Skip NavigationSkip to Content
Return Return to Search Results

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

  1. Author:
    Rohban, Mohammad H
    Fuller, Ashley M
    Tan, Ceryl
    Goldstein, Jonathan T
    Syangtan, Deepsing
    Gutnick, Amos
    DeVine, Ann
    Nijsure, Madhura P
    Rigby,Megan
    Sacher, Joshua R
    Corsello, Steven M
    Peppler, Grace B
    Bogaczynska, Marta
    Boghossian, Andrew
    Ciotti, Gabrielle E
    Hands, Allison T
    Mekareeya, Aroonroj
    Doan, Minh
    Gale, Jennifer P
    Derynck, Rik
    Turbyville,Tommy
    Boerckel, Joel D
    Singh, Shantanu
    Kiessling, Laura L
    Schwarz, Thomas L
    Varelas, Xaralabos
    Wagner, Florence F
    Kafri, Ran
    Eisinger-Mathason, T S Karin
    Carpenter, Anne E

  2. Author Address

    Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Abramson Family Cancer Research Institute, Department of Pathology & Laboratory Medicine, Penn Sarcoma Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Department of Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada., Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA., FM Kirby Neurobiology Center, Boston Children 39;s Hospital, and Department of Neurobiology, Harvard Medical School, Boston, MA, USA., Departments of Orthopaedic Surgery & Bioengineering, University of Pennsylvania, Philadelphia, PA, USA., Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Center for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA., Departments of Cell/Tissue Biology and Anatomy, University of California, San Francisco, San Francisco, CA, USA., Abramson 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., Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: anne@broadinstitute.org.,
    1. Year: 2022
    2. Date: Sep 01
    3. Epub Date: 2022 09 01
  2. Journal: Cell Systems
    1. 13
    2. 9
    3. Pages: 724-736.e9
  4. Type of Article: Article
  1. 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. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1016/j.cels.2022.08.003
  3. PMID: 36057257
  4. View record in Web of Science®
  5. WOS: 000898548300005
  6. PII : S2405-4712(22)00330-1

Library Notes

  1. Fiscal Year: FY2022-2023
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel