Decomposing Oncogenic Transcriptional Signatures to Generate Maps of Divergent Cellular States
| Autor: | Jonathan Liang, Andrew J. Aguirre, David A. Barbie, Jong Wook Kim, Huwate Yeerna, Karina Meneses-Cime, Pablo Tamayo, Emily Damato, Mahmoud Ghandi, Jason Park, Kate Medetgul-Ernar, Chen-Hsiang Yeang, Michelle Stewart, Barbara A. Weir, Aviad Tsherniak, Jill P. Mesirov, David Thomas, Gabriella Alexe, William C. Hahn, Eliezer M. Van Allen, Taylor B. Cavazos, Paul A. Clemons, Russell W. Jenkins, Jesse S. Boehm, John G. Doench, Ofir Cohen, Stephanie Ting, Shunsuke Kitajima, Levi A. Garraway, Arthur Liberzon, Omar O. Abudayyeh, David J. Konieczkowski, John H McDermott, Clarence K. Mah, Aravind Subramanian, Francisca Vazquez |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
oncogenic pathway Disease matrix factorization Neoplasms 2.1 Biological and endogenous factors Reference map Aetiology Precision Medicine ras Cancer Genetics Tumor Genome Gene Expression Regulation Neoplastic oncoGPS Identification (biology) Biotechnology cellular states transcriptional signatures Histology MAP Kinase Signaling System precision medicine Computational biology Biology Cell Line Pathology and Forensic Medicine 03 medical and health sciences Cell Line Tumor Cancer genome Bayesian nomogram Biomarkers Tumor Humans drug sensitivity genetic dependency Neoplastic Gene Expression Profiling Human Genome Cell Biology Precision medicine Ras pathway Good Health and Well Being Genes ras 030104 developmental biology Gene Expression Regulation Genes inferential model Biochemistry and Cell Biology Biomarkers |
| Zdroj: | Cell systems, vol 5, iss 2 |
| ISSN: | 2405-4712 |
| Popis: | 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 thesealterations is necessary to guide appropriatetherapeutic 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 theirunderlying cellular states. We applied the methodology to the RAS pathway and identifiednine 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 aspart of individualized precision medicine paradigms. |
| Databáze: | OpenAIRE |
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