CEP-IP with CMRF in SEA-AD Microglia: A Mitochondrial Co-expression Module Linked to Cognition

In the SEA-AD microglia snRNA-seq dataset, higher Module post-IP% for an MT-CO3 mitochondrial co-expression module is linked to worse cognition (MMSE and CASI; FDR<0.05) across M4, PVM_3, and PVM_1.

• Why it matters: Routine snRNA-seq mitochondrial filtering (%MT or mitochondrial gene removal) may discard transcriptomic signals that relate to cognitive performance in Alzheimer’s disease, but this connection has been rarely tested.
• What they did: A transcriptome-wide screen in SEA-AD microglia identified an MT-CO3 module with eight co-expressed mitochondrial genes; the CEP-IP pipeline with CMRF used per-cell Spearman and Kendall scores, an inflection point, and a cross-validated copula boundary to isolate module cells.
• The result: Module post-IP% remained significantly associated with worse MMSE/CASI after adjustment for tissue quality, plaque burden, tangle burden, and contamination and after doublet removal, and it repeated beyond chance within donors; no per-cell %MT cutoff reproduced the module cells.