Evidence map›Paper›PMID 36057257›Full record

ArticleCell systems2022

Virtual screening for small-molecule pathway regulators by image-profile matching.

Mohammad H Rohban, Ashley M Fuller, Ceryl Tan, Jonathan T Goldstein, Deepsing Syangtan, Amos Gutnick, Ann DeVine, Madhura P Nijsure, Megan Rigby, Joshua R Sacher and 20 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell systems, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
10.3field-weighted citation impact, top 2% of its field
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

22 citing papers in PubMed, 39 citations in OpenAlex.

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  16. Assessing the performance of the Cell Painting assay across different imaging systems.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2023
    Article
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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

30 authors at 10 institutions in 2 countries.

Mohammad H RohbanImaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Ashley M FullerAbramson Family Cancer Research Institute, Department of Pathology & Laboratory Medicine, Penn Sarcoma Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Ceryl TanDepartment of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Department of Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Jonathan T GoldsteinCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Deepsing SyangtanDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Amos GutnickFM Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
Ann DeVineAbramson Family Cancer Research Institute, Department of Pathology & Laboratory Medicine, Penn Sarcoma Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Madhura P NijsureDepartments of Orthopaedic Surgery & Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Megan RigbyFrederick National Laboratory for Cancer Research, Frederick, MD, USA.
Joshua R SacherCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Steven M CorselloCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Grace B PepplerDepartment of Biochemistry, Boston University School of Medicine, Boston, MA, USA.
Marta BogaczynskaDepartments of Cell/Tissue Biology and Anatomy, University of California, San Francisco, San Francisco, CA, USA.
Andrew BoghossianCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Gabrielle E CiottiAbramson Family Cancer Research Institute, Department of Pathology & Laboratory Medicine, Penn Sarcoma Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Allison T HandsCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Aroonroj MekareeyaCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Minh DoanImaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jennifer P GaleCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Rik DerynckDepartments of Cell/Tissue Biology and Anatomy, University of California, San Francisco, San Francisco, CA, USA.
Thomas TurbyvilleFrederick National Laboratory for Cancer Research, Frederick, MD, USA.
Joel D BoerckelDepartments of Orthopaedic Surgery & Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Shantanu SinghImaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Laura L KiesslingDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Thomas L SchwarzFM Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
Xaralabos VarelasDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Florence F WagnerCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Ran KafriDepartment of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Department of Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada.
T S Karin Eisinger-MathasonAbramson Family Cancer Research Institute, Department of Pathology & Laboratory Medicine, Penn Sarcoma Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Electronic address: karineis@pennmedicine.upenn.edu.
Anne E CarpenterImaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: anne@broadinstitute.org.
Broad Institute · USUniversity of Pennsylvania · USMassachusetts Institute of Technology · USCancer Research Institute · USFrederick National Laboratory for Cancer Research · USUniversity of California, San Francisco · USUniversity of Toronto · CABoston Children's Hospital · USBoston University · USHarvard University · US

Funding

TRAINING GRANT IN HEMOSTASIS AND THROMBOSIST32HL007971 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Rodney M Camire · 2001 to 2026
$10.6M
Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SCOTT Loren POMEROY, MUSTAFA SAHIN · 2021 to 2026
$9.4M
Synthetic Ligands for Modulating Immune Cell ResponsesR01AI055258 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI KIESSLING, LAURA L · 2003 to 2024
$7.8M
Extracting rich information from biological imagesR35GM122547 · NIGMS · BROAD INSTITUTE, INC. · PI Anne E. Carpenter · 2017 to 2026
$6.2M
The role and regulation of Hippo pathway in sarcomagenesisR01CA229688 · NCI · UNIVERSITY OF PENNSYLVANIA · PI EISINGER, TZIPORA SARAH KARIN · 2019 to 2023
$2.1M
Osteoprogenitor mobilization for bone development and repairR01AR073809 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI BOERCKEL, JOEL D · 2019 to 2023
$1.7M
Development of multifunctional probes for profiling microbial glycansU01CA231079 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI IMPERIALI, BARBARA, KIESSLING, LAURA L · 2018 to 2020
$1.4M
Targeting casein kinase 1-alpha for cancer therapyK08CA230220 · NCI · STANFORD UNIVERSITY · PI CORSELLO, STEVEN MUNTEAN · 2018 to 2022
$1.0M
CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001ENCI NIH HHS K08 CA230220NCI NIH HHS R01 CA229688NCI NIH HHS U01 CA231079NHLBI NIH HHS T32 HL007971NIAID NIH HHS R01 AI055258NIAMS NIH HHS R01 AR073809NICHD NIH HHS P50 HD105351NIGMS NIH HHS R35 GM122547
6 · The paper itself

Abstract

Identifying the chemical regulators of biological pathways is a time-consuming bottleneck in developing therapeutics and research compounds. Typically, thousands to millions of candidate small molecules are tested in target-based biochemical screens or phenotypic cell-based screens, both expensive experiments customized to each disease. Here, our uncustomized, virtual, profile-based screening approach instead identifies compounds that match to pathways based on the phenotypic information in public cell image data, created using the Cell Painting assay. Our straightforward correlation-based computational strategy retrospectively uncovered the expected, known small-molecule regulators for 32% of positive-control gene queries. In prospective, discovery mode, we efficiently identified new compounds related to three query genes and validated them in subsequent gene-relevant assays, including compounds that phenocopy or pheno-oppose YAP1 overexpression and kill a Yap1-dependent sarcoma cell line. This image-profile-based approach could replace many customized labor- and resource-intensive screens and accelerate the discovery of biologically and therapeutically useful compounds.

Indexed as

Prospective StudiesCell LineRetrospective Studiescomputational drug discoverydrug screeningHippo/Yap1 pathwayimage-based profilingvirtual screening

Identifiers

PMID36057257
PMCPMC9509476
OpenAlexW4294275214

What OpenQuestion holds

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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.