Label-free identification of protein aggregates using deep learning. 2023

Khalid A Ibrahim, and Kristin S Grußmayer, and Nathan Riguet, and Lely Feletti, and Hilal A Lashuel, and Aleksandra Radenovic
Laboratory of Nanoscale Biology, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

Protein misfolding and aggregation play central roles in the pathogenesis of various neurodegenerative diseases (NDDs), including Huntington's disease, which is caused by a genetic mutation in exon 1 of the Huntingtin protein (Httex1). The fluorescent labels commonly used to visualize and monitor the dynamics of protein expression have been shown to alter the biophysical properties of proteins and the final ultrastructure, composition, and toxic properties of the formed aggregates. To overcome this limitation, we present a method for label-free identification of NDD-associated aggregates (LINA). Our approach utilizes deep learning to detect unlabeled and unaltered Httex1 aggregates in living cells from transmitted-light images, without the need for fluorescent labeling. Our models are robust across imaging conditions and on aggregates formed by different constructs of Httex1. LINA enables the dynamic identification of label-free aggregates and measurement of their dry mass and area changes during their growth process, offering high speed, specificity, and simplicity to analyze protein aggregation dynamics and obtain high-fidelity information.

UI MeSH Term Description Entries
D011499 Protein Processing, Post-Translational Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility. Amino Acid Modification, Post-Translational,Post-Translational Modification,Post-Translational Protein Modification,Posttranslational Modification,Protein Modification, Post-Translational,Amino Acid Modification, Posttranslational,Post-Translational Amino Acid Modification,Post-Translational Modifications,Post-Translational Protein Processing,Posttranslational Amino Acid Modification,Posttranslational Modifications,Posttranslational Protein Processing,Protein Processing, Post Translational,Protein Processing, Posttranslational,Amino Acid Modification, Post Translational,Modification, Post-Translational,Modification, Post-Translational Protein,Modification, Posttranslational,Modifications, Post-Translational,Modifications, Post-Translational Protein,Modifications, Posttranslational,Post Translational Amino Acid Modification,Post Translational Modification,Post Translational Modifications,Post Translational Protein Modification,Post Translational Protein Processing,Post-Translational Protein Modifications,Processing, Post-Translational Protein,Processing, Posttranslational Protein,Protein Modification, Post Translational,Protein Modifications, Post-Translational
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006816 Huntington Disease A familial disorder inherited as an autosomal dominant trait and characterized by the onset of progressive CHOREA and DEMENTIA in the fourth or fifth decade of life. Common initial manifestations include paranoia; poor impulse control; DEPRESSION; HALLUCINATIONS; and DELUSIONS. Eventually intellectual impairment; loss of fine motor control; ATHETOSIS; and diffuse chorea involving axial and limb musculature develops, leading to a vegetative state within 10-15 years of disease onset. The juvenile variant has a more fulminant course including SEIZURES; ATAXIA; dementia; and chorea. (From Adams et al., Principles of Neurology, 6th ed, pp1060-4) Huntington Chorea,Juvenile Huntington Disease,Akinetic-Rigid Variant of Huntington Disease,Chorea, Chronic Progressive Hereditary (Huntington),Chronic Progressive Hereditary Chorea (Huntington),Huntington Chronic Progressive Hereditary Chorea,Huntington Disease, Akinetic-Rigid Variant,Huntington Disease, Juvenile,Huntington Disease, Juvenile-Onset,Huntington Disease, Late Onset,Huntington's Chorea,Huntington's Disease,Juvenile-Onset Huntington Disease,Late-Onset Huntington Disease,Progressive Chorea, Chronic Hereditary (Huntington),Progressive Chorea, Hereditary, Chronic (Huntington),Akinetic Rigid Variant of Huntington Disease,Chorea, Huntington,Chorea, Huntington's,Huntington Disease, Akinetic Rigid Variant,Huntington Disease, Juvenile Onset,Huntington Disease, Late-Onset,Juvenile Onset Huntington Disease,Late Onset Huntington Disease
D000071058 Huntingtin Protein A protein that is highly expressed in the nervous system as well as other tissues; its size and structure vary due to polymorphisms. Expanded CAG TRINUCLEOTIDE REPEATS have been identified in the Huntingtin (HD) Gene of patients with HUNTINGTON DISEASE and are associated with abnormal PROTEIN AGGREGATES. Huntingtin interacts with proteins involved in a variety of gene expression and cellular processes; it is also essential for embryonic development. Huntington Disease Protein,IT15 Protein
D000077321 Deep Learning Supervised or unsupervised machine learning methods that use multiple layers of data representations generated by nonlinear transformations, instead of individual task-specific ALGORITHMS, to build and train neural network models. Hierarchical Learning,Learning, Deep,Learning, Hierarchical
D066329 Protein Aggregates Any mixture of secondary, tertiary, or quaternary protein molecules which appear as clumps in or outside the cell. Protein Aggregate,Aggregate, Protein,Aggregates, Protein

Related Publications

Khalid A Ibrahim, and Kristin S Grußmayer, and Nathan Riguet, and Lely Feletti, and Hilal A Lashuel, and Aleksandra Radenovic
November 2023, Biosensors,
Khalid A Ibrahim, and Kristin S Grußmayer, and Nathan Riguet, and Lely Feletti, and Hilal A Lashuel, and Aleksandra Radenovic
August 2019, Cytometry. Part A : the journal of the International Society for Analytical Cytology,
Khalid A Ibrahim, and Kristin S Grußmayer, and Nathan Riguet, and Lely Feletti, and Hilal A Lashuel, and Aleksandra Radenovic
March 2016, Scientific reports,
Khalid A Ibrahim, and Kristin S Grußmayer, and Nathan Riguet, and Lely Feletti, and Hilal A Lashuel, and Aleksandra Radenovic
January 2022, BME frontiers,
Khalid A Ibrahim, and Kristin S Grußmayer, and Nathan Riguet, and Lely Feletti, and Hilal A Lashuel, and Aleksandra Radenovic
December 2021, Nature cell biology,
Khalid A Ibrahim, and Kristin S Grußmayer, and Nathan Riguet, and Lely Feletti, and Hilal A Lashuel, and Aleksandra Radenovic
March 2023, Small (Weinheim an der Bergstrasse, Germany),
Khalid A Ibrahim, and Kristin S Grußmayer, and Nathan Riguet, and Lely Feletti, and Hilal A Lashuel, and Aleksandra Radenovic
August 2023, Scientific data,
Khalid A Ibrahim, and Kristin S Grußmayer, and Nathan Riguet, and Lely Feletti, and Hilal A Lashuel, and Aleksandra Radenovic
December 2022, ACS sensors,
Khalid A Ibrahim, and Kristin S Grußmayer, and Nathan Riguet, and Lely Feletti, and Hilal A Lashuel, and Aleksandra Radenovic
August 2023, Heliyon,
Khalid A Ibrahim, and Kristin S Grußmayer, and Nathan Riguet, and Lely Feletti, and Hilal A Lashuel, and Aleksandra Radenovic
May 2024, Nature reviews. Molecular cell biology,
Copied contents to your clipboard!