Identification of Low Population States in Cryo-EM Using Deep Learning

Cryo-EM has made extraordinary headway towards becoming a semi-automated, high-throughput structure determination technique. In the general workflow, high-to-medium population states are grouped into two- and three-dimensional classes, from which structures can be obtained with near-atomic resolution and subsequently analyzed to interpret function. However, low population states, which are also functionally important, are often discarded. Here, we describe a technique whereby low population states can be efficiently identified with minimal human effort via a deep convolutional neural network classifier. We use this deep learning classifier to describe a transient, low population state of bacteriophage A511 in the midst of infecting its bacterial host. This method can be used to further automate data collection and identify other functionally important low population states.