Paper List

期刊: ArXiv Preprint
发布日期: 2026-03-12
Structural BiologyComputational Biology

SHREC: A Spectral Embedding-Based Approach for Ab-Initio Reconstruction of Helical Molecules

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Guy Shapira, Yoel Shkolnisky
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IN SHORT: This paper addresses the core bottleneck in cryo-EM helical reconstruction: eliminating the dependency on accurate initial symmetry parameter estimation, which is traditionally obtained through error-prone trial-and-error or prior knowledge.

核心创新

  • Methodology Introduces SHREC, the first algorithm that directly recovers projection angles from 2D cryo-EM images without requiring prior knowledge of helical symmetry parameters (rise, twist, or pitch).
  • Methodology Leverages the mathematical insight that projections of helical segments form a one-dimensional manifold, enabling recovery through spectral embedding techniques.
  • Methodology Requires only knowledge of the specimen's axial symmetry group (Cn), significantly reducing the prior information needed compared to traditional methods.

主要结论

  • SHREC successfully recovers projection angles and helical parameters directly from 2D images, validated on public datasets, achieving high-resolution reconstructions.
  • The method is proven mathematically: projections of helical segments form a 1D manifold (Lemma 1.9), and the angle between segments θ is directly related to their axial displacement (θ = 2π/P * (t2 - t1), Lemma 1.6).
  • By eliminating the initial symmetry estimation step, SHREC provides a more robust and automated pathway, reducing a major source of error in ab-initio helical reconstruction.
研究空白: Current helical reconstruction methods (e.g., Fourier-Bessel, IHRSR, RELION/cryoSPARC pipelines) are fundamentally limited by their dependency on accurate initial symmetry parameter estimates. Poor initialization leads to convergence to incorrect solutions, making the process unreliable, non-automated, and sensitive to user expertise.

摘要: Cryo-electron microscopy (cryo-EM) has emerged as a powerful technique for determining the three-dimensional structures of biological molecules at near-atomic resolution. However, reconstructing helical assemblies presents unique challenges due to their inherent symmetry and the need to determine unknown helical symmetry parameters. Traditional approaches require an accurate initial estimation of these parameters, which is often obtained through trial and error or prior knowledge. These requirements can lead to incorrect reconstructions, limiting the reliability of ab initio helical reconstruction. In this work, we present SHREC (Spectral Helical REConstruction), an algorithm that directly recovers the projection angles of helical segments from their two-dimensional cryo-EM images, without requiring prior knowledge of helical symmetry parameters. Our approach leverages the insight that projections of helical segments form a one-dimensional manifold, which can be recovered using spectral embedding techniques. Experimental validation on publicly available datasets demonstrates that SHREC achieves high resolution reconstructions while accurately recovering helical parameters, requiring only knowledge of the specimen’s axial symmetry group. By eliminating the need for initial symmetry estimates, SHREC offers a more robust and automated pathway for determining helical structures in cryo-EM.