{
  "version": 3,
  "created_at": "2026-07-08T13:17:04.367Z",
  "task_summary": "Personalized pMHC + effector-target therapy plan for an index-case atopic-march EoE patient from HLA-II typing and GWAS profile",
  "agents": [],
  "phases": [
    {
      "name": "Plan",
      "delegations": [
        {
          "steps": [
            {
              "title": "Personalized epitope panel across all 4 MHC-II molecules",
              "description": "Extract DRB1*07:01 and DRB1*15:01 allergen-epitope burden from the existing 13-allele mhcnuggets panel; run mhcnuggets afresh for the two DQ heterodimers DQ2.2 (HLA-DQA102:01-DQB102:02) and DQ6.2 (HLA-DQA101:02-DQB106:02) against the same 2,424 15-mers from the 10 food allergens. Combine into the patient's personalized panel: per-allergen strong-binder counts and top cores for each of the 4 functional molecules. Deliverable: patient_epitope_panel.csv (allergen × molecule strong-binder matrix + ranked cores), noting which allergens this patient presents most heavily."
            },
            {
              "title": "Literature review — patient HLA haplotypes",
              "description": "Retrieve real citations (OpenAlex, verified DOIs) on DR7-DQ2.2 and DR15-DQ6.2 in EoE, atopic/allergic disease, and — critically — DQ2.2 in celiac disease/gluten presentation (relevant to this patient's wheat/gliadin handling). Summarize each haplotype's association direction and mechanism. No fabricated citations. Deliverable: DOI-verified reference notes for the plan's HLA section."
            },
            {
              "title": "Literature review + annotation of the 7 GWAS SNPs",
              "description": "For each SNP (rs653178/SH2B3-12q24, rs12619285/2, rs4296977/7, rs1131896/6p21-HLA, rs9880192/3q28, rs301806/1, rs2239633/14q11): map to nearest gene(s) and trait axis, confirm reported direction of effect, and retrieve supporting GWAS literature (OpenAlex; cross-check the session's prior EoE GWAS overlap). Deliverable: patient_gwas_annotation.csv (SNP, chr, locus/gene, trait axis, genotype, effect direction, citation), grounded in retrieved records."
            },
            {
              "title": "Composite genetic-risk interpretation",
              "description": "Integrate the 7 SNPs into an eosinophil-axis vs allergic-axis risk read for this patient (most alleles risk/eosinophil-elevating), interpreted against the full atopic-march phenotype (eczema, allergic rhinitis, asthma, food+environmental allergy, EoE). Relate to EoE effector biology (CCL26/IL1RL1/ALOX15) and flag where genetic + clinical load argues for combining antigen-directed therapy with effector blockade. Feeds the profile figure and target assessment."
            },
            {
              "title": "Assess IL-33/ST2, SIGLEC6, CCL26 for this patient",
              "description": "Score each of the three Phase-3 protein-design targets against THIS patient's profile: (a) IL1RL1/ST2 — alarmin axis upstream of the whole type-2 march (asthma+eczema+EoE); check whether rs1131896 (6p21) tags the IL1RL1/atopy signal or is HLA-distinct, using retrieved literature. (b) CCL26/eotaxin-3 — eosinophil-recruitment effector, matched to the patient's eosinophil-axis SNP load. (c) SIGLEC6 — EoE-specific mast target, tissue-restricted (EoE-local arm). For each: mechanistic fit to the patient's multi-organ vs EoE-local disease, relevant retrieved citations, and how it complements the pMHC antigen-directed arm. Deliverable: patient_target_assessment.csv (target, axis, systemic vs local relevance, SNP linkage, fit score, rationale, citations)."
            },
            {
              "title": "Composite profile figure",
              "description": "Render index_case_profile.png (publication-styled via figure-style): (panel A) personalized epitope burden by allergen × the 4 MHC-II molecules; (panel B) genetic-risk summary across the 7 SNPs by axis; (panel C) three-target fit for this patient (systemic reach vs EoE-local, SNP/phenotype linkage). One integrated index-case molecular portrait."
            },
            {
              "title": "Synthesize the personalized therapy plan",
              "description": "Write personalized_therapy_plan_index_case.md: (1) patient molecular + clinical profile (4 MHC-II molecules, 7-SNP genetic risk, atopic march); (2) allergens/epitopes to target given THIS patient's presentation, incl. DQ2.2-gluten; (3) pMHC-anergy reagent design personalized to their alleles (which cores on which molecule); (4) effector/receptor-target arm — which of IL-33/ST2, CCL26, SIGLEC6 fits this patient and why, systemic (atopic march) vs EoE-local, informed by the SNP load; (5) integrated combination rationale (upstream antigen-directed + downstream effector blockade); (6) ex vivo per-patient validation path (Task 3 assay); (7) explicit clinical/research disclaimer and limitations. All claims grounded; all citations retrieved."
            },
            {
              "title": "Bundle index-case deliverables",
              "description": "Assemble patient_epitope_panel.csv, patient_gwas_annotation.csv, patient_target_assessment.csv, index_case_profile.png, personalized_therapy_plan_index_case.md into index_case_deliverables.tar.gz and save all artifacts. Close with a short summary contrasting this patient's personalized design (antigen-directed + effector-target selection) with the generic platform."
            }
          ]
        }
      ],
      "id": "phase-0"
    }
  ],
  "desired_outputs": [
    "patient_epitope_panel.csv — personalized epitopes across all 4 MHC-II molecules",
    "patient_gwas_annotation.csv — 7 SNPs mapped to genes/traits/direction with retrieved citations",
    "patient_target_assessment.csv — IL-33/ST2, SIGLEC6, CCL26 scored for this patient's SNP + atopic-march profile",
    "index_case_profile.png — personalized epitope + genetic-risk + target-fit visualization",
    "personalized_therapy_plan_index_case.md — synthesized personalized therapy design",
    "index_case_deliverables.tar.gz — bundle"
  ],
  "feasibility": {
    "rationale": "All four of the patient's MHC-II molecules (DRB1*07:01, DRB1*15:01, DQ2.2, DQ6.2) are covered by the mhcnuggets predictor; DRB1*07:01/*15:01 burden is already computed. The three protein-design targets (IL1RL1/ST2, SIGLEC6, CCL26) are fully characterized from Phase 3. Literature on the HLA haplotypes, 7 GWAS SNPs, and the target-atopy links is retrievable via OpenAlex. The patient's phenotype is the full atopic march (eczema, allergic rhinitis, asthma, food+environmental allergy, EoE), which strengthens the rationale for the alarmin/eosinophil targets. This is a research/hackathon exercise, not clinical care: outputs are hypothesis-generating; any real decision requires a qualified clinician with full patient context plus prospective wet-lab validation.",
    "confidence": "high"
  }
}