通过时间正则化对比学习,让模型理解细胞动态变化。
DynaCLR: Contrastive Learning of Cellular Dynamics with Temporal Regularization
- 结合单细胞追踪与时间感知采样,学习时序一致的细胞表征。
- 在稀疏标注下实现细胞状态高效识别,跨模态迁移效果好。
- 适合药物、微生物等扰动下的细胞动态比较分析。
我们提出DynaCLR,一种基于时间序列图像对比学习的自监督方法,用于嵌入细胞和细胞器的动态特征。该方法融合单细胞追踪与时间感知对比采样,学习具有强鲁棒性与时序一致性的细胞动态表征。其嵌入结果在分布内和分布外数据集上均表现良好,可支持多种下游任务,且仅需少量人工标注。我们展示了利用荧光与无标记成像通道进行人机协同的高效细胞状态标注。DynaCLR支持多样化生物学分析:细胞分裂与感染分类、异质性细胞迁移模式聚类、从荧光到无标记通道的跨模态状态蒸馏、异步响应与断裂轨迹对齐,以及发现感染引起的细胞器反应。该方法适用于药理学、微生物学和遗传学扰动下细胞动态的比较分析。我们提供了基于PyTorch的训练与推理代码(https://github.com/mehta-lab/viscy),以及用于真实空间和嵌入空间轨迹可视化与标注的GUI工具(https://github.com/czbiohub-sf/napari-iohub)。
原文摘要 · Abstract (English)
We report DynaCLR, a self-supervised method for embedding cell and organelle Dynamics via Contrastive Learning of Representations of time-lapse images. DynaCLR integrates single-cell tracking and time-aware contrastive sampling to learn robust, temporally regularized representations of cell dynamics. DynaCLR embeddings generalize effectively to in-distribution and out-of-distribution datasets, and can be used for several downstream tasks with sparse human annotations. We demonstrate efficient annotations of cell states with a human-in-the-loop using fluorescence and label-free imaging channels. DynaCLR method enables diverse downstream biological analyses: classification of cell division and infection, clustering heterogeneous cell migration patterns, cross-modal distillation of cell states from fluorescence to label-free channel, alignment of asynchronous cellular responses and broken cell tracks, and discovering organelle response due to infection. DynaCLR is a flexible method for comparative analyses of dynamic cellular responses to pharmacological, microbial, and genetic perturbations. We provide PyTorch-based implementations of the model training and inference pipeline (https://github.com/mehta-lab/viscy) and a GUI (https://github.com/czbiohub-sf/napari-iohub) for the visualization and annotation of trajectories of cells in the real space and the embedding space.
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