• Home
  • Search
  • Bayesian Perspective for Orientation Determination in Cryo-EM with Application to Structural Heterogeneity Analysis
  • https://doi.org/10.1101/2024.12.04.626841Copy DOI Icon

Bayesian Perspective for Orientation Determination in Cryo-EM with Application to Structural Heterogeneity Analysis

  • Oct 12, 2025
  • bioRxiv
  • Sheng Xu +3 more
Show More
  • Abstract
  • Literature Map
  • References
  • Similar Papers
Abstract

Accurate orientation estimation is a crucial component of 3D molecular structure reconstruction, both in single-particle cryo-electron microscopy (cryo-EM) and in the increasingly popular field of cryo-electron tomography (cryo-ET). The dominant approach, which involves searching for the orientation that maximizes cross-correlation relative to given templates, is sub-optimal, particularly under low signal-to-noise conditions. In this work, we propose a Bayesian framework for more accurate and flexible orientation estimation, with the minimum mean square error (MMSE) estimator serving as a key example. Through simulations, we demonstrate that the MMSE estimator consistently outperforms the cross-correlation-based method, especially in challenging low signal-to-noise scenarios, and we provide a theoretical framework that supports these improvements.When incorporated into iterative refinement algorithms in the 3D reconstruction pipeline, the MMSE estimator markedly improves reconstruction accuracy, reduces model bias, and enhances robustness to the “Einstein from Noise” artifact. Crucially, we demonstrate that orientation estimation accuracy has a decisive effect on downstream structural heterogeneity analysis. In particular, integrating the MMSE-based pose estimator into frameworks for continuous heterogeneity recovery yields accuracy improvements approaching those obtained with ground-truth poses, establishing MMSE-based pose estimation as a key enabler of high-fidelity conformational landscape reconstruction. These findings indicate that the proposed Bayesian framework could substantially advance cryo-EM and cryo-ET by enhancing the accuracy, robustness, and reliability of 3D molecular structure reconstruction, thereby facilitating deeper insights into complex biological systems.

Similar Papers
  • Research Article
  • Citations16

Minimum mean square error estimation in linear regression

  • Nov 01, 1993
  • Journal of Statistical Planning and Inference
  • Erkki P Liski +2
  • Research Article
  • Citations234

A Bayesian estimation approach for speech enhancement using hidden Markov models

  • Apr 01, 1992
  • IEEE Transactions on Signal Processing
  • Y Ephraim
  • Research Article

Simplified LS and Modified MMSE Estimators for Channel Estimation of OFDM

  • Jun 01, 2014
  • CVR Journal of Science & Technology
  • B Janardhana Rao +1
  • Research Article

A Context for Training - Based Approximation in Randomly Correlated Rician Mimo Channels with Rician Disruption

  • Jan 01, 2014
  • Figshare
  • Kakileti Pradeep +1
  • Research Article

A Context for Training - Based Approximation in Randomly Correlated Rician Mimo Channels with Rician Disruption

  • Jan 01, 2014
  • IOSR Journal of Electronics and Communication Engineering
  • Kakileti Pradeep +1
  • Research Article
  • Citations8

Two dimension angle of arrival-based precoding for pilot contamination reduction in multi-cell massive MIMO systems

  • Apr 03, 2020
  • Wireless Networks
  • Ehab Ali +6
  • Conference Article
  • Citations5

Speech enhancement using an Improved MMSE estimator with Laplacian prior

  • Dec 01, 2010
  • M Rashidi-Nejad +2
  • Research Article
  • Citations79

Quaternion-Based Kalman Filter With Vector Selection for Accurate Orientation Tracking

  • Oct 01, 2012
  • IEEE Transactions on Instrumentation and Measurement
  • Zhi-Qiang Zhang +2
  • Research Article
  • Citations275

Massive MIMO With Spatially Correlated Rician Fading Channels

  • May 01, 2019
  • IEEE Transactions on Communications
  • Ozgecan Ozdogan +2
  • Conference Article
  • Citations5

Channel estimation and data detection with tracking channel variation in MIMO system using ZF-based SAGE algorithm

  • Jan 01, 2005
  • T Someya +1
  • Conference Article
  • Citations3

Low-complexity receiver for OFDM in doubly-selective channels

  • Dec 01, 2003
  • P Schniter
  • Research Article
  • Citations11

Information Rates for Channels with Fading, Side Information and Adaptive Codewords.

  • Apr 27, 2023
  • Entropy
  • Gerhard Kramer
  • Conference Article
  • Citations5

A MMSE filter for range sidelobe reduction

  • Jul 24, 2000
  • N Goodman +1
  • Research Article
  • Citations19

An MMSE approach to nonlocal image denoising: Theory and practical implementation

  • Jan 27, 2012
  • Journal of Visual Communication and Image Representation
  • Chul Lee +2
  • Research Article
  • Citations282

A Framework for Training-Based Estimation in Arbitrarily Correlated Rician MIMO Channels With Rician Disturbance

  • Mar 01, 2010
  • IEEE Transactions on Signal Processing
  • E Bjornson +1
Cactus Communications logo

Copyright 2026 Cactus Communications. All rights reserved.