In silicoPreprint

Model infers spatial neighborhoods in dissociated single cells

The computational tool predicted cellular proximity across brain regions and identified age-associated neighborhood remodeling in an 8-month Alzheimer dataset.

bioRxiv

In brain tissue transcriptomic datasets, researchers tested ProxiNet, a computational framework designed to infer cellular proximity from dissociated single-cell RNA sequencing. While spatial transcriptomics captures intact tissue architecture, dissociated single-cell methods lose spatial context. ProxiNet trains on spatial reference data to learn expression signatures of pairwise cell proximity and transfers those relationships to dissociated cells.

The framework predicted proximity across brain regions and across different spatial technologies. In datasets with known coordinates, it recovered anatomical structures and reproducible tissue organization. When applied to dissociated single-cell data, ProxiNet revealed cellular neighborhoods and candidate cell communication programs. In an Alzheimer dataset, the model detected age-associated neighborhood remodeling, including an altered neighborhood at 8 months marked by distinct astrocyte and neuronal transcriptional states.

Why it matters

Mapping how cellular neighborhoods reorganize over time could clarify how localized cell-to-cell communication programs change during aging and neurodegeneration.

Caveats

The findings were reported in a preprint and rely on computational inference, meaning the predicted spatial relationships and communication programs require direct experimental confirmation.

The paper

ProxiNet transfers spatially learned cellular proximity to dissociated single-cell transcriptomes

Whitehead Institute for Biomedical Research

bioRxiv · 30 Sep 2026 · Preprint, not peer-reviewed

doi.org/10.64898/2026.09.25.754372