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A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations.
Litichevskiy, Lev; Peckner, Ryan; Abelin, Jennifer G; Asiedu, Jacob K; Creech, Amanda L; Davis, John F; Davison, Desiree; Dunning, Caitlin M; Egertson, Jarrett D; Egri, Shawn; Gould, Joshua; Ko, Tak; Johnson, Sarah A; Lahr, David L; Lam, Daniel; Liu, Zihan; Lyons, Nicholas J; Lu, Xiaodong; MacLean, Brendan X; Mungenast, Alison E; Officer, Adam; Natoli, Ted E; Papanastasiou, Malvina; Patel, Jinal; Sharma, Vagisha; Toder, Courtney; Tubelli, Andrew A; Young, Jennie Z; Carr, Steven A; Golub, Todd R; Subramanian, Aravind; MacCoss, Michael J; Tsai, Li-Huei; Jaffe, Jacob D.
Afiliação
  • Litichevskiy L; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Peckner R; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Abelin JG; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Asiedu JK; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Creech AL; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Davis JF; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Davison D; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Dunning CM; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Egertson JD; University of Washington, Department of Genome Sciences, 3720 15th Avenue NE, Seattle, WA 98195, USA.
  • Egri S; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Gould J; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Ko T; Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
  • Johnson SA; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Lahr DL; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Lam D; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Liu Z; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Lyons NJ; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Lu X; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • MacLean BX; University of Washington, Department of Genome Sciences, 3720 15th Avenue NE, Seattle, WA 98195, USA.
  • Mungenast AE; Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
  • Officer A; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Natoli TE; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Papanastasiou M; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Patel J; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Sharma V; University of Washington, Department of Genome Sciences, 3720 15th Avenue NE, Seattle, WA 98195, USA.
  • Toder C; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Tubelli AA; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Young JZ; Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
  • Carr SA; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Golub TR; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • Subramanian A; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
  • MacCoss MJ; University of Washington, Department of Genome Sciences, 3720 15th Avenue NE, Seattle, WA 98195, USA.
  • Tsai LH; Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
  • Jaffe JD; The Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. Electronic address: jjaffe@broadinstitute.org.
Cell Syst ; 6(4): 424-443.e7, 2018 Apr 25.
Article em En | MEDLINE | ID: mdl-29655704
ABSTRACT
Although the value of proteomics has been demonstrated, cost and scale are typically prohibitive, and gene expression profiling remains dominant for characterizing cellular responses to perturbations. However, high-throughput sentinel assays provide an opportunity for proteomics to contribute at a meaningful scale. We present a systematic library resource (90 drugs × 6 cell lines) of proteomic signatures that measure changes in the reduced-representation phosphoproteome (P100) and changes in epigenetic marks on histones (GCP). A majority of these drugs elicited reproducible signatures, but notable cell line- and assay-specific differences were observed. Using the "connectivity" framework, we compared signatures across cell types and integrated data across assays, including a transcriptional assay (L1000). Consistent connectivity among cell types revealed cellular responses that transcended lineage, and consistent connectivity among assays revealed unexpected associations between drugs. We further leveraged the resource against public data to formulate hypotheses for treatment of multiple myeloma and acute lymphocytic leukemia. This resource is publicly available at https//clue.io/proteomics.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fosfoproteínas / Bases de Dados Factuais Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fosfoproteínas / Bases de Dados Factuais Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article