Deep learning-based denoising for unbiased analysis of morphology and stiffness in amyloid fibrils

Understanding the morphology of amyloid fibrils is crucial for comprehending the aggregation and degradation mechanisms of abnormal proteins implicated in various diseases, such as Alzheimer's disease, Parkinson's disease, type II diabetes, and various forms of amyloidosis. Atomic force microscopy (AFM) stands as the most representative method for studying amyloid fibril morphology. However, obstacles in AFM images, including noise, salt, and amorphous aggregates, often impede accurate sample quantification. In this study, we developed denoising software employing a U-Net deep learning architecture to address this issue. The software efficiently eliminated various impediments that interfere with fibril analysis in noisy AFM images, thereby facilitating precise quantification of amyloid fibrils. We also developed automated fibril analysis technologies using the denoised AFM images, leading to quicker, more precise, and more objective assessments of fibril morphology. Furthermore, we presented a method for fibril stiffness extraction from a modulus image through mask creation based on a denoised height image. Our approach secures time efficiency and precision in analyzing amyloid morphology, and we believe it will significantly advance the currently stagnant research on amyloid-related diseases.