Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, USA.
Department of Computer Science, Stanford University, Stanford, USA.
BMC Bioinformatics. 2022 May 28;23(1):195. doi: 10.1186/s12859-022-04738-3.
Determining cell identity in volumetric images of tagged neuronal nuclei is an ongoing challenge in contemporary neuroscience. Frequently, cell identity is determined by aligning and matching tags to an "atlas" of labeled neuronal positions and other identifying characteristics. Previous analyses of such C. elegans datasets have been hampered by the limited accuracy of such atlases, especially for neurons present in the ventral nerve cord, and also by time-consuming manual elements of the alignment process.
We present a novel automated alignment method for sparse and incomplete point clouds of the sort resulting from typical C. elegans fluorescence microscopy datasets. This method involves a tunable learning parameter and a kernel that enforces biologically realistic deformation. We also present a pipeline for creating alignment atlases from datasets of the recently developed NeuroPAL transgene. In combination, these advances allow us to label neurons in volumetric images with confidence much higher than previous methods.
We release, to the best of our knowledge, the most complete full-body C. elegans 3D positional neuron atlas, incorporating positional variability derived from at least 7 animals per neuron, for the purposes of cell-type identity prediction for myriad applications (e.g., imaging neuronal activity, gene expression, and cell-fate).
在标记神经元核的体积图像中确定细胞身份是当代神经科学的一个持续挑战。通常,通过将标记与“图谱”中的标记神经元位置和其他识别特征对齐和匹配来确定细胞身份。以前对这些 C. elegans 数据集的分析受到图谱准确性的限制,尤其是对于存在于腹神经索中的神经元,并且还受到对齐过程中耗时的手动元素的限制。
我们提出了一种新的自动对准方法,用于从典型的 C. elegans 荧光显微镜数据集产生的稀疏和不完整的点云。该方法涉及可调学习参数和核,以强制生物现实的变形。我们还提出了一种从最近开发的 NeuroPAL 转基因数据集创建对齐图谱的管道。结合使用,这些进展使我们能够以比以前的方法更高的置信度对体积图像中的神经元进行标记。
我们发布了迄今为止最完整的全虫体 C. elegans 3D 位置神经元图谱,该图谱纳入了至少每个神经元 7 只动物的位置变异性,用于预测众多应用(例如,成像神经元活动、基因表达和细胞命运)的细胞类型身份。