Wang Dali, Lu Zheng, Xu Yichi, Wang Z I, Santella Anthony, Bao Zhirong
Department of Electrical Engineering and Computer Science, University of Tennessee, Knoxville, TN 37934, USA.
Environmental Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA.
IEEE Access. 2019;7:148967-148974. doi: 10.1109/access.2019.2940161. Epub 2019 Sep 9.
Cell shapes provide crucial biological information on complex tissues. Different cell types often have distinct cell shapes, and collective shape changes usually indicate morphogenetic events and mechanisms. The identification and detection of collective cell shape changes in an extensive collection of 3D time-lapse images of complex tissues is an important step in assaying such mechanisms but is a tedious and time-consuming task. Machine learning provides new opportunities to automatically detect cell shape changes. However, it is challenging to generate sufficient training samples for pattern identification through deep learning because of a limited amount of images and annotations. We present a deep learning approach with minimal well-annotated training samples and apply it to identify multicellular rosettes from 3D live images of the embryo with fluorescently labeled cell membranes. Our strategy is to combine two approaches, namely, feature transfer and generative adversarial networks (GANs), to boost image classification with small training samples. Specifically, we use a GAN framework and conduct an unsupervised training to capture the general characteristics of cell membrane images with 11,250 unlabelled images. We then transfer the structure of the GAN discriminator into a new Alex-style neural network for further learning with several dozen labeled samples. Our experiments showed that with 10-15 well-labeled rosette images and 30-40 randomly selected nonrosette images our approach can identify rosettes with more than 80% accuracy and capture more than 90% of the model accuracy achieved with a training data et that is five times larger. We also established a public benchmark dataset for rosette detection. This GAN-based transfer approach can be applied to the study of other cellular structures with minimal training samples.
细胞形状为复杂组织提供了关键的生物学信息。不同的细胞类型通常具有独特的细胞形状,而集体形状变化通常表明形态发生事件和机制。在大量复杂组织的3D延时图像中识别和检测集体细胞形状变化是分析此类机制的重要一步,但却是一项繁琐且耗时的任务。机器学习为自动检测细胞形状变化提供了新机会。然而,由于图像和注释数量有限,通过深度学习生成足够的训练样本用于模式识别具有挑战性。我们提出了一种使用最少注释良好的训练样本的深度学习方法,并将其应用于从具有荧光标记细胞膜的胚胎3D实时图像中识别多细胞玫瑰花结。我们的策略是结合两种方法,即特征转移和生成对抗网络(GAN),以利用少量训练样本提升图像分类。具体而言,我们使用GAN框架并进行无监督训练,以利用11250张未标记图像捕捉细胞膜图像的一般特征。然后,我们将GAN判别器的结构转移到一个新的Alex风格神经网络中,以便使用几十个标记样本进行进一步学习。我们的实验表明,使用10 - 15张注释良好的玫瑰花结图像和30 - 40张随机选择的非玫瑰花结图像,我们的方法能够以超过80%的准确率识别玫瑰花结,并且能够获得使用五倍大的训练数据集所达到的模型准确率的90%以上。我们还建立了一个用于玫瑰花结检测的公共基准数据集。这种基于GAN的转移方法可以应用于使用最少训练样本的其他细胞结构研究。