Gap: Modality-Dependent Divergence in SEA-AD Cell-State Vulnerability Calls

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Description

Across the SEA-AD dataset, cell-state vulnerability calls show systematic divergence depending on which modality is used for measurement. snRNA-seq compositional analyses and MERFISH spatial transcriptomics produce non-concordant vulnerability rankings for the same cell populations, particularly for Layer 2/3 IT excitatory neurons and PVALB+ interneurons. Resolving this modality-concordance gap is necessary before any causal intervention targeting a specific cell state can be justified. Closing it requires a joint scCODA/Dirichlet analysis of matched snRNA-seq and MERFISH donors using the SEA-AD AWS registry data. Sources: doi:10.1038/s41593-024-01774-5 (atlas), doi:10.1038/s41586-024-07871-6 (community trajectories), https://registry.opendata.aws/allen-sea-ad-atlas/ (data access), https://github.com/AllenInstitute/SEA-AD_2024 (reproducibility code).

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