Date Published: June 01, 2017
Publisher: International Union of Crystallography
Author(s): Ardan Patwardhan.
The Electron Microscopy Data Bank (EMDB), the public archive for three-dimensional EM reconstructions, is an invaluable resource for obtaining a birds-eye view of trends affecting the field of cryo-EM. EMDB is growing rapidly, with almost a quarter of the entries having been released over the past year.
Recent technological advances such as the introduction of the direct electron detector have transformed the field of cryo-EM and the landscape of molecular and cellular structural biology (Kühlbrandt, 2014 ▸; Bai et al., 2015 ▸; Eisenstein, 2016 ▸). Structures achieving resolutions that were once considered to be the preserve of the more established structural techniques of X-ray crystallography and nuclear magnetic resonance (NMR) are becoming a routine occurrence. At the same time, there is a greater emphasis on trying to understand the cellular context of macromolecules by placing sub-tomogram averages into tomographic reconstructions and by exploiting correlative imaging techniques (Davies et al., 2011 ▸; Mattei et al., 2016 ▸).
This analysis is based primarily on the metadata included with the publicly released EMDB entries. The information is taken at face value and includes details about the sample, microscopy, image processing and validation (for example, the reported resolution). In order to obtain this information I used the EMDB advanced search that is available via a web form (http://emdb-empiar.org/emsearch) and an API, and the EMStats web service that provides dynamic interactive charts on the current state of the EMDB (http://emdb-empiar.org/emstats). The API queries are summarized in Table 1 ▸. Author affiliation information is not available from EMDB metadata directly. In order to obtain this information, a Python script was written to query PubMed for author affiliation information from publications related to EMDB entries. Manual cleanup of this data had to be performed in Excel to remove redundancy (e.g. ‘UK’ and ‘United Kingdom’). It should also be noted that there are limitations to the consistency of author affiliation information obtained from PubMed in terms of the format and comprehensiveness (prior to 2012 it is only available for corresponding authors, and even now it may not be provided for all authors), which may have some impact on the analysis presented. Moreover, no attempt is made to distinguish between the relative contributions of multiple authors, and all are treated equally.
There were 4431 released entries by the end of 2016, of which 1065 were released in 2016: an increase of over 50% when compared with the 640 entries released in 2015, suggesting a rapid acceleration in the pace of depositions (Fig. 1 ▸). Extrapolation of the curve (x4 curve fitted in Excel with R2 = 0.9994) points to around 10 000 entries by 2020.
The trends in the EMDB underscore the fast-paced changes currently taking place in the cryo-EM field driven by game-changing technologies such as the direct electron detector. Headline high-resolution structures in the past few years have demonstrated the potential of the technique in a wider structural context and have prompted widespread biomedical interest and even adoption by the pharmaceutical industry [for example, the Cambridge Pharmaceutical Cryo-EM Research Consortium (including Astex Pharmaceuticals, AstraZeneca, GlaxoSmithKline, Heptares Therapeutics and UCB, MRC–LMB and the University of Cambridge’s Nanoscience Centre), Novartis, Genentech and Pfizer]. Major investments are under way to set up and expand cryo-EM facilities worldwide, which are likely to substantially increase the available capacity to produce cryo-EM structures. In fact, EMDB trends show that while the US, Germany and the UK continue to maintain leadership in the field, cryo-EM activity has risen rapidly in China to the point where they rank fourth in the number of structures being produced, and that in general a democratization has been taking place, with a substantially broadened base of countries and institutes involved (Stuart et al., 2016 ▸). Furthermore, the rising number of ET structures underlines the growing importance associated with understanding biomacromolecular structure and function in the cellular context. The extrapolated value of 10 000 structures by 2020, which essentially amounts to a doubling of the number of structures being deposited yearly, therefore seems a credible prospect.