arXiv:2509.20753stat.MLcs.LG2025-09

用概率图模型加速生物制造数字孪生,从少而杂的数据中快速推断机制。

RAPTOR-GEN: RApid PosTeriOR GENerator for Bayesian Learning in Biomanufacturing

  • 基于多尺度概率知识图谱和随机微分方程构建机制驱动的贝叶斯框架
  • 在稀疏异构数据下实现隐状态推断与不可计算似然的显式近似
  • 适合生物制造领域研究者,尤其关注过程机理建模与高效推断的人

生物制药制造对公共健康至关重要,但受限于生物工艺的复杂性与变异性,难以实现快速、按需生产。为克服这一挑战,我们提出一种机制引导的贝叶斯学习框架 RAPTOR-GEN,用于从稀疏且异构的实验数据中加速智能数字孪生的构建。该框架基于多尺度概率知识图谱(pKG),以随机微分方程(SDE)为基础模型,捕捉生物过程的非线性动态。RAPTOR-GEN由两部分构成:(i) 一种可解释的元模型,融合线性噪声近似(LNA)并利用生物工艺结构信息,结合序贯学习策略融合异构稀疏数据,实现隐状态变量推断与不可计算似然函数的显式逼近;(ii) 一种高效的贝叶斯后验采样方法,通过朗之万扩散(LD)利用推导似然的梯度加速后验探索。该方法将LNA推广至避免步长选择难题,实现机制参数的稳健学习,并具备可证明的有限样本性能保证。我们开发了误差可控的快速鲁棒算法,数值实验验证其在揭示生物制造过程底层调控机制方面的有效性。

原文摘要 · Abstract (English)

Biopharmaceutical manufacturing is vital to public health but lacks the agility for rapid, on-demand production of biotherapeutics due to the complexity and variability of bioprocesses. To overcome this, we introduce RApid PosTeriOR GENerator (RAPTOR-GEN), a mechanism-informed Bayesian learning framework designed to accelerate intelligent digital twin development from sparse and heterogeneous experimental data. This framework is built on a multi-scale probabilistic knowledge graph (pKG), formulated as a stochastic differential equation (SDE)-based foundational model that captures the nonlinear dynamics of bioprocesses. RAPTOR-GEN consists of two ingredients: (i) an interpretable metamodel integrating linear noise approximation (LNA) that exploits the structural information of bioprocessing mechanisms and a sequential learning strategy to fuse heterogeneous and sparse data, enabling inference of latent state variables and explicit approximation of the intractable likelihood function; and (ii) an efficient Bayesian posterior sampling method that utilizes Langevin diffusion (LD) to accelerate posterior exploration by exploiting the gradients of the derived likelihood. It generalizes the LNA approach to circumvent the challenge of step size selection, facilitating robust learning of mechanistic parameters with provable finite-sample performance guarantees. We develop a fast and robust RAPTOR-GEN algorithm with controllable error. Numerical experiments demonstrate its effectiveness in uncovering the underlying regulatory mechanisms of biomanufacturing processes.

贝叶斯学习数字孪生生物制造概率建模

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