Marc Aurèle Gilles1, Amit Singer2. 1. Program in Applied and Computational Mathematics, Princeton University, Fine Hall, Washington Road, Princeton, NJ 08544-1000, United States. Electronic address: mg6942@princeton.edu. 2. Department of Mathematics and PACM, Princeton University, Fine Hall, Washington Road, Princeton, NJ 08544-1000, United States.
Abstract
BACKGROUND AND OBJECTIVE: Wilson statistics describe well the power spectrum of proteins at high frequencies. Therefore, it has found several applications in structural biology, e.g., it is the basis for sharpening steps used in cryogenic electron microscopy (cryo-EM). A recent paper gave the first rigorous proof of Wilson statistics based on a formalism of Wilson's original argument. This new analysis also leads to statistical estimates of the scattering potential of proteins that reveal a correlation between neighboring Fourier coefficients. Here we exploit these estimates to craft a novel prior that can be used for Bayesian inference of molecular structures. METHODS: We describe the properties of the prior and the computation of its hyperparameters. We then evaluate the prior on two synthetic linear inverse problems, and compare against a popular prior in cryo-EM reconstruction at a range of SNRs. RESULTS: We show that the new prior effectively suppresses noise and fills-in low SNR regions in the spectral domain. Furthermore, it improves the resolution of estimates on the problems considered for a wide range of SNR and produces Fourier Shell Correlation curves that are insensitive to masking effects. CONCLUSIONS: We analyze the assumptions in the model, discuss relations to other regularization strategies, and postulate on potential implications for structure determination in cryo-EM.
BACKGROUND AND OBJECTIVE: Wilson statistics describe well the power spectrum of proteins at high frequencies. Therefore, it has found several applications in structural biology, e.g., it is the basis for sharpening steps used in cryogenic electron microscopy (cryo-EM). A recent paper gave the first rigorous proof of Wilson statistics based on a formalism of Wilson's original argument. This new analysis also leads to statistical estimates of the scattering potential of proteins that reveal a correlation between neighboring Fourier coefficients. Here we exploit these estimates to craft a novel prior that can be used for Bayesian inference of molecular structures. METHODS: We describe the properties of the prior and the computation of its hyperparameters. We then evaluate the prior on two synthetic linear inverse problems, and compare against a popular prior in cryo-EM reconstruction at a range of SNRs. RESULTS: We show that the new prior effectively suppresses noise and fills-in low SNR regions in the spectral domain. Furthermore, it improves the resolution of estimates on the problems considered for a wide range of SNR and produces Fourier Shell Correlation curves that are insensitive to masking effects. CONCLUSIONS: We analyze the assumptions in the model, discuss relations to other regularization strategies, and postulate on potential implications for structure determination in cryo-EM.
Authors: Dari Kimanius; Gustav Zickert; Takanori Nakane; Jonas Adler; Sebastian Lunz; Carola-Bibiane Schönlieb; Ozan Öktem; Sjors H W Scheres Journal: IUCrJ Date: 2021-01-01 Impact factor: 4.769