A computational suite for the structural and functional characterization of amyloid aggregates.

Image processing analysis automation fluorescence microscopy neurodegenerative disease protein aggregate characterisation super-resolution imaging

Journal

Cell reports methods
ISSN: 2667-2375
Titre abrégé: Cell Rep Methods
Pays: United States
ID NLM: 9918227360606676

Informations de publication

Date de publication:
26 06 2023
Historique:
received: 24 10 2022
revised: 11 04 2023
accepted: 17 05 2023
medline: 11 7 2023
pubmed: 10 7 2023
entrez: 10 7 2023
Statut: epublish

Résumé

We developed the aggregate characterization toolkit (ACT), a fully automated computational suite based on existing and widely used core algorithms to measure the number, size, and permeabilizing activity of recombinant and human-derived aggregates imaged with diffraction-limited and super-resolution microscopy methods at high throughput. We have validated ACT on simulated ground-truth images of aggregates mimicking those from diffraction-limited and super-resolution microscopies and showcased its use in characterizing protein aggregates from Alzheimer's disease. ACT is developed for high-throughput batch processing of images collected from multiple samples and is available as an open-source code. Given its accuracy, speed, and accessibility, ACT is expected to be a fundamental tool in studying human and non-human amyloid intermediates, developing early disease stage diagnostics, and screening for antibodies that bind toxic and heterogeneous human amyloid aggregates.

Identifiants

pubmed: 37426747
doi: 10.1016/j.crmeth.2023.100499
pii: S2667-2375(23)00128-5
pmc: PMC10326375
doi:

Substances chimiques

Protein Aggregates 0
Amyloid 0
Amyloidogenic Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

100499

Subventions

Organisme : Medical Research Council
Pays : United Kingdom

Informations de copyright

© 2023 The Authors.

Déclaration de conflit d'intérêts

The authors declare no competing interests.

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Auteurs

Zengjie Xia (Z)

Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
UK Dementia Research Institute, University of Cambridge, Cambridge CB2 0AH, UK.

Yunzhao Wu (Y)

Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
UK Dementia Research Institute, University of Cambridge, Cambridge CB2 0AH, UK.

Jeff Yui Long Lam (JYL)

Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
UK Dementia Research Institute, University of Cambridge, Cambridge CB2 0AH, UK.

Ziwei Zhang (Z)

Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
UK Dementia Research Institute, University of Cambridge, Cambridge CB2 0AH, UK.

Melanie Burke (M)

Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
UK Dementia Research Institute, University of Cambridge, Cambridge CB2 0AH, UK.

Emre Fertan (E)

Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
UK Dementia Research Institute, University of Cambridge, Cambridge CB2 0AH, UK.

Rohan T Ranasinghe (RT)

Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
UK Dementia Research Institute, University of Cambridge, Cambridge CB2 0AH, UK.

Eric Hidari (E)

Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
UK Dementia Research Institute, University of Cambridge, Cambridge CB2 0AH, UK.

John S H Danial (JSH)

Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
UK Dementia Research Institute, University of Cambridge, Cambridge CB2 0AH, UK.

David Klenerman (D)

Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
UK Dementia Research Institute, University of Cambridge, Cambridge CB2 0AH, UK.

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Classifications MeSH