{ "pipeline_name": "pseudo-loss / macse-frameshift-relax (Tool Validation #16)", "external_aligner_reference": "MACSE v2.07 (Ranwez et al., 2018 โ€” Multiple Alignment of Coding Sequences Accounting for Frameshifts and Stop Codons)", "external_codon_ml_reference": "PAML v4.10.10 codeml (Yang, 2007 โ€” M0 1-Ratio, Branch 2-Ratio Free omega_fg, and Branch Neutral Fixed omega_fg=1.0)", "runie_tensor_backend": "candle-core 0.9.2 (CPU F64 Tensor GA-MCMC & K_min Step-Up Marginalization)", "grid_size": 36, "frozen_params": { "fs_lr_cost": 14.0, "stop_lr_cost": 17.0, "gap_open_cost": 7.0, "gap_ext_cost": 1.0 }, "dev_grid_top8": [ { "rank": 1, "params": { "fs_lr_cost": 14.0, "stop_lr_cost": 17.0, "gap_open_cost": 7.0, "gap_ext_cost": 1.0 }, "dev_frameshift_recall": 1.0, "dev_frameshift_precision": 1.0, "dev_stop_recall": 1.0, "dev_aa_column_identity": 1.0, "dev_artifact_false_positives": 0, "balanced_score": 0.9996 }, { "rank": 2, "params": { "fs_lr_cost": 14.0, "stop_lr_cost": 17.0, "gap_open_cost": 7.0, "gap_ext_cost": 2.0 }, "dev_frameshift_recall": 1.0, "dev_frameshift_precision": 1.0, "dev_stop_recall": 1.0, "dev_aa_column_identity": 1.0, "dev_artifact_false_positives": 0, "balanced_score": 0.9995 }, { "rank": 3, "params": { "fs_lr_cost": 10.0, "stop_lr_cost": 11.0, "gap_open_cost": 7.0, "gap_ext_cost": 1.0 }, "dev_frameshift_recall": 1.0, "dev_frameshift_precision": 1.0, "dev_stop_recall": 1.0, "dev_aa_column_identity": 1.0, "dev_artifact_false_positives": 0, "balanced_score": 0.9994 }, { "rank": 4, "params": { "fs_lr_cost": 14.0, "stop_lr_cost": 17.0, "gap_open_cost": 5.0, "gap_ext_cost": 1.0 }, "dev_frameshift_recall": 1.0, "dev_frameshift_precision": 1.0, "dev_stop_recall": 1.0, "dev_aa_column_identity": 1.0, "dev_artifact_false_positives": 0, "balanced_score": 0.9994 }, { "rank": 5, "params": { "fs_lr_cost": 10.0, "stop_lr_cost": 11.0, "gap_open_cost": 7.0, "gap_ext_cost": 2.0 }, "dev_frameshift_recall": 1.0, "dev_frameshift_precision": 1.0, "dev_stop_recall": 1.0, "dev_aa_column_identity": 1.0, "dev_artifact_false_positives": 0, "balanced_score": 0.9993 }, { "rank": 6, "params": { "fs_lr_cost": 14.0, "stop_lr_cost": 17.0, "gap_open_cost": 5.0, "gap_ext_cost": 2.0 }, "dev_frameshift_recall": 1.0, "dev_frameshift_precision": 1.0, "dev_stop_recall": 1.0, "dev_aa_column_identity": 1.0, "dev_artifact_false_positives": 0, "balanced_score": 0.9993 }, { "rank": 7, "params": { "fs_lr_cost": 10.0, "stop_lr_cost": 11.0, "gap_open_cost": 5.0, "gap_ext_cost": 1.0 }, "dev_frameshift_recall": 1.0, "dev_frameshift_precision": 1.0, "dev_stop_recall": 1.0, "dev_aa_column_identity": 1.0, "dev_artifact_false_positives": 0, "balanced_score": 0.9992 }, { "rank": 8, "params": { "fs_lr_cost": 10.0, "stop_lr_cost": 11.0, "gap_open_cost": 5.0, "gap_ext_cost": 2.0 }, "dev_frameshift_recall": 1.0, "dev_frameshift_precision": 1.0, "dev_stop_recall": 1.0, "dev_aa_column_identity": 1.0, "dev_artifact_false_positives": 0, "balanced_score": 0.9991 } ], "development_summary": { "scope_name": "Development Set (6 Cohorts, 60 Taxa)", "cohorts_count": 6, "sequences_count": 60, "total_codons": 4800, "gen1_naive_frameshift_recall": 0.0, "gen1_naive_spurious_stops": 26, "gen1_naive_relax_k_mae": 0.2875, "native_frameshifts_called": 17, "macse_frameshifts_called": 17, "frameshift_site_recall": 1.0, "frameshift_site_precision": 1.0, "native_stops_called": 16, "macse_stops_called": 16, "stop_site_recall": 1.0, "stop_site_precision": 1.0, "mean_aa_column_identity_vs_macse": 1.0, "m2_lnl_pearson_r": 1.0, "m2_lnl_mae": 5.6859, "omega_fg_pearson_r": 0.9999, "omega_fg_mae": 0.0032, "relax_k_pearson_r": 1.0, "relax_k_mae": 0.0021, "classification_concordance_pct": 100.0, "negative_control_false_positives": 0 }, "reserve_summary": { "scope_name": "Untouched Reserve Set (6 Cohorts, 60 Taxa)", "cohorts_count": 6, "sequences_count": 60, "total_codons": 4800, "gen1_naive_frameshift_recall": 0.0, "gen1_naive_spurious_stops": 22, "gen1_naive_relax_k_mae": 0.4021, "native_frameshifts_called": 17, "macse_frameshifts_called": 17, "frameshift_site_recall": 1.0, "frameshift_site_precision": 1.0, "native_stops_called": 16, "macse_stops_called": 16, "stop_site_recall": 1.0, "stop_site_precision": 1.0, "mean_aa_column_identity_vs_macse": 1.0, "m2_lnl_pearson_r": 1.0, "m2_lnl_mae": 6.1258, "omega_fg_pearson_r": 0.9999, "omega_fg_mae": 0.0033, "relax_k_pearson_r": 0.9999, "relax_k_mae": 0.0045, "classification_concordance_pct": 100.0, "negative_control_false_positives": 0 }, "combined_12_cohort_summary": { "scope_name": "Combined 12-Cohort Benchmark (120 Taxa, 960 Focal Codons)", "cohorts_count": 12, "sequences_count": 120, "total_codons": 9600, "gen1_naive_frameshift_recall": 0.0, "gen1_naive_spurious_stops": 48, "gen1_naive_relax_k_mae": 0.3448, "native_frameshifts_called": 34, "macse_frameshifts_called": 34, "frameshift_site_recall": 1.0, "frameshift_site_precision": 1.0, "native_stops_called": 32, "macse_stops_called": 32, "stop_site_recall": 1.0, "stop_site_precision": 1.0, "mean_aa_column_identity_vs_macse": 1.0, "m2_lnl_pearson_r": 1.0, "m2_lnl_mae": 5.9059, "omega_fg_pearson_r": 0.9999, "omega_fg_mae": 0.0032, "relax_k_pearson_r": 1.0, "relax_k_mae": 0.0033, "classification_concordance_pct": 100.0, "negative_control_false_positives": 0 }, "runie_step_up_traces": [ { "generation": 1, "tier_label": "Tier 1: Exploratory (Gen-1 Baseline Failure)", "pipeline_dag": [ "gotoh-msa", "codon-selection-yn00" ], "log_likelihood": -142.8, "kmin_gate_reward": -18.5, "bic_penalty": 2.4, "unnormalized_log_posterior": -163.7, "posterior_probability": 0.0, "log_bayes_factor_vs_gen1": 0.0, "kmin_passed": false, "summary_verdict": "REJECTED (0๐Ÿงช -> zero-star-calibration-dump.json): Naive triplet aligner misses 100% of `!` frameshifts (recall = 0.0%), induces 48 spurious downstream stop codons, and inflates RELAX k MAE to 0.3448." }, { "generation": 2, "tier_label": "Gen-2 Autonomous Tool Synthesis & 36-Grid Dev Calibration", "pipeline_dag": [ "gotoh-msa", "macse-frameshift-relax (dev-grid)" ], "log_likelihood": -38.4, "kmin_gate_reward": -4.2, "bic_penalty": 3.6, "unnormalized_log_posterior": -46.2, "posterior_probability": 0.0, "log_bayes_factor_vs_gen1": 117.5, "kmin_passed": false, "summary_verdict": "INTERMEDIATE: Synthesized 3-frame coding DP (`-1 bp` `!`, `-2 bp` `!!`, `+1 bp` `!`, internal `*`) and calibrated (fs_lr_cost=10.0, stop_lr_cost=17.0) on 6 dev cohorts; added 5-bp homopolymer + sister-clade sharing filter to eliminate singleton ABCA4/HBB base-call artifacts." }, { "generation": 3, "tier_label": "Tier 2: Validation (6 Untouched Reserve Cohorts vs MACSE v2.07 & PAML v4.10.10)", "pipeline_dag": [ "gotoh-msa", "macse-frameshift-relax", "paml-branch-relax-3model" ], "log_likelihood": -11.2, "kmin_gate_reward": 6.4, "bic_penalty": 4.2, "unnormalized_log_posterior": -9.0, "posterior_probability": 0.0002, "log_bayes_factor_vs_gen1": 154.7, "kmin_passed": true, "summary_verdict": "PASSED (2๐Ÿงช Technical Validation): 100.0% `!` frameshift recall, 100.0% `*` stop recall, 100.00% AA column identity vs MACSE v2.07; Branch 2-Ratio lnL r = 1.0000 and RELAX k MAE = 0.0033 vs PAML v4.10.10 across 12 cohorts (0 false positives)." }, { "generation": 4, "tier_label": "Tier 3: Scientific (Convergent Pseudogenization & Protective Knockout Synthesis)", "pipeline_dag": [ "gotoh-msa", "macse-frameshift-relax", "paml-branch-relax-3model", "gnomad-protective-ko-synthesis" ], "log_likelihood": -4.15, "kmin_gate_reward": 8.9, "bic_penalty": 4.95, "unnormalized_log_posterior": -0.2, "posterior_probability": 0.9998, "log_bayes_factor_vs_gen1": 163.5, "kmin_passed": true, "summary_verdict": "MAP OPTIMUM (P = 0.9998, ln BF_10 = +163.50): Separates true unitary pseudogenes (GULO, UOX, MMP20, ENAM, TAS1R2) and protective human knockout candidates (ANGPTL3, CASP12, HSD17B13) from essential housekeeping genes (ACTB, GAPDH) and singleton homopolymer errors (ABCA4, HBB) with 100.0% concordance." } ], "runie_map_posterior": 0.9998, "runie_log_bf10": 163.5, "zero_beaker_reject_id": "REJECT-2026-026-PSEUDO-LOSS-GEN1-NAIVE-TRIPLET", "cohorts": [ { "cohort_id": "DEV-01-GULO", "scope": "development", "role": "pseudogene-loss", "gene_symbol": "GULO", "full_name": "L-Gulonolactone Oxidase (Vitamin C Biosynthesis)", "refseq_anchor_accession": "NM_178747.3", "foreground_clade": "Haplorhini Primates (Homo, Pan, Gorilla, Macaca #1)", "gnomad_plof_context": "Fixed human pseudogene GULOP (NR_002939.1); dietary ascorbate auxotrophy", "taxa_count": 10, "focal_codons": 80, "gen1_naive_frameshifts_called": 0, "gen1_naive_stops_called": 8, "gen1_naive_omega_fg": 0.7306, "gen1_naive_relax_k": 0.0888, "native_frameshift_sites": [ [ "Loss_1", [ 24 ] ], [ "Loss_2", [ 24 ] ], [ "Loss_3", [ 24 ] ], [ "Loss_4", [ 24 ] ] ], "macse_frameshift_sites": [ [ "Loss_1", [ 24 ] ], [ "Loss_2", [ 24 ] ], [ "Loss_3", [ 24 ] ], [ "Loss_4", [ 24 ] ] ], "native_stop_sites": [ [ "Loss_1", [ 52 ] ], [ "Loss_2", [ 52 ] ], [ "Loss_3", [ 52 ] ], [ "Loss_4", [ 52 ] ] ], "macse_stop_sites": [ [ "Loss_1", [ 52 ] ], [ "Loss_2", [ 52 ] ], [ "Loss_3", [ 52 ] ], [ "Loss_4", [ 52 ] ] ], "frameshift_exact_match": true, "stop_exact_match": true, "column_aa_identity_vs_macse": 1.0, "shared_across_sister_lineages": true, "singleton_homopolymer_artifact": false, "native_models": { "m0_lnl": -973.4137, "m0_kappa": 2.5552, "m0_omega": 0.1549, "branch_2ratio_lnl": -955.5988, "omega_bg": 0.0283, "omega_fg": 0.3444, "branch_neutral_fg1_lnl": -965.4254, "lrt_relax_2vs1": 35.6299, "p_value_relax": 2.394277953315721e-9, "lrt_neutral_fg1": 19.6533, "p_value_neutral_fg1": 9.292105164681986e-6, "relax_intensity_k": 0.299, "wall_ms": 16028.7677 }, "paml_models": { "m0_lnl": -966.159, "m0_kappa": 2.5768, "m0_omega": 0.1505, "branch_2ratio_lnl": -948.404, "omega_bg": 0.0275, "omega_fg": 0.3422, "branch_neutral_fg1_lnl": -958.3627, "lrt_relax_2vs1": 35.5101, "p_value_relax": 2.5461165392531512e-9, "lrt_neutral_fg1": 19.9175, "p_value_neutral_fg1": 8.092885766990898e-6, "relax_intensity_k": 0.2985, "wall_ms": 0.7729 }, "delta_m0_lnl": 7.2547, "delta_2ratio_lnl": 7.1948, "delta_neutral_lnl": 7.0627, "delta_omega_bg": 0.0008, "delta_omega_fg": 0.0022, "delta_relax_k": 0.0005, "native_classification": "True Pseudogene / Relaxed Selection (Shared Loss + Neutral Drift)", "reference_classification": "True Pseudogene / Relaxed Selection (Shared Loss + Neutral Drift)", "classification_concordant": true, "ascii_focal_alignment_window": "Cohort: DEV-01-GULO (GULO) | RefSeq Anchor: NM_178747.3 | Focal Codons 20..31\nCodon (1-based) 20 21 22 23 24 25 26 27 28 29 30 31 \nTaxon_A GCC CGG CAG CAG AAC AAG AAA GTG AAG GTG GTG GGT \nTaxon_B GCC CGT CAG CAG AAC AAG AAA GTG AAG GTG GTG GGT \nLoss_1 GCC CGG CAG CAG A!C AAG AAA GTG AAG GTT GCG GGT \nLoss_2 GAC CGT CAG CAG A!C AAG AAA GTG AAG GTT GTG GGT \nLoss_1 AA/State A R Q Q ! K K V K V A G \nConservation : * * * ! * * * : : : : \nShannon Entropy โ–‚ โ– โ– โ– โ–„ โ– โ– โ– โ–‚ โ–‚ โ–‚ โ–‚ " }, { "cohort_id": "DEV-02-UOX", "scope": "development", "role": "pseudogene-loss", "gene_symbol": "UOX", "full_name": "Urate Oxidase / Uricase (Purine Degradation)", "refseq_anchor_accession": "NM_009474.4", "foreground_clade": "Hominoidea (Homo, Pan, Gorilla, Pongo #1)", "gnomad_plof_context": "Fixed hominoid pseudogene UOXp (NR_003569.1; Arg30Ter + frameshift)", "taxa_count": 10, "focal_codons": 80, "gen1_naive_frameshifts_called": 0, "gen1_naive_stops_called": 4, "gen1_naive_omega_fg": 0.8722, "gen1_naive_relax_k": 0.0523, "native_frameshift_sites": [ [ "Loss_1", [ 46 ] ], [ "Loss_2", [ 46 ] ], [ "Loss_3", [ 46 ] ], [ "Loss_4", [ 46 ] ] ], "macse_frameshift_sites": [ [ "Loss_1", [ 46 ] ], [ "Loss_2", [ 46 ] ], [ "Loss_3", [ 46 ] ], [ "Loss_4", [ 46 ] ] ], "native_stop_sites": [ [ "Loss_1", [ 30 ] ], [ "Loss_2", [ 30 ] ], [ "Loss_3", [ 30 ] ], [ "Loss_4", [ 30 ] ] ], "macse_stop_sites": [ [ "Loss_1", [ 30 ] ], [ "Loss_2", [ 30 ] ], [ "Loss_3", [ 30 ] ], [ "Loss_4", [ 30 ] ] ], "frameshift_exact_match": true, "stop_exact_match": true, "column_aa_identity_vs_macse": 1.0, "shared_across_sister_lineages": true, "singleton_homopolymer_artifact": false, "native_models": { "m0_lnl": -972.1063, "m0_kappa": 2.2633, "m0_omega": 0.2245, "branch_2ratio_lnl": -957.9596, "omega_bg": 0.0714, "omega_fg": 0.5092, "branch_neutral_fg1_lnl": -961.3459, "lrt_relax_2vs1": 28.2934, "p_value_relax": 1.0447324826213739e-7, "lrt_neutral_fg1": 6.7725, "p_value_neutral_fg1": 0.009257222208258966, "relax_intensity_k": 0.2556, "wall_ms": 16151.8142 }, "paml_models": { "m0_lnl": -964.1313, "m0_kappa": 2.24, "m0_omega": 0.2183, "branch_2ratio_lnl": -950.2787, "omega_bg": 0.0702, "omega_fg": 0.4985, "branch_neutral_fg1_lnl": -954.0048, "lrt_relax_2vs1": 27.7051, "p_value_relax": 1.4157170718549245e-7, "lrt_neutral_fg1": 7.4521, "p_value_neutral_fg1": 0.006336389607815079, "relax_intensity_k": 0.2621, "wall_ms": 1.0153 }, "delta_m0_lnl": 7.975, "delta_2ratio_lnl": 7.6809, "delta_neutral_lnl": 7.3411, "delta_omega_bg": 0.0012, "delta_omega_fg": 0.0107, "delta_relax_k": 0.0065, "native_classification": "True Pseudogene / Relaxed Selection (Shared Loss + Neutral Drift)", "reference_classification": "True Pseudogene / Relaxed Selection (Shared Loss + Neutral Drift)", "classification_concordant": true, "ascii_focal_alignment_window": "Cohort: DEV-02-UOX (UOX) | RefSeq Anchor: NM_009474.4 | Focal Codons 42..53\nCodon (1-based) 42 43 44 45 46 47 48 49 50 51 52 53 \nTaxon_A AGG TCC AAG AAG GAT TAC CTA CAC GGT GAT AAT TCC \nTaxon_B AGA TCC AAG AAG GAT TAC CTA CAC GGT GAT AAC TCT \nLoss_1 AGG CCT AAG AAG G!T TAC CTA CAT GGT GAT AAT TCC \nLoss_2 AGG TCC AAG AAG G!T TAC CTA CAC GGT GAC AAT TCC \nLoss_1 AA/State R P K K ! Y L H G D N S \nConservation : : * * ! * * * * * * * \nShannon Entropy โ–‚ โ–‚ โ– โ– โ–„ โ– โ– โ– โ– โ– โ– โ– " }, { "cohort_id": "DEV-03-ANGPTL3", "scope": "development", "role": "protective-ko", "gene_symbol": "ANGPTL3", "full_name": "Angiopoietin-Like 3 (Lipoprotein Lipase Inhibitor)", "refseq_anchor_accession": "NM_014495.4", "foreground_clade": "Convergent Marine Diving Clade & Human Homozygous pLoF (#1)", "gnomad_plof_context": "gnomAD v4 homozygous pLoF tolerated (p.Ser17Ter): -62% TG, -39% CAD risk (Evinacumab target)", "taxa_count": 10, "focal_codons": 80, "gen1_naive_frameshifts_called": 0, "gen1_naive_stops_called": 11, "gen1_naive_omega_fg": 1.2024, "gen1_naive_relax_k": 0.0, "native_frameshift_sites": [ [ "Loss_1", [ 19 ] ], [ "Loss_2", [ 19 ] ], [ "Loss_3", [ 19 ] ], [ "Loss_4", [ 19 ] ] ], "macse_frameshift_sites": [ [ "Loss_1", [ 19 ] ], [ "Loss_2", [ 19 ] ], [ "Loss_3", [ 19 ] ], [ "Loss_4", [ 19 ] ] ], "native_stop_sites": [ [ "Loss_1", [ 41 ] ], [ "Loss_2", [ 41 ] ], [ "Loss_3", [ 41 ] ], [ "Loss_4", [ 41 ] ] ], "macse_stop_sites": [ [ "Loss_1", [ 41 ] ], [ "Loss_2", [ 41 ] ], [ "Loss_3", [ 41 ] ], [ "Loss_4", [ 41 ] ] ], "frameshift_exact_match": true, "stop_exact_match": true, "column_aa_identity_vs_macse": 1.0, "shared_across_sister_lineages": true, "singleton_homopolymer_artifact": false, "native_models": { "m0_lnl": -867.608, "m0_kappa": 2.4538, "m0_omega": 0.1234, "branch_2ratio_lnl": -851.507, "omega_bg": 0.0199, "omega_fg": 0.2884, "branch_neutral_fg1_lnl": -862.6587, "lrt_relax_2vs1": 32.202, "p_value_relax": 1.3933850154762857e-8, "lrt_neutral_fg1": 22.3034, "p_value_neutral_fg1": 2.330723217839647e-6, "relax_intensity_k": 0.3174, "wall_ms": 15865.2668 }, "paml_models": { "m0_lnl": -862.6914, "m0_kappa": 2.4015, "m0_omega": 0.1177, "branch_2ratio_lnl": -846.6752, "omega_bg": 0.0193, "omega_fg": 0.2848, "branch_neutral_fg1_lnl": -858.0245, "lrt_relax_2vs1": 32.0324, "p_value_relax": 1.5204705148560713e-8, "lrt_neutral_fg1": 22.6986, "p_value_neutral_fg1": 1.8974210427166173e-6, "relax_intensity_k": 0.3181, "wall_ms": 0.6399 }, "delta_m0_lnl": 4.9166, "delta_2ratio_lnl": 4.8318, "delta_neutral_lnl": 4.6342, "delta_omega_bg": 0.0006, "delta_omega_fg": 0.0036, "delta_relax_k": 0.0007, "native_classification": "Protective Knockout Candidate (Shared pLoF + Neutral Drift)", "reference_classification": "Protective Knockout Candidate (Shared pLoF + Neutral Drift)", "classification_concordant": true, "ascii_focal_alignment_window": "Cohort: DEV-03-ANGPTL3 (ANGPTL3) | RefSeq Anchor: NM_014495.4 | Focal Codons 15..26\nCodon (1-based) 15 16 17 18 19 20 21 22 23 24 25 26 \nTaxon_A TCT CCA GAG CCA AAA TCA AGA TTT GCT ATG TTA GAC \nTaxon_B TCT CCA GAG CCA AAA TCA AGA TTT GCC ATG TTA GAC \nLoss_1 TCT GCA GAG CCA A!A TCA AGA TTT GCT ATG TTA GAC \nLoss_2 TCT CCA GAA CCA A!A TCA AGA TTT GCT ATG TTA GAC \nLoss_1 AA/State S A E P ! S R F A M L D \nConservation * : : * ! * : : * * * * \nShannon Entropy โ– โ–‚ โ–‚ โ– โ–„ โ– โ–‚ โ–‚ โ– โ– โ– โ– " }, { "cohort_id": "DEV-04-MMP20", "scope": "development", "role": "pseudogene-loss", "gene_symbol": "MMP20", "full_name": "Matrix Metalloproteinase-20 / Enamelysin", "refseq_anchor_accession": "NM_004771.4", "foreground_clade": "Edentulous Mysticeti Baleen Whales & Manis (#1)", "gnomad_plof_context": "Convergent enamel trait loss across toothless mammals", "taxa_count": 10, "focal_codons": 80, "gen1_naive_frameshifts_called": 0, "gen1_naive_stops_called": 17, "gen1_naive_omega_fg": 0.6505, "gen1_naive_relax_k": 0.1656, "native_frameshift_sites": [ [ "Loss_1", [ 28 ] ], [ "Loss_2", [ 28 ] ], [ "Loss_3", [ 28 ] ], [ "Loss_4", [ 28 ] ] ], "macse_frameshift_sites": [ [ "Loss_1", [ 28 ] ], [ "Loss_2", [ 28 ] ], [ "Loss_3", [ 28 ] ], [ "Loss_4", [ 28 ] ] ], "native_stop_sites": [ [ "Loss_1", [ 58 ] ], [ "Loss_2", [ 58 ] ], [ "Loss_3", [ 58 ] ], [ "Loss_4", [ 58 ] ] ], "macse_stop_sites": [ [ "Loss_1", [ 58 ] ], [ "Loss_2", [ 58 ] ], [ "Loss_3", [ 58 ] ], [ "Loss_4", [ 58 ] ] ], "frameshift_exact_match": true, "stop_exact_match": true, "column_aa_identity_vs_macse": 1.0, "shared_across_sister_lineages": true, "singleton_homopolymer_artifact": false, "native_models": { "m0_lnl": -977.3552, "m0_kappa": 2.0538, "m0_omega": 0.2284, "branch_2ratio_lnl": -967.7232, "omega_bg": 0.0741, "omega_fg": 0.3877, "branch_neutral_fg1_lnl": -976.2643, "lrt_relax_2vs1": 19.2641, "p_value_relax": 0.00001139205745037418, "lrt_neutral_fg1": 17.0821, "p_value_neutral_fg1": 0.000035817575926625414, "relax_intensity_k": 0.3641, "wall_ms": 15971.4598 }, "paml_models": { "m0_lnl": -969.9029, "m0_kappa": 2.1025, "m0_omega": 0.2224, "branch_2ratio_lnl": -960.394, "omega_bg": 0.073, "omega_fg": 0.3856, "branch_neutral_fg1_lnl": -969.0866, "lrt_relax_2vs1": 19.018, "p_value_relax": 0.00001295931678827799, "lrt_neutral_fg1": 17.3852, "p_value_neutral_fg1": 0.00003053774379719078, "relax_intensity_k": 0.3641, "wall_ms": 2.2387 }, "delta_m0_lnl": 7.4523, "delta_2ratio_lnl": 7.3292, "delta_neutral_lnl": 7.1777, "delta_omega_bg": 0.0011, "delta_omega_fg": 0.0021, "delta_relax_k": 0.0, "native_classification": "True Pseudogene / Relaxed Selection (Shared Loss + Neutral Drift)", "reference_classification": "True Pseudogene / Relaxed Selection (Shared Loss + Neutral Drift)", "classification_concordant": true, "ascii_focal_alignment_window": "Cohort: DEV-04-MMP20 (MMP20) | RefSeq Anchor: NM_004771.4 | Focal Codons 24..35\nCodon (1-based) 24 25 26 27 28 29 30 31 32 33 34 35 \nTaxon_A GGA CAC CAG ATT GGT GAG ATG GTT GCA AGA GGA AGC \nTaxon_B AGA CAC CAG ATT GGT GAG ATG GTT GCA AGA GGA AGC \nLoss_1 GGA CAC CAG ATT G!T GAG ATG GTT GCA ATA GGA AGC \nLoss_2 GGT CAC GAG ATT G!T GAG ATG GTC CCA AGA GGA AGT \nLoss_1 AA/State G H Q I ! E M V A I G S \nConservation : * : * ! * * * : : : * \nShannon Entropy โ–ƒ โ– โ–‚ โ– โ–„ โ– โ– โ– โ–‚ โ–„ โ–‚ โ– " }, { "cohort_id": "DEV-05-ACTB-CTRL", "scope": "development", "role": "negative-control-purifying", "gene_symbol": "ACTB", "full_name": "Beta-Actin (Intact Housekeeping Negative Control)", "refseq_anchor_accession": "NM_001101.5", "foreground_clade": "Primate Crown Clade (#1 โ€” Intact Purifying Control)", "gnomad_plof_context": "gnomAD v4 pLI = 1.00, LOEUF = 0.08 (essential cytoskeletal gene; LoF lethal)", "taxa_count": 10, "focal_codons": 80, "gen1_naive_frameshifts_called": 0, "gen1_naive_stops_called": 0, "gen1_naive_omega_fg": 0.0134, "gen1_naive_relax_k": 0.7491, "native_frameshift_sites": [], "macse_frameshift_sites": [], "native_stop_sites": [], "macse_stop_sites": [], "frameshift_exact_match": true, "stop_exact_match": true, "column_aa_identity_vs_macse": 1.0, "shared_across_sister_lineages": false, "singleton_homopolymer_artifact": false, "native_models": { "m0_lnl": -646.8074, "m0_kappa": 9.7174, "m0_omega": 0.0081, "branch_2ratio_lnl": -645.82, "omega_bg": 0.0032, "omega_fg": 0.0134, "branch_neutral_fg1_lnl": -710.5598, "lrt_relax_2vs1": 1.975, "p_value_relax": 0.15992234795351892, "lrt_neutral_fg1": 129.4796, "p_value_neutral_fg1": 1e-16, "relax_intensity_k": 0.7491, "wall_ms": 15493.5963 }, "paml_models": { "m0_lnl": -644.4257, "m0_kappa": 9.7569, "m0_omega": 0.008, "branch_2ratio_lnl": -643.4503, "omega_bg": 0.0031, "omega_fg": 0.0132, "branch_neutral_fg1_lnl": -708.2788, "lrt_relax_2vs1": 1.951, "p_value_relax": 0.1624837649158696, "lrt_neutral_fg1": 129.6571, "p_value_neutral_fg1": 1e-16, "relax_intensity_k": 0.7487, "wall_ms": 22.917 }, "delta_m0_lnl": 2.3817, "delta_2ratio_lnl": 2.3697, "delta_neutral_lnl": 2.281, "delta_omega_bg": 0.0001, "delta_omega_fg": 0.0002, "delta_relax_k": 0.0004, "native_classification": "Intact Purifying Selection", "reference_classification": "Intact Purifying Selection", "classification_concordant": true, "ascii_focal_alignment_window": "Cohort: DEV-05-ACTB-CTRL (ACTB) | RefSeq Anchor: NM_001101.5 | Focal Codons 24..35\nCodon (1-based) 24 25 26 27 28 29 30 31 32 33 34 35 \nTaxon_A ATC GTG GGG CGC CCC AGG CAC CAG GGC GTG ATG GTG \nTaxon_B ATC GTG GGG CGC CCT AGG CAC CAG GGC GTG ATG GTG \nLoss_1 ATT GTG GGT CGC CCC AGG CAC CAG GGC GTG ATG CTG \nLoss_2 ATC GTT GGG CGC CCC AGG CAC CAG GGC GTG ATG GTG \nLoss_1 AA/State I V G R P R H Q G V M L \nConservation * * * * * * : * * * * : \nShannon Entropy โ– โ– โ– โ– โ– โ– โ–‚ โ– โ– โ– โ– โ–‚ " }, { "cohort_id": "DEV-06-ABCA4-ARTIFACT", "scope": "development", "role": "negative-control-artifact", "gene_symbol": "ABCA4", "full_name": "Retinal ATP-Binding Cassette Transporter (Localized 6G Homopolymer Repeat Indel / Slippage)", "refseq_anchor_accession": "NM_000350.3", "foreground_clade": "Lineage with Singleton 6G Homopolymer Indel (#1 โ€” Frame Restored Downstream)", "gnomad_plof_context": "Pathogenic Stargardt macular dystrophy if inactivated; localized 6G repeat indel/slippage preserves downstream reading frame & purifying selection", "taxa_count": 10, "focal_codons": 80, "gen1_naive_frameshifts_called": 0, "gen1_naive_stops_called": 2, "gen1_naive_omega_fg": 0.3042, "gen1_naive_relax_k": 0.3934, "native_frameshift_sites": [ [ "Loss_1", [ 31 ] ] ], "macse_frameshift_sites": [ [ "Loss_1", [ 31 ] ] ], "native_stop_sites": [], "macse_stop_sites": [], "frameshift_exact_match": true, "stop_exact_match": true, "column_aa_identity_vs_macse": 1.0, "shared_across_sister_lineages": false, "singleton_homopolymer_artifact": true, "native_models": { "m0_lnl": -700.8414, "m0_kappa": 2.1681, "m0_omega": 0.0417, "branch_2ratio_lnl": -700.4023, "omega_bg": 0.0498, "omega_fg": 0.0285, "branch_neutral_fg1_lnl": -735.192, "lrt_relax_2vs1": 0.8782, "p_value_relax": 0.3487027240966108, "lrt_neutral_fg1": 69.5795, "p_value_neutral_fg1": 1e-16, "relax_intensity_k": 1.1861, "wall_ms": 15824.7887 }, "paml_models": { "m0_lnl": -695.9999, "m0_kappa": 2.2192, "m0_omega": 0.0408, "branch_2ratio_lnl": -695.693, "omega_bg": 0.0489, "omega_fg": 0.0283, "branch_neutral_fg1_lnl": -730.5902, "lrt_relax_2vs1": 0.6137, "p_value_relax": 0.43339421276781626, "lrt_neutral_fg1": 69.7944, "p_value_neutral_fg1": 1e-16, "relax_intensity_k": 1.1816, "wall_ms": 0.6453 }, "delta_m0_lnl": 4.8415, "delta_2ratio_lnl": 4.7093, "delta_neutral_lnl": 4.6018, "delta_omega_bg": 0.0009, "delta_omega_fg": 0.0002, "delta_relax_k": 0.0045, "native_classification": "Localized Homopolymer Repeat Indel / Artifact (Frame Preserved, Purifying Kept)", "reference_classification": "Localized Homopolymer Repeat Indel / Artifact (Frame Preserved, Purifying Kept)", "classification_concordant": true, "ascii_focal_alignment_window": "Cohort: DEV-06-ABCA4-ARTIFACT (ABCA4) | RefSeq Anchor: NM_000350.3 | Focal Codons 27..38\nCodon (1-based) 27 28 29 30 31 32 33 34 35 36 37 38 \nTaxon_A CTG CCG TGG CTC CAG GGG GGG GGC TGC AAT GTG AAC \nTaxon_B CTG CCG TGG CTC CAG GGT GGG GGC TGC AAT GTG AAC \nLoss_1 CTG CCG TGG CTC CA! GGG GGG GGC TGC AAT GTG AAC \nLoss_2 CTG CCG TGG CTT CAG GGG GGT GGC TGC AAT GTT AAC \nLoss_1 AA/State L P W L ! G G G C N V N \nConservation * * * * ! * : * * * * * \nShannon Entropy โ– โ– โ– โ– โ–„ โ– โ–‚ โ– โ– โ– โ– โ– " }, { "cohort_id": "RES-01-ENAM", "scope": "reserve", "role": "pseudogene-loss", "gene_symbol": "ENAM", "full_name": "Enamelin (Extracellular Matrix Enamel Protein)", "refseq_anchor_accession": "NM_031889.3", "foreground_clade": "Edentulous Mysticeti Baleen Whales (#1)", "gnomad_plof_context": "Shared frameshift & nonsense fixation across baleen whales", "taxa_count": 10, "focal_codons": 80, "gen1_naive_frameshifts_called": 0, "gen1_naive_stops_called": 11, "gen1_naive_omega_fg": 1.4632, "gen1_naive_relax_k": 0.0, "native_frameshift_sites": [ [ "Loss_1", [ 22 ] ], [ "Loss_2", [ 22 ] ], [ "Loss_3", [ 22 ] ], [ "Loss_4", [ 22 ] ] ], "macse_frameshift_sites": [ [ "Loss_1", [ 22 ] ], [ "Loss_2", [ 22 ] ], [ "Loss_3", [ 22 ] ], [ "Loss_4", [ 22 ] ] ], "native_stop_sites": [ [ "Loss_1", [ 49 ] ], [ "Loss_2", [ 49 ] ], [ "Loss_3", [ 49 ] ], [ "Loss_4", [ 49 ] ] ], "macse_stop_sites": [ [ "Loss_1", [ 49 ] ], [ "Loss_2", [ 49 ] ], [ "Loss_3", [ 49 ] ], [ "Loss_4", [ 49 ] ] ], "frameshift_exact_match": true, "stop_exact_match": true, "column_aa_identity_vs_macse": 1.0, "shared_across_sister_lineages": true, "singleton_homopolymer_artifact": false, "native_models": { "m0_lnl": -885.0308, "m0_kappa": 2.7596, "m0_omega": 0.2367, "branch_2ratio_lnl": -878.2589, "omega_bg": 0.0841, "omega_fg": 0.376, "branch_neutral_fg1_lnl": -886.5557, "lrt_relax_2vs1": 13.5438, "p_value_relax": 0.000233126121931527, "lrt_neutral_fg1": 16.5935, "p_value_neutral_fg1": 0.000046333227923128496, "relax_intensity_k": 0.3951, "wall_ms": 15875.2149 }, "paml_models": { "m0_lnl": -877.8115, "m0_kappa": 2.7931, "m0_omega": 0.2299, "branch_2ratio_lnl": -871.3829, "omega_bg": 0.0832, "omega_fg": 0.3713, "branch_neutral_fg1_lnl": -879.9144, "lrt_relax_2vs1": 12.8573, "p_value_relax": 0.0003362505271896566, "lrt_neutral_fg1": 17.0629, "p_value_neutral_fg1": 0.000036182060320439866, "relax_intensity_k": 0.3983, "wall_ms": 3.9217 }, "delta_m0_lnl": 7.2193, "delta_2ratio_lnl": 6.876, "delta_neutral_lnl": 6.6413, "delta_omega_bg": 0.0009, "delta_omega_fg": 0.0047, "delta_relax_k": 0.0032, "native_classification": "True Pseudogene / Relaxed Selection (Shared Loss + Neutral Drift)", "reference_classification": "True Pseudogene / Relaxed Selection (Shared Loss + Neutral Drift)", "classification_concordant": true, "ascii_focal_alignment_window": "Cohort: RES-01-ENAM (ENAM) | RefSeq Anchor: NM_031889.3 | Focal Codons 18..29\nCodon (1-based) 18 19 20 21 22 23 24 25 26 27 28 29 \nTaxon_A CAC ATG CCC CGA ATG CCT GGA TTT AGC AGT AAA AGT \nTaxon_B CAC ATG CCC CGA ATG CCT GGA TTT AGC AGT AAA AGT \nLoss_1 CAC ATG CCC CGA A!G CCT GGA TTT AGT AGT AAA AGT \nLoss_2 CAC GTG CCC CGA A!G CCT GGA TTT AGC AGT AAA AGT \nLoss_1 AA/State H M P R ! P G F S S K S \nConservation * : : * ! * : * * * : * \nShannon Entropy โ– โ–‚ โ–„ โ– โ–„ โ– โ–‚ โ– โ– โ– โ–‚ โ– " }, { "cohort_id": "RES-02-CASP12", "scope": "reserve", "role": "protective-ko", "gene_symbol": "CASP12", "full_name": "Caspase-12 (Inflammatory Cytokine Protease)", "refseq_anchor_accession": "NM_009808.4", "foreground_clade": "Homininae Pseudogene Clade (Homo NR_000038.2 Arg125Ter #1)", "gnomad_plof_context": "gnomAD v4 common homozygous stop-gain/frameshift; confers resistance to severe sepsis", "taxa_count": 10, "focal_codons": 80, "gen1_naive_frameshifts_called": 0, "gen1_naive_stops_called": 9, "gen1_naive_omega_fg": 0.8217, "gen1_naive_relax_k": 0.0475, "native_frameshift_sites": [ [ "Loss_1", [ 32 ] ], [ "Loss_2", [ 32 ] ], [ "Loss_3", [ 32 ] ], [ "Loss_4", [ 32 ] ] ], "macse_frameshift_sites": [ [ "Loss_1", [ 32 ] ], [ "Loss_2", [ 32 ] ], [ "Loss_3", [ 32 ] ], [ "Loss_4", [ 32 ] ] ], "native_stop_sites": [ [ "Loss_1", [ 55 ] ], [ "Loss_2", [ 55 ] ], [ "Loss_3", [ 55 ] ], [ "Loss_4", [ 55 ] ] ], "macse_stop_sites": [ [ "Loss_1", [ 55 ] ], [ "Loss_2", [ 55 ] ], [ "Loss_3", [ 55 ] ], [ "Loss_4", [ 55 ] ] ], "frameshift_exact_match": true, "stop_exact_match": true, "column_aa_identity_vs_macse": 1.0, "shared_across_sister_lineages": true, "singleton_homopolymer_artifact": false, "native_models": { "m0_lnl": -850.476, "m0_kappa": 1.3067, "m0_omega": 0.1577, "branch_2ratio_lnl": -827.4894, "omega_bg": 0.0149, "omega_fg": 0.429, "branch_neutral_fg1_lnl": -831.9548, "lrt_relax_2vs1": 45.9731, "p_value_relax": 1.2058121505674371e-11, "lrt_neutral_fg1": 8.9308, "p_value_neutral_fg1": 0.0028041509583135666, "relax_intensity_k": 0.2011, "wall_ms": 16476.5456 }, "paml_models": { "m0_lnl": -844.394, "m0_kappa": 1.342, "m0_omega": 0.151, "branch_2ratio_lnl": -821.6326, "omega_bg": 0.0145, "omega_fg": 0.4217, "branch_neutral_fg1_lnl": -826.22, "lrt_relax_2vs1": 45.5227, "p_value_relax": 1.5173315811720887e-11, "lrt_neutral_fg1": 9.1748, "p_value_neutral_fg1": 0.0024537893193673456, "relax_intensity_k": 0.204, "wall_ms": 0.6709 }, "delta_m0_lnl": 6.082, "delta_2ratio_lnl": 5.8568, "delta_neutral_lnl": 5.7348, "delta_omega_bg": 0.0004, "delta_omega_fg": 0.0073, "delta_relax_k": 0.0029, "native_classification": "Protective Knockout Candidate (Shared pLoF + Neutral Drift)", "reference_classification": "Protective Knockout Candidate (Shared pLoF + Neutral Drift)", "classification_concordant": true, "ascii_focal_alignment_window": "Cohort: RES-02-CASP12 (CASP12) | RefSeq Anchor: NM_009808.4 | Focal Codons 28..39\nCodon (1-based) 28 29 30 31 32 33 34 35 36 37 38 39 \nTaxon_A AAA ATA GGG GAA AGT GCG AGT TTC ATC CTG AAC AAG \nTaxon_B AAA ATA GGG GAA AGT GCG AGT TTC ATC CTG AAC AAG \nLoss_1 AAA ATA GGG GAA !GT GCG AGT TTC AGC CTG AAC AAG \nLoss_2 AAA CTA GGG GAA !GT GCG AGT TTC TTC CTG AAC AAG \nLoss_1 AA/State K I G E ! A S F S L N K \nConservation * : * * ! * * * : * * : \nShannon Entropy โ– โ–‚ โ– โ– โ–„ โ– โ– โ– โ–„ โ– โ– โ–‚ " }, { "cohort_id": "RES-03-HSD17B13", "scope": "reserve", "role": "protective-ko", "gene_symbol": "HSD17B13", "full_name": "17-Beta-Hydroxysteroid Dehydrogenase 13 (Hepatic Lipid Droplet Enzyme)", "refseq_anchor_accession": "NM_178135.5", "foreground_clade": "Homozygous Splice/Frameshift Loss Clade (rs72613567 #1)", "gnomad_plof_context": "gnomAD v4 homozygous pLoF tolerated: -37% to -49% MASH cirrhosis & HCC risk", "taxa_count": 10, "focal_codons": 80, "gen1_naive_frameshifts_called": 0, "gen1_naive_stops_called": 9, "gen1_naive_omega_fg": 1.004, "gen1_naive_relax_k": 0.0, "native_frameshift_sites": [ [ "Loss_1", [ 27 ] ], [ "Loss_2", [ 27 ] ], [ "Loss_3", [ 27 ] ], [ "Loss_4", [ 27 ] ] ], "macse_frameshift_sites": [ [ "Loss_1", [ 27 ] ], [ "Loss_2", [ 27 ] ], [ "Loss_3", [ 27 ] ], [ "Loss_4", [ 27 ] ] ], "native_stop_sites": [ [ "Loss_1", [ 48 ] ], [ "Loss_2", [ 48 ] ], [ "Loss_3", [ 48 ] ], [ "Loss_4", [ 48 ] ] ], "macse_stop_sites": [ [ "Loss_1", [ 48 ] ], [ "Loss_2", [ 48 ] ], [ "Loss_3", [ 48 ] ], [ "Loss_4", [ 48 ] ] ], "frameshift_exact_match": true, "stop_exact_match": true, "column_aa_identity_vs_macse": 1.0, "shared_across_sister_lineages": true, "singleton_homopolymer_artifact": false, "native_models": { "m0_lnl": -941.7781, "m0_kappa": 2.1, "m0_omega": 0.1936, "branch_2ratio_lnl": -937.9002, "omega_bg": 0.1061, "omega_fg": 0.2894, "branch_neutral_fg1_lnl": -951.3213, "lrt_relax_2vs1": 7.7559, "p_value_relax": 0.0053539064076119506, "lrt_neutral_fg1": 26.8421, "p_value_neutral_fg1": 2.211841110828618e-7, "relax_intensity_k": 0.5528, "wall_ms": 16246.5092 }, "paml_models": { "m0_lnl": -933.7748, "m0_kappa": 2.1071, "m0_omega": 0.1897, "branch_2ratio_lnl": -930.0142, "omega_bg": 0.1036, "omega_fg": 0.2888, "branch_neutral_fg1_lnl": -943.3621, "lrt_relax_2vs1": 7.5211, "p_value_relax": 0.006098030549005361, "lrt_neutral_fg1": 26.6957, "p_value_neutral_fg1": 2.385876449070624e-7, "relax_intensity_k": 0.5479, "wall_ms": 0.9285 }, "delta_m0_lnl": 8.0033, "delta_2ratio_lnl": 7.886, "delta_neutral_lnl": 7.9592, "delta_omega_bg": 0.0025, "delta_omega_fg": 0.0006, "delta_relax_k": 0.0049, "native_classification": "Protective Knockout Candidate (Shared pLoF + Neutral Drift)", "reference_classification": "Protective Knockout Candidate (Shared pLoF + Neutral Drift)", "classification_concordant": true, "ascii_focal_alignment_window": "Cohort: RES-03-HSD17B13 (HSD17B13) | RefSeq Anchor: NM_178135.5 | Focal Codons 23..34\nCodon (1-based) 23 24 25 26 27 28 29 30 31 32 33 34 \nTaxon_A TCT GTG GCT GGG GAG ATT GTT CTC ATT ACT GGA GCT \nTaxon_B TCT GTG GCC GGG GAG ATT GTT CTC ATT ACT GGA GCC \nLoss_1 TCT GTG GCT GGG G!G ATT GTT CTC ATT ACT GGA GCT \nLoss_2 TAT GTG GCT GGG G!G ATT GTT CTC ATT ACC GGA GCT \nLoss_1 AA/State S V A G ! I V L I T G A \nConservation : : : * ! : * * * * : * \nShannon Entropy โ–‚ โ–‚ โ–‚ โ– โ–„ โ–„ โ– โ– โ– โ– โ–‚ โ– " }, { "cohort_id": "RES-04-TAS1R2", "scope": "reserve", "role": "pseudogene-loss", "gene_symbol": "TAS1R2", "full_name": "Taste Receptor Type 1 Member 2 (Sweet Taste Receptor)", "refseq_anchor_accession": "NM_152232.5", "foreground_clade": "Obligate Carnivore Felidae Clade (Felis, Panthera #1)", "gnomad_plof_context": "Convergent sweet-receptor pseudogenization in obligate carnivores", "taxa_count": 10, "focal_codons": 80, "gen1_naive_frameshifts_called": 0, "gen1_naive_stops_called": 8, "gen1_naive_omega_fg": 0.7137, "gen1_naive_relax_k": 0.1076, "native_frameshift_sites": [ [ "Loss_1", [ 35 ] ], [ "Loss_2", [ 35 ] ], [ "Loss_3", [ 35 ] ], [ "Loss_4", [ 35 ] ] ], "macse_frameshift_sites": [ [ "Loss_1", [ 35 ] ], [ "Loss_2", [ 35 ] ], [ "Loss_3", [ 35 ] ], [ "Loss_4", [ 35 ] ] ], "native_stop_sites": [ [ "Loss_1", [ 61 ] ], [ "Loss_2", [ 61 ] ], [ "Loss_3", [ 61 ] ], [ "Loss_4", [ 61 ] ] ], "macse_stop_sites": [ [ "Loss_1", [ 61 ] ], [ "Loss_2", [ 61 ] ], [ "Loss_3", [ 61 ] ], [ "Loss_4", [ 61 ] ] ], "frameshift_exact_match": true, "stop_exact_match": true, "column_aa_identity_vs_macse": 1.0, "shared_across_sister_lineages": true, "singleton_homopolymer_artifact": false, "native_models": { "m0_lnl": -878.7052, "m0_kappa": 2.7735, "m0_omega": 0.113, "branch_2ratio_lnl": -871.9626, "omega_bg": 0.0445, "omega_fg": 0.1993, "branch_neutral_fg1_lnl": -892.3474, "lrt_relax_2vs1": 13.4852, "p_value_relax": 0.00024052253846608627, "lrt_neutral_fg1": 40.7695, "p_value_neutral_fg1": 1.7207183570832025e-10, "relax_intensity_k": 0.5183, "wall_ms": 15811.5658 }, "paml_models": { "m0_lnl": -871.2722, "m0_kappa": 2.7367, "m0_omega": 0.1104, "branch_2ratio_lnl": -865.0461, "omega_bg": 0.0441, "omega_fg": 0.1939, "branch_neutral_fg1_lnl": -886.1038, "lrt_relax_2vs1": 12.4523, "p_value_relax": 0.0004175613970390398, "lrt_neutral_fg1": 42.1155, "p_value_neutral_fg1": 8.646196989305611e-11, "relax_intensity_k": 0.5254, "wall_ms": 1.9249 }, "delta_m0_lnl": 7.433, "delta_2ratio_lnl": 6.9165, "delta_neutral_lnl": 6.2436, "delta_omega_bg": 0.0004, "delta_omega_fg": 0.0054, "delta_relax_k": 0.0071, "native_classification": "True Pseudogene / Relaxed Selection (Shared Loss + Neutral Drift)", "reference_classification": "True Pseudogene / Relaxed Selection (Shared Loss + Neutral Drift)", "classification_concordant": true, "ascii_focal_alignment_window": "Cohort: RES-04-TAS1R2 (TAS1R2) | RefSeq Anchor: NM_152232.5 | Focal Codons 31..42\nCodon (1-based) 31 32 33 34 35 36 37 38 39 40 41 42 \nTaxon_A GAG TAT GAA GTG AAG GTG ATA GGC TAC AAC CTC ATG \nTaxon_B GAG TAT GAA GTG AAG GTG ATA GGC TAC AAC CTC ATG \nLoss_1 GAA TAT GAA GTG A!G GTG ATA GGC TAC AAC CTT ATG \nLoss_2 GAA TAT GAA GTG A!G GTG ATA TGC TAC AAC CCC ATG \nLoss_1 AA/State E Y E V ! V I G Y N L M \nConservation * * * * ! * * : * * : : \nShannon Entropy โ– โ– โ– โ– โ–„ โ– โ– โ–‚ โ– โ– โ–‚ โ–‚ " }, { "cohort_id": "RES-05-GAPDH-CTRL", "scope": "reserve", "role": "negative-control-purifying", "gene_symbol": "GAPDH", "full_name": "Glyceraldehyde-3-Phosphate Dehydrogenase (Reserve Purifying Control)", "refseq_anchor_accession": "NM_002046.7", "foreground_clade": "Primate Crown Clade (#1 โ€” Intact Purifying Control)", "gnomad_plof_context": "gnomAD v4 essential glycolytic enzyme (intact purifying selection)", "taxa_count": 10, "focal_codons": 80, "gen1_naive_frameshifts_called": 0, "gen1_naive_stops_called": 0, "gen1_naive_omega_fg": 0.0395, "gen1_naive_relax_k": 0.7458, "native_frameshift_sites": [], "macse_frameshift_sites": [], "native_stop_sites": [], "macse_stop_sites": [], "frameshift_exact_match": true, "stop_exact_match": true, "column_aa_identity_vs_macse": 1.0, "shared_across_sister_lineages": false, "singleton_homopolymer_artifact": false, "native_models": { "m0_lnl": -668.5074, "m0_kappa": 5.7865, "m0_omega": 0.0256, "branch_2ratio_lnl": -667.4953, "omega_bg": 0.0131, "omega_fg": 0.0395, "branch_neutral_fg1_lnl": -706.6049, "lrt_relax_2vs1": 2.0242, "p_value_relax": 0.15480848037294925, "lrt_neutral_fg1": 78.2191, "p_value_neutral_fg1": 1e-16, "relax_intensity_k": 0.7458, "wall_ms": 16099.6603 }, "paml_models": { "m0_lnl": -663.8155, "m0_kappa": 6.0281, "m0_omega": 0.0243, "branch_2ratio_lnl": -662.9548, "omega_bg": 0.0128, "omega_fg": 0.038, "branch_neutral_fg1_lnl": -702.6265, "lrt_relax_2vs1": 1.7215, "p_value_relax": 0.18950226767596168, "lrt_neutral_fg1": 79.3434, "p_value_neutral_fg1": 1e-16, "relax_intensity_k": 0.7504, "wall_ms": 1.7064 }, "delta_m0_lnl": 4.6919, "delta_2ratio_lnl": 4.5405, "delta_neutral_lnl": 3.9784, "delta_omega_bg": 0.0003, "delta_omega_fg": 0.0015, "delta_relax_k": 0.0046, "native_classification": "Intact Purifying Selection", "reference_classification": "Intact Purifying Selection", "classification_concordant": true, "ascii_focal_alignment_window": "Cohort: RES-05-GAPDH-CTRL (GAPDH) | RefSeq Anchor: NM_002046.7 | Focal Codons 24..35\nCodon (1-based) 24 25 26 27 28 29 30 31 32 33 34 35 \nTaxon_A AAT GAC CCC TTC ATT GAC CTC AAC TAC ATG GTT TAC \nTaxon_B AAT GAC CCC TTC ATT GAC CTC AAC TAC ATG GTT TAC \nLoss_1 AAT GAT CCC TTC ATT GAC CTC AAC TAC ATG GTT TAC \nLoss_2 AAC GAC CCC TTC ATT GAC CTC AAT TAC ATG GTT TAT \nLoss_1 AA/State N D P F I D L N Y M V Y \nConservation * * * * : * * * * * * * \nShannon Entropy โ– โ– โ– โ– โ–‚ โ– โ– โ– โ– โ– โ– โ– " }, { "cohort_id": "RES-06-HBB-ARTIFACT", "scope": "reserve", "role": "negative-control-artifact", "gene_symbol": "HBB", "full_name": "Hemoglobin Subunit Beta (Reserve Localized 5A Homopolymer Repeat Indel / Slippage)", "refseq_anchor_accession": "NM_000518.5", "foreground_clade": "Lineage with Singleton 5A Homopolymer Indel (#1 โ€” Frame Restored Downstream)", "gnomad_plof_context": "Pathogenic beta-thalassemia if inactivated; localized 5A repeat indel/slippage preserves downstream reading frame & purifying selection", "taxa_count": 10, "focal_codons": 80, "gen1_naive_frameshifts_called": 0, "gen1_naive_stops_called": 1, "gen1_naive_omega_fg": 0.2119, "gen1_naive_relax_k": 0.4222, "native_frameshift_sites": [ [ "Loss_1", [ 29 ] ] ], "macse_frameshift_sites": [ [ "Loss_1", [ 29 ] ] ], "native_stop_sites": [], "macse_stop_sites": [], "frameshift_exact_match": true, "stop_exact_match": true, "column_aa_identity_vs_macse": 1.0, "shared_across_sister_lineages": false, "singleton_homopolymer_artifact": true, "native_models": { "m0_lnl": -695.3294, "m0_kappa": 4.7415, "m0_omega": 0.0192, "branch_2ratio_lnl": -694.5312, "omega_bg": 0.0257, "omega_fg": 0.0081, "branch_neutral_fg1_lnl": -741.482, "lrt_relax_2vs1": 1.5963, "p_value_relax": 0.20642929837130874, "lrt_neutral_fg1": 93.9015, "p_value_neutral_fg1": 1e-16, "relax_intensity_k": 1.3142, "wall_ms": 15403.8083 }, "paml_models": { "m0_lnl": -690.4855, "m0_kappa": 4.8287, "m0_omega": 0.0186, "branch_2ratio_lnl": -689.8521, "omega_bg": 0.0253, "omega_fg": 0.0081, "branch_neutral_fg1_lnl": -736.7359, "lrt_relax_2vs1": 1.2668, "p_value_relax": 0.2603653254332986, "lrt_neutral_fg1": 93.7677, "p_value_neutral_fg1": 1e-16, "relax_intensity_k": 1.3097, "wall_ms": 1.3879 }, "delta_m0_lnl": 4.8439, "delta_2ratio_lnl": 4.6791, "delta_neutral_lnl": 4.7461, "delta_omega_bg": 0.0004, "delta_omega_fg": 0.0, "delta_relax_k": 0.0045, "native_classification": "Localized Homopolymer Repeat Indel / Artifact (Frame Preserved, Purifying Kept)", "reference_classification": "Localized Homopolymer Repeat Indel / Artifact (Frame Preserved, Purifying Kept)", "classification_concordant": true, "ascii_focal_alignment_window": "Cohort: RES-06-HBB-ARTIFACT (HBB) | RefSeq Anchor: NM_000518.5 | Focal Codons 25..36\nCodon (1-based) 25 26 27 28 29 30 31 32 33 34 35 36 \nTaxon_A GGC AGG CTG CTG AAA AAC TAC CCT TGG ACC CAG AGG \nTaxon_B GGC AGG CTG CTG AAA AAT TAC CCT TGG ACC CAG AGG \nLoss_1 GGC AGG CTG CTG A!A AAC TAC CCT TGG ACC CAG AGG \nLoss_2 GGT AGG CTG CTG AAA AAC TAT CCT TGG ACC CAG AGA \nLoss_1 AA/State G R L L ! N Y P W T Q R \nConservation * * * * ! * * * * * * * \nShannon Entropy โ– โ– โ– โ– โ–‚ โ– โ– โ– โ– โ– โ– โ– " } ], "total_duration_ms": 29517 }