{ "study_id": "STUDY-25-DUAL-TRACK-INFORMATION-RECOVERY", "discovery_id": 102, "slug": "dual-track-partitioning-information-recovery", "validation_set_id": "VAL-SET-035-DUAL-TRACK-IDR-REPEAT-RECOVERY-30COHORT", "generated_at": "2026-11-04T04:10:00Z", "tier_trajectory": "Full Step-Up Trajectory (Tier 1 Exploratory -> Tier 2 Blinded Validation -> Tier 3 Scientific Synthesis)", "prior_beaker_depth": 5, "posterior_beaker_rating": 5, "posterior_z_score": 6.84, "stage_1_tier1_exploratory": { "tier": 1, "taxa_count": 36, "sequence_volume_mb": 3.42, "information_loss_audit_by_regime": [ { "regime": "Unpartitioned Full-Length MSA (No Reduction)", "phylo_mi_retained_pct": 41.2, "physio_clinical_mi_retained_pct": 52.4, "combined_mi_retained_pct": 46.8, "rcfv": 0.168, "crown_ufboot_pct": 41.0, "failure_mode": "Repeat register shifts (38.4%) and compositional drift (RCFV = 0.168) corrupt both deep trees and alignment of regulatory repeats" }, { "regime": "Strict Pfam Core-Only Cropping (Error B — SLiMs & IDRs Discarded)", "phylo_mi_retained_pct": 73.2, "physio_clinical_mi_retained_pct": 18.4, "combined_mi_retained_pct": 45.8, "rcfv": 0.024, "crown_ufboot_pct": 69.5, "failure_mode": "Deletes 14-48 aa flanking mechanosensory/allosteric SLiMs (-784.2 nats) and discards 100% of IDR/repeat physiological traits" }, { "regime": "Single-Track Sub-Domain Partitioning (Core + SLiM Retained; Quarantined Repeats Discarded)", "phylo_mi_retained_pct": 99.6, "physio_clinical_mi_retained_pct": 34.8, "combined_mi_retained_pct": 67.2, "rcfv": 0.020, "crown_ufboot_pct": 100.0, "failure_mode": "Resolves deep phylogeny (100% UFBoot) but loses 64.2%-81.8% of shallow physiological stiffness, condensate LLPS, and foetal myopathy signal" }, { "regime": "Coupled Dual-Track Partitioning (Track 1: Core + SLiM Tree [+] Track 2: Quarantined Repeat Biophysical, Copy-Number & Multi-Stage PSI Vector + Off-Diagonal SW Rescue)", "phylo_mi_retained_pct": 99.6, "physio_clinical_mi_retained_pct": 99.2, "combined_mi_retained_pct": 99.4, "rcfv": 0.020, "crown_ufboot_pct": 100.0, "failure_mode": "Pareto-optimal: preserves 99.6% deep phylogenetic MI and recovers 99.2% shallow biophysical/clinical MI" } ] }, "stage_2_tier2_blinded_validation": { "tier": 2, "cohorts_total": 30, "dev_cohorts": 22, "reserve_cohorts": 8, "sequence_volume_mb": 3.84, "concordant_cohorts": 26, "mean_concordant_d_ctx": 0.07, "untouched_reserve_posterior_z": 6.48, "context_anomalies_isolated": [ { "blind_token": "BLIND-INFOLOCK-04", "taxa": "Sorex araneus / Mus musculus vs. Homo sapiens (Cardiac Titin TTN)", "repository_label": "Near-identical vertebrate cardiac Titin orthologs (Kinase d_ML = 0.018)", "single_track_loss": "78.4% loss of myocardial diastolic stiffness variance when PEVK is discarded", "dual_track_recovery": "Track 2 PEVK contour length (412 aa N2B vs. 2,174 aa N2BA) + PPAKV Glu/Lys charge ratio predicts 8.4x diastolic stiffness shift (r^2 = 0.91)", "z_blind": 6.24, "z_ctx_single_track": 0.48, "d_ctx": 5.76 }, { "blind_token": "BLIND-INFOLOCK-11", "taxa": "Homo sapiens TTN Exon 168 Homozygous p.Arg11842Ter", "repository_label": "Likely Benign adult cardiac variant (Adult LV PSI = 0.06)", "single_track_loss": "81.8% loss of recessive congenital myopathy sensitivity under adult-only PSI masking", "dual_track_recovery": "Track 2 developmental splice matrix (Foetal Skeletal PSI = 0.96 + bi-allelic phasing) flags pathogenic Salih congenital core myopathy (OR = 41.8)", "z_blind": 6.62, "z_ctx_single_track": 0.18, "d_ctx": 6.44 }, { "blind_token": "BLIND-INFOLOCK-18", "taxa": "Schizosaccharomyces pombe vs. Homo sapiens RPB1 CTD (PDB: 1F8A)", "repository_label": "Quarantined C-terminal (YSPTSPS)n low-complexity repeat tail", "single_track_loss": "74.6% loss of transcriptional condensate phase-separation and Pin1/SR-protein coupling signal", "dual_track_recovery": "Track 2 heptad copy-number & non-canonical distal Lys/Thr motif vector (29 vs. 52 heptads) recovers Pin1 (1F8A) and spliceosomal LLPS saturation threshold", "z_blind": 5.98, "z_ctx_single_track": 0.36, "d_ctx": 5.62 }, { "blind_token": "BLIND-INFOLOCK-25", "taxa": "Danio rerio ttna Exons 188-194 (14.2-kb Intrachromosomal Inversion)", "repository_label": "Unaligned gap in collinear Phase-1 exon anchor chain", "single_track_loss": "6.8% local exon sensitivity loss when restricting strictly to collinear diagonal DP band", "dual_track_recovery": "Track 2 off-diagonal Smith-Waterman (SW-RBH) rescue pass recovers all 7 inverted Phase-1 Ig exons at 99.1% identity", "z_blind": 6.19, "z_ctx_single_track": 0.31, "d_ctx": 5.88 } ] }, "stage_3_tier3_scientific_synthesis": { "tier": 3, "taxa_count": 80, "sequence_volume_mb": 7.62, "cumulative_superfamilies": 25, "cumulative_taxa": 512, "cumulative_sequence_mb": 26.86, "hypotheses_ledger": [ { "id": "H1", "system": "Titin PEVK Spring Biophysical Stiffness Track (Vertebrata)", "single_track_mi_pct": 21.6, "dual_track_mi_pct": 99.4, "rcfv_drop": "0.176 -> 0.021 (-88.1%)", "delta_lnl": 642.8, "posterior_z": 6.84 }, { "id": "H2", "system": "Developmental Foetal-Skeletal vs. Adult-Cardiac PSI Track (TTN & NEB)", "single_track_mi_pct": 18.2, "dual_track_mi_pct": 99.2, "rcfv_drop": "0.184 -> 0.022 (-88.0%)", "delta_lnl": 418.6, "posterior_z": 6.52 }, { "id": "H3", "system": "RNA Pol II RPB1 (YSPTSPS)n Heptad Copy & Pin1 Condensate Track (PDB: 1F8A)", "single_track_mi_pct": 25.4, "dual_track_mi_pct": 99.1, "rcfv_drop": "0.148 -> 0.020 (-86.5%)", "delta_lnl": 346.2, "posterior_z": 6.18 }, { "id": "H4", "system": "Synaptic Dlg/PSD-95 Linker LLPS & Off-Diagonal Exon Inversion Rescue (PDB: 1BE9)", "single_track_mi_pct": 35.8, "dual_track_mi_pct": 99.5, "rcfv_drop": "0.162 -> 0.020 (-87.7%)", "delta_lnl": 276.8, "posterior_z": 5.96 } ], "runie_model_comparison": [ { "rank": "1st (Best)", "architecture": "Minimizer Synteny -> Dual-Track Plan-7 HMM (Track 1: Core + SLiM Tree [+] Track 2: Repeat Charge/Copy/Dual-PSI Vector + Off-Diagonal SW-RBH Rescue) -> Kabsch 3D (1TKI/2F8V/1F8A) -> Potts DCA -> RP16 Supermatrix -> BIONJ ML Tree (LG+C60+F+R4)", "marginal_lnl": -218412.6, "delta_lnl": 0.0, "rcfv": 0.020, "combined_mi_pct": 99.4, "posterior_z": 6.84 }, { "rank": "2nd (Nearest)", "architecture": "Single-Track Sub-Domain Partitioning (Track 1: Core + SLiM Retained; Quarantined IDRs/Repeats Discarded; Collinear Band Only) -> *MAFFT L-INS-i -> *IQ-TREE 2 (LG+F+G4)", "marginal_lnl": -218896.8, "delta_lnl": -484.2, "rcfv": 0.020, "combined_mi_pct": 67.2, "posterior_z": 5.12 }, { "rank": "3rd (Medium)", "architecture": "*HMMER3 Strict Pfam Core-Only Cropping (14-48 aa Flanking SLiMs & All Quarantined Repeats Discarded) -> *MAFFT -> *IQ-TREE 2", "marginal_lnl": -219196.8, "delta_lnl": -784.2, "rcfv": 0.024, "combined_mi_pct": 45.8, "posterior_z": 3.48 }, { "rank": "4th (Rejected)", "architecture": "Unpartitioned Full-Length *MAFFT / Gotoh MSA (PEVK Spring, CTD Heptads & Tandem Register Shifts Retained) -> *IQ-TREE 2 (LG+F+G4)", "marginal_lnl": -220097.0, "delta_lnl": -1684.4, "rcfv": 0.168, "combined_mi_pct": 46.8, "posterior_z": 1.08 } ] } }