Department of Electronic Engineering, University of Rome Tor Vergata, Rome, Italy.
Department of Chemical Science and Technologies, University of Rome Tor Vergata, Rome, Italy.
Sci Rep. 2020 May 6;10(1):7653. doi: 10.1038/s41598-020-64246-3.
We describe a novel method to achieve a universal, massive, and fully automated analysis of cell motility behaviours, starting from time-lapse microscopy images. The approach was inspired by the recent successes in application of machine learning for style recognition in paintings and artistic style transfer. The originality of the method relies i) on the generation of atlas from the collection of single-cell trajectories in order to visually encode the multiple descriptors of cell motility, and ii) on the application of pre-trained Deep Learning Convolutional Neural Network architecture in order to extract relevant features to be used for classification tasks from this visual atlas. Validation tests were conducted on two different cell motility scenarios: 1) a 3D biomimetic gels of immune cells, co-cultured with breast cancer cells in organ-on-chip devices, upon treatment with an immunotherapy drug; 2) Petri dishes of clustered prostate cancer cells, upon treatment with a chemotherapy drug. For each scenario, single-cell trajectories are very accurately classified according to the presence or not of the drugs. This original approach demonstrates the existence of universal features in cell motility (a so called "motility style") which are identified by the DL approach in the rationale of discovering the unknown message in cell trajectories.
我们描述了一种新颖的方法,可以从延时显微镜图像开始,实现对细胞运动行为的通用、大规模和全自动分析。该方法的灵感来自于机器学习在绘画风格识别和艺术风格迁移中的最新应用成功。该方法的创新性在于:i)从单细胞轨迹的集合中生成图谱,以便直观地编码细胞运动的多个描述符;ii)应用预训练的深度学习卷积神经网络架构,以便从该图谱中提取相关特征,用于分类任务。在两种不同的细胞运动场景中进行了验证测试:1)在器官芯片设备中与乳腺癌细胞共培养的免疫细胞 3D 仿生凝胶,在接受免疫治疗药物治疗后;2)集群前列腺癌细胞的培养皿,在接受化疗药物治疗后。对于每种情况,单细胞轨迹都根据药物的存在与否非常准确地进行分类。这种原始方法证明了细胞运动中存在通用特征(所谓的“运动风格”),DL 方法通过发现细胞轨迹中的未知信息来识别这些特征。