{
  "schema": "astropome-biology-evidence.v1",
  "curated_date": "2026-10-24",
  "study_ids": [
    "dna-research-synthesis-20261023",
    "dna-global-completion-20261022",
    "dna-resource-delay-20261022",
    "dna-mechanism-validation-20261022",
    "dna-human-calibration-20261022",
    "dna-hct116-reanalysis-20261023",
    "dna-hct116-denominator-recovery-20261023"
  ],
  "provenance": "Curated from retained computational study and public-data audit records. This supplement does not claim that the original study artifacts are hosted in a public repository.",
  "publication_status": "Research synthesis and a single agent-assisted research case study; not peer reviewed.",
  "curation_scope": "Selected aggregate results, definitions, explicit limits, and source artifact hashes. No new simulations, empirical fits, biological experiments, bulk data recovery, or author outreach were performed for this update.",
  "reproducibility_limit": "This is a portable evidence summary, not a complete reproducibility release. Hashes identify retained source files; they do not establish independent timestamps, independent replication, or public availability of those files.",
  "source_artifacts": [
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      "id": "synthesis",
      "study_id": "dna-research-synthesis-20261023",
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      "bytes": 4038,
      "availability": "Retained study artifact; not included in this public supplement."
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      "id": "global",
      "study_id": "dna-global-completion-20261022",
      "artifact": "runs/main/summary.json",
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      "bytes": 123046,
      "availability": "Retained study artifact; not included in this public supplement."
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    {
      "id": "resource",
      "study_id": "dna-resource-delay-20261022",
      "artifact": "runs/main/summary.json",
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      "bytes": 4398689,
      "availability": "Retained study artifact; not included in this public supplement."
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      "id": "geometry",
      "study_id": "dna-mechanism-validation-20261022",
      "artifact": "geometry/summary.json",
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      "bytes": 5936,
      "availability": "Retained study artifact; not included in this public supplement."
    },
    {
      "id": "ablation",
      "study_id": "dna-mechanism-validation-20261022",
      "artifact": "ablation/summary.json",
      "sha256": "08c4790519973f9164434cbf380ea144f14ac5e0182650687955b1f54b7159c8",
      "bytes": 477193,
      "availability": "Retained study artifact; not included in this public supplement."
    },
    {
      "id": "joint",
      "study_id": "dna-mechanism-validation-20261022",
      "artifact": "ablation/joint-outcomes.csv",
      "sha256": "bed319cf20e25dd6c361fb8ea86c79774acbe9f53b67658ace705b8c3c5cd72d",
      "bytes": 4687,
      "availability": "Retained study artifact; not included in this public supplement."
    },
    {
      "id": "clock",
      "study_id": "dna-human-calibration-20261022",
      "artifact": "clock-identifiability/summary.json",
      "sha256": "e4505953caa7d408f9edbbb6aaf2bbb9b7783d53601543c708f7b0b9519470eb",
      "bytes": 11648,
      "availability": "Retained study artifact; not included in this public supplement."
    },
    {
      "id": "audit",
      "study_id": "dna-hct116-reanalysis-20261023",
      "artifact": "integrated-audit.json",
      "sha256": "d7ef36a481f6fae881082c8222850de5f8a833e764d5082e6c7c9f39e9eed46f",
      "bytes": 3219,
      "availability": "Retained study artifact; not included in this public supplement."
    },
    {
      "id": "nanopore",
      "study_id": "dna-hct116-reanalysis-20261023",
      "artifact": "nanopore/summary.json",
      "sha256": "1973e563f270989af414cf5b61e2b68863dd757fa109583b533dd1dc6907aeb5",
      "bytes": 3972,
      "availability": "Retained study artifact; not included in this public supplement."
    },
    {
      "id": "location",
      "study_id": "dna-hct116-denominator-recovery-20261023",
      "artifact": "recovery-assessment.json",
      "sha256": "41698f9f9ab91d56e05e716e0862f526498d34176a70549c0760af5289c76107",
      "bytes": 3018,
      "availability": "Retained study artifact; not included in this public supplement."
    },
    {
      "id": "fcs_headers",
      "study_id": "dna-hct116-denominator-recovery-20261023",
      "artifact": "fcs-search/header-audit-summary.json",
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      "bytes": 3350,
      "availability": "Retained study artifact; not included in this public supplement."
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    {
      "id": "window_scan",
      "study_id": "dna-hct116-denominator-recovery-20261023",
      "artifact": "nanopore-search/cached-scan-summary.json",
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      "bytes": 652,
      "availability": "Retained study artifact; not included in this public supplement."
    }
  ],
  "definitions": {
    "genome_model": "One hypothetical circular genome of 6.4 billion base pairs; fixed candidate licenses and constant fork speed unless explicitly rescaled.",
    "base_fork_speed_bp_per_min": 1500,
    "comparison_deadline_min": 480,
    "deadline_status": "An illustrative whole-genome comparison criterion, not a measured completion time for the HCT116 samples.",
    "completion": "Every modeled base has been replicated; not an average fraction or a detection-limited empirical endpoint.",
    "effective_resource_unit": "Capacity to support one fork. It is not a measured number of protein molecules or an intact replisome reused unchanged.",
    "initiation_intensity": "Actual new initiations divided by the integral of unreplicated DNA length over the observation interval. Units: initiations per unreplicated Mb per minute.",
    "independence": "The 200 paired layouts are synthetic configurations, not independent biological cells. Reused layouts, conditions and event records must not be counted as additional biological replicates."
  },
  "opening_comparison": {
    "genome_bp": 6400000000,
    "fork_speed_bp_per_min": 1500,
    "single_bidirectional_origin_years": 4.056075240195706,
    "equally_spaced_40000_origins_min": 53.333333333333336,
    "random_40000_origins_expected_h": 9.932322575951577,
    "comparison_deadline_h": 8,
    "deadline_provenance": "Comparison criterion; not measured HCT116 completion time",
    "single_origin_formula": "L/(2v); two forks from one bidirectional origin, without parallelism across multiple origins.",
    "equally_spaced_formula": "L/(2vN) for N=40000 origins fired simultaneously.",
    "random_origin_formula": "E[max gap]=(L/N)*H_N, where H_N is the Nth harmonic number; E[T]=E[max gap]/(2v) for simultaneous independent uniform origin positions on a circle.",
    "analytic_expected_random_completion_min": 595.9393545570946,
    "saved_random_layout_mean_completion_min": 586.2937819689975,
    "saved_random_layout_median_completion_min": 582.5519804329872,
    "saved_random_layout_complete_by480": {
      "count": 2,
      "n": 200
    },
    "critical_distinction": "Exactly equally spaced origins are a separate analytic construction from one origin placed uniformly at random within each equal segment. The latter saved simulation has median completion about 1.77 hours, not 53 minutes.",
    "corrected_inference": "Completion time alone cannot reject simultaneous initiation when origin spacing is unspecified."
  },
  "terminal_gap_example": {
    "model_id": "hard_gate_k16000_d30",
    "licensed_candidates": 400000,
    "capacity_units": 16000,
    "return_delay_min": 30,
    "initiation_law": "hard_gate: per-candidate hazard 0.001/min when at least two free units remain, otherwise zero.",
    "deadline_min": 480,
    "mean_replicated_percent_at_deadline": 99.97949452045958,
    "rounded_mean_replicated_percent": 99.98,
    "completed_by_deadline": {
      "count": 0,
      "n": 200
    },
    "mean_remaining_bp_at_deadline": 1312350.6905866144,
    "mean_largest_remaining_gap_bp_at_deadline": 228991.86010797418,
    "completion_median_min": 551.0032980818539,
    "interpretation": "99.98% is the mean replicated fraction over 200 synthetic configurations. Zero of 200 means none had completed the whole model genome by 480 minutes. It is not an experimental completion rate."
  },
  "geometry_control": {
    "n_layouts": 200,
    "licensed_candidates": 400000,
    "maximum_coverable_candidate_free_gap_bp": 1440000,
    "maximum_initial_candidate_free_gap_bp_across_layouts": 286728.3693289757,
    "geometrically_impossible_layouts": 0,
    "paired_unlimited_failures": 0,
    "comparison_40000_candidate_geometrically_impossible_layouts": 198,
    "interpretation": "The 400000-candidate resource model has no layout that is impossible by the ideal geometry-only bound; its paired unlimited control completed all 200 layouts. The 40000-candidate model is a different candidate inventory. Intervals between origins that actually fired cannot be treated as intervals that originally contained no candidates."
  },
  "recycling_contrast": {
    "common_conditions": {
      "licensed_candidates": 400000,
      "capacity_units": 24000,
      "initiation_law": "free_fraction: per-candidate hazard=lambda0*free/K, subject to two units being available.",
      "lambda0_per_min": 1,
      "initial_loading_time_scale_min": 30,
      "fork_speed_bp_per_min": 1500,
      "n_paired_layouts": 200,
      "parameter_status": "Effective initiation and initial supply parameters are model assumptions, not measured HCT116 binding or supply rates."
    },
    "conditions": [
      {
        "model": "binding_1_load_30_wait_0",
        "delay_min": 0,
        "n": 200,
        "success_at480": 200,
        "completion_median_min": 255.94400819897487,
        "completion_q95_min": 270.2128598996139
      },
      {
        "model": "binding_1_load_30_wait_480",
        "delay_min": 480,
        "n": 200,
        "success_at480": 0,
        "completion_median_min": 637.1191528042696,
        "completion_q95_min": 648.5569450052999
      }
    ],
    "interpretation": "Changing only the effective return delay from zero to 480 minutes changed deadline completion from 200/200 to 0/200 in this model. A 480-minute delay blocks reuse before the deadline but does not permanently remove recycling after the deadline.",
    "joint_shape_and_completion_audit": {
      "n_conditions": 12,
      "n_layouts_per_condition": 200,
      "n_model_trials": 2400,
      "joint_pass_count": 0,
      "criterion": "Descriptive hump on the prespecified range with mean unreplicated DNA-time exposure at least 1% of the original exposure, together with at least 95% observed completion by 480 minutes.",
      "limit": "Zero of 12 conditions passed this joint descriptive rule. Some successful conditions have a clear descent outside the 1% support range. This is not proof that no hump exists and is not an empirical goodness-of-fit test."
    }
  },
  "clock_scaling_control": {
    "n_synthetic_layouts": 1,
    "n_replays": 2,
    "event_records_compared": 112973,
    "conditions": [
      {
        "scale": 1,
        "v_bp_min": 1500.0,
        "lambda0_min": 1.0,
        "loading_tau_min": 30,
        "completion_min": 263.64013975623465,
        "completed_by480": true,
        "actual_fired": 50486
      },
      {
        "scale": 2,
        "v_bp_min": 750.0,
        "lambda0_min": 0.5,
        "loading_tau_min": 60,
        "completion_min": 527.2802795124693,
        "completed_by480": false,
        "actual_fired": 50486
      }
    ],
    "completion_h": [
      4.394002329270577,
      8.788004658541155
    ],
    "max_scaled_event_time_error_min": 0.0,
    "normalization": "Plot time as t/T and initiation intensity as I(t)*T. The latter has units Mb^-1, not dimensionless units.",
    "transformation": "t_prime=2*t; v_prime=v/2; lambda_prime=lambda/2; loading_tau_prime=2*loading_tau; return_delay_prime=2*return_delay (zero here). I_prime(2*t)=I(t)/2.",
    "interpretation": "An uncalibrated relative-time/relative-amplitude curve cannot identify physical completion time. A matched absolute clock or speed measurement would break this symmetry. This does not prove nonidentifiability once such measurements are supplied.",
    "limit": "One configuration with two time scales, not 112973 independent experiments and not a fitted human replication curve."
  },
  "public_data_audit": {
    "dataset": "HCT116, GSE320256, Figshare article 29242556",
    "primary_public_urls": [
      "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE320256",
      "https://doi.org/10.1038/s41467-026-73333-4"
    ],
    "nanopore_sample_count": 12,
    "published_ratio_values_reproduced": 24,
    "origin_calls": 362,
    "termination_calls": 270,
    "filtered_fork_rows": 3544,
    "filtered_read_ids_summed_after_within_sample_deduplication": 3540,
    "all_origin_read_sets_disjoint_from_filtered_fork_read_sets": true,
    "all_termination_read_sets_disjoint_from_filtered_fork_read_sets": true,
    "same_aliquot_FCS_matches_confirmed": 0,
    "FCS_header_records_audited": 973,
    "WSP_files_audited": 1051,
    "absolute_I_by_S_phase_age_identified": false,
    "functional_factor_recovery_delay_identified": false,
    "whole_genome_deadline_validated": false,
    "limits": [
      "The published event-to-filtered-fork ratios are legitimate published observables; disjoint read sets do not by themselves invalidate those ratios. They are not new initiations divided by unreplicated DNA-time.",
      "An origin call can represent initiation before the labeling window. It is not necessarily a newly initiated origin during that window.",
      "All sequenced bases, all callable bases and unreplicated S-phase DNA-time are different denominators.",
      "Instrument acquisition time and DNA content are not an independently calibrated clock from S-phase entry.",
      "The inspected public records did not establish same-aliquot FCS-to-Nanopore mapping. No claim is made that such records do not exist elsewhere.",
      "A calibrated asynchronous exposure-weighted mean might be estimable with additional records and detection corrections; that does not identify late-S I(t) without S-phase age information.",
      "This audit neither estimates a functional factor return-time distribution nor validates eight-hour completion in matched HCT116 conditions."
    ]
  },
  "closeout": {
    "decision_date": "2026-10-23",
    "investigation_closed": true,
    "author_inquiry_sent": false,
    "bulk_cold_storage_restoration_performed": false,
    "additional_curve_fit_started_for_synthesis": false,
    "reason": "Further recovery of read-level records without an S-phase age axis would not resolve the original question about late-stage initiation and whole-genome deadline completion.",
    "biological_novelty_established": false,
    "contribution": "Correction of an intuitive explanation, explicit model-conditional results, a bounded public-data denominator audit, and a record of research scope drift and the decision to stop.",
    "agent_case_study_limit": "This is one documented research trajectory. It does not establish a general causal claim about autonomous research agents or novelty relative to all prior agent case studies."
  },
  "claim_boundaries": [
    "No central per-origin progress controller is required in the computational construction. Biological molecular communication and cell-cycle regulation are not excluded.",
    "Recycling can support later initiation and completion under specified initiation, supply and candidate-placement assumptions. Reuse alone has not been validated as the explanation for matched HCT116 I(t) and deadline completion.",
    "Mitotic DNA synthesis is not simulated here. Its existence does not guarantee repair of all residual gaps or establish S-phase completion by eight hours.",
    "The work does not claim a new biological mechanism. Existing biological studies and the synthetic results have distinct evidentiary roles."
  ]
}