Pre-Training on In Vitro and Fine-Tuning on Patient-Derived Data Improves Deep Neural Networks for Anti-Cancer Drug-Sensitivity Prediction
- Large-scale databases that report the inhibitory capacities of many combinations of candidate drug compounds and cultivated cancer cell lines have driven the development of preclinical drug-sensitivity models based on machine learning. However, cultivated cell lines have devolved from human cancer cells over years or even decades under selective pressure in culture conditions. Moreover, models that have been trained on in vitro data cannot account for interactions with other types of cells. Drug-response data that are based on patient-derived cell cultures, xenografts, and organoids, on the other hand, are not available in the quantities that are needed to train high-capacity machine-learning models. We found that pre-training deep neural network models of drug sensitivity on in vitro drug-sensitivity databases before fine-tuning the model parameters on patient-derived data improves the models’ accuracy and improves the biological plausibility of the features, compared to training only on patient-derived data. From our experiments, weLarge-scale databases that report the inhibitory capacities of many combinations of candidate drug compounds and cultivated cancer cell lines have driven the development of preclinical drug-sensitivity models based on machine learning. However, cultivated cell lines have devolved from human cancer cells over years or even decades under selective pressure in culture conditions. Moreover, models that have been trained on in vitro data cannot account for interactions with other types of cells. Drug-response data that are based on patient-derived cell cultures, xenografts, and organoids, on the other hand, are not available in the quantities that are needed to train high-capacity machine-learning models. We found that pre-training deep neural network models of drug sensitivity on in vitro drug-sensitivity databases before fine-tuning the model parameters on patient-derived data improves the models’ accuracy and improves the biological plausibility of the features, compared to training only on patient-derived data. From our experiments, we can conclude that pre-trained models outperform models that have been trained on the target domains in the vast majority of cases.…
Verfasserangaben: | Paul PrasseORCiDGND, Pascal IversenORCiD, Matthias LienhardORCiDGND, Kristina Thedinga, Ralf HerwigORCiD, Tobias SchefferORCiD |
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URN: | urn:nbn:de:kobv:517-opus4-577341 |
DOI: | https://doi.org/10.25932/publishup-57734 |
ISSN: | 1866-8372 |
Titel des übergeordneten Werks (Deutsch): | Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe |
Schriftenreihe (Bandnummer): | Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (1300) |
Verlag: | Universitätsverlag Potsdam |
Verlagsort: | Potsdam |
Publikationstyp: | Postprint |
Sprache: | Englisch |
Datum der Erstveröffentlichung: | 30.01.2023 |
Erscheinungsjahr: | 2022 |
Veröffentlichende Institution: | Universität Potsdam |
Datum der Freischaltung: | 30.01.2023 |
Freies Schlagwort / Tag: | anti-cancer drugs; deep neural networks; drug-sensitivity prediction |
Seitenanzahl: | 14 |
Erste Seite: | 1 |
Letzte Seite: | 14 |
Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Informatik und Computational Science |
DDC-Klassifikation: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Peer Review: | Referiert |
Publikationsweg: | Open Access / Green Open-Access |
Lizenz (Deutsch): | CC-BY - Namensnennung 4.0 International |
Externe Anmerkung: | Bibliographieeintrag der Originalveröffentlichung/Quelle |