Advances in Xmipp for Cryo–Electron Microscopy: From Xmipp to Scipion

Abstract

Xmipp is an open-source software package consisting of multiple programs for processing data originating from electron microscopy and electron tomography, designed and managed by the Biocomputing Unit of the Spanish National Center for Biotechnology, although with contributions from many other developers over the world. During its 25 years of existence, Xmipp underwent multiple changes and updates. While there were many publications related to new programs and functionality added to Xmipp, there is no single publication on the Xmipp as a package since 2013. In this article, we give an overview of the changes and new work since 2013, describe technologies and techniques used during the development, and take a peek at the future of the package.

MDSPACE: Extracting Continuous Conformational Landscapes from Cryo-EM Single Particle Datasets Using 3D-to-2D Flexible Fitting based on Molecular Dynamics Simulation

“…The resulting clusters of particle images in the PCA space can be manually refined (by adding or removing data, including removal of outliers). The 3D reconstruction of the EM maps from the clusters is obtained by direct Fourier interpolation using Xmipp [63,64].…”

“…To rigid-body pre-align the initial conformation with the particle images, we performed 4 iterations of projection matching between the images and the density map from the initial conformation, in Xmipp [63,64], using the angular sampling rate of 7°, 5°, 3°, and 2° over the 4 iterations as well as no limit on the angular search in the first iteration and a limit on the angular search range of 10°, 6°, and 4° in the other three iterations. As the initial conformation is very different from the target conformations in the images, the projection matching gives only a rough alignment.…”

Scipion3: A workflow engine for cryo-electron microscopy image processing and structural biology

“…Thus, many image-processing software for cryo-EM have been developed without a coordination effort to unify data and metadata conventions. Most popular software such as Relion ( 17 ) , Cryosparc ( 18 ) , EMAN2 ( 19 ) , Xmipp ( 20 ) , cistem ( 21 ) , motioncor2 ( 22 ) , and so forth are able to read and write a common image file format such as mrc, but when it comes to the metadata, they all define their own specification. This is the case for Relion or Xmipp using .star ( 23 ) files with their own labels, Cryosparc using NumPy ( 24 ) saved files (.cs), or EMAN2 handling a mixture of .hdf, .json, and .box files.…”

MDTOMO: Continuous conformational variability analysis in cryo electron subtomogram data using flexible fitting based on Molecular Dynamics simulations

“…Following a method that adds Gaussian noise before and after the CTF 37 , three sets of images were obtained corresponding to a SNR of 0.05, 0.03, and 0.01. The synthetic subtomograms were obtained from the simulated images using weighted back-projection in Fourier space 38 . The subtomograms were aligned using STA based on the FRM algorithm 30 in Scipion.…”