用于活体肝移植恢复的供体特异性数字孪生模型。

Donor-specific digital twin for living donor liver transplant recovery.

作者信息

Halder Suvankar, Lawrence Michael C, Testa Giuliano, Periwal Vipul

机构信息

Laboratory of Biological Modeling, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, United States.

Baylor Scott & White Research Institute, Dallas, TX, 75204, United States.

出版信息

Biol Methods Protoc. 2025 May 10;10(1):bpaf037. doi: 10.1093/biomethods/bpaf037. eCollection 2025.

Abstract

The remarkable capacity of the liver to regenerate its lost mass after resection makes living donor liver transplantation a successful treatment option. However, donor heterogeneity significantly influences recovery trajectories, highlighting the need for individualized monitoring. With the rising incidence of liver diseases, safer transplant procedures and improved donor care are urgently needed. Current clinical markers provide only limited snapshots of recovery, making it challenging to predict long-term outcomes. Following partial hepatectomy, precise liver mass recovery requires tightly regulated hepatocyte proliferation. We identified distinct gene expression patterns associated with liver regeneration by analyzing blood-derived gene expression measurements from twelve donors followed over a year. Using a deep learning-based framework, we integrated these patterns with a mathematical model of hepatocyte transitions to develop a personalized, progressive mechanistic digital twin-a virtual liver model that predicts donor-specific recovery trajectories. Central to our approach is a mechanistically identifiable latent space, defined by variables derived from a physiologically grounded differential equation model of liver regeneration, which enables biologically interpretable, bidirectional mapping between gene expression data and model dynamics. This approach integrates clinical genomics and computational modeling to enhance post-surgical care, ensuring safer transplants and improved donor recovery.

摘要

肝脏在切除后能够显著再生其丢失的组织质量,这使得活体供肝移植成为一种成功的治疗选择。然而,供体的异质性显著影响恢复轨迹,凸显了个性化监测的必要性。随着肝脏疾病发病率的上升,迫切需要更安全的移植程序和更好的供体护理。目前的临床标志物只能提供有限的恢复情况快照,难以预测长期结果。部分肝切除术后,精确的肝脏质量恢复需要严格调控肝细胞增殖。我们通过分析12名供体在一年多时间里血液来源的基因表达测量数据,确定了与肝脏再生相关的不同基因表达模式。利用基于深度学习的框架,我们将这些模式与肝细胞转变的数学模型相结合,开发了一个个性化的、渐进的机械数字孪生模型——一个虚拟肝脏模型,可预测供体特异性的恢复轨迹。我们方法的核心是一个可从机制上识别的潜在空间,由源自肝脏再生生理基础微分方程模型的变量定义,它能够在基因表达数据和模型动态之间进行生物学上可解释的双向映射。这种方法整合了临床基因组学和计算建模,以加强术后护理,确保移植更安全,供体恢复更好。

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