# Improved Cryo-EM Pose Estimation and 3D Classification through Latent-Space Disentanglement

arXiv: https://arxiv.org/abs/2308.04956 · HTML: https://mlsanity.com/paper/2308.04956/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Builds on 9 of its 30 references that are in the map.
- First posted on arXiv 9 Aug 2023.

## Builds on (most cited first, 9 of 9)

- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [Fourier Features Let Networks Learn High Frequency Functions in Low Dimensional Domains](https://mlsanity.com/paper/2006.10739/) (2020)
- [Reconstructing continuous distributions of 3D protein structure from cryo-EM images](https://mlsanity.com/paper/1909.05215/) (2019)
- [CryoAI: Amortized Inference of Poses for Ab Initio Reconstruction of 3D Molecular Volumes from Real Cryo-EM Images](https://mlsanity.com/paper/2203.08138/) (2022)
- [Amortized Inference for Heterogeneous Reconstruction in Cryo-EM](https://mlsanity.com/paper/2210.07387/) (2022)
- [Deep Generative Modeling for Volume Reconstruction in Cryo-Electron Microscopy](https://mlsanity.com/paper/2201.02867/) (2022)
- [Inferring a Continuous Distribution of Atom Coordinates from Cryo-EM Images using VAEs](https://mlsanity.com/paper/2106.14108/) (2021)
- [Differentiable probabilistic models of scientific imaging with the Fourier slice theorem](https://mlsanity.com/paper/1906.07582/) (2019)
- [Hyper-Molecules: on the Representation and Recovery of Dynamical Structures, with Application to Flexible Macro-Molecular Structures in Cryo-EM](https://mlsanity.com/paper/1907.01589/) (2019)

## Built on by (most cited first, 1 of 1)

- [Recovering a Molecule's 3D Dynamics from Liquid-phase Electron Microscopy Movies](https://mlsanity.com/paper/2308.11927/) (2023)

## Abstract (arXiv)

Due to the extremely low signal-to-noise ratio (SNR) and unknown poses (projection angles and image shifts) in cryo-electron microscopy (cryo-EM) experiments, reconstructing 3D volumes from 2D images is very challenging. In addition to these challenges, heterogeneous cryo-EM reconstruction requires conformational classification. In popular cryo-EM reconstruction algorithms, poses and conformation classification labels must be predicted for every input cryo-EM image, which can be computationally costly for large datasets. An emerging class of methods adopted the amortized inference approach. In these methods, only a subset of the input dataset is needed to train neural networks for the estimation of poses and conformations. Once trained, these neural networks can make pose/conformation predictions and 3D reconstructions at low cost for the entire dataset during inference. Unfortunately, when facing heterogeneous reconstruction tasks, it is hard for current amortized-inference-based methods to effectively estimate the conformational distribution and poses from entangled latent variables. Here, we propose a self-supervised variational autoencoder architecture called "HetACUMN" based on amortized inference. We employed an auxiliary conditional pose prediction task by inverting the order of encoder-decoder to explicitly enforce the disentanglement of conformation and pose predictions. Results on simulated datasets show that HetACUMN generated more accurate conformational classifications than other amortized or non-amortized methods. Furthermore, we show that HetACUMN is capable of performing heterogeneous 3D reconstructions of a real experimental dataset.