DeepCryoPicker: Fully Automated Deep Neural Network for Single Protein Particle Picking in cryo-EM

Cryo-electron microscopy (Cryo-EM) is widely used in the determination of the three-dimensional (3D) structures of macromolecules. Particle picking from 2D micrographs remains a challenging early step in the Cryo-EM pipeline due to the diversity of particle shapes and the extremely low signal-to-noise ratio (SNR) of micrographs. Because of these issues, significant human intervention is often required to generate a high-quality set of particles for input to the downstream structure determination steps. Here we propose a fully automated approach (DeepCryoPicker) for single particle picking based on deep learning. It first uses automated unsupervised learning to generate particle training datasets. Then it trains a deep neural network to classify particles automatically. Results indicate that the DeepCryoPicker compares favorably with semi-automated methods such as DeepEM, DeepPicker and RELION, with the significant advantage of not requiring human intervention.