{
  "version": 3,
  "created_at": "2026-07-08T13:13:25.006Z",
  "task_summary": "Personalized pMHC therapy plan for an index-case EoE patient from their 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), and note which allergens this specific 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 (directly relevant to this patient's wheat/gliadin epitope handling). Summarize what is established about each haplotype's association direction and mechanism. No fabricated citations; every reference traced to a retrieval call. Deliverable: notes feeding the plan's HLA section with a DOI-verified reference list."
            },
            {
              "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 the reported direction of effect, and retrieve supporting GWAS literature (OpenAlex; cross-check against the session's prior EoE GWAS overlap where relevant). Deliverable: patient_gwas_annotation.csv (SNP, chr, locus/gene, trait axis, patient genotype, effect direction, citation) — values grounded in retrieved records, not recalled."
            },
            {
              "title": "Composite genetic-risk interpretation",
              "description": "Integrate the 7 SNPs into an eosinophil-axis vs allergic-axis risk read for this patient (most alleles are risk/eosinophil-elevating). Relate to the EoE effector biology from prior phases (CCL26/IL1RL1/ALOX15 eosinophil program) and flag where the genetic load argues for combining antigen-directed therapy with effector blockade. Deliverable: index_case_profile.png — a two-panel figure (personalized epitope burden by allergen×MHC-II molecule; genetic-risk summary across the 7 SNPs), publication-styled."
            },
            {
              "title": "Synthesize the personalized therapy plan",
              "description": "Write personalized_therapy_plan_index_case.md: (1) patient molecular profile (4 MHC-II molecules + genetic risk); (2) which allergens/epitopes to target given THIS patient's presentation, incl. the DQ2.2-gluten consideration; (3) pMHC-anergy reagent design personalized to their alleles (which cores loaded on which molecule); (4) how the GWAS eosinophil load modulates strategy (mono vs combination with effector-target blockade); (5) the ex vivo validation path (per-patient T-cell assay from Task 3); (6) explicit clinical/research disclaimer and limitations (computational epitopes, no wet-lab data, decisions require a clinician). All claims grounded; all citations retrieved."
            },
            {
              "title": "Bundle index-case deliverables",
              "description": "Assemble patient_epitope_panel.csv, patient_gwas_annotation.csv, index_case_profile.png, personalized_therapy_plan_index_case.md into index_case_deliverables.tar.gz and save all artifacts. Provide a short closing summary of what this patient's personalized design looks like versus 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",
    "index_case_profile.png — personalized epitope + genetic-risk 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, and DRB1*07:01/*15:01 burden is already computed. Literature on the HLA haplotypes and the 7 GWAS SNPs is retrievable via OpenAlex (key available). This is a research/hackathon exercise, not clinical care: the output is a hypothesis-generating personalized-therapy design, and any real decision requires a qualified clinician with the full patient context plus prospective wet-lab validation.",
    "confidence": "high"
  }
}