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bioRxiv · 10.64898/2026.03.17.712386

Cryo-EM image processing of amyloid filaments in RELION-5.1

Lövestam, S.·Shi, J.·Li, D.·Jamali, K.·Scheres, S.
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Abstract

We present new tools for the structure determination of amyloid filaments from electron cryo-microscopy (cryo-EM) images. We introduce a new algorithm for automated filament picking, based on their characteristic 4.75 [A] repeat signal; we implement the new auto-picker in a fully automated procedure for on-the-fly pre-processing of cryo-EM data sets of amyloid filaments; we present a graphical tool to select filament types based on bi-hierarchical clustering of filaments and 2D class assignments; and we introduce a denoising neural network for Blush regularisation that is re-trained on amyloid reconstructions. The implementation of these tools in release 5.1 of our open-software package RELION ensures broad applicability. We demonstrate their usefulness on two experimental data sets, including a previously described data set on recombinant human islet amyloid protein (hIAPP) with the S20G mutation for which we identify two new filament types.

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Lövestam, S., Shi, J., Li, D., Jamali, K., Scheres, S.. 2026-03-17. Cryo-EM image processing of amyloid filaments in RELION-5.1. https://doi.org/10.64898/2026.03.17.712386

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