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| Main Authors: | , , , , , , , , |
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| Format: | Preprint |
| Published: |
2025
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| Subjects: | |
| Online Access: | https://arxiv.org/abs/2505.20775 |
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| _version_ | 1866911126440116224 |
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| author | Scheurer, Fabian Hammer, Alexander Schubert, Mario Steiner, Robert-Patrick Gamm, Oliver Guan, Kaomei Sonntag, Frank Malberg, Hagen Schmidt, Martin |
| author_facet | Scheurer, Fabian Hammer, Alexander Schubert, Mario Steiner, Robert-Patrick Gamm, Oliver Guan, Kaomei Sonntag, Frank Malberg, Hagen Schmidt, Martin |
| contents | Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are an important resource for the identification of new therapeutic targets and cardioprotective drugs. After differentiation iPSC-CMs show an immature, fetal-like phenotype. Cultivation of iPSC-CMs in lipid-supplemented maturation medium (MM) strongly enhances their structural, metabolic and functional phenotype. Nevertheless, assessing iPSC-CM maturation state remains challenging as most methods are time consuming and go in line with cell damage or loss of the sample. To address this issue, we developed a non-invasive approach for automated classification of iPSC-CM maturity through interpretable artificial intelligence (AI)-based analysis of beat characteristics derived from video-based motion analysis. In a prospective study, we evaluated 230 video recordings of early-state, immature iPSC-CMs on day 21 after differentiation (d21) and more mature iPSC-CMs cultured in MM (d42, MM). For each recording, 10 features were extracted using Maia motion analysis software and entered into a support vector machine (SVM). The hyperparameters of the SVM were optimized in a grid search on 80 % of the data using 5-fold cross-validation. The optimized model achieved an accuracy of 99.5 $\pm$ 1.1 % on a hold-out test set. Shapley Additive Explanations (SHAP) identified displacement, relaxation-rise time and beating duration as the most relevant features for assessing maturity level. Our results suggest the use of non-invasive, optical motion analysis combined with AI-based methods as a tool to assess iPSC-CMs maturity and could be applied before performing functional readouts or drug testing. This may potentially reduce the variability and improve the reproducibility of experimental studies. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2505_20775 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | Non-invasive maturity assessment of iPSC-CMs based on optical maturity characteristics using interpretable AI Scheurer, Fabian Hammer, Alexander Schubert, Mario Steiner, Robert-Patrick Gamm, Oliver Guan, Kaomei Sonntag, Frank Malberg, Hagen Schmidt, Martin Machine Learning Signal Processing Cell Behavior Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are an important resource for the identification of new therapeutic targets and cardioprotective drugs. After differentiation iPSC-CMs show an immature, fetal-like phenotype. Cultivation of iPSC-CMs in lipid-supplemented maturation medium (MM) strongly enhances their structural, metabolic and functional phenotype. Nevertheless, assessing iPSC-CM maturation state remains challenging as most methods are time consuming and go in line with cell damage or loss of the sample. To address this issue, we developed a non-invasive approach for automated classification of iPSC-CM maturity through interpretable artificial intelligence (AI)-based analysis of beat characteristics derived from video-based motion analysis. In a prospective study, we evaluated 230 video recordings of early-state, immature iPSC-CMs on day 21 after differentiation (d21) and more mature iPSC-CMs cultured in MM (d42, MM). For each recording, 10 features were extracted using Maia motion analysis software and entered into a support vector machine (SVM). The hyperparameters of the SVM were optimized in a grid search on 80 % of the data using 5-fold cross-validation. The optimized model achieved an accuracy of 99.5 $\pm$ 1.1 % on a hold-out test set. Shapley Additive Explanations (SHAP) identified displacement, relaxation-rise time and beating duration as the most relevant features for assessing maturity level. Our results suggest the use of non-invasive, optical motion analysis combined with AI-based methods as a tool to assess iPSC-CMs maturity and could be applied before performing functional readouts or drug testing. This may potentially reduce the variability and improve the reproducibility of experimental studies. |
| title | Non-invasive maturity assessment of iPSC-CMs based on optical maturity characteristics using interpretable AI |
| topic | Machine Learning Signal Processing Cell Behavior |
| url | https://arxiv.org/abs/2505.20775 |