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A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles.
Subramanian, Aravind; Narayan, Rajiv; Corsello, Steven M; Peck, David D; Natoli, Ted E; Lu, Xiaodong; Gould, Joshua; Davis, John F; Tubelli, Andrew A; Asiedu, Jacob K; Lahr, David L; Hirschman, Jodi E; Liu, Zihan; Donahue, Melanie; Julian, Bina; Khan, Mariya; Wadden, David; Smith, Ian C; Lam, Daniel; Liberzon, Arthur; Toder, Courtney; Bagul, Mukta; Orzechowski, Marek; Enache, Oana M; Piccioni, Federica; Johnson, Sarah A; Lyons, Nicholas J; Berger, Alice H; Shamji, Alykhan F; Brooks, Angela N; Vrcic, Anita; Flynn, Corey; Rosains, Jacqueline; Takeda, David Y; Hu, Roger; Davison, Desiree; Lamb, Justin; Ardlie, Kristin; Hogstrom, Larson; Greenside, Peyton; Gray, Nathanael S; Clemons, Paul A; Silver, Serena; Wu, Xiaoyun; Zhao, Wen-Ning; Read-Button, Willis; Wu, Xiaohua; Haggarty, Stephen J; Ronco, Lucienne V; Boehm, Jesse S.
Afiliación
  • Subramanian A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Narayan R; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Corsello SM; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Peck DD; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Natoli TE; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Lu X; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Gould J; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Davis JF; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Tubelli AA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Asiedu JK; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Lahr DL; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Hirschman JE; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Liu Z; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Donahue M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Julian B; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Khan M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Wadden D; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Smith IC; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Lam D; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Liberzon A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Toder C; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Bagul M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Orzechowski M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Enache OM; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Piccioni F; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Johnson SA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Lyons NJ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Berger AH; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Shamji AF; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Brooks AN; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Vrcic A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Flynn C; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Rosains J; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Takeda DY; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Hu R; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Davison D; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Lamb J; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ardlie K; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Hogstrom L; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Greenside P; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Gray NS; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Clemons PA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Silver S; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Wu X; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Zhao WN; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Read-Button W; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Wu X; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Haggarty SJ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Ronco LV; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Boehm JS; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cell ; 171(6): 1437-1452.e17, 2017 Nov 30.
Article en En | MEDLINE | ID: mdl-29195078
ABSTRACT
We previously piloted the concept of a Connectivity Map (CMap), whereby genes, drugs, and disease states are connected by virtue of common gene-expression signatures. Here, we report more than a 1,000-fold scale-up of the CMap as part of the NIH LINCS Consortium, made possible by a new, low-cost, high-throughput reduced representation expression profiling method that we term L1000. We show that L1000 is highly reproducible, comparable to RNA sequencing, and suitable for computational inference of the expression levels of 81% of non-measured transcripts. We further show that the expanded CMap can be used to discover mechanism of action of small molecules, functionally annotate genetic variants of disease genes, and inform clinical trials. The 1.3 million L1000 profiles described here, as well as tools for their analysis, are available at https//clue.io.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Perfilación de la Expresión Génica Límite: Humans Idioma: En Revista: Cell Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Perfilación de la Expresión Génica Límite: Humans Idioma: En Revista: Cell Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos
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