NeuriteNet: A Convolutional Neural Network for determining morphological differences in neurite growth

Background During development or regeneration, neurons extend processes (i.e., neurites) via mechanisms that can be readily analyzed in culture. However, defining the impact of a drug or genetic manipulation on such mechanisms can be challenging due to the complex arborization and heterogeneous patterns of neurite growth in vitro. New Method NeuriteNet is a Convolutional Neural Network (CNN) sorting model that uses a novel adaptation of the XRAI saliency map overlay, which is a region-based attribution method. NeuriteNet compares neuronal populations based on differences in neurite growth patterns, sorts them into respective groups, and overlays a saliency map indicating which areas differentiated the image for the sorting procedure. Results In this study, we demonstrate that NeuriteNet effectively sorts images corresponding to dissociated neurons into control and treatment groups according to known morphological differences. Furthermore, the saliency map overlay highlights the distinguishing features of the neuron when sorting the images into treatment groups. NeuriteNet also identifies novel morphological differences in neurites of neurons cultured from control and genetically modified mouse strains. Comparison with Existing Methods Unlike other neurite analysis platforms, NeuriteNet does not require manual manipulations, such as segmentation of neurites prior to analysis, and is more accurate than experienced researchers for categorizing neurons according to their pattern of neurite growth. Conclusions NeuriteNet can be used to effectively screen for morphological differences in a heterogeneous group of neurons and to provide feedback on the key features distinguishing those groups via the saliency map overlay. Highlights NeuriteNet is a machine learning model developed to identify differences in control and experimental groups of cultured neurons based on morphological criteria. NeuriteNet’s saliency map highlights the features of the image that associate the neuron with a particular group. NeuriteNet outperforms trained researchers in assigning neurons to control or experimental groups with a known morphological difference as well as those with no previously described difference.