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Spatial Omics Analysis - Reference Data import https://github.com/mims-harvard/ToolUniverse/blob/e2520a96/skills/tooluniverse-spatial-omics-analysis/reference-data.md e2520a96 2026-06-26 prompt accepted upstream false

Spatial Omics Analysis - Reference Data

Reference tables for cell type markers, immune checkpoints, ligand-receptor pairs, and validation methods.


Cell Type Marker Genes

Use these to assign cell types when user does not provide annotations.

Cell Type Key Markers Extended Markers
Epithelial CDH1, EPCAM, KRT18, KRT19 KRT8, KRT14, MUC1
Mesenchymal/Fibroblast VIM, COL1A1, COL3A1, FAP, ACTA2 PDGFRA, PDGFRB
Endothelial PECAM1, VWF, CDH5 KDR, FLT1
T cell (CD8+) CD8A, CD8B GZMA, GZMB, PRF1, IFNG
T cell (CD4+) CD4 IL2, IL4, IL17A, FOXP3 (Treg)
Regulatory T cell FOXP3, IL2RA CTLA4, TIGIT
B cell CD19, MS4A1, CD79A IGHG1, IGHM
Plasma cell SDC1 (CD138), XBP1 IGHG1, MZB1
M1 Macrophage CD68, NOS2, TNF IL1B, CXCL10
M2 Macrophage CD68, CD163, MRC1 ARG1, IL10
Dendritic cell ITGAX (CD11c), HLA-DRA CD80, CD86
NK cell NCAM1 (CD56), NKG7 GNLY, KLRD1
Neutrophil FCGR3B, CXCR2 S100A8, S100A9
Mast cell KIT, TPSAB1 CPA3, HDC
Neuronal SNAP25, SYP, MAP2, NEFL RBFOX3, TUBB3
Hepatocyte ALB, HNF4A, CYP3A4 APOB, TTR

Cell Type Assignment Rules

  • Check each gene against known cell type markers
  • Use HPA tissue/cell type expression data for validation
  • Confidence: high (3+ markers match), medium (2 markers), low (1 marker)

Immune Checkpoint Reference

Checkpoint Gene Ligand Therapeutic Antibody
PD-1/PD-L1 PDCD1/CD274 CD274, PDCD1LG2 Pembrolizumab, Nivolumab, Atezolizumab
CTLA-4 CTLA4 CD80, CD86 Ipilimumab
TIM-3 HAVCR2 LGALS9 Sabatolimab
LAG-3 LAG3 HLA class II Relatlimab
TIGIT TIGIT PVR, PVRL2 Tiragolumab
VISTA VSIR PSGL1 -

Ligand-Receptor Pairs

Known ligand-receptor pairs to check in SVG lists:

Category Ligand Receptor
Growth factors EGF EGFR
Growth factors HGF MET
Growth factors VEGF KDR
Growth factors FGF FGFR
Growth factors PDGF PDGFRA/B
Cytokines TNF TNFR
Cytokines IL6 IL6R
Cytokines IFNG IFNGR
Cytokines TGFB1 TGFBR1/2
Chemokines CXCL12 CXCR4
Chemokines CCL2 CCR2
Chemokines CXCL10 CXCR3
Immune checkpoints CD274 (PD-L1) PDCD1 (PD-1)
Immune checkpoints CD80/CD86 CTLA4
Immune checkpoints LGALS9 HAVCR2 (TIM-3)
Notch signaling DLL1/3/4 NOTCH1/2/3/4
Notch signaling JAG1/2 NOTCH1/2
Wnt signaling WNT ligands FZD receptors
Adhesion CDH1 CDH1 (homotypic)
Adhesion ITGA/B integrins ECM
Hedgehog SHH PTCH1

Enrichment Interpretation Guide

Pathway Category Spatial Interpretation
Signaling (RTK, Wnt, Notch, Hedgehog) Cell-cell communication
Metabolic pathways Tissue metabolic zonation
Immune pathways Immune infiltration/exclusion
ECM/adhesion Tissue structure and remodeling
Cell cycle/proliferation Growth zones
Apoptosis/stress Damage zones

Validation Recommendations Template

Priority Target Method Rationale Feasibility
High Key SVG smFISH / RNAscope Validate spatial pattern at single-molecule level Medium
High Druggable target IHC on serial sections Confirm protein expression in spatial domain High
High Ligand-receptor pair Proximity ligation assay (PLA) Confirm physical interaction at tissue level Medium
Medium Domain markers Multiplexed IF (CODEX/IBEX) Validate multiple markers simultaneously Low-Medium
Medium Pathway Spatial metabolomics (MALDI/DESI) Confirm metabolic pathway activity Low
Low Novel interaction Co-culture + conditioned media Functional validation of predicted interaction Medium

Literature Search Strategy

  1. Tissue + spatial: "{tissue} spatial transcriptomics"
  2. Disease + spatial: "{disease} spatial omics"
  3. Gene + tissue: "{top_gene} {tissue} expression" for key SVGs
  4. Zonation (if relevant): "{tissue} zonation gene expression"
  5. Technology: "{technology} {tissue}"