A methodology using Gaussian-based density map approximation to assess sets of cryo-electron microscopy density maps

This article presents a methodology to assess a set of density maps, as used in the Blind Assessment Phase of the 2015/2016 Map Challenge (EMDataBank Validation Challenges). The synthetic and experimental cryo-electron microscopy (cryo-EM) density maps obtained by different single particle analysis protocols and by different participants, submitted in the Challenge Phase for assessment, were analyzed with this methodology and the obtained results are presented and discussed here. The goal of using such a methodology was to blindly identify the density maps with globally similar structural information, meaning the maps with the structural information mostly “reproduced” by different protocols. To this end, the density maps are “coarsened” using Gaussian-based approximations, with the same input approximation parameters for all maps of the target biological complex. The approximated maps are then represented in a common reduced-dimension (here, 3D) space of their correlation-coefficient-based distances, in which close maps mean similar maps. The distance analysis allows identifying maps with the most “reproduced” structural information by different protocols. The obtained results are also discussed taking into account the detailed information about the protocols that has been released after the end of the Blind Assessment Phase.