arXiv:2505.02514cs.LGq-bio.QM2025-05中稿 · the 47th Annual In…

用深度学习找药物代谢关键影响因素,准确识别年龄、基因等重要因素。

Uncovering Population PK Covariates from VAE-Generated Latent Spaces

  • 用变分自编码器压缩药代动力学数据,提取潜在特征。
  • 结合L1正则回归,准确识别年龄、基因等关键影响因子,MAPE仅2.26%。
  • 无需先验假设,适合新药研发与个体化用药研究。

群体药代动力学(PopPK)建模是理解药物在不同人群中的行为并实现个性化给药的重要工具。其核心挑战在于识别影响药物吸收的协变量,这些关系常呈复杂非线性。传统方法难以捕捉数据中的隐藏模式。本研究提出一种数据驱动、模型无关的方法,将变分自编码器(VAE)与LASSO回归结合,从模拟的他克莫司(tacrolimus)药代动力学谱中挖掘关键协变量。VAE将高维药代动力学信号压缩至结构化的潜在空间,重建误差均方百分比(MAPE)为2.26%。随后通过LASSO回归将患者特征映射至潜在空间,利用L1正则化实现稀疏特征选择。该方法在不同正则化强度下持续识别出临床相关的协变量,包括单核苷酸多态性(SNP)、年龄、白蛋白和血红蛋白,同时有效剔除无关特征。所提出的VAE-LASSO方法为协变量筛选提供了一种可扩展、可解释且完全数据驱动的解决方案,具有广阔的应用前景。

原文摘要 · Abstract (English)

Population pharmacokinetic (PopPK) modelling is a fundamental tool for understanding drug behaviour across diverse patient populations and enabling personalized dosing strategies to improve therapeutic outcomes. A key challenge in PopPK analysis lies in identifying and modelling covariates that influence drug absorption, as these relationships are often complex and nonlinear. Traditional methods may fail to capture hidden patterns within the data. In this study, we propose a data-driven, model-free framework that integrates Variational Autoencoders (VAEs) deep learning model and LASSO regression to uncover key covariates from simulated tacrolimus pharmacokinetic (PK) profiles. The VAE compresses high-dimensional PK signals into a structured latent space, achieving accurate reconstruction with a mean absolute percentage error (MAPE) of 2.26%. LASSO regression is then applied to map patient-specific covariates to the latent space, enabling sparse feature selection through L1 regularization. This approach consistently identifies clinically relevant covariates for tacrolimus including SNP, age, albumin, and hemoglobin which are retained across the tested regularization strength levels, while effectively discarding non-informative features. The proposed VAE-LASSO methodology offers a scalable, interpretable, and fully data-driven solution for covariate selection, with promising applications in drug development and precision pharmacotherapy.

药代动力学VAELASSO个性化用药

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