{
 "signature": {
  "n_genes": 567,
  "up": 383,
  "down": 184,
  "min_studies": 6,
  "CCL26": {
   "log2FC": 4.56,
   "k": 9,
   "n_up": 9,
   "padj": 0.00034
  }
 },
 "mast": {
  "eoe_pct": 2.63,
  "healthy_pct": 0.19,
  "fold": 14.0,
  "mwu_p": 7.2e-05
 },
 "pseudotime": {
  "EoE": 4.2,
  "Healthy": 14.4
 },
 "gwas": {
  "n_genes": 7,
  "genes": [
   "DDAH1",
   "CAPN14",
   "IFFO2",
   "MT2A",
   "DSG1",
   "NRXN1",
   "ST6GAL1"
  ],
  "CAPN14_OR": 1.77,
  "DSG1_OR": 2.22,
  "IFFO2_OR": 1.826
 },
 "cohorts": {
  "n_datasets": 57,
  "n_bulk_cohorts": 9,
  "n_samples": 235,
  "eoe": 152,
  "control": 83
 },
 "cells": {
  "total": 166420,
  "healthy_samples": 12,
  "eoe_samples": 11
 },
 "terminal_diff": {
  "eoe_pct": 5.4,
  "healthy_pct": 17.9,
  "note": "marker-based terminal-differentiation fraction (phase-1/2 definition); diffusion-pseudotime top-decile gives 4.2 vs 14.4 \u2014 same direction"
 },
 "ppi": {
  "class": "refractory-persistent (all 3 leads)",
  "CCL26_persist": 6.1,
  "IL1RL1_persist": 2.85,
  "SIGLEC6_persist": 3.59
 },
 "druggability": {
  "top20_secreted_or_surface_frac": 1.0
 },
 "leads": {
  "SIGLEC6": {
   "modality": "depleting mAb / ADC (afucosylated IgG1)",
   "epitope": "Ig-V domain 28-123, Arg cluster (R122/R100/R109-114) or acidic face",
   "esm_mean_entropy": 0.601,
   "companion": "SIGLEC6+ mast fraction (IHC/flow)",
   "siglec6_pos_eoe": 84.5,
   "siglec6_pos_healthy": 34.2,
   "siglec6_p": 3e-31,
   "addr_mild": 80.0,
   "addr_severe": 92.0,
   "differentiation": "no EoE agent depletes mast cells; orthogonal to dupilumab/anti-IL-33/IL-13"
  },
  "IL1RL1": {
   "modality": "blocking IgG1 (astegolimab-class, LALA) or soluble ST2 decoy",
   "epitope": "IL-33 interface 1781 \u00c5\u00b2 (4KC3), Ig2/Ig3 hotspots Y119/F245/L308",
   "esm_mean_entropy": 0.794,
   "companion": "soluble ST2 (sST2) serum ELISA",
   "addr_mild": 92.0,
   "addr_severe": 100.0,
   "differentiation": "receptor-side blockade complements ligand antibodies (tozorakimab/itepekimab)"
  },
  "CCL26": {
   "modality": "neutralizing IgG1 or CCR3 small-molecule antagonist",
   "epitope": "CCR3-engagement surface 24-94, N-loop/40s loop (disulfide-rigid)",
   "esm_mean_entropy": 0.771,
   "companion": "eotaxin-3 tissue mRNA / serum ELISA",
   "addr_mild": 98.0,
   "addr_severe": 100.0,
   "escape_caveat": "H39 (entropy 2.34) inside N-loop; co-engage rigid 40s loop or favor CCR3 route",
   "differentiation": "effector-specific eosinophil-recruitment blockade; universal across endotypes (~99%)"
  }
 }
}