Automatic Annotation of Sites of Metabolism from Biotransformation Data
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| Název: | Automatic Annotation of Sites of Metabolism from Biotransformation Data |
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| Autoři: | Roxane Axel Jacob, Angelica Mazzolari, Johannes Kirchmair |
| Zdroj: | J Chem Inf Model |
| Informace o vydavateli: | American Chemical Society (ACS), 2025. |
| Rok vydání: | 2025 |
| Témata: | Automation, 106005 Bioinformatik, 106005 Bioinformatics, 301207 Pharmazeutische Chemie, Biotransformation, Article, 301207 Pharmaceutical chemistry |
| Popis: | Computational models predicting the sites of metabolism (SOM) of small organic molecules have become invaluable tools for studying and optimizing the metabolic properties of xenobiotics. However, the performance of SOM predictors has shown signs of plateauing in recent years, primarily due to the limited availability of training data. While vast amounts of biotransformation data in the form of substrate-metabolite pairs exist, their potential for SOM prediction remains largely untapped due to the absence of annotations. Annotating SOMs requires expert knowledge and is highly time-consuming. To address this challenge, we introduce AutoSOM, the first open-source tool that automatically extracts SOMs by mapping structural differences using transformation rules. AutoSOM is both fast and highly accurate, achieving over 90% labeling accuracy on a diverse validation set of 5,000+ reactions within minutes. Moreover, its annotation process is fully transparent and interpretable, which we hope will facilitate its adoption in high-stakes downstream applications such as drug discovery campaigns and regulatory assessments. Beyond accelerating annotation, AutoSOM enables standardized and consistent SOM labeling across institutions without requiring direct data sharing. This capability lays the foundation for federated learning approaches in metabolism prediction, fostering collaborative model improvement while preserving data confidentiality. |
| Druh dokumentu: | Article Other literature type |
| ISSN: | 1549-960X 1549-9596 |
| DOI: | 10.26434/chemrxiv-2025-wrjm9 |
| DOI: | 10.26434/chemrxiv-2025-wrjm9-v2 |
| DOI: | 10.1021/acs.jcim.5c00819 |
| Přístupová URL adresa: | https://ucrisportal.univie.ac.at/de/publications/225f2d08-640e-48d3-a457-f71142f0db7d https://doi.org/10.1021/acs.jcim.5c00819 |
| Rights: | CC BY URL: http://creativecommons.org/licenses/by/4.0/This article is licensed under CC-BY 4.0 |
| Přístupové číslo: | edsair.doi.dedup.....9d4794365e1ed9083914fabc97fcb9be |
| Databáze: | OpenAIRE |
Nájsť tento článok vo Web of Science | Abstrakt: | Computational models predicting the sites of metabolism (SOM) of small organic molecules have become invaluable tools for studying and optimizing the metabolic properties of xenobiotics. However, the performance of SOM predictors has shown signs of plateauing in recent years, primarily due to the limited availability of training data. While vast amounts of biotransformation data in the form of substrate-metabolite pairs exist, their potential for SOM prediction remains largely untapped due to the absence of annotations. Annotating SOMs requires expert knowledge and is highly time-consuming. To address this challenge, we introduce AutoSOM, the first open-source tool that automatically extracts SOMs by mapping structural differences using transformation rules. AutoSOM is both fast and highly accurate, achieving over 90% labeling accuracy on a diverse validation set of 5,000+ reactions within minutes. Moreover, its annotation process is fully transparent and interpretable, which we hope will facilitate its adoption in high-stakes downstream applications such as drug discovery campaigns and regulatory assessments. Beyond accelerating annotation, AutoSOM enables standardized and consistent SOM labeling across institutions without requiring direct data sharing. This capability lays the foundation for federated learning approaches in metabolism prediction, fostering collaborative model improvement while preserving data confidentiality. |
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| ISSN: | 1549960X 15499596 |
| DOI: | 10.26434/chemrxiv-2025-wrjm9 |