PT - JOURNAL ARTICLE AU - Thorsten Wagner AU - Felipe Merino AU - Markus Stabrin AU - Toshio Moriya AU - Claudia Antoni AU - Amir Apelbaum AU - Philine Hagel AU - Oleg Sitsel AU - Tobias Raisch AU - Daniel Prumbaum AU - Dennis Quentin AU - Daniel Roderer AU - Sebastian Tacke AU - Birte Siebolds AU - Evelyn Schubert AU - Tanvir R. Shaikh AU - Pascal Lill AU - Christos Gatsogiannis AU - Stefan Raunser TI - SPHIRE-crYOLO: A fast and accurate fully automated particle picker for cryo-EM AID - 10.1101/356584 DP - 2019 Jan 01 TA - bioRxiv PG - 356584 4099 - http://biorxiv.org/content/early/2019/03/13/356584.short 4100 - http://biorxiv.org/content/early/2019/03/13/356584.full AB - Selecting particles from digital micrographs is an essential step in single particle electron cryomicroscopy (cryo-EM). Since manual selection of complete datasets typically comprising many thousands of particles is a tedious and time-consuming process, many automatic particle pickers have been developed in the past few decades. However, non-ideal datasets pose a challenge to particle picking. Here, we present a novel automated particle picking software called crYOLO, which is based on the deep learning object detection system “You Only Look Once” (YOLO). After training the network with 500 – 2,500 particles per dataset, it automatically recognizes particles with high recall and precision reaching a speed of up to five micrographs per second. Importantly, we demonstrate a powerful general network trained on more than 40 datasets to select previously unseen datasets, thus paving the way for completely automated “on-the-fly” cryo-EM data pre-processing during data acquisition. CrYOLO is available as a standalone program under http://sphire.mpg.de/ and will be part of the image processing workflow in SPHIRE.