arXiv:2606.26520cs.LGcs.AI2026-06

用多路径动态预测和拉曼数据融合,提前精准预判细胞培养过程走向。

Multipath Adaptive Gated Bottleneck Latent ODE with Raman Data Fusion for Cell Culture Process Forecasting

论文配图:Multipath Adaptive Gated Bottleneck Latent ODE with Raman Data Fusion for Cell Culture Process Forecasting
图 1 · 摘自论文原文
  • 引入可变门控与掩码感知瓶颈,增强稀疏数据下的建模能力。
  • 通过局部相似轨迹检索生成多条可能路径,准确率优于单一预测。
  • 拉曼光谱数据融合显著提升早期预测可靠性,适合生物工艺优化场景。

哺乳动物细胞培养是许多生物制药生产的核心,但过程控制困难:关键参数随时间漂移,异常趋势常发现过晚。早期多日预测可实现及时补料、采样与调控,但受制于测量稀疏不规则、不同细胞系与培养基差异大,以及早期行为相似却未来分化的挑战。本文提出结合门控瓶颈潜在微分方程(GB-Latent ODE)与多路径即时微调(MP-JIT-FT)的自适应框架。GB-Latent ODE通过可学习的变量门控和掩码感知瓶颈压缩高维稀疏输入,提升小样本学习性能。对部分观测的运行,MP-JIT-FT检索历史相似轨迹,聚类局部邻域为候选状态,并为每类状态微调独立模型,输出多条合理路径及基于重构的置信度评分。进一步融合拉曼光谱数据:机器学习软传感器将密集拉曼谱转化为伪观测,丰富稀疏离线数据,增强训练鲁棒性。在38组5L补料分批反应器实验(覆盖14种条件)上,结合拉曼融合的MP-JIT-FT平均排名最优,9个目标变量中有8个超越全局潜式微分方程基线。通过局部发散度量分析,多路径优势在早期相似但后期分化时最大,而拉曼融合在早期动力学具代表性时效果最佳。

原文摘要 · Abstract (English)

Mammalian cell-culture processes underpin the manufacture of many biopharmaceuticals, yet keeping a run on track is hard: critical process parameters drift over days, and an off-specification trend is often confirmed too late to intervene. Early-stage, multi-day forecasts could enable timely adjustment of feeding, sampling, and control, but bioprocess forecasting is challenging because measurements are sparse and irregularly sampled, operating conditions are heterogeneous across cell lines and media, and runs with near-identical early behaviour can diverge into different futures. We propose an adaptive framework combining a Gated Bottleneck Latent Ordinary Differential Equation (GB-Latent ODE) with Multi-Path Just-In-Time Fine Tuning (MP-JIT-FT). The GB-Latent ODE augments the stan dard Latent ODE with learnable variable-wise gating and a mask-aware bottleneck that compress high-dimensional sparse inputs, improving learning under limited data. Given a partially observed run, MP-JIT-FT retrieves similar historical trajectories, clusters the local neighbourhood into candidate regimes, and fine-tunes a separate model per regime to produce multiple plausible paths, each with a reconstruction-based confidence score, not a single averaged forecast. We further fuse Raman spectroscopy data: a machine-learning soft sensor turns dense Raman spectra into pseudo-observations that enrich the sparse offline measurements for more robust training. On 38 fed-batch 5L bioreactor runs spanning 14 conditions, MP-JIT-FT with Raman fusion achieves the best average rank and outperforms a global Latent ODE baseline on 8 of 9 target variables. Using local-divergence metrics, we show the multi-path gains are largest when locally similar prefixes diverge, whereas Raman fusion helps most when early dynamics are representative of later behaviour.

生物工艺多路径预测拉曼光谱时序建模

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