PT  - JOURNAL ARTICLE
AU  - Dari Kimanius
AU  - Liyi Dong
AU  - Grigory Sharov
AU  - Takanori Nakane
AU  - Sjors H.W. Scheres
TI  - New tools for automated cryo-EM single-particle analysis in RELION-4.0
AID  - 10.1101/2021.09.30.462538
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.09.30.462538
4099  - http://biorxiv.org/content/early/2021/09/30/2021.09.30.462538.short
4100  - http://biorxiv.org/content/early/2021/09/30/2021.09.30.462538.full
AB  - We describe new tools for the processing of electron cryo-microscopy (cryo-EM) images in the fourth major release of the RELION software. In particular, we introduce VDAM, a Variable-metric gradient Descent algorithm with Adaptive Moments estimation, for image refinement; a convolutional neural network for unsupervised selection of 2D classes; and a flexible framework for the design and execution of multiple jobs in pre-defined workflows. In addition, we present a stand-alone utility called MDCatch that links the execution of jobs within this framework with metadata gathering during microscope data acquisition. The new tools are aimed at providing fast and robust procedures for unsupervised cryo-EM structure determination, with potential applications for on-the-fly processing and the development of flexible, high-throughput structure determination pipelines. We illustrate their potential on twelve publicly available cryo-EM data sets.Competing Interest StatementThe authors have declared no competing interest.