Label-free identification of protein aggregates using deep learning
Khalid A. Ibrahim (École Polytechnique Fédérale de Lausanne)
Kristin S. Grußmayer (TU Delft - BN/Kristin Grussmayer Lab, Kavli institute of nanoscience Delft)
Nathan Riguet (École Polytechnique Fédérale de Lausanne)
Lely Feletti (École Polytechnique Fédérale de Lausanne)
Hilal A. Lashuel (École Polytechnique Fédérale de Lausanne)
Aleksandra Radenovic (École Polytechnique Fédérale de Lausanne)
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Abstract
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.
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