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| Item Type: | Article |
|---|---|
| Title: | Deep-learning analysis of micropattern-based organoids enables high-throughput drug screening of Huntington's disease models |
| Creators Name: | Metzger, J.J. and Pereda, C. and Adhikari, A. and Haremaki, T. and Galgoczi, S. and Siggia, E.D. and Brivanlou, A.H. and Etoc, F. |
| Abstract: | Organoids are carrying the promise of modeling complex disease phenotypes and serving as a powerful basis for unbiased drug screens, potentially offering a more efficient drug-discovery route. However, unsolved technical bottlenecks of reproducibility and scalability have prevented the use of current organoids for high-throughput screening. Here, we present a method that overcomes these limitations by using deep-learning-driven analysis for phenotypic drug screens based on highly standardized micropattern-based neural organoids. This allows us to distinguish between disease and wild-type phenotypes in complex tissues with extremely high accuracy as well as quantify two predictors of drug success: efficacy and adverse effects. We applied our approach to Huntington's disease (HD) and discovered that bromodomain inhibitors revert complex phenotypes induced by the HD mutation. This work demonstrates the power of combining machine learning with phenotypic drug screening and its successful application to reveal a potentially new druggable target for HD. |
| Keywords: | Organoids, Deep Learning, Bromodomains, Huntington's Disease |
| Source: | Cell Reports Methods |
| ISSN: | 2667-2375 |
| Publisher: | Elsevier |
| Volume: | 2 |
| Number: | 9 |
| Page Range: | 100297 |
| Date: | 19 September 2022 |
| Official Publication: | https://doi.org/10.1016/j.crmeth.2022.100297 |
| PubMed: | View item in PubMed |
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