Cunningham Christian, Sun Bo
Department of Physics, Oregon State University, Corvallis, OR 97331, United States of America.
Phys Biol. 2025 Apr 24;22(3). doi: 10.1088/1478-3975/adcd37.
The morphology and morphodynamics of cells as important biomarkers of the cellular state are widely appreciated in both fundamental research and clinical applications. Quantification of cell morphology often requires a large number of geometric measures that form a high-dimensional feature vector. This mathematical representation creates barriers to communicating, interpreting, and visualizing data. Here, we develop a deep learning-based algorithm to project 13-dimensional (13D) morphological feature vectors into 2-dimensional (2D) morphological latent space (MLS). We show that the projection has less than 5% information loss and separates the different migration phenotypes of metastatic breast cancer cells. Using the projection, we demonstrate the phenotype-dependent motility of breast cancer cells in the 3D extracellular matrix, and the continuous cell state change upon drug treatment. We also find that dynamics in the 2D MLS quantitatively agrees with the morphodynamics of cells in the 13D feature space, preserving the diffusive power and the Lyapunov exponent of cell shape fluctuations even though the dimensional reduction projection is highly nonlinear. Our results suggest that MLS is a powerful tool to represent and understand the cell morphology and morphodynamics.
细胞的形态学和形态动力学作为细胞状态的重要生物标志物,在基础研究和临床应用中都得到了广泛认可。细胞形态的量化通常需要大量形成高维特征向量的几何测量值。这种数学表示给数据的交流、解释和可视化带来了障碍。在此,我们开发了一种基于深度学习的算法,将13维(13D)形态特征向量投影到二维(2D)形态潜在空间(MLS)中。我们表明,这种投影的信息损失小于5%,并能区分转移性乳腺癌细胞的不同迁移表型。利用该投影,我们展示了乳腺癌细胞在三维细胞外基质中的表型依赖性运动性,以及药物处理后细胞状态的持续变化。我们还发现,二维MLS中的动力学与13D特征空间中细胞的形态动力学在数量上是一致的,即使降维投影是高度非线性的,也能保留细胞形状波动的扩散能力和李雅普诺夫指数。我们的结果表明,MLS是一种表征和理解细胞形态及形态动力学的强大工具。