{
  "study_id": "STUDY-021-PLACOZOA-PORIFERA-SUBDOMAIN-PARTITIONING",
  "validation_set_id": "VAL-SET-031-PLACOZOA-PORIFERA-SUBDOMAIN-24COHORT",
  "discovery_slug": "placozoa-porifera-epithelial-subdomain",
  "generated_at": "2026-11-03T19:42:00Z",
  "scope_trajectory": "Tier 1 Exploratory -> Tier 2 Dual-Pass Blinded Validation -> Tier 3 Scientific Synthesis",
  "beaker_prior": 5,
  "beaker_posterior": 5,
  "summary_metrics": {
    "tier1_cohorts": 8,
    "tier1_scale_kb": 344,
    "tier1_posterior_z": 3.54,
    "tier1_beakers": 3,
    "tier2_cohorts": 24,
    "tier2_dev_cohorts": 12,
    "tier2_reserve_cohorts": 12,
    "tier2_scale_kb": 960,
    "tier2_concordant_cohorts": 20,
    "tier2_concordant_mean_abs_delta_z": 0.0,
    "tier2_anomalies_intercepted": "4/4",
    "tier2_rcfv_before": 0.168,
    "tier2_rcfv_after": 0.021,
    "tier2_rcfv_reduction_pct": 87.5,
    "tier2_posterior_z": 4.38,
    "tier2_beakers": 4,
    "tier3_cohorts": 32,
    "tier3_taxa": 64,
    "tier3_scale_mb": 1.72,
    "tier3_parahoxozoa_ufboot_unpartitioned_pct": 44.2,
    "tier3_agnotozoa_artifact_ufboot_unpartitioned_pct": 68.4,
    "tier3_parahoxozoa_ufboot_partitioned_pct": 99.4,
    "tier3_agnotozoa_ufboot_partitioned_pct": 1.6,
    "tier3_delta_lnL_nats": 288.6,
    "tier3_au_test_p": 0.0004,
    "tier3_posterior_z": 5.24,
    "tier3_beakers": 5,
    "cross_kingdom_cumulative_families": 13,
    "cross_kingdom_cumulative_taxa": 256,
    "cross_kingdom_cumulative_scale_mb": 9.76
  },
  "tier1_exploratory": {
    "description": "8-cohort exploratory sweep (344 kb) profiling Classical Cadherin (TaCDH / AqCDH / CDH1), Integrin Beta (TaITGB / AqITGB / ITGB1/3), and Apical-Basal Polarity (Dlg / Scribble / Par-3 / Par-6) + Septate-Junction Neurexin IV across Placozoa, Porifera, Cnidaria, Ctenophora, Bilateria, and Choanoflagellata.",
    "cohorts": [
      { "id": "EXP-01", "locus": "Classical Cadherin Full-Length (TaCDH XP_002114987.1 vs. AqCDH XP_003383912.1)", "length_kb": 48, "rcfv": 0.168, "omega_core": 0.041, "omega_repeat": 0.684, "rate_ratio_w2_w1": 7.96, "parahoxozoa_ufboot_pct": 44.2, "note": "31-34 variable peripheral EC repeats + mucin stalk drive AT-rich Porifera+Placozoa LBA (68.4% UFBoot)" },
      { "id": "EXP-02", "locus": "Cadherin EC1-EC2 3xCa2+ Hinge + Cytoplasmic CBD/JMD Clasp (PDB:1EDH)", "length_kb": 38, "rcfv": 0.021, "tm_score": 0.908, "rmsd_a": 1.21, "mfdca_j_ij": 1.638, "parahoxozoa_ufboot_pct": 99.4, "note": "Quarantining EC3-EC34 repeats while retaining CBD beta-catenin & JMD p120-catenin clasps resolves Parahoxozoa" },
      { "id": "EXP-03", "locus": "Integrin Beta Full-Length (TaITGB XP_002111432.1 vs. AqITGB XP_003385104.1)", "length_kb": 46, "rcfv": 0.154, "omega_core": 0.036, "omega_repeat": 0.642, "parahoxozoa_ufboot_pct": 47.8, "note": "Cysteine-rich I-EGF1-4 stalk repeats and leg loops inflate RCFV" },
      { "id": "EXP-04", "locus": "Integrin Beta-I MIDAS DXSXS Core + Cytoplasmic NPXY Talin Clasp (PDB:1JV2)", "length_kb": 36, "rcfv": 0.022, "tm_score": 0.924, "rmsd_a": 1.09, "mfdca_j_ij": 1.694, "parahoxozoa_ufboot_pct": 99.5, "note": "Conserved Mg2+ MIDAS pocket + cytoplasmic NPXY/NXXY Talin/Kindlin clasp across Porifera, Placozoa, and Bilateria" },
      { "id": "EXP-05", "locus": "Dlg / PSD-95 / Scribble Apical-Basal Scaffold Full-Length", "length_kb": 44, "rcfv": 0.162, "omega_core": 0.039, "omega_repeat": 0.712, "parahoxozoa_ufboot_pct": 45.6, "note": "AT-rich poly-Asn/Ser/Pro inter-PDZ low-complexity linkers in Trichoplax & Amphimedon cause LBA" },
      { "id": "EXP-06", "locus": "Dlg PDZ1-3 GLGF Groove + SH3-GK Hook & L27 Clasp (PDB:1BE9)", "length_kb": 40, "rcfv": 0.020, "tm_score": 0.938, "rmsd_a": 1.02, "mfdca_j_ij": 1.612, "parahoxozoa_ufboot_pct": 99.3, "note": "Intramolecular SH3-GK hook + L27 oligomerization SLiM conserved across Metazoa" },
      { "id": "EXP-07", "locus": "Parahoxozoan Pleated Septate-Junction Triad (Neurexin IV / Neuroglian / Coracle FERM)", "length_kb": 50, "rcfv": 0.023, "mfdca_j_ij": 1.576, "parahoxozoa_ufboot_pct": 99.2, "note": "Synapomorphic belt-desmosome / septate-junction barrier complex shared by Placozoa + Cnidaria + Bilateria" },
      { "id": "EXP-08", "locus": "Trichoplax 43.1 kb Mitochondrial Genome (NC_008151.2) Unfiltered Supermatrix", "length_kb": 42, "rcfv": 0.174, "parahoxozoa_ufboot_pct": 38.0, "note": "Group-I/II self-splicing intron LAGLIDADG ORFs distort branch lengths unless spliced exons are isolated" }
    ]
  },
  "tier2_dual_pass_blind_validation": {
    "description": "24-cohort Dual-Pass Blinded SHA-256 De-Identified vs. Context-Aware Validation (12 Development DEV-01..DEV-12 + 12 Untouched Reserve RES-01..RES-12, 960 kb).",
    "concordant_cohorts_count": 20,
    "concordant_mean_abs_delta_z": 0.0,
    "discordant_anomalies": [
      {
        "cohort_id": "DEV-04",
        "sha256_token": "BLIND-COHORT-8f2a9c41d0",
        "published_label": "Trichoplax TaCDH + Amphimedon AqCDH Full-Length Concatenated Alignment supporting Porifera+Placozoa Clade",
        "blinded_extrapolation": "Chimeric multi-domain protein: 22% conserved beta-sandwich Ca2+-hinge core (ω = 0.041) + 78% non-homologous AT-rich EC3-EC34 tandem repeats & mucin stalk (ω = 0.684, RCFV = 0.168)",
        "z_blind": 5.28,
        "z_ctx": 1.46,
        "abs_delta_z": 3.82,
        "remediation": "Quarantine EC3-EC34 peripheral repeat arrays (Error Type A) and retain EC1-EC2 3xCa2+ hinge + cytoplasmic CBD/JMD catenin clasps (Error Type B), reducing RCFV by 87.5% (0.168 -> 0.021)."
      },
      {
        "cohort_id": "DEV-10",
        "sha256_token": "BLIND-COHORT-3e71b508a2",
        "published_label": "Trichoplax adhaerens XP_002116408.1 Truncated Cadherin Annotated as Lacking Catenin-Binding Domain (CBD)",
        "blinded_extrapolation": "Intact 3' terminal exon encoding a canonical 34-aa beta-catenin-binding groove (DSLSSL...EED) and p120-catenin JMD clasp split across adjacent genomic contig boundary",
        "z_blind": 4.94,
        "z_ctx": 1.48,
        "abs_delta_z": 3.46,
        "remediation": "Re-stitch 3' terminal exon from H1/H2 Hoilungia & Trichoplax RNA-seq transcripts, restoring the complete CBD/JMD catenin-binding SLiM (|J_ij| = 1.638)."
      },
      {
        "cohort_id": "RES-05",
        "sha256_token": "BLIND-COHORT-c490d127f6",
        "published_label": "Amphimedon queenslandica Draft Contig NW_003546512.1 Putative Sponge Cadherin-Like Repeat Protein",
        "blinded_extrapolation": "Prokaryotic GC-rich (64.8% GC) Type-I secretion RTX (GGXGXDXUX) calcium-binding repeat toxin from marine Rhodobacteraceae symbiont (tetranucleotide D_KL = 6.92x vs. sponge host 35.8% GC)",
        "z_blind": 5.12,
        "z_ctx": 0.94,
        "abs_delta_z": 4.18,
        "remediation": "Quarantine bacterial symbiont RTX contig via tetranucleotide D_KL and Shine-Dalgarno screening before metazoan orthology clustering."
      },
      {
        "cohort_id": "RES-11",
        "sha256_token": "BLIND-COHORT-71a8e439b1",
        "published_label": "Trichoplax adhaerens Mitochondrial COX1-COB Supermatrix (NC_008151.2) with Unexcised Intronic ORFs",
        "blinded_extrapolation": "Coding exons interrupted by 6 group-I/II self-splicing introns encoding fast-evolving LAGLIDADG/GIY-YIG homing endonucleases (ω = 0.79) frameshifting C-terminal alignment columns",
        "z_blind": 4.86,
        "z_ctx": 0.95,
        "abs_delta_z": 3.91,
        "remediation": "Excise group-I/II self-splicing intronic ORFs using conserved exon-junction splice boundaries prior to amino-acid translation."
      }
    ]
  },
  "tier3_scientific_synthesis": {
    "description": "32-cohort / 1.72 Mb / 64-taxon scientific synthesis across Placozoa (Trichoplax adhaerens, Hoilungia hongkongensis), Porifera (Amphimedon queenslandica, Oscarella carmela, Sycon ciliatum, Ephydatia muelleri, Aphrocallistes vastus), Cnidaria (Nematostella vectensis, Hydra vulgaris, Acropora millepora, Clytia hemisphaerica), Ctenophora (Mnemiopsis leidyi, Hormiphora californiensis), Bilateria, and Choanoflagellata/Filasterea outgroups.",
    "hypotheses": [
      {
        "id": "H1",
        "title": "Sub-Domain Substitution-Rate Decoupling & Parahoxozoa Topological Rescue",
        "status": "Accepted (5🧪)",
        "z_score": 5.34,
        "metrics": {
          "rate_ratio_w2_w1": 7.96,
          "omega_w1": 0.041,
          "omega_w2": 0.684,
          "rcfv_unpartitioned": 0.168,
          "rcfv_partitioned": 0.021,
          "rcfv_reduction_pct": 87.5,
          "parahoxozoa_ufboot_pct": 99.4,
          "delta_lnL_nats": 288.6
        }
      },
      {
        "id": "H2",
        "title": "Classical Cadherin EC1-EC2 3xCa2+ Hinge (PDB:1EDH) & Integrin Beta-I MIDAS (PDB:1JV2) 3D Conservation",
        "status": "Accepted (5🧪)",
        "z_score": 5.18,
        "metrics": {
          "cadherin_tm_score": 0.908,
          "cadherin_rmsd_a": 1.21,
          "cadherin_mfdca_j_ij": 1.638,
          "integrin_tm_score": 0.924,
          "integrin_rmsd_a": 1.09,
          "integrin_mfdca_j_ij": 1.694,
          "metazoa_integrin_ufboot_pct": 99.5
        }
      },
      {
        "id": "H3",
        "title": "Apical-Basal Polarity PDZ-SH3-GK Core (PDB:1BE9) & Parahoxozoan Septate-Junction Synapomorphy",
        "status": "Accepted (5🧪)",
        "z_score": 4.96,
        "metrics": {
          "dlg_pdz_tm_score": 0.938,
          "dlg_pdz_rmsd_a": 1.02,
          "dlg_mfdca_j_ij": 1.612,
          "septate_junction_ufboot_pct": 99.3
        }
      },
      {
        "id": "H4",
        "title": "Falsification Control: Constrained Porifera+Placozoa ('Agnotozoa') Monophyly & Epithelial-Deficiency Hypothesis",
        "status": "Falsified Control (1🧪)",
        "z_score": 0.94,
        "metrics": {
          "agnotozoa_ufboot_before_pct": 68.4,
          "agnotozoa_ufboot_after_pct": 1.6,
          "delta_lnL_penalty_nats": -288.6,
          "au_test_p": 0.0004
        }
      }
    ]
  }
}