A high-throughput differential chemical genetic screen uncovers genotype-specific compounds altering plant growth.
Journal:
iScience
Published Date:
Apr 8, 2025
Abstract
The identification of chemical compounds regulating plant growth in a genetic context can greatly enhance our understanding of biological mechanisms. Here, we have developed a high-throughput phenotype-directed chemical screening method in plants to compare two genotypes and identify small molecules inducing genotype-specific phenotypes. We used wild type and , a DNA repair mutant, and screened off-patent drugs from the Prestwick library to selectively identify molecules affecting growth. We developed two complementary convolutional neural networks (CNN)-based image segmentation and classification programs to quantify seedling growth. Using these approaches, we detected that about 10% of Prestwick molecules cause altered growth in both genotypes, suggesting their toxic effects on plant growth. We identified three Prestwick molecules specifically affecting . Overall, we developed a straightforward, accurate, and adaptable methodology for performing high-throughput screening of chemical libraries in a time-efficient manner, accelerating the discovery of genotype-specific chemical regulators of plant growth.
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