Clustering polymorphs of tau and IAPP fibrils with the CHEP algorithm.

Recent steps towards automation have improved the quality and efficiency of the entire cryo-electron microscopy workflow, from sample preparation to image processing. Most of the image processing steps are now quite automated, but there are still a few steps which need the specific intervention of researchers. One such step is the identification and separation of helical protein polymorphs at early stages of image processing. Here, we tested and evaluated our recent clustering approach on three datasets containing amyloid fibrils, demonstrating that the proposed unsupervised clustering method automatically and effectively identifies the polymorphs from cryo-EM images. As an automated polymorph separation method, it has the potential to complement automated helical picking, which typically cannot easily distinguish between polymorphs with subtle differences in morphology, and is therefore a useful tool for the image processing and structure determination of helical proteins.