arXiv:2604.07557cs.LGq-bio.QM2026-04被引 2

用生成模型为小样本孕产期数据造虚拟病人,保持真实特征分布。

Validated Synthetic Patient Generation for Small Longitudinal Cohorts: Coagulation Dynamics Across Pregnancy

  • 基于霍普菲尔德网络的随机注意力机制,将真实患者存为记忆模式生成合成数据。
  • 在23名患者、72个特征的小样本下,合成数据与真实数据统计和机制一致。
  • 适合孕产健康、罕见病等小样本研究,支持机制建模与假设生成。

小规模纵向队列(如母体健康、罕见病、早期试验)因招募慢、数据稀疏,难以支撑可靠建模。本文提出多重加权随机注意力(SA)生成框架,基于现代霍普菲尔德网络,将真实患者谱型作为连续能量场中的记忆模式存储。生成分布为有限混合模型,每个成分以一个存储谱型为中心。通过朗之万动力学生成报告队列,直接采样同一分布可复现其保真度与成员推断结果。多重性权重在推理时增强特定子群,无需重训练。应用于23名患者的纵向凝血数据(含72个特征,覆盖孕前及一、三孕季),其中3人患多囊卵巢综合征,5人发展为先兆子痫。在统计、结构与机制测试中,包括一个独立设定但基于相同队列校准的凝血模型(对生成器盲),合成谱型在该样本量下与真实谱型高度匹配。基于合成数据校准的模型,预测保留的真实患者TGA值,表现不亚于基于真实数据校准的模型。结果证明了该方法在小样本纵向队列中用于机制校准与假设生成的可行性。

原文摘要 · Abstract (English)

Small longitudinal cohorts, common in maternal health, rare diseases, and early-phase trials, limit computational modeling because enrollment is slow and the data are too sparse to train reliable models. We present multiplicity-weighted Stochastic Attention (SA), a generative framework based on modern Hopfield networks. Stochastic attention stores real patient profiles as memory patterns in a continuous energy landscape. The resulting distribution is a finite mixture with one component centered on each stored profile. We generated the reported cohort with Langevin dynamics; direct sampling from the same distribution reproduced its fidelity and membership-inference results. Multiplicity weights amplify selected subgroups at inference time without retraining. We applied the method to longitudinal coagulation data from 23 patients, with 72 features measured before pregnancy and during the first and third trimesters. The cohort included three patients with polycystic ovary syndrome and five who developed preeclampsia. Across statistical, structural, and mechanistic tests, including a separately specified coagulation model that was blind to the generator but calibrated on the same cohort, the synthetic profiles closely matched the real profiles under the measures applied at this sample size. A model calibrated on synthetic profiles predicted held-out real-patient TGA measurements as well as one calibrated on real profiles. These results provide proof of concept for using SA in the tested modeling tasks, including mechanistic calibration and hypothesis generation, with very small longitudinal cohorts.

生成模型小样本孕产健康合成数据

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