School of Medicine, University of Galway, Galway, Ireland; Engineering Mathematics and Computing Lab (EMCL), Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, Heidelberg, Germany; Data Mining and Uncertainty Quantification (DMQ), Heidelberg Institute for Theoretical Studies (HITS), Heidelberg, Germany.
Division of Child Neurology and Metabolic Medicine, Center for Child and Adolescent Medicine, Heidelberg University, Medical Faculty, Heidelberg, Germany.
Cell Metab. 2024 Aug 6;36(8):1882-1897.e7. doi: 10.1016/j.cmet.2024.05.006. Epub 2024 Jun 3.
Comprehensive whole-body models (WBMs) accounting for organ-specific dynamics have been developed to simulate adult metabolism, but such models do not exist for infants. Here, we present a resource of 360 organ-resolved, sex-specific models of newborn and infant metabolism (infant-WBMs) spanning the first 180 days of life. These infant-WBMs were parameterized to represent the distinct metabolic characteristics of newborns and infants, including nutrition, energy requirements, and thermoregulation. We demonstrate that the predicted infant growth was consistent with the recommendation by the World Health Organization. We assessed the infant-WBMs' reliability and capabilities for personalization by simulating 10,000 newborns based on their blood metabolome and birth weight. Furthermore, the infant-WBMs accurately predicted changes in known biomarkers over time and metabolic responses to treatment strategies for inherited metabolic diseases. The infant-WBM resource holds promise for personalized medicine, as the infant-WBMs could be a first step to digital metabolic twins for newborn and infant metabolism.
综合考虑器官特异性动力学的全身模型（WBM）已被开发用于模拟成人代谢，但目前还没有针对婴儿的此类模型。在这里，我们提出了一个资源，其中包含 360 个器官分辨率、性别特异性的新生儿和婴儿代谢模型（婴儿-WBM），涵盖了生命的前 180 天。这些婴儿-WBM 经过参数化处理，可代表新生儿和婴儿的独特代谢特征，包括营养、能量需求和体温调节。我们证明，预测的婴儿生长与世界卫生组织的建议一致。我们通过基于血液代谢组和出生体重模拟 10,000 名新生儿，评估了婴儿-WBM 的可靠性和个性化能力。此外，婴儿-WBM 准确预测了已知生物标志物随时间的变化以及对遗传代谢疾病治疗策略的代谢反应。婴儿-WBM 资源有望用于个性化医疗，因为婴儿-WBM 可以作为新生儿和婴儿代谢的数字代谢双胞胎的第一步。
