用轨迹模型分析NK细胞杀伤行为,提升预测准确性。
BLINK: Behavioral Latent Modeling of NK Cell Cytotoxicity
- 基于轨迹的递归状态空间模型,捕捉细胞动态交互
- 在长时间录像中准确预测细胞凋亡累积与杀伤结果
- 可解释的隐变量揭示细胞行为模式与交互阶段
细胞相互作用动力学的机器学习模型有望揭示细胞行为机制。自然杀伤(NK)细胞的杀伤作用是此类动态的典型代表,通常通过时间分辨的多通道荧光显微镜研究。尽管肿瘤细胞死亡事件可在单帧中标注,但NK细胞的杀伤结果需通过细胞间长期互动形成,无法仅靠逐帧分类可靠推断。我们提出BLINK,一种基于轨迹的递归状态空间模型,作为NK-肿瘤相互作用的细胞世界模型。BLINK从部分观测的NK-肿瘤交互序列中学习隐含的动力学,并预测逐渐累积的凋亡增量,最终形成杀伤结果。在长期时间推移的NK-肿瘤记录实验中,该模型显著提升了杀伤结果检测能力,并能预测未来结果;同时提供可解释的隐变量表示,将NK细胞轨迹归纳为连贯的行为模式与时间结构化的交互阶段。BLINK为单细胞水平上量化评估和结构化建模NK杀伤行为提供了统一框架。
原文摘要 · Abstract (English)
Machine learning models of cellular interaction dynamics hold promise for understanding cell behavior. Natural killer (NK) cell cytotoxicity is a prominent example of such interaction dynamics and is commonly studied using time-resolved multi-channel fluorescence microscopy. Although tumor cell death events can be annotated at single frames, NK cytotoxic outcome emerges over time from cellular interactions and cannot be reliably inferred from frame-wise classification alone. We introduce BLINK, a trajectory-based recurrent state-space model that serves as a cell world model for NK-tumor interactions. BLINK learns latent interaction dynamics from partially observed NK-tumor interaction sequences and predicts apoptosis increments that accumulate into cytotoxic outcomes. Experiments on long-term time-lapse NK-tumor recordings show improved cytotoxic outcome detection and enable forecasting of future outcomes, together with an interpretable latent representation that organizes NK trajectories into coherent behavioral modes and temporally structured interaction phases. BLINK provides a unified framework for quantitative evaluation and structured modeling of NK cytotoxic behavior at the single-cell level.
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