{
  "version": 3,
  "created_at": "2026-07-08T04:43:34.083Z",
  "task_summary": "Draft Paper B: EoE omics discovery + validation + three-therapeutic-design manuscript with 5 composed figures",
  "agents": [],
  "phases": [
    {
      "name": "Plan",
      "delegations": [
        {
          "steps": [
            {
              "title": "Audit existing analysis artifacts + read design briefs",
              "description": "Read the three design briefs (SIGLEC6_design_brief.md, IL1RL1_design_brief.md, CCL26_design_brief.md), the revised_target_dossier.csv, revised_design_dossier.csv, and the phase-1/2 reports to extract exact numbers, interface residues, epitope-conservation stats, developability flags, and companion-Dx specs. Cross-check every value against source CSVs (interface BSA, epitope tables, druggability). Produce a verified fact-sheet (handoff/paperB_facts.json) so all downstream prose and figure annotations draw from computed values, not the pasted summary. No new analysis."
            },
            {
              "title": "Figure 1 — Discovery meta-signature",
              "description": "Compose a multi-panel Figure 1 using figure-composer: (a) meta-signature volcano highlighting canonical EoE markers (CCL26/eotaxin-3, etc.) with correct up/down direction; (b) pathway/TF enrichment bars (IFN, IL-6/JAK-STAT, NF-κB up; barrier/keratinization down); (c) multi-omics support panel (fraction of signature genes corroborated across miRNA/methylation/proteomics). Pull data from eoe_meta_signature_highconf.csv, enrich_up/down.csv, multiomics_support_fullsignature.csv. Publication-grade via figure-style. Save figure1_discovery.png."
            },
            {
              "title": "Figure 2 — Single-cell landscape",
              "description": "Compose Figure 2: (a) UMAP overview colored by cell type; (b) composition shift EoE vs control showing ~13-fold mast-cell expansion with the MWU statistic; (c) mast-cell state markers; (d) key cell-type marker dotplot. Source: sc_umap_overview, sc_composition.csv, mastcell_states, sc_marker_dotplot, sc_celltype_de.csv. Re-render panels at publication quality rather than reusing raw PNGs where resolution/labels need improvement. Save figure2_singlecell.png."
            },
            {
              "title": "Figure 3 — Validation",
              "description": "Compose Figure 3: (a) epithelial diffusion-pseudotime showing differentiation arrest (terminal-diff fraction EoE 5.4% vs healthy 17.9%); (b) cross-cohort endotype gradient (reproducible mild→severe across 6 cohorts); (c) GWAS risk-gene overlap (7 signature genes, susceptibility-weighted); (d) PPI-refractory persistence — targets normalizing in PPI responders but persisting in non-responders. Source: epithelial_pseudotime.csv, differentiation_map, endotype_crosscohort, gwas_target_overlap.csv, ppi_response_triage. Save figure3_validation.png."
            },
            {
              "title": "Figure 4 — Target prioritization landscape",
              "description": "Compose Figure 4: a prioritization view integrating druggability (secreted/surface-accessible), effect size, cell-type specificity, endotype addressability, and patient-positivity for the shortlist, with the three leads (SIGLEC6, IL1RL1/ST2, CCL26) highlighted. Source: target_druggability.csv, revised_target_dossier.csv, target_addressable_by_endotype.csv, target_patient_positivity.csv. Save figure4_target_landscape.png + the dossier as a formatted table."
            },
            {
              "title": "Figure 5 — Three therapeutic design specifications",
              "description": "Compose Figure 5, one column per lead (SIGLEC6 depleting Ab/ADC; IL1RL1/ST2 blocking Ab on the IL-33/ST2 interface; CCL26 neutralization): row 1 structure render (AF or experimental PDB), row 2 interface/epitope map with ESM conservation, row 3 developability + companion-Dx summary. Source: the three *_design_brief.md, iface_*.csv, esm_epitope_*.csv, developability_screen, companion_dx_specs.csv, PDB files. Save figure5_designs.png."
            },
            {
              "title": "Draft manuscript prose",
              "description": "Write the full Paper B manuscript (Results-forward analyses paper: Abstract, Intro, Results by stream = Discovery/Validation/Design, Discussion, Methods) expanding the three seed paragraphs into figure-anchored sections. Every number computed from the fact-sheet; measured-vs-framed distinction respected. Reuse and extend the verified citation set (CrossRef-checked) from the Perspective, adding target-specific references as needed. Save paperB_analyses_manuscript.md."
            },
            {
              "title": "Verify citations + render DOCX + save",
              "description": "CrossRef-verify any new DOIs (verify_dois). Resolve figure markers to paths and render to DOCX (render_manuscript_docx), verify embedded image count and key strings (verify_docx). Save paperB_analyses_manuscript.md + .docx + all five figures + tables as artifacts. Report the deliverable set with artifact links."
            }
          ]
        }
      ],
      "id": "phase-0"
    }
  ],
  "desired_outputs": [
    "Full Paper B manuscript (markdown + DOCX) with verified numbers and citations",
    "Figure 1: Discovery meta-signature (volcano + pathway + multi-omics support)",
    "Figure 2: Single-cell landscape (UMAP + composition + mast expansion + markers)",
    "Figure 3: Validation (differentiation arrest + endotype gradient + GWAS + PPI-refractory)",
    "Figure 4: Target prioritization landscape",
    "Figure 5: Three therapeutic design specifications (SIGLEC6, IL1RL1/ST2, CCL26)",
    "Target dossier + design-spec tables"
  ],
  "feasibility": {
    "rationale": "Nearly all analyses already exist as artifacts (meta-signature, single-cell, pseudotime, endotypes, GWAS, PPI, three design briefs with interface/epitope/developability data). Work is figure composition, prose, verified metrics, and citations — not new computation. Design section is grounded in three existing briefs and real PDB structures.",
    "confidence": "high"
  }
}