Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Rohban, MH, Fuller, AM, Tan, C, Goldstein, JT, Syangtan, D, Gutnick, A, DeVine, A, Nijsure, MP, Rigby, M, Sacher, JR, Corsello, SM, Peppler, GB, Bogaczynska, M, Boghossian, A, Ciotti, GE, Hands, AT, Mekareeya, A, Doan, M, Gale, JP, Derynck, R, Turbyville, T, Boerckel, JD, Singh, S, Kiessling, LL, Schwarz, TL, Varelas, X, Wagner, FF, Kafri, R, Eisinger-Mathason, TSKarin, Carpenter, AE |
Journal | Cell Syst |
Date Published | 2022 Sep 01 |
ISSN | 2405-4720 |
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. |
DOI | 10.1016/j.cels.2022.08.003 |
Pubmed | |
Alternate Journal | Cell Syst |
PubMed ID | 36057257 |
Cell Syst DOI:10.1016/j.cels.2022.08.003
Virtual screening for small-molecule pathway regulators by image-profile matching.
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