Machine Learning Classification Reveals Robust Morphometric Biomarker of Glial and Neuronal Arbors

Neurons and glia are the two main cell classes in the nervous systems of most animals. Although functionally distinct, neurons and glia are both characterized by multiple branching arbors stemming from the cell bodies. Glial processes are generally known to form smaller trees than neuronal dendrites. However, the full extent of morphological differences between neurons and glia in multiple species and brain regions has not yet been characterized, nor is it known whether these cells can be reliably distinguished based on geometric features alone. Here, we show that multiple supervised learning algorithms (K-nearest neighbor, random forest, and support vector machine) deployed on a large database of morphological reconstructions can systematically classify neuronal and glial arbors with nearly perfect accuracy and precision. Moreover, we report multiple morphometric properties, both size-related and size-independent, that differ substantially between these cell types. In particular, we newly identify an individual morphometric measurement, Average Branch Euclidean Length (ABEL) that can robustly separate neurons from glia across multiple animal models, a broad diversity of experimental conditions, and anatomical areas, with the notable exception of the cerebellum. We discuss the practical utility and physiological interpretation of this discovery.