AI Article Synopsis
- - Morphological profiling is an approach that helps identify the cellular targets of chemical compounds by comparing their impact on yeast cell shapes to those of genetically altered (gene-deleted) cells.
- - A new high-throughput platform was created to efficiently assess yeast morphology using drug-sensitive strains and advanced imaging techniques, allowing for faster and more reliable predictions of compound targets.
- - Using this platform, researchers investigated a new compound called poacidiene, discovering it impacts the DNA damage response and shows promise as an antifungal agent against plant pathogens.
Article Abstract
Morphological profiling is an omics-based approach for predicting intracellular targets of chemical compounds in which the dose-dependent morphological changes induced by the compound are systematically compared to the morphological changes in gene-deleted cells. In this study, we developed a reliable high-throughput (HT) platform for yeast morphological profiling using drug-hypersensitive strains to minimize compound use, HT microscopy to speed up data generation and analysis, and a generalized linear model to predict targets with high reliability. We first conducted a proof-of-concept study using six compounds with known targets: bortezomib, hydroxyurea, methyl methanesulfonate, benomyl, tunicamycin, and echinocandin B. Then we applied our platform to predict the mechanism of action of a novel diferulate-derived compound, poacidiene. Morphological profiling of poacidiene implied that it affects the DNA damage response, which genetic analysis confirmed. Furthermore, we found that poacidiene inhibits the growth of phytopathogenic fungi, implying applications as an effective antifungal agent. Thus, our platform is a new whole-cell target prediction tool for drug discovery.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795194 | PMC |
| http://dx.doi.org/10.1038/s41540-022-00212-1 | DOI Listing |
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