CenSegNet: a generalist high-throughput deep learning framework for centrosome phenotyping at spatial and single-cell resolution in heterogeneous tissues.

Centrosome abnormalities (CA) are a hallmark of epithelial cancers, yet their spatial complexity and phenotypic heterogeneity remain poorly understood due to limitations in conventional image analysis. Here we present CenSegNet (Centrosome Segmentation Network), a modular deep learning framework for high-throughput segmentation of centrosomes and epithelial architecture, enabling accurate and generalisable centrosome phenotyping at spatial and single-cell resolution across imaging modalities and tissue contexts. Applied to tissue microarrays comprising 911 breast cancer cores from 127 patients, CenSegNet enables large-scale, spatially resolved quantification of numerical and structural CA. We show that these CA subtypes are mechanistically uncoupled, exhibiting distinct spatial distributions, age-dependent dynamics, and associations with tumour grade, hormone receptor status, genomic alterations and nodal involvement. Structural CA are associated with overall survival, whereas discordant CA profiles at tumour margins correlate with local tumour aggressiveness and stromal remodelling. These findings establish CenSegNet as a scalable platform for spatially resolved centrosome phenotyping, enabling systematic investigation of centrosome biology and its dysregulation in cancer and other epithelial diseases.