A Dimension Reduction Method for cryo-EM Image Analysis

I-Ping Tu – Academia Sinica


In the field of structural biology, X-ray crystallography and NMR spectroscopy have been two major high-resolution techniques. The former requires crystallization of macromolecules while the latter is a solution method but would meet limit when the macromolecule is large. Very recently, breakthrough in the camera together with microscopy automation, advancement of algorithm and GPU-accelerated computations has transformed cryo-EM to become a standard technique to solve structures of macromolecules at near atomic resolution. In contrast to X-ray crystallography, single particle cryo-EM does not need crystalline sample because it focuses the transmitted electrons to directly provide electron density information of a macromolecule. As such, atomic structures of several difficult macromolecules not amenable to X-ray crystallography have now been rapidly revealed by single particle cryo-EM and single particle cryo-EM has been chosen as the method of 2015 by Nature Method. Because biological molecules are extremely vulnerable, very low doses of electrons are used by cryo-EM, leading to very noisy images. Here, we proposed a dimension reduction method 2stageDR to a set of single-particle cryo-electron-microscopy (cryo-EM) images and demonstrated that 2stageDR can realize e ffective de-noising.