# A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes

## TL;DR

A new tool called MorphOMICs maps microglial shapes in the brain, revealing differences based on brain regions and sex.

## Contribution

MorphOMICs introduces a topological data analysis method to map microglial morphology without feature-selection bias.

## Key findings

- Microglial morphologies vary by brain region and sex in adult mice.
- Sex-specific morphological differences decrease with maturation but increase in neurodegeneration models.
- Microglia do not recover to original shapes after repeated ketamine exposure.

## Abstract

Environmental cues influence the highly dynamic morphology of microglia. Strategies to characterize these changes usually involve user-selected morphometric features, which preclude the identification of a spectrum of context-dependent morphological phenotypes. Here we develop MorphOMICs, a topological data analysis approach, which enables semiautomatic mapping of microglial morphology into an atlas of cue-dependent phenotypes and overcomes feature-selection biases and biological variability. We extract spatially heterogeneous and sexually dimorphic morphological phenotypes for seven adult mouse brain regions. This sex-specific phenotype declines with maturation but increases over the disease trajectories in two neurodegeneration mouse models, with females showing a faster morphological shift in affected brain regions. Remarkably, microglia morphologies reflect an adaptation upon repeated exposure to ketamine anesthesia and do not recover to control morphologies. Finally, we demonstrate that both long primary processes and short terminal processes provide distinct insights to morphological phenotypes. MorphOMICs opens a new perspective to characterize microglial morphology.

Colombo et al. build a morphological spectrum of over 40,000 microglia across development and disease with a topological data analysis approach that allows mapping of new conditions along these sex-region-specific and brain-region-specific atlases.