Amortized Inference for Heterogeneous Reconstruction in Cryo-EM

Axel Levy, Gordon Wetzstein, Julien Martel, Frédéric Poitevin, Ellen D. Zhong

Research output: Chapter in Book/Report/Conference proceedingConference contribution

7 Scopus citations

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.

Original languageEnglish (US)
Title of host publicationAdvances in Neural Information Processing Systems 35 - 36th Conference on Neural Information Processing Systems, NeurIPS 2022
EditorsS. Koyejo, S. Mohamed, A. Agarwal, D. Belgrave, K. Cho, A. Oh
PublisherNeural information processing systems foundation
ISBN (Electronic)9781713871088
StatePublished - 2022
Event36th Conference on Neural Information Processing Systems, NeurIPS 2022 - New Orleans, United States
Duration: Nov 28 2022Dec 9 2022

Publication series

NameAdvances in Neural Information Processing Systems
Volume35
ISSN (Print)1049-5258

Conference

Conference36th Conference on Neural Information Processing Systems, NeurIPS 2022
Country/TerritoryUnited States
CityNew Orleans
Period11/28/2212/9/22

All Science Journal Classification (ASJC) codes

  • Computer Networks and Communications
  • Information Systems
  • Signal Processing

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