Li Ting, Chen Xi, Tong Weida
FDA National Center for Toxicological Research, Jefferson, AR, USA.
NPJ Digit Med. 2024 Nov 5;7(1):310. doi: 10.1038/s41746-024-01317-z.
Translational research in toxicology has significantly benefited from transcriptomic profiling, particularly in drug safety. However, its application has predominantly focused on limited organs, notably the liver, due to resource constraints. This paper presents TransTox, an innovative AI model using a generative adversarial network (GAN) method to facilitate the bidirectional translation of transcriptomic profiles between the liver and kidney under drug treatment. TransTox demonstrates robust performance, validated across independent datasets and laboratories. First, the concordance between real experimental data and synthetic data generated by TransTox was demonstrated in characterizing toxicity mechanisms compared to real experimental settings. Second, TransTox proved valuable in gene expression predictive models, where synthetic data could be used to develop gene expression predictive models or serve as "digital twins" for diagnostic applications. The TransTox approach holds the potential for multi-organ toxicity assessment with AI and advancing the field of precision toxicology.
毒理学中的转化研究从转录组分析中受益匪浅,尤其是在药物安全性方面。然而,由于资源限制,其应用主要集中在有限的器官上,特别是肝脏。本文介绍了TransTox,这是一种创新的人工智能模型,它使用生成对抗网络(GAN)方法来促进药物治疗下肝脏和肾脏之间转录组图谱的双向转化。TransTox表现出强大的性能,在独立数据集和实验室中得到了验证。首先,与真实实验设置相比,在表征毒性机制方面,证明了真实实验数据与TransTox生成的合成数据之间的一致性。其次,TransTox在基因表达预测模型中被证明是有价值的,其中合成数据可用于开发基因表达预测模型或作为诊断应用的“数字孪生”。TransTox方法具有利用人工智能进行多器官毒性评估以及推动精准毒理学领域发展的潜力。