Axel Levy

All Publications

• Amortized Inference for Heterogeneous Reconstruction in Cryo-EM. Advances in neural information processing systems Levy, A., Wetzstein, G., Martel, J., Poitevin, F., Zhong, E. D. 2022; 35: 13038-13049

  Abstract

  Cryo-electron microscopy (cryo-EM) is an imaging modality that provides unique insights into the dynamics of proteins and other building blocks of life. The algorithmic challenge of jointly estimating the poses, 3D structure, and conformational heterogeneity of a biomolecule from millions of noisy and randomly oriented 2D projections in a computationally efficient manner, however, remains unsolved. Our method, cryoFIRE, performs ab initio heterogeneous reconstruction with unknown poses in an amortized framework, thereby avoiding the computationally expensive step of pose search while enabling the analysis of conformational heterogeneity. Poses and conformation are jointly estimated by an encoder while a physics-based decoder aggregates the images into an implicit neural representation of the conformational space. We show that our method can provide one order of magnitude speedup on datasets containing millions of images without any loss of accuracy. We validate that the joint estimation of poses and conformations can be amortized over the size of the dataset. For the first time, we prove that an amortized method can extract interpretable dynamic information from experimental datasets.

  View details for PubMedID 37529401

• Deep Generative Modeling for Volume Reconstruction in Cryo-Electron Microscopy. Journal of structural biology Donnat, C., Levy, A., Poitevin, F., Zhong, E. D., Miolane, N. 2022: 107920

  Abstract

  Advances in cryo-electron microscopy (cryo-EM) for high-resolution imaging of biomolecules in solution have provided new challenges and opportunities for algorithm development for 3D reconstruction. Next-generation volume reconstruction algorithms that combine generative modelling with end-to-end unsupervised deep learning techniques have shown promise, but many technical and theoretical hurdles remain, especially when applied to experimental cryo-EM images. In light of the proliferation of such methods, we propose here a critical review of recent advances in the field of deep generative modelling for cryo-EM reconstruction. The present review aims to (i) provide a unified statistical framework using terminology familiar to machine learning researchers with no specific background in cryo-EM, (ii) review the current methods in this framework, and (iii) outline outstanding bottlenecks and avenues for improvements in the field.

  View details for DOI 10.1016/j.jsb.2022.107920

  View details for PubMedID 36356882

• CryoAI: Amortized Inference of Poses for Ab Initio Reconstruction of 3D Molecular Volumes from Real Cryo-EM Images. Computer vision - ECCV ... : ... European Conference on Computer Vision : proceedings. European Conference on Computer Vision Levy, A., Poitevin, F., Martel, J., Nashed, Y., Peck, A., Miolane, N., Ratner, D., Dunne, M., Wetzstein, G. 2022; 13681: 540-557

  Abstract

  Cryo-electron microscopy (cryo-EM) has become a tool of fundamental importance in structural biology, helping us understand the basic building blocks of life. The algorithmic challenge of cryo-EM is to jointly estimate the unknown 3D poses and the 3D electron scattering potential of a biomolecule from millions of extremely noisy 2D images. Existing reconstruction algorithms, however, cannot easily keep pace with the rapidly growing size of cryo-EM datasets due to their high computational and memory cost. We introduce cryoAI, an ab initio reconstruction algorithm for homogeneous conformations that uses direct gradient-based optimization of particle poses and the electron scattering potential from single-particle cryo-EM data. CryoAI combines a learned encoder that predicts the poses of each particle image with a physics-based decoder to aggregate each particle image into an implicit representation of the scattering potential volume. This volume is stored in the Fourier domain for computational efficiency and leverages a modern coordinate network architecture for memory efficiency. Combined with a symmetrized loss function, this framework achieves results of a quality on par with state-of-the-art cryo-EM solvers for both simulated and experimental data, one order of magnitude faster for large datasets and with significantly lower memory requirements than existing methods.

  View details for DOI 10.1007/978-3-031-19803-8_32

  View details for PubMedID 36745134