic identification of oncogenic KRAS synthetic lethal interactionsU01CA199253 · NCI · BROAD INSTITUTE, INC. · PI HAHN, WILLIAM C. · 2015 to 2019
$3.7MRegulation and function of IKKe in breast cancer initiation and maintenanceR01CA130988 · NCI · DANA-FARBER CANCER INST · PI HAHN, WILLIAM C. · 2009 to 2018
$3.5MLINCS Data Coordination and Integration CenterU01HG008699 · NHGRI · BROAD INSTITUTE, INC. · PI GOLUB, TODD R., SUBRAMANIAN, ARAVIND · 2015 to 2019
$3.2MGenePattern Notebooks for Cancer ResearchU24CA194107 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MESIROV, JILL P. · 2015 to 2019
$2.8MMolecular Signatures to Characterize the Oncogenic State of Individual TumorsR01CA154480 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TAMAYO, PABLO · 2011 to 2015
$2.0MNCATS NIH HHS UL1 TR001102NCI NIH HHS R01 CA109467NCI NIH HHS R01 CA121941NCI NIH HHS R01 CA130988NCI NIH HHS R01 CA154480NCI NIH HHS U01 CA176058NCI NIH HHS U01 CA199253NCI NIH HHS U24 CA194107NHGRI NIH HHS U01 HG008699NIGMS NIH HHS R01 GM074024NIGMS NIH HHS T32 GM007753
Abstract
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.
Indexed as
Gene Expression Regulation, NeoplasticBiomarkers, TumorCell Line, TumorGene Expression ProfilingGenes, rasGenomeHumansMAP Kinase Signaling SystemNeoplasmsPrecision MedicineBiomarkers, TumorBayesian nomogramcellular statesdrug sensitivitygenetic dependencyinferential modelmatrix factorizationoncogenic pathwayoncoGPSprecision medicinetranscriptional signatures
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