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Bibliographic Details
Main Authors: Shekarforoush, Shayan, Lindell, David B., Brubaker, Marcus A., Fleet, David J.
Format: Preprint
Published: 2025
Subjects:
Online Access:https://arxiv.org/abs/2506.09063
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author Shekarforoush, Shayan
Lindell, David B.
Brubaker, Marcus A.
Fleet, David J.
author_facet Shekarforoush, Shayan
Lindell, David B.
Brubaker, Marcus A.
Fleet, David J.
contents Cryo-EM is a transformational paradigm in molecular biology where computational methods are used to infer 3D molecular structure at atomic resolution from extremely noisy 2D electron microscope images. At the forefront of research is how to model the structure when the imaged particles exhibit non-rigid conformational flexibility and compositional variation where parts are sometimes missing. We introduce a novel 3D reconstruction framework with a hierarchical Gaussian mixture model, inspired in part by Gaussian Splatting for 4D scene reconstruction. In particular, the structure of the model is grounded in an initial process that infers a part-based segmentation of the particle, providing essential inductive bias in order to handle both conformational and compositional variability. The framework, called CryoSPIRE, is shown to reveal biologically meaningful structures on complex experimental datasets, and establishes a new state-of-the-art on CryoBench, a benchmark for cryo-EM heterogeneity methods.
format Preprint
id arxiv_https___arxiv_org_abs_2506_09063
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Reconstructing Heterogeneous Biomolecules via Hierarchical Gaussian Mixtures and Part Discovery
Shekarforoush, Shayan
Lindell, David B.
Brubaker, Marcus A.
Fleet, David J.
Quantitative Methods
Computer Vision and Pattern Recognition
Machine Learning
Image and Video Processing
Cryo-EM is a transformational paradigm in molecular biology where computational methods are used to infer 3D molecular structure at atomic resolution from extremely noisy 2D electron microscope images. At the forefront of research is how to model the structure when the imaged particles exhibit non-rigid conformational flexibility and compositional variation where parts are sometimes missing. We introduce a novel 3D reconstruction framework with a hierarchical Gaussian mixture model, inspired in part by Gaussian Splatting for 4D scene reconstruction. In particular, the structure of the model is grounded in an initial process that infers a part-based segmentation of the particle, providing essential inductive bias in order to handle both conformational and compositional variability. The framework, called CryoSPIRE, is shown to reveal biologically meaningful structures on complex experimental datasets, and establishes a new state-of-the-art on CryoBench, a benchmark for cryo-EM heterogeneity methods.
title Reconstructing Heterogeneous Biomolecules via Hierarchical Gaussian Mixtures and Part Discovery
topic Quantitative Methods
Computer Vision and Pattern Recognition
Machine Learning
Image and Video Processing
url https://arxiv.org/abs/2506.09063