# Addressing preferred orientation in single-particle cryo-EM through AI-generated auxiliary particles

arXiv: https://arxiv.org/abs/2309.14954 · HTML: https://mlsanity.com/paper/2309.14954/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 7 of its 46 references that are in the map.
- First posted on arXiv 26 Sep 2023.

## Builds on (most cited first, 7 of 7)

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [Residual Dense Network for Image Super-Resolution](https://mlsanity.com/paper/1802.08797/) (2018)
- [NVAE: A Deep Hierarchical Variational Autoencoder](https://mlsanity.com/paper/2007.03898/) (2020)
- [Generating Sentences from a Continuous Space](https://mlsanity.com/paper/1511.06349/) (2015)
- [Ladder Variational Autoencoders](https://mlsanity.com/paper/1602.02282/) (2016)
- [Very Deep VAEs Generalize Autoregressive Models and Can Outperform Them on Images](https://mlsanity.com/paper/2011.10650/) (2020)
- [Learn from Unpaired Data for Image Restoration: A Variational Bayes Approach](https://mlsanity.com/paper/2204.10090/) (2022)

## Abstract (arXiv)

The single-particle cryo-EM field faces the persistent challenge of preferred orientation, lacking general computational solutions. We introduce cryoPROS, an AI-based approach designed to address the above issue. By generating the auxiliary particles with a conditional deep generative model, cryoPROS addresses the intrinsic bias in orientation estimation for the observed particles. We effectively employed cryoPROS in the cryo-EM single particle analysis of the hemagglutinin trimer, showing the ability to restore the near-atomic resolution structure on non-tilt data. Moreover, the enhanced version named cryoPROS-MP significantly improves the resolution of the membrane protein NaX using the no-tilted data that contains the effects of micelles. Compared to the classical approaches, cryoPROS does not need special experimental or image acquisition techniques, providing a purely computational yet effective solution for the preferred orientation problem. Finally, we conduct extensive experiments that establish the low risk of model bias and the high robustness of cryoPROS.