{
  "version": 3,
  "created_at": "2026-07-12T04:38:40.946Z",
  "task_summary": "Mine CD4+ T-cell perturb-seq for EoE Th2 regulators and pMHC-platform targets",
  "agents": [],
  "phases": [
    {
      "name": "Plan",
      "delegations": [
        {
          "steps": [
            {
              "title": "Load DE resource + build EoE gene panel",
              "description": "Once GWCD4i.DE_stats.h5ad finishes downloading, load with anndata (backed mode). Define the EoE-relevant Th2 effector panel among MEASURED genes (IL13, IL5, IL4, IL4R, TSLP, IL17RB, PTGDR2, IL2, IFNG, GATA3, STAT6, and a Th1/Treg contrast set) and the perturbation universe. Emit a QC table: n perturbations per condition, on-target knockdown efficiency distribution, and a coverage table confirming which EoE genes are measured vs perturbed. Save eoe_gene_panel.csv and de_qc_summary.csv."
            },
            {
              "title": "Rank T-cell regulators of Th2 cytokines (IL13/IL5/IL4)",
              "description": "For each measured EoE cytokine column, extract the full perturbation vector (log_fc, zscore, adj_p_value) across Rest/Stim8hr/Stim48hr. Rank perturbations whose knockdown significantly increases or decreases each cytokine (FDR<0.1). Produce ranked regulator tables per cytokine and a combined 'Th2 driver score' aggregating IL13+IL5+IL4 effects. Deliverables: regulators_of_IL13.csv etc., combined th2_cytokine_regulators.csv, and a volcano plot per cytokine (zscore vs -log10FDR) highlighting top positive/negative regulators."
            },
            {
              "title": "Th2/Th1 polarization regulator synthesis",
              "description": "Integrate the authors' own Th2_Th1_polarization_signature_DE and polarization_prediction_regulator_coefficients tables with my cytokine-level ranks to find convergent regulators that both (a) shift the Th2/Th1 polarization signature and (b) directly regulate IL13/IL5/IL4. Cross-reference against the functional clustering (clustering_downstream_genes) to see which regulatory module the top hits belong to. Deliverable: th2_polarization_convergent_regulators.csv and a scatter of polarization-signature effect vs cytokine effect."
            },
            {
              "title": "Prioritize pMHC-platform-relevant targets",
              "description": "Filter the regulator + Th2-marker hits for genes encoding cell-surface / secreted / receptor proteins (using the repo's cytokine_receptors, catalytic_receptors, gpcr, and surface annotations plus UniProt subcellular localization) to separate: (i) surface receptors that mark pathogenic Th2 cells — antibody/CAR/pMHC-directed candidates; (ii) intracellular master regulators — signature/biomarker candidates. Score each on effect size, Th2 selectivity, druggability class, and stimulation-context specificity. Deliverable: eoe_target_prioritization.csv ranked table with rationale column, plus a heatmap of top-20 targets × condition."
            },
            {
              "title": "Condition-specificity + robustness heatmap",
              "description": "For the top prioritized targets, build a heatmap of their effect (zscore) on the EoE cytokine panel across the three culture conditions, annotated with cross-donor and cross-guide reproducibility (from DE_stats.obs correlation fields) so hackathon reviewers can see which hits are robust vs stim-context-specific. Deliverable: top_targets_condition_heatmap.png and robustness_annotated table."
            },
            {
              "title": "Compile EoE target-discovery brief",
              "description": "Write a markdown report (eoe_perturbseq_target_brief.md) synthesizing: the CCL26/POSTN reframing, the top T-cell regulators of the Th2 cytokine axis, the pMHC-platform target shortlist with mechanistic rationale, and explicit next steps linking to the protein-design stream (which surface targets to pursue for binder/pMHC design). Embed the key figures. Save all artifacts."
            }
          ]
        }
      ],
      "id": "phase-0"
    }
  ],
  "feasibility": {
    "rationale": "The genome-wide DE resource (33,983 perturbation×condition rows × 10,282 genes, with logFC/p/FDR/z layers) is public and downloading now. CCL26/POSTN themselves are epithelial/fibroblast effectors absent from T cells, but their upstream drivers (IL13, IL5, IL4, IL4R, TSLP, IL17RB, PTGDR2) are measured and perturbed, so the regulator-mapping and target-prioritization aims are well supported by the data actually present.",
    "confidence": "high"
  }
}