Deep learning-enabled phenotyping reveals distinct patterns of neurodegeneration induced by aging and cold-shock

Abstract Access to quantitative information is crucial to obtain a deeper understanding of biological systems. In addition to being low-throughput, traditional image-based analysis is mostly limited to error-prone qualitative or semi-quantitative assessment of phenotypes, particularly for complex subcellular morphologies. In this work, we apply deep learning to perform quantitative image-based analysis of complex neurodegeneration patterns exhibited by the PVD neuron in C. elegans. We apply a Convolutional Neural Network algorithm (Mask R-CNN) to identify neurodegenerative sub-cellular protrusions that appear after cold-shock or as a result of aging. A multiparametric phenotypic profile captures the unique morphological changes induced by each perturbation. We identify that acute cold-shock-induced neurodegeneration is reversible and depends on rearing temperature, and importantly, that aging and cold-shock induce distinct neuronal beading patterns.