Multi-CryoGAN: Reconstruction of Continuous Conformations in Cryo-EM Using Generative Adversarial Networks

Harshit Gupta, Thong Huy Phan, Jaejun Yoo, Michael Unser

TL;DR: We reconstruct continuous conformations of biomolecules from their Cryo-EM measurements without hidden variable (pose or conformation) estimation.

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Abstract: We propose a deep-learning-based reconstruction method for cryo-electron microscopy (Cryo-EM) that can model multiple conformations of a nonrigid biomolecule in a standalone manner. Cryo-EM produces many noisy projections from separate instances of the same but randomly oriented biomolecule. Current methods rely on pose and conformation estimation which are inefficient for the reconstruction of continuous conformations that carries valuable information. We introduce Multi-CryoGAN, which sidesteps the additional processing by casting the volume reconstruction into the distribution matching problem. By introducing a manifold mapping module, Multi-CryoGAN can learn continuous structural heterogeneity without pose estimation nor clustering. We also give a theoretical guarantee of recovery of the true conformations. Our method can successfully reconstruct 3D protein complexes on synthetic 2D Cryo-EM datasets for both continuous and discrete structural variability scenarios. Multi-CryoGAN is the first model that can reconstruct continuous conformations of a biomolecule from Cryo-EM images in a fully unsupervised and end-to-end manner.

Keywords: Cryo-EM, Inverse problem, Image reconstruction, Generative Adversarial Networks, Continuous protein conformations