CRYO-EM: BREAKTHROUGHS IN CHEMISTRY, STRUCTURAL BIOLOGY, AND STATISTICAL UNDERPINNINGS By

Cryogenic electron microscopy (cryo-EM) has revolutionized structural biology, organic and medicinal chemistry, molecular and cellular physiology, and its fundamental importance was recognized in the 2017 Nobel Prize in Chemistry. Herein we first review the statistical underpinnings of high-resolution 3D image reconstruction from 2D cryo-EM data that have three characteristic features: missing data, high noise level, and massive datasets. We then discuss challenges and opportunities for statistical science posed by high-resolution structure determination using cryo-EM, and review recent advances in high-dimensional multivariate analysis, dimension reduction, maximum a posteriori estimation of latent variables, hidden Markov models and uncertainty quantification in this connection.