Spatial Fc-Engagement Programs in Lecanemab-Treated Microglia Oppose

This repository contains the complete R analysis script and allpublication figures (Figures 1–5) accompanying the manuscript "SpatialFc-Engagement Programs in Lecanemab-Treated Microglia OpposeAlzheimer's Disease Transcriptomic Signatures: An Integrative SpatialTranscriptomic Analysis."The single integrated script(lecanemab_spatial_integrated_analysis.R) reproduces the fullanalytical pipeline: (1) ingestion of spatial transcriptomic (.h5ad)and scRNA-seq (10x MTX) data from GEO accessions GSE297667 andGSE297665; (2) pseudobulk differential expression across fiveplaque-distance zones (0–25, 25–50, 50–100, 100–250, >250 µm) usingedgeR quasi-likelihood GLMs, followed by Reactome pathway enrichmentusing fgsea; (3) microglial identity and state scoring forcompositional control; (4) pathway-level reversal analysis comparinglecanemab-associated spatial signatures against Alzheimer's diseasesignatures from four independent human bulk transcriptomic datasets(GSE33000, GSE44770, GSE5281, GSE48350), aggregated byinverse-variance weighted fixed-effect meta-analysis; (5)leave-one-section-out robustness analysis of spatial moduletrajectories; and (6) generation of all publication figures.All input data are publicly available from NCBI GEO. The GSE48350dataset required NES sign-correction (contrast coded Control vs AD insource matrix); this is documented in the script and manuscriptMethods. Scripts are written in R (≥ 4.4.0) and depend onBioconductor packages (edgeR, limma, fgsea, SingleCellExperiment,zellkonverter, GEOquery) and CRAN packages (msigdbr, mgcv, data.table,ggplot2, patchwork). Full instructions are provided in README.md.