用深度学习从微流控轨迹高效分类肿瘤细胞表型,兼顾准确与可解释性。
Data-Efficient and Interpretable Classification of Circulating Tumor Cell Phenotypes in Microfluidic Devices via Deep Learning

- 设计局部轨迹增强策略SubSeq,提升小样本下的学习效果
- 准确识别细胞表型,较基线方法提升分类性能
- 揭示局部轨迹段的关键生物物理信息,适合医学诊断研究者
准确分类循环肿瘤细胞(CTC)表型有助于评估转移潜力。无标记微流控装置通过流体动力学障碍,将细胞尺寸和柔韧性等细微生物物理特性转化为独特的运动轨迹。然而,轨迹由高度非线性的流体结构相互作用决定,从轨迹反推细胞表型的逆问题在解析上难以求解。尽管深度神经网络(DNN)已成为解决该逆问题的有效手段,但其性能受限于轨迹数据稀缺及缺乏物理可解释性。为此,本文提出一种可解释且数据高效的轨迹驱动CTC分类DNN框架。为缓解数据不足,提出子序列(SubSeq)增强策略,在训练中随机提取有信息量的局部轨迹片段,促进模型学习局部模式。进一步采用梯度加权类激活映射(Grad-CAM)定位驱动预测的关键轨迹特征及微流控器件物理区域。实验表明,SubSeq在多个基线和增强方法上均提升分类准确率。可解释性分析显示,局部轨迹段包含丰富相关生物物理信息,验证了SubSeq的有效性,并揭示全长轨迹存在冗余。该框架将微流控结构视为细胞机械特性的物理编码器,为未来诊断设备设计提供机制洞察。
原文摘要 · Abstract (English)
Accurate classification of circulating tumor cell (CTC) phenotypes can provide valuable information for assessing metastatic potential. Label free microfluidic devices provide a hydrodynamic obstacle course that transforms subtle biophysical characteristics of CTCs, including size and deformability, into distinct kinematic trajectories. However, the highly nonlinear fluid structure interactions governing these trajectories make the inverse problem of inferring cellular phenotype from trajectory data analytically intractable. While deep neural networks (DNNs) have emerged as a powerful approach for addressing this inverse problem, their effectiveness is constrained by the limited availability of trajectory data and the lack of physical interpretability. To address these challenges, we propose an interpretable and data efficient DNN framework for trajectory based CTC classification. To mitigate the scarcity of data, we develop Subsequence (SubSeq), a targeted augmentation strategy that randomly extracts informative local trajectory segments during training to promote learning from localized patterns. We further apply Gradient Weighted Class Activation Mapping to identify the trajectory features and physical regions of the microfluidic device that drive model predictions. Experimental results demonstrate that SubSeq improves classification accuracy over the evaluated baseline and augmentation methods. Furthermore, interpretability analysis suggests that localized trajectory segments contain substantial biophysical information relevant to accurate classification. This provides justification for SubSeq and also highlights the redundancy of full-length trajectories. More broadly, the proposed framework views microfluidic geometries as physical encoders of cellular mechanical properties, providing mechanistic insights that may inform the future design of diagnostic devices.
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