Reconstructing Heterogeneous Biomolecules via Hierarchical Gaussian Mixtures and Part Discovery

• URL: http://arxiv.org/abs/2506.09063v1
• Date: Fri, 06 Jun 2025 22:38:54 GMT
• Title: Reconstructing Heterogeneous Biomolecules via Hierarchical Gaussian Mixtures and Part Discovery
• Authors: Shayan Shekarforoush, David B. Lindell, Marcus A. Brubaker, David J. Fleet,
• Abstract summary: 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.<n>We introduce a novel 3D reconstruction framework with a hierarchical Gaussian mixture model, inspired in part by Gaussian Splatting for 4D scene reconstruction.<n>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.
• Score: 30.195615398809043
• License: http://creativecommons.org/licenses/by/4.0/
• Abstract: 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.

Related papers

• CryoGS: Gaussian Splatting for Cryo-EM Homogeneous Reconstruction [55.2480439325792]
  cryogenic electron microscopy (cryo-EM) facilitates the determination of macromolecular structures at near-atomic resolution.<n>The core computational task in single-particle cryo-EM is to reconstruct the 3D electrostatic potential of a molecule.<n>We introduce cryoGS, a GMM-based method that integrates Gaussian splatting with the physics of cryo-EM image formation.
  arXiv  Detail & Related papers  (2025-08-06T23:24:43Z)
• DiffSpectra: Molecular Structure Elucidation from Spectra using Diffusion Models [66.41802970528133]
  Molecular structure elucidation from spectra is a foundational problem in chemistry.<n>Traditional methods rely heavily on expert interpretation and lack scalability.<n>We present DiffSpectra, a generative framework that directly infers both 2D and 3D molecular structures from multi-modal spectral data.
  arXiv  Detail & Related papers  (2025-07-09T13:57:20Z)
• Mixture of neural fields for heterogeneous reconstruction in cryo-EM [29.837972881181102]
  We present Hydra, an approach that models both conformational and compositional heterogeneity fully ab initio.<n>We employ a new likelihood-based loss function and demonstrate the effectiveness of our approach on synthetic datasets composed of mixtures of proteins.
  arXiv  Detail & Related papers  (2024-12-12T16:26:38Z)
• ShapeMamba-EM: Fine-Tuning Foundation Model with Local Shape Descriptors and Mamba Blocks for 3D EM Image Segmentation [49.42525661521625]
  This paper presents ShapeMamba-EM, a specialized fine-tuning method for 3D EM segmentation. It is tested over a wide range of EM images, covering five segmentation tasks and 10 datasets.
  arXiv  Detail & Related papers  (2024-08-26T08:59:22Z)
• CryoBench: Diverse and challenging datasets for the heterogeneity problem in cryo-EM [3.424647356090208]
  Cryo-electron microscopy (cryo-EM) is a powerful technique for determining high-resolution 3D biomolecular structures from imaging data.<n>Here, we introduce CryoBench, a suite of datasets, metrics, and benchmarks for heterogeneous reconstruction in cryo-EM.
  arXiv  Detail & Related papers  (2024-08-10T11:48:14Z)
• CryoChains: Heterogeneous Reconstruction of Molecular Assembly of Semi-flexible Chains from Cryo-EM Images [3.0828074702828623]
  We propose CryoChains that encodes large deformations of biomolecules via rigid body transformation of their chains. Our data experiments on the human GABAtextsubscriptB and heat shock protein show that CryoChains gives a biophysically-grounded quantification of the heterogeneous conformations of biomolecules.
  arXiv  Detail & Related papers  (2023-06-12T17:57:12Z)
• Functional-Group-Based Diffusion for Pocket-Specific Molecule Generation and Elaboration [63.23362798102195]
  We propose D3FG, a functional-group-based diffusion model for pocket-specific molecule generation and elaboration. D3FG decomposes molecules into two categories of components: functional groups defined as rigid bodies and linkers as mass points. In the experiments, our method can generate molecules with more realistic 3D structures, competitive affinities toward the protein targets, and better drug properties.
  arXiv  Detail & Related papers  (2023-05-30T06:41:20Z)
• MUDiff: Unified Diffusion for Complete Molecule Generation [104.7021929437504]
  We present a new model for generating a comprehensive representation of molecules, including atom features, 2D discrete molecule structures, and 3D continuous molecule coordinates. We propose a novel graph transformer architecture to denoise the diffusion process. Our model is a promising approach for designing stable and diverse molecules and can be applied to a wide range of tasks in molecular modeling.
  arXiv  Detail & Related papers  (2023-04-28T04:25:57Z)
• CryoFormer: Continuous Heterogeneous Cryo-EM Reconstruction using Transformer-based Neural Representations [49.49939711956354]
  Cryo-electron microscopy (cryo-EM) allows for the high-resolution reconstruction of 3D structures of proteins and other biomolecules. It is still challenging to reconstruct the continuous motions of 3D structures from noisy and randomly oriented 2D cryo-EM images. We propose CryoFormer, a new approach for continuous heterogeneous cryo-EM reconstruction.
  arXiv  Detail & Related papers  (2023-03-28T18:59:17Z)
• Heterogeneous reconstruction of deformable atomic models in Cryo-EM [30.864688165021054]
  We describe a heterogeneous reconstruction method based on an atomistic representation whose deformation is reduced to a handful of collective motions. We show for each distribution that our approach is able to recapitulate the intermediate atomic models with atomic-level accuracy.
  arXiv  Detail & Related papers  (2022-09-29T22:35:35Z)
• Deep learning based mixed-dimensional GMM for characterizing variability in CryoEM [0.0]
  CryoEM provides direct visualization of individual macromolecules in different conformational and compositional states. We present a machine learning algorithm to determine a conformational landscape for proteins or complexes. We demonstrate this method on several different biomolecular systems to explore compositional and conformational changes at a range of scales.
  arXiv  Detail & Related papers  (2021-01-25T19:05:23Z)

This list is automatically generated from the titles and abstracts of the papers in this site.

This site does not guarantee the quality of this site (including all information) and is not responsible for any consequences.