arXiv:2601.21334cs.CV2026-01被引 1

发现病理大模型能隐式捕捉疾病进展轨迹,提升模型可解释性与泛化能力。

Do Pathology Foundation Models Encode Disease Progression? A Pseudotime Analysis of Visual Representations

  • 用扩散伪时间法分析模型表征空间,揭示疾病状态的连续演化方向
  • 所有病理模型均显著优于随机基线,最高轨迹保真度达τ>0.78
  • 轨迹保真度可预测少样本分类性能,适合关注模型生物学意义的研究者

在离散采样的图像上训练的视觉基础模型在分类任务中表现优异,但其表征是否蕴含训练数据中的连续过程仍不明确。这一问题在计算病理学中尤为重要:若模型隐含地捕获了连续疾病进展,则更贴近生物学本质,支持更强泛化,并可实现对疾病转变相关特征的定量分析。本文采用源自单细胞转录组学的扩散伪时间方法,探究基础模型在表征空间中是否将疾病状态组织为连贯的进展方向。在四种癌症进展和六种模型中,所有病理专用模型均显著优于零假设基线,仅使用视觉信息的模型在结直肠锯齿状癌(CRC-Serrated)数据集上达到最高保真度(τ > 0.78)。基于参考疾病上的轨迹保真度排名,能高度预测在未见疾病上的少样本分类性能(ρ = 0.92);探索性分析显示,沿推断轨迹细胞类型组成平滑变化,与已知基质重塑模式一致。结果表明,视觉基础模型可从独立的静态观测中隐式学习连续过程,且轨迹保真度是超越下游性能的表征质量新指标。该框架不仅适用于病理领域,也可推广至其他通过静态快照观察连续过程的场景。

原文摘要 · Abstract (English)

Vision foundation models trained on discretely sampled images achieve strong performance on classification benchmarks, yet whether their representations encode the continuous processes underlying their training data remains unclear. This question is especially pertinent in computational pathology, where we posit that models whose latent representations implicitly capture continuous disease progression may better reflect underlying biology, support more robust generalization, and enable quantitative analyses of features associated with disease transitions. Using diffusion pseudotime, a method developed to infer developmental trajectories from single-cell transcriptomics, we probe whether foundation models organize disease states along coherent progression directions in representation space. Across four cancer progressions and six models, we find that all pathology-specific models recover trajectory orderings significantly exceeding null baselines, with vision-only models achieving the highest fidelities $(τ> 0.78$ on CRC-Serrated). Model rankings by trajectory fidelity on reference diseases strongly predict few-shot classification performance on held-out diseases ($ρ= 0.92$), and exploratory analysis shows cell-type composition varies smoothly along inferred trajectories in patterns consistent with known stromal remodeling. Together, these results demonstrate that vision foundation models can implicitly learn to represent continuous processes from independent static observations, and that trajectory fidelity provides a complementary measure of representation quality beyond downstream performance. While demonstrated in pathology, this framework could be applied to other domains where continuous processes are observed through static snapshots.

病理分析大模型表征疾病进展伪时间

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