Analysis Proposal
Analysis Question
Can we validate the relationship between ent-gene-28e2cb01 and microglia through expression evidence in neurodegeneration-relevant datasets?
Datasets
Human Brain Cell Atlas (HBCA) single-nucleus RNA-seq referenceAllen Brain Cell Atlas microglial snRNA-seq profilesNuclei from the dorsolateral prefrontal cortex (DLPFC) - PsychENCODEADNI post-mortem brain tissue bulk RNA-seq with microglial deconvolution
Methods
Query gene expression levels in microglial clusters from snRNA-seq data using established markers (TYROBP, CX3CR1, TREM2) as positive controls for cell-type annotation accuracyPerform differential expression analysis comparing microglia vs. other brain cell types to quantify cell-type specificity scoresCross-validate against published microglia-specific gene signatures (e.g., 257-gene human microglial catalog from Geirsdottir et al., 2019) using overlap statistics and rank correlationApply Bayesian integration across datasets to compute posterior probability of cell-type-specific expression
Expected Outputs
- Cell-type specificity score (tau or specificity metric) for ent-gene-28e2cb01 in microglia relative to neuronal, astrocytic, and oligodendrocyte populations
- Statistical significance (adjusted p-value) from differential expression comparing microglial vs. non-microglial cells with log2 fold-change magnitude
- Cross-dataset concordance report indicating whether expression is validated in ≥2 independent datasets or contradicting evidence found
- Final trust score update recommendation (increase, maintain, or decrease confidence) for the expressed_in edge based on accumulated evidence weight