2022
DOI: 10.1093/toxsci/kfac046
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Optimization of the TeraTox Assay for Preclinical Teratogenicity Assessment

Abstract: Current animal-free methods to assess teratogenicity of drugs under development still deliver high numbers of false negatives. To improve the sensitivity of human teratogenicity prediction, we characterized the TeraTox test, a newly developed multi-lineage differentiation assay using 3D human induced pluripotent stem cells. TeraTox produces as primary output concentration-dependent cytotoxicity and altered gene expression induced by each test compound. These data are fed into an interpretable machine-learning … Show more

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Cited by 15 publications
(6 citation statements)
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“…To evaluate the performance of our final model embryoTox, we compared it with other available state-of-the-art ap-proaches. While recently Jiang et al 39 and Jaklin and colleagues 40 published supervised machine learning approaches, built using human teratogenicity data, to assess chemical reproductive toxicity, unfortunately neither provided their source code or model making direct comparison challenging. Our final model, embryoTox, outperformed both approaches (Table 3).…”
Section: ■ Results and Discussionmentioning
confidence: 99%
“…To evaluate the performance of our final model embryoTox, we compared it with other available state-of-the-art ap-proaches. While recently Jiang et al 39 and Jaklin and colleagues 40 published supervised machine learning approaches, built using human teratogenicity data, to assess chemical reproductive toxicity, unfortunately neither provided their source code or model making direct comparison challenging. Our final model, embryoTox, outperformed both approaches (Table 3).…”
Section: ■ Results and Discussionmentioning
confidence: 99%
“…[ 119 ]. By 2022, Manuela Jaklin had developed the TeraTox system, a machine-learning algorithm with the ability to examine concentration-dependent cytotoxicity and changes in genetic expression induced by pharmaceutical compounds in hiPSC-derived embryoid bodies [ 100 ]. Particularly, during the COVID-19 pandemic in 2020, the DeepNEU was deployed for modelling lung aiPSC infection with SARS-CoV-2, facilitating the rapidly identification of antiviral therapeutic targets and opportunities for drug repurposing [ 61 ].…”
Section: Discussionmentioning
confidence: 99%
“…CNS: central nervous system; hiPSC: human induced pluripotent stem cells; NEP: neuroepithelial precursor; NPC: neural progenitor cell; MEA: microelectrode array; PNS: peripheral nervous system; RoFA: rosette formation assay. Jaklin et al, 2022;Spreng et al, 2022) now allow sufficient throughput for screening applications and it is likely that such assays will add additional information to the IVB in the future.…”
Section: The Dnt In Vitro Battery (Ivb)mentioning
confidence: 99%