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Information Hub:

• The analysis conversation (more detail) : https://app.thedrylab.com/share/wLRjnJxzWVYz
• Files (image, excels, code) generated from the conversation can be found here: https://drive.google.com/drive/folders/1uaE57IyQTB9ty-g-NpAjQiUPdyM5qQRN?usp=sharing </aside>

Executive Summary

This comprehensive analysis of the E-MTAB-8077 multi-organ endothelial cell dataset successfully identified and prioritized 118 liver-specific cell surface therapeutic targets through systematic integration of single-cell transcriptomics, spatial analysis, and druggability assessment. The study analyzed 38,983 endothelial cells from 10 organs, revealing distinct molecular specialization patterns and establishing a robust pipeline for liver-directed therapeutic interventions.

Dataset Characterization and Multi-Organ UMAP Analysis

Key Findings

• Comprehensive atlas construction: Successfully integrated and analyzed 38,983 high-quality endothelial cells from 10 organs (brain, colon, heart, kidney, liver, lung, muscle, small intestine, spleen, testis) using 5,359 common genes, identifying 20 distinct clusters through graph-based clustering with resolution 0.5
• Organ-specific clustering patterns: UMAP visualization revealed clear tissue-specific endothelial specialization with liver endothelial cells (4,168 cells, 10.7%) forming distinct clusters alongside organ-enriched populations from brain (Cluster 3), lung (Cluster 4), and liver (Cluster 5)

• Dual organizational principles: Identified both highly organ-restricted clusters and pan-organ endothelial subtypes, indicating fundamental endothelial programs that transcend tissue boundaries while maintaining specialized functions for local microenvironments

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Output Files

• cell_metadata.csv – Metadata for each cell, including cluster and organ information.
• umap_by_clusters.png – UMAP visualization colored by cell clusters.
• umap_by_organ.png – UMAP visualization colored by organ of origin.
• umap_combined.png – Combined UMAP plot integrating clusters and organs. </aside>

Liver Endothelial Cell Molecular Specialization

Key Findings

• Differential expression analysis: Identified 891 significantly upregulated genes in liver endothelial cells compared to other organs (p_adj < 0.05), with 482 high-confidence liver-specific genes showing LogFC > 0.5, demonstrating extensive molecular specialization
• Top liver-specific markers: Lgmn (legumain) shows highest specificity with 3.68-fold enrichment (73.4% liver vs 13.8% others), followed by Apoe (3.37-fold), Lgals1 (3.18-fold), Cd59a (3.10-fold), and Man2a1 (2.91-fold), representing distinct functional categories
• Functional pathway enrichment: Liver-specific genes cluster into lipid metabolism (Apoe, Agpat5), immune regulation (Lgmn, Cd59a, Il6st), lysosomal processing (Lgals1, Lamp2, Ctsl), and specialized transport (Slc29a1, Sepp1), reflecting hepatic physiological demands