Evidence map›Paper›PMID 39375446›Full record

ArticleNature biotechnology2025

Scalable, compressed phenotypic screening using pooled perturbations.

Nuo Liu, Walaa E Kattan, Benjamin E Mead, Conner Kummerlowe, Thomas Cheng, Sarah Ingabire, Jaime H Cheah, Christian K Soule, Anita Vrcic, Jane K McIninch and 14 more

Abstract read
In one paragraph

Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Functional Neurogenomics to Dissect Disease Mechanisms Across Models.Annual review of genomics and human genetics · 2025
    Review
  10. Review
  11. Gene regulation technologies for gene and cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  12. Article
  13. Article
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

24 authors.

Nuo Liu *Institute for Medical Engineering and Science (IMES) and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Walaa E Kattan *Institute for Medical Engineering and Science (IMES) and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0599-9744
Benjamin E Mead *Institute for Medical Engineering and Science (IMES) and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-7258-7777
Conner Kummerlowe *Institute for Medical Engineering and Science (IMES) and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Thomas ChengInstitute for Medical Engineering and Science (IMES) and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Sarah IngabireInstitute for Medical Engineering and Science (IMES) and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Jaime H CheahKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Christian K SouleKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Anita VrcicCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jane K McIninchCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sergio TrianaInstitute for Medical Engineering and Science (IMES) and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Manuel GuzmanInstitute for Medical Engineering and Science (IMES) and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Tyler T DaoInstitute for Medical Engineering and Science (IMES) and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Joshua M PetersRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Kristen E LowderBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Lorin CrawfordMicrosoft Research, Cambridge, MA, USA.
Ava P AminiMicrosoft Research, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-8601-6040
Paul C BlaineyKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-4889-8783
William C HahnBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2840-9791
Brian ClearyFaculty of Computing and Data Sciences, Boston University, Boston, MA, USA.ORCID http://orcid.org/0000-0003-0825-7129
Bryan BrysonRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-1716-6712
Peter S WinterBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Srivatsan RaghavanBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-5374-9918
Alex K ShalekInstitute for Medical Engineering and Science (IMES) and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA. shalek@mit.edu.ORCID http://orcid.org/0000-0001-5670-8778

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Jacqueline A. Lees · 1985 to 2026
$93.9M
Molecular Analysis of the Host Immune Response in LeprosyR01AI022553 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ROBERT L MODLIN · 1989 to 2026
$15.7M
Defining the impact of drug use on immune function and fitness against HIV-1DP1DA053731 · NIDA · MASSACHUSETTS GENERAL HOSPITAL · PI SHALEK, ALEX K · 2021 to 2025
$5.9M
Graduate Training in Computational and Systems BiologyT32GM087237 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BURGE, CHRISTOPHER B · 2009 to 2023
$4.6M
Development and implementation of multiplex methods to understand the biology and heterogeneity of patient-derived cancer modelsU01CA250549 · NCI · DANA-FARBER CANCER INST · PI HAHN, WILLIAM C. · 2020 to 2022
$2.9M
IL-26 in host defense against infection by intracellular bacteria in skinR01AR073252 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MODLIN, ROBERT L · 2019 to 2023
$2.1M
Regulation and targeting of tumor cell states and plasticity in pancreatic cancerK08CA260442 · NCI · DANA-FARBER CANCER INST · PI Srivatsan Raghavan · 2022 to 2026
$1.5M
NCI NIH HHS K08 CA260442NCI NIH HHS P30 CA014051NCI NIH HHS U01 CA250549NIAID NIH HHS R01 AI022553NIAMS NIH HHS R01 AR073252NIDA NIH HHS DP1 DA053731NIGMS NIH HHS T32 GM087237U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) 1DP1DA053731
6 · The paper itself

Abstract

High-throughput phenotypic screens using biochemical perturbations and high-content readouts are constrained by limitations of scale. To address this, we establish a method of pooling exogenous perturbations followed by computational deconvolution to reduce required sample size, labor and cost. We demonstrate the increased efficiency of compressed experimental designs compared to conventional approaches through benchmarking with a bioactive small-molecule library and a high-content imaging readout. We then apply compressed screening in two biological discovery campaigns. In the first, we use early-passage pancreatic cancer organoids to map transcriptional responses to a library of recombinant tumor microenvironment protein ligands, uncovering reproducible phenotypic shifts induced by specific ligands distinct from canonical reference signatures and correlated with clinical outcome. In the second, we identify the pleotropic modulatory effects of a chemical compound library with known mechanisms of action on primary human peripheral blood mononuclear cell immune responses. In sum, our approach empowers phenotypic screens with information-rich readouts to advance drug discovery efforts and basic biological inquiry.

Indexed as

High-Throughput Screening AssaysPancreatic NeoplasmsDrug DiscoveryHumansLeukocytes, MononuclearOrganoidsPhenotypeSmall Molecule LibrariesTumor MicroenvironmentSmall Molecule Libraries

Identifiers

PMID39375446
PMCPMC12339377

What Socratic holds

Textmetadata
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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 Socratic graph.