Evidence map›Paper›PMID 29655704›Full record

ArticleCell systems2018

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

Lev Litichevskiy, Ryan Peckner, Jennifer G Abelin, Jacob K Asiedu, Amanda L Creech, John F Davis, Desiree Davison, Caitlin M Dunning, Jarrett D Egertson, Shawn Egri and 24 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell systems, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

50 citing papers in PubMed.

  1. Review
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  5. Review
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  7. Pathway Analysis Interpretation in the Multi-Omic Era.Biotech (Basel (Switzerland)) · 2025
    Review
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  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. CRISP(e)R drug discovery.Nature chemical biology · 2022
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

34 authors.

Lev LitichevskiyThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Ryan PecknerThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Jennifer G AbelinThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Jacob K AsieduThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Amanda L CreechThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
John F DavisThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Desiree DavisonThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Caitlin M DunningThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Jarrett D EgertsonUniversity of Washington, Department of Genome Sciences, 3720 15th Avenue NE, Seattle, WA 98195, USA.
Shawn EgriThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Joshua GouldThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Tak KoDepartment of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Sarah A JohnsonThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
David L LahrThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Daniel LamThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Zihan LiuThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Nicholas J LyonsThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Xiaodong LuThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Brendan X MacLeanUniversity of Washington, Department of Genome Sciences, 3720 15th Avenue NE, Seattle, WA 98195, USA.
Alison E MungenastDepartment of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Adam OfficerThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Ted E NatoliThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Malvina PapanastasiouThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Jinal PatelThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Vagisha SharmaUniversity of Washington, Department of Genome Sciences, 3720 15th Avenue NE, Seattle, WA 98195, USA.
Courtney ToderThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Andrew A TubelliThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Jennie Z YoungDepartment of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Steven A CarrThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Todd R GolubThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Aravind SubramanianThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Michael J MacCossUniversity of Washington, Department of Genome Sciences, 3720 15th Avenue NE, Seattle, WA 98195, USA.
Li-Huei TsaiDepartment of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Jacob D JaffeThe Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. Electronic address: jjaffe@broadinstitute.org.

Funding

Discovering existing medicines that abrogate cellular responses to SARS CoV-2 infectionU54HL127366 · NHLBI · BROAD INSTITUTE, INC. · PI GOLUB, TODD R. · 2014 to 2020
$14.3M
There and Back Again: Epigenetic Reinforcement of Cellular Signaling States - OverallU54HG008097 · NHGRI · BROAD INSTITUTE, INC. · PI JAFFE, JACOB DAVID · 2014 to 2019
$9.3M
LINCS Data Coordination and Integration CenterU01HG008699 · NHGRI · BROAD INSTITUTE, INC. · PI GOLUB, TODD R., SUBRAMANIAN, ARAVIND · 2015 to 2019
$3.2M
NHGRI NIH HHS U01 HG008699NHGRI NIH HHS U54 HG008097NHLBI NIH HHS U54 HL127366
6 · The paper itself

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.

Indexed as

Databases, FactualAlgorithmsCell LineChromatography, LiquidDatasets as TopicGene Expression RegulationHistone CodeHumansMass SpectrometryPharmacological and Toxicological PhenomenaPhosphoproteinsProteomicsSignal TransductionSoftwarePhosphoproteinsdrug discoveryepigeneticsGCPL1000LINCS projectmass spectrometrymechanism of actionP100proteomicssignaling

Identifiers

PMID29655704
PMCPMC5951639

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.