Evidence map›Paper›PMID 25024206›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Toward performance-diverse small-molecule libraries for cell-based phenotypic screening using multiplexed high-dimensional profiling.

Mathias J Wawer, Kejie Li, Sigrun M Gustafsdottir, Vebjorn Ljosa, Nicole E Bodycombe, Melissa A Marton, Katherine L Sokolnicki, Mark-Anthony Bray, Melissa M Kemp, Ellen Winchester and 15 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.

0numbers the graph read from it
0cells of the map it votes in
99citing 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

99 citing papers in PubMed.

  1. Article
  2. Learned Conformational Space and Pharmacophore Into Molecular Foundational Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. A morphology and secretome map of pyroptosis.Molecular biology of the cell · 2025
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Evaluating batch correction methods for image-based cell profiling.bioRxiv : the preprint server for biology · 2024
    Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

39 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Mathias J WawerCenter for the Science of Therapeutics.
Kejie LiCenter for the Science of Therapeutics.
Sigrun M GustafsdottirCenter for the Science of Therapeutics.
Vebjorn LjosaImaging Platform.
Nicole E BodycombeCenter for the Science of Therapeutics.
Melissa A MartonGenomics Platform.
Katherine L SokolnickiImaging Platform.
Mark-Anthony BrayImaging Platform.
Melissa M KempCenter for the Science of Therapeutics.
Ellen WinchesterGenomics Platform.
Bradley TaylorGenomics Platform.
George B GrantGenomics Platform.
C Suk-Yee HonCenter for the Science of Therapeutics.
Jeremy R DuvallCenter for the Development of Therapeutics, and.
J Anthony WilsonCenter for the Science of Therapeutics.
Joshua A BittkerCenter for the Development of Therapeutics, and.
Vlado DančíkCenter for the Science of Therapeutics,Mathematical Institute of the Slovak Academy of Sciences, 04001 Košice, Slovak Republic.
Rajiv NarayanCancer Program, Broad Institute, Cambridge, MA 02142; and.
Aravind SubramanianCancer Program, Broad Institute, Cambridge, MA 02142; and.
Wendy WincklerGenomics Platform.
Todd R GolubCancer Program, Broad Institute, Cambridge, MA 02142; and.
Anne E CarpenterImaging Platform.
Alykhan F ShamjiCenter for the Science of Therapeutics.
Stuart L SchreiberCenter for the Science of Therapeutics, stuart_schreiber@harvard.edu pclemons@broadinstitute.org.
Paul A ClemonsCenter for the Science of Therapeutics, stuart_schreiber@harvard.edu pclemons@broadinstitute.org.

Funding

User Driven ProjectU54HG005032 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SCHREIBER, STUART L · 2008 to 2013
$88.1M
The Incubator ProjectP50GM069721 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SCHREIBER, STUART L · 2003 to 2012
$21.3M
Large scale gene expression analysis of cellular statesU54HG006093 · NHGRI · BROAD INSTITUTE, INC. · PI GOLUB, TODD R., SUBRAMANIAN, ARAVIND · 2010 to 2013
$9.1M
NHGRI NIH HHS U54 HG005032NHGRI NIH HHS U54HG005032NHGRI NIH HHS U54 HG006093NIGMS NIH HHS P50 GM069721NIGMS NIH HHS P50-GM069721
6 · The paper itself

Abstract

High-throughput screening has become a mainstay of small-molecule probe and early drug discovery. The question of how to build and evolve efficient screening collections systematically for cell-based and biochemical screening is still unresolved. It is often assumed that chemical structure diversity leads to diverse biological performance of a library. Here, we confirm earlier results showing that this inference is not always valid and suggest instead using biological measurement diversity derived from multiplexed profiling in the construction of libraries with diverse assay performance patterns for cell-based screens. Rather than using results from tens or hundreds of completed assays, which is resource intensive and not easily extensible, we use high-dimensional image-based cell morphology and gene expression profiles. We piloted this approach using over 30,000 compounds. We show that small-molecule profiling can be used to select compound sets with high rates of activity and diverse biological performance.

Indexed as

Gene Expression ProfilingCell Line, TumorDrug Evaluation, PreclinicalGene Expression RegulationHumansbiological activitybiological performance diversitychemical diversitychemical similarity

Identifiers

PMID25024206
PMCPMC4121832

What OpenQuestion holds

Textmetadata
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.