Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators
Abstract In silico trials for drug safety assessment require many high-fidelity 3D cardiac simulations to predict drug-induced QT interval prolongation, which is often computationally prohibitive. To streamline this process, we developed sex-specific emulators for a fast prediction of QT interval, t...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | npj Digital Medicine |
| Online Access: | https://doi.org/10.1038/s41746-024-01370-8 |
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| author | Paula Dominguez-Gomez Alberto Zingaro Laura Baldo-Canut Caterina Balzotti Borje Darpo Christopher Morton Mariano Vázquez Jazmin Aguado-Sierra |
| author_facet | Paula Dominguez-Gomez Alberto Zingaro Laura Baldo-Canut Caterina Balzotti Borje Darpo Christopher Morton Mariano Vázquez Jazmin Aguado-Sierra |
| author_sort | Paula Dominguez-Gomez |
| collection | DOAJ |
| description | Abstract In silico trials for drug safety assessment require many high-fidelity 3D cardiac simulations to predict drug-induced QT interval prolongation, which is often computationally prohibitive. To streamline this process, we developed sex-specific emulators for a fast prediction of QT interval, trained on a dataset of 900 simulations. Our results show significant differences between 3D and 0D single-cell models as risk levels increase, underscoring the ability of 3D modeling to capture more complex cardiac responses. The emulators demonstrated an average error of 4% compared to simulations, allowing for efficient global sensitivity analysis and fast replication of in silico clinical trials. This approach enables rapid, multi-dose drug testing on standard hardware, addressing critical industry challenges around trial design, assay variability, and cost-effective safety evaluations. By integrating these emulators into drug development, we can improve preclinical reliability and advance the practical application of digital twins in biomedicine. |
| format | Article |
| id | doaj-art-980aa71dc7aa44d9b3bce3614168392f |
| institution | DOAJ |
| issn | 2398-6352 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Digital Medicine |
| spelling | doaj-art-980aa71dc7aa44d9b3bce3614168392f2025-08-20T02:43:35ZengNature Portfolionpj Digital Medicine2398-63522024-12-017111810.1038/s41746-024-01370-8Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulatorsPaula Dominguez-Gomez0Alberto Zingaro1Laura Baldo-Canut2Caterina Balzotti3Borje Darpo4Christopher Morton5Mariano Vázquez6Jazmin Aguado-Sierra7ELEM Biotech S.L.ELEM Biotech S.L.ELEM Biotech S.L.ELEM Biotech S.L.ClarioELEM Biotech S.L.ELEM Biotech S.L.ELEM Biotech S.L.Abstract In silico trials for drug safety assessment require many high-fidelity 3D cardiac simulations to predict drug-induced QT interval prolongation, which is often computationally prohibitive. To streamline this process, we developed sex-specific emulators for a fast prediction of QT interval, trained on a dataset of 900 simulations. Our results show significant differences between 3D and 0D single-cell models as risk levels increase, underscoring the ability of 3D modeling to capture more complex cardiac responses. The emulators demonstrated an average error of 4% compared to simulations, allowing for efficient global sensitivity analysis and fast replication of in silico clinical trials. This approach enables rapid, multi-dose drug testing on standard hardware, addressing critical industry challenges around trial design, assay variability, and cost-effective safety evaluations. By integrating these emulators into drug development, we can improve preclinical reliability and advance the practical application of digital twins in biomedicine.https://doi.org/10.1038/s41746-024-01370-8 |
| spellingShingle | Paula Dominguez-Gomez Alberto Zingaro Laura Baldo-Canut Caterina Balzotti Borje Darpo Christopher Morton Mariano Vázquez Jazmin Aguado-Sierra Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators npj Digital Medicine |
| title | Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators |
| title_full | Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators |
| title_fullStr | Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators |
| title_full_unstemmed | Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators |
| title_short | Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators |
| title_sort | fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators |
| url | https://doi.org/10.1038/s41746-024-01370-8 |
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