Spatially resolved molecular signatures of Lewy body dementia and the Impact of APOE4

This repository contains the computational methods used in the study: "Spatially resolved molecular signatures of Lewy body dementia and the Impact of APOE4" by Jin et al. This study investigates the spatial transcriptomic signatures of Lewy body dementia (LBD) with a focus on the impact of APOE4 genotype. Our analysis examines the molecular differences between APOE3 and APOE4 carriers in LBD patients.

• processAndIntegrate.r: QC, filtering, normalization and integration of spatial data using Seurat and Harmony.
• spacexrDeconvolution.r: Cell type deconvolution using SpaceXR.
• spacexr_functions.r: Custom extensions for SpaceXR.
• figures.R: Visualization scripts for all manuscript figures.
• dotplot_IPA.R: Visualization of Ingenuity Pathway Analysis results.
• upsetPlots.r: UpSet plots for differentially expressed gene intersections.
• stats.R: Statistical analysis of LB annotations across layers, genotypes, and disease states.

The analysis follows these key steps:

1. Processing and integration of spatial transcriptomics data
2. Cell type deconvolution using snRNA-seq reference data
3. Annotation of spatial spots for LB status and cortical layers
4. Differential expression analysis between APOE genotypes
5. Pathway analysis and visualization

Na Zhao (zhao.na@mayo.edu), Mayo Clinic, Department of Neuroscience for more information.