用物理约束神经网络预测乙肝感染动态,支持缺数据和噪声数据下的精准参数估计。
Exploration of Hepatitis B Virus Infection Dynamics through Physics-Informed Deep Learning Approach
- 基于疾病先验知识的神经网络框架,融合病毒动力学模型与数据
- 在9只感染黑猩猩的数据上准确估计关键参数,即使部分数据缺失
- 适用于乙肝机制研究者,尤其适合处理不完整或含噪实验数据
准确预测病毒性疾病爆发对指导公共卫生响应、防止大规模死亡至关重要。近年来,物理信息神经网络(PINNs)展现出捕捉病毒感染复杂动态并可靠预测其未来演化的潜力。然而,尽管进展显著,其在疾病建模中的应用仍有限。标准PINNs虽擅长前向模拟,但在逆问题中从稀疏或含噪实验数据估计关键生物参数时面临挑战。为此,近期提出的疾病信息神经网络(DINNs)提供了更稳健的参数估计方法。本文将DINNs应用于最近提出的乙肝病毒(HBV)感染动力学模型,该模型包含四个组分:未感染和感染肝细胞、含rcDNA的衣壳及游离病毒。我们通过该方法研究了参数范围变化、数据噪声、样本量、网络结构和学习率的影响。基于来自九只感染黑猩猩的实验数据,DINNs能可靠估计模型参数,即使某些系统组分数据缺失也能捕捉感染动态并预测未来进程。此外,它识别出决定乙肝是否被清除或持续的关键参数。
原文摘要 · Abstract (English)
Accurate forecasting of viral disease outbreaks is crucial for guiding public health responses and preventing widespread loss of life. In recent years, Physics-Informed Neural Networks (PINNs) have emerged as a promising framework that can capture the intricate dynamics of viral infection and reliably predict its future progression. However, despite notable advances, the application of PINNs in disease modeling remains limited. Standard PINNs are effective in simulating disease dynamics through forward modeling but often face challenges in estimating key biological parameters from sparse or noisy experimental data when applied in an inverse framework. To overcome these limitations, a recent extension known as Disease Informed Neural Networks (DINNs) has emerged, offering a more robust approach to parameter estimation tasks. In this work, we apply this DINNs technique on a recently proposed hepatitis B virus (HBV) infection dynamics model to predict infection transmission within the liver. This model consists of four compartments: uninfected and infected hepatocytes, rcDNA-containing capsids, and free viruses. Leveraging the power of DINNs, we study the impacts of (i) variations in parameter range, (ii) experimental noise in data, (iii) sample sizes, (iv) network architecture and (v) learning rate. We employ this methodology in experimental data collected from nine HBV-infected chimpanzees and observe that it reliably estimates the model parameters. DINNs can capture infection dynamics and predict their future progression even when data of some compartments of the system are missing. Additionally, it identifies the influential model parameters that determine whether the HBV infection is cleared or persists within the host.
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