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A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations.

Cell systems | 2018

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.

Pubmed ID: 29655704 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


YAPC (cell line)

RRID:CVCL_1794

Cell line YAPC is a Cancer cell line with a species of origin Homo sapiens (Human)

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Cytoscape (software resource)

RRID:SCR_003032

Software platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.

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MATLAB (software resource)

RRID:SCR_001622

Multi paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.

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Gene Expression Omnibus (GEO) (data repository)

RRID:SCR_007303

Functional genomics data repository supporting MIAME-compliant data submissions. Includes microarray-based experiments measuring the abundance of mRNA, genomic DNA, and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. Array- and sequence-based data are accepted. Collection of curated gene expression DataSets, as well as original Series and Platform records. The database can be searched using keywords, organism, DataSet type and authors. DataSet records contain additional resources including cluster tools and differential expression queries.

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Python Programming Language (software resource)

RRID:SCR_008394

Programming language for all operating systems that lets users work more quickly and integrate their systems more effectively. Often compared to Tcl, Perl, Ruby, Scheme or Java. Some of its key distinguishing features include very clear and readable syntax, strong introspection capabilities, intuitive object orientation, natural expression of procedural code, full modularity, exception-based error handling, high level dynamic data types, extensive standard libraries and third party modules for virtually every task, extensions and modules easily written in C, C (or Java for Python, or .NET languages for IronPython), and embeddable within applications as a scripting interface.

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R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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Skyline (software resource)

RRID:SCR_014080

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WA09 (cell line)

RRID:CVCL_9773

Cell line WA09 is a Embryonic stem cell with a species of origin Homo sapiens (Human)

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PC-3 (cell line)

RRID:CVCL_0035

Cell line PC-3 is a Cancer cell line with a species of origin Homo sapiens (Human)

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MCF-7 (cell line)

RRID:CVCL_0031

Cell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)

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A-549 (cell line)

RRID:CVCL_0023

Cell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)

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A-375 (cell line)

RRID:CVCL_0132

Cell line A-375 is a Cancer cell line with a species of origin Homo sapiens (Human)

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YAPC (cell line)

RRID:CVCL_1794

Cell line YAPC is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

YAPC (cell line)

RRID:CVCL_1794

Cell line YAPC is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions