Statistical analysis and data mining of digital reconstructions of dendritic morphologies.

Neuronal morphology is diverse among animal species, developmental stages, brain regions, and cell types. The geometry of individual neurons also varies substantially even within the same cell class. Moreover, specific histological, imaging, and reconstruction methodologies can differentially affect morphometric measures. The quantitative characterization of neuronal arbors is necessary for in-depth understanding of the structure-function relationship in nervous systems. The large collection of community-contributed digitally reconstructed neurons available at NeuroMorpho.Org constitutes a "big data" research opportunity for neuroscience discovery beyond the approaches typically pursued in single laboratories. To illustrate these potential and related challenges, we present a database-wide statistical analysis of dendritic arbors enabling the quantification of major morphological similarities and differences across broadly adopted metadata categories. Furthermore, we adopt a complementary unsupervised approach based on clustering and dimensionality reduction to identify the main morphological parameters leading to the most statistically informative structural classification. We find that specific combinations of measures related to branching density, overall size, tortuosity, bifurcation angles, arbor flatness, and topological asymmetry can capture anatomically and functionally relevant features of dendritic trees. The reported results only represent a small fraction of the relationships available for data exploration and hypothesis testing enabled by sharing of digital morphological reconstructions.