Sorzano, C. O. S. / Carazo, J. M. Cryo-Electron Microscopy: The field of 1,000^+ methods. 2022. Journal of structural biology, Vol. 214, p. 107861
Cryo-Electron Microscopy (CryoEM) is currently a well-established method to elucidate a biological macromolecule's three-dimensional (3D) structure. Its success is due to technological and methodological advances in several fronts: sample preparation, electron optics and detection, image acquisition, image processing, and map interpretation. The first methods started in the late 1960s and, since then, new methods on all fronts have continuously been published, maturating the field as we know it now. In terms of publications, we can distinguish several periods, witnessing a substantial acceleration of methodological publications in recent years, pointing out to an increased interest in the domain. On the other hand, this accelerated increase of methods development may confuse practitioners about which method they should be using (and how) and highlight the importance of paying attention to establishing best practices for methods reporting and usage. In this paper, we analyze the trends identified in over 1,000 methodological papers. Our focus is primarily on computational image processing methods. However, our list also covers some aspects of sample preparation and image acquisition. Several interesting ideas stem out from this study: (1) Single Particle Analysis (SPA) has largely accelerated in the last decade and sample preparation methods in the last five years; (2) Electron Tomography is not yet in a rapidly growing phase, but it is foreseeable that it will soon be; (3) the work horses of SPA are 3D classification, 3D reconstruction, and 3D alignment, and there have been many papers on these topics, which are not considered to be solved yet, but ever improving; and (4) since the resolution revolution, atomic modelling has also caught on as a hot topic.