{
  "benchmark_source": {
    "path": "${MUTATIONSIEVE_PROJECT_ROOT}\\benchmark\\benchmark.json",
    "sha256": "f360677d69e69b2b19a3e6144b6cddf7ee6dbf376b0bacd4b1a00fd535de373c"
  },
  "claims_boundary": "Hand-constructed aligned-BAM regression fixtures, including conditionally topped-up controls, verify deterministic software behavior only. Their coupled alignment fields were not jointly produced by a pinned production aligner against the intended full reference, so they are not synthetic-read validation. They establish neither analytical nor clinical sensitivity, specificity, PPV, NPV, limit of blank, LoD95, precision, reproducibility, or transportability.",
  "comparators": [
    {
      "name": "transparent_pileup_baseline",
      "requirements": "same normalized truth, regions, samples, and callability",
      "status": "NOT_RUN"
    },
    {
      "name": "GATK_Mutect2_or_HaplotypeCaller_as_assay_appropriate",
      "requirements": "pinned container/digest and identical evaluation mask",
      "status": "NOT_RUN"
    },
    {
      "name": "Strelka2_or_LoFreq_as_assay_appropriate",
      "requirements": "pinned container/digest and identical evaluation mask",
      "status": "NOT_RUN"
    }
  ],
  "confidence_intervals": "two-sided Clopper-Pearson exact",
  "failed_hypotheses": [],
  "false_positives": [],
  "hypothesis_register": [
    {
      "hypothesis": "At least one designed SNV is called by exact normalized allele match.",
      "id": "SWV-REP-SNV",
      "observed": {
        "true_positives": 10,
        "truth_total": 10
      },
      "prespecified_gate": "true_positives >= 1 when class denominator > 0",
      "scope": "synthetic software representation only",
      "status": "PASSED"
    },
    {
      "hypothesis": "At least one designed MNV is called by exact normalized allele match.",
      "id": "SWV-REP-MNV",
      "observed": {
        "true_positives": 2,
        "truth_total": 2
      },
      "prespecified_gate": "true_positives >= 1 when class denominator > 0",
      "scope": "synthetic software representation only",
      "status": "PASSED"
    },
    {
      "hypothesis": "At least one designed INS is called by exact normalized allele match.",
      "id": "SWV-REP-INS",
      "observed": {
        "true_positives": 7,
        "truth_total": 8
      },
      "prespecified_gate": "true_positives >= 1 when class denominator > 0",
      "scope": "synthetic software representation only",
      "status": "PASSED"
    },
    {
      "hypothesis": "At least one designed DEL is called by exact normalized allele match.",
      "id": "SWV-REP-DEL",
      "observed": {
        "true_positives": 7,
        "truth_total": 7
      },
      "prespecified_gate": "true_positives >= 1 when class denominator > 0",
      "scope": "synthetic software representation only",
      "status": "PASSED"
    },
    {
      "hypothesis": "At least one designed COMPLEX is called by exact normalized allele match.",
      "id": "SWV-REP-COMPLEX",
      "observed": {
        "true_positives": 2,
        "truth_total": 2
      },
      "prespecified_gate": "true_positives >= 1 when class denominator > 0",
      "scope": "synthetic software representation only",
      "status": "PASSED"
    },
    {
      "hypothesis": "The synthetic calibration negative has no selected positive calls.",
      "id": "SWV-CAL-FP",
      "observed": {
        "false_positives": 0,
        "samples": 1
      },
      "prespecified_gate": "false_positives == 0",
      "scope": "single deterministic synthetic negative; not a limit-of-blank study",
      "status": "PASSED"
    },
    {
      "hypothesis": "The prespecified off-target truth remains in the intention-to-test denominator as a no-call miss.",
      "id": "SWV-CALLABILITY",
      "observed": {
        "challenge_samples": 1,
        "false_negatives_intention_to_test": 1,
        "sample_statuses": [
          "PARTIAL_COVERAGE_NO_CALL"
        ],
        "truth_interval_not_callable_misses": 1,
        "truth_no_call": 1
      },
      "prespecified_gate": "one challenge; truth_no_call == 1; one intention-to-test miss explicitly caused by a non-callable interval; sample status is a no-call",
      "scope": "explicit no-call denominator behavior",
      "status": "PASSED"
    },
    {
      "display_name": "Representation-equivalent control recovery",
      "hypothesis": "Every realized allele in the hand-constructed aligned-BAM fixture, except the one prespecified off-target no-call challenge, is selected as a representation-equivalent call.",
      "id": "SWV-REPRESENTATION-RECALL",
      "observed": {
        "false_negatives_intention_to_test": 1,
        "prespecified_no_call_truth": 1,
        "true_positives_intention_to_test": 28,
        "truth_total_intention_to_test": 29
      },
      "prespecified_gate": "true_positives_intention_to_test == truth_total_intention_to_test - prespecified_no_call_truth, and all misses are that challenge",
      "scope": "deterministic representation-equivalent control recovery; not synthetic-read validation or analytical/clinical sensitivity",
      "status": "PASSED"
    },
    {
      "hypothesis": "The required hash-identified SpikeForge control is generated and its output-integrity verification passes.",
      "id": "SWV-SPIKEFORGE-INTEROPERABILITY",
      "observed": {
        "status": "PASS",
        "verification": {
          "added": 0,
          "fields_touched": [
            "cigar",
            "qual",
            "seq",
            "tag:NM"
          ],
          "header_identical": false,
          "header_note": "header differs only by one appended SpikeForge @PG record",
          "header_ok": true,
          "identical": 4747,
          "input_records": 4800,
          "modified": 53,
          "ok": true,
          "output_records": 4800,
          "removed": 0,
          "summary": "[PASS] in=4800 out=4800 identical=4747 modified=53 added=0 removed=0 unexpected=0",
          "unexpected": []
        }
      },
      "prespecified_gate": "control.status == PASS",
      "scope": "cross-project software interoperability",
      "status": "PASSED"
    },
    {
      "hypothesis": "The explicit UMI control uses UMI families as its primary unit.",
      "id": "SWV-UMI-CONSENSUS",
      "observed": {
        "primary_analysis_units": [
          "explicit_umi_family"
        ],
        "samples": 1
      },
      "prespecified_gate": "one UMI control and explicit_umi_family in primary_analysis_units",
      "scope": "explicit UMI-family end-to-end software behavior",
      "status": "PASSED"
    },
    {
      "hypothesis": "An MGI-labelled case cannot load an Illumina PoN.",
      "id": "SWV-CHANGED-ASSAY-FAIL-CLOSED",
      "observed": {
        "expected": "strict PoN platform identity mismatch",
        "observed_error": "PoN compatibility identity mismatch (sequencing_platforms: PoN=['ILLUMINA'], runtime=['MGI'])",
        "status": "PASSED"
      },
      "prespecified_gate": "strict incompatible PoN attempt raises identity mismatch",
      "scope": "declared-platform resource compatibility",
      "status": "PASSED"
    },
    {
      "display_name": "SpikeForge structural edit-output integrity",
      "hypothesis": "SpikeForge-edited aligned records pass the native structural-field and local-distribution audit.",
      "id": "SWV-SPIKEFORGE-REALISM",
      "observed": {
        "checked_fields": [
          "NM",
          "RG",
          "TLEN",
          "mapq",
          "mean base quality",
          "read length",
          "soft-clipped bases"
        ],
        "counts": {
          "background": 3567,
          "edited": 96,
          "planted": 0
        },
        "findings": [
          {
            "detail": "median 1.0 vs 0.0 in nearby real reads (KS D=0.55, p=7.5e-26) -- expected: the edit adds a mismatch",
            "field": "NM",
            "group": "edited",
            "severity": "expected",
            "stat": 0.5520833333333333
          }
        ],
        "ok": true,
        "skipped": "",
        "summary": "[PASS] edited=96 planted=0 background=3567 errors=0 separable=0 shifted=0"
      },
      "prespecified_gate": "external_realism_audit.ok == true",
      "scope": "structural edit-output integrity/distribution check; not alignment realism, synthetic-read validation, or biological performance",
      "status": "PASSED"
    },
    {
      "hypothesis": "Within every realization-gated control run, every designed synthetic allele is realized in at least one primary unit.",
      "id": "SWV-CONTROL-REALIZATION",
      "observed": {
        "control_generation_accounting": {
          "aggregation_unit": "allele_primary_unit_observations; summed counts are not unique physical fragments across alleles",
          "all_declared_simulator_floors_satisfied": true,
          "interpretation": "forced_top_up_primary_units are disclosed deterministic control construction; caller recovery from these controls is not an analytical or clinical sensitivity estimate",
          "schema": "mutationsieve.benchmark-control-generation-accounting.v1",
          "simulator": {
            "declared_minimum_primary_units": 75,
            "floor_prioritized_primary_units": 75,
            "forced_top_up_primary_units": 67,
            "ordinary_selected_floor_contributions": 8,
            "ordinary_selection_events": 131,
            "positive_truth_alleles": 25,
            "primary_units_realized": 192,
            "truth_alleles": 25,
            "truth_alleles_with_declared_floor": 25,
            "truth_alleles_with_forced_top_up": 24
          },
          "simulator_runs_in_realization_gate": 6,
          "spikeforge_truth_alleles": 3
        },
        "designed_truth_alleles": 28,
        "every_included_run_complete": true,
        "realized_truth_alleles": 28,
        "runs": [
          {
            "complete": true,
            "designed_truth_alleles": 0,
            "realized_truth_alleles": 0,
            "sample": "CALIBRATION_NEGATIVE"
          },
          {
            "complete": true,
            "designed_truth_alleles": 4,
            "realized_truth_alleles": 4,
            "sample": "DEVELOPMENT_POSITIVE"
          },
          {
            "complete": true,
            "designed_truth_alleles": 8,
            "realized_truth_alleles": 8,
            "sample": "LOCKBOX_POSITIVE"
          },
          {
            "complete": true,
            "designed_truth_alleles": 3,
            "realized_truth_alleles": 3,
            "sample": "LOCKBOX_SPIKEFORGE"
          },
          {
            "complete": true,
            "designed_truth_alleles": 8,
            "realized_truth_alleles": 8,
            "sample": "STRESS_FFPE_LOW_DEPTH"
          },
          {
            "complete": true,
            "designed_truth_alleles": 4,
            "realized_truth_alleles": 4,
            "sample": "CHANGED_ASSAY_MGI"
          },
          {
            "complete": true,
            "designed_truth_alleles": 1,
            "realized_truth_alleles": 1,
            "sample": "UMI_CONSENSUS_POSITIVE"
          }
        ]
      },
      "prespecified_gate": "for every included run: realized_truth_alleles == designed_truth_alleles",
      "scope": "control-generation adequacy, separate from caller performance",
      "status": "PASSED"
    }
  ],
  "intention_to_test": true,
  "matching": "one-to-one exact normalized CHROM/POS/REF/ALT",
  "metrics": {
    "ALL": {
      "callability": {
        "confidence": 0.95,
        "denominator": 29,
        "estimate": 0.9655172413793104,
        "lower": 0.822355704511277,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 28,
        "upper": 0.9991273531164201
      },
      "callable_bases": 64000,
      "called_total": 28,
      "false_negatives_callable": 0,
      "false_negatives_intention_to_test": 1,
      "false_positives": 0,
      "false_positives_per_callable_mb": 0.0,
      "ppa_callable_only": {
        "confidence": 0.95,
        "denominator": 28,
        "estimate": 1.0,
        "lower": 0.8765638814997362,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 28,
        "upper": 1.0
      },
      "ppa_intention_to_test": {
        "confidence": 0.95,
        "denominator": 29,
        "estimate": 0.9655172413793104,
        "lower": 0.822355704511277,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 28,
        "upper": 0.9991273531164201
      },
      "precision": {
        "confidence": 0.95,
        "denominator": 28,
        "estimate": 1.0,
        "lower": 0.8765638814997362,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 28,
        "upper": 1.0
      },
      "true_positives": 28,
      "truth_callable": 28,
      "truth_no_call": 1,
      "truth_total_intention_to_test": 29
    },
    "COMPLEX": {
      "callability": {
        "confidence": 0.95,
        "denominator": 2,
        "estimate": 1.0,
        "lower": 0.15811388300841903,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 2,
        "upper": 1.0
      },
      "callable_bases": 64000,
      "called_total": 2,
      "false_negatives_callable": 0,
      "false_negatives_intention_to_test": 0,
      "false_positives": 0,
      "false_positives_per_callable_mb": 0.0,
      "ppa_callable_only": {
        "confidence": 0.95,
        "denominator": 2,
        "estimate": 1.0,
        "lower": 0.15811388300841903,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 2,
        "upper": 1.0
      },
      "ppa_intention_to_test": {
        "confidence": 0.95,
        "denominator": 2,
        "estimate": 1.0,
        "lower": 0.15811388300841903,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 2,
        "upper": 1.0
      },
      "precision": {
        "confidence": 0.95,
        "denominator": 2,
        "estimate": 1.0,
        "lower": 0.15811388300841903,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 2,
        "upper": 1.0
      },
      "true_positives": 2,
      "truth_callable": 2,
      "truth_no_call": 0,
      "truth_total_intention_to_test": 2
    },
    "DEL": {
      "callability": {
        "confidence": 0.95,
        "denominator": 7,
        "estimate": 1.0,
        "lower": 0.5903836027749967,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 7,
        "upper": 1.0
      },
      "callable_bases": 64000,
      "called_total": 7,
      "false_negatives_callable": 0,
      "false_negatives_intention_to_test": 0,
      "false_positives": 0,
      "false_positives_per_callable_mb": 0.0,
      "ppa_callable_only": {
        "confidence": 0.95,
        "denominator": 7,
        "estimate": 1.0,
        "lower": 0.5903836027749967,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 7,
        "upper": 1.0
      },
      "ppa_intention_to_test": {
        "confidence": 0.95,
        "denominator": 7,
        "estimate": 1.0,
        "lower": 0.5903836027749967,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 7,
        "upper": 1.0
      },
      "precision": {
        "confidence": 0.95,
        "denominator": 7,
        "estimate": 1.0,
        "lower": 0.5903836027749967,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 7,
        "upper": 1.0
      },
      "true_positives": 7,
      "truth_callable": 7,
      "truth_no_call": 0,
      "truth_total_intention_to_test": 7
    },
    "INS": {
      "callability": {
        "confidence": 0.95,
        "denominator": 8,
        "estimate": 0.875,
        "lower": 0.4734903291247935,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 7,
        "upper": 0.9968402764687481
      },
      "callable_bases": 64000,
      "called_total": 7,
      "false_negatives_callable": 0,
      "false_negatives_intention_to_test": 1,
      "false_positives": 0,
      "false_positives_per_callable_mb": 0.0,
      "ppa_callable_only": {
        "confidence": 0.95,
        "denominator": 7,
        "estimate": 1.0,
        "lower": 0.5903836027749967,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 7,
        "upper": 1.0
      },
      "ppa_intention_to_test": {
        "confidence": 0.95,
        "denominator": 8,
        "estimate": 0.875,
        "lower": 0.4734903291247935,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 7,
        "upper": 0.9968402764687481
      },
      "precision": {
        "confidence": 0.95,
        "denominator": 7,
        "estimate": 1.0,
        "lower": 0.5903836027749967,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 7,
        "upper": 1.0
      },
      "true_positives": 7,
      "truth_callable": 7,
      "truth_no_call": 1,
      "truth_total_intention_to_test": 8
    },
    "MNV": {
      "callability": {
        "confidence": 0.95,
        "denominator": 2,
        "estimate": 1.0,
        "lower": 0.15811388300841903,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 2,
        "upper": 1.0
      },
      "callable_bases": 64000,
      "called_total": 2,
      "false_negatives_callable": 0,
      "false_negatives_intention_to_test": 0,
      "false_positives": 0,
      "false_positives_per_callable_mb": 0.0,
      "ppa_callable_only": {
        "confidence": 0.95,
        "denominator": 2,
        "estimate": 1.0,
        "lower": 0.15811388300841903,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 2,
        "upper": 1.0
      },
      "ppa_intention_to_test": {
        "confidence": 0.95,
        "denominator": 2,
        "estimate": 1.0,
        "lower": 0.15811388300841903,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 2,
        "upper": 1.0
      },
      "precision": {
        "confidence": 0.95,
        "denominator": 2,
        "estimate": 1.0,
        "lower": 0.15811388300841903,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 2,
        "upper": 1.0
      },
      "true_positives": 2,
      "truth_callable": 2,
      "truth_no_call": 0,
      "truth_total_intention_to_test": 2
    },
    "SNV": {
      "callability": {
        "confidence": 0.95,
        "denominator": 10,
        "estimate": 1.0,
        "lower": 0.6915028921812392,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 10,
        "upper": 1.0
      },
      "callable_bases": 64000,
      "called_total": 10,
      "false_negatives_callable": 0,
      "false_negatives_intention_to_test": 0,
      "false_positives": 0,
      "false_positives_per_callable_mb": 0.0,
      "ppa_callable_only": {
        "confidence": 0.95,
        "denominator": 10,
        "estimate": 1.0,
        "lower": 0.6915028921812392,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 10,
        "upper": 1.0
      },
      "ppa_intention_to_test": {
        "confidence": 0.95,
        "denominator": 10,
        "estimate": 1.0,
        "lower": 0.6915028921812392,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 10,
        "upper": 1.0
      },
      "precision": {
        "confidence": 0.95,
        "denominator": 10,
        "estimate": 1.0,
        "lower": 0.6915028921812392,
        "method": "two-sided Clopper-Pearson exact binomial interval",
        "numerator": 10,
        "upper": 1.0
      },
      "true_positives": 10,
      "truth_callable": 10,
      "truth_no_call": 0,
      "truth_total_intention_to_test": 10
    }
  },
  "misses": [
    {
      "callability_state": "LOW_DEPTH",
      "reason": "truth_interval_not_callable",
      "sample": "EXPLICIT_NO_CALL_EDGE",
      "split": "stress",
      "truth_index": 0,
      "variant": {
        "alt": "GAC",
        "chrom": "chrSynthetic",
        "id": "msv_a34cf055a561d8892250dea40da26760",
        "key": "chrSynthetic:3500:G>GAC",
        "kind": "INS",
        "pos": 3500,
        "pos0": 3499,
        "pos1": 3500,
        "ref": "G"
      }
    }
  ],
  "nonpassing_hypotheses": [],
  "overall_pass": true,
  "purpose": "offline_deterministic_software_verification",
  "representation_equivalent_metrics": {
    "false_negatives": 1,
    "false_positives": 0,
    "method": "record_exact_plus_bounded_covering_MNV_vs_nonoverlapping_substitution_components",
    "query_precision": {
      "confidence": 0.95,
      "denominator": 28,
      "estimate": 1.0,
      "lower": 0.8765638814997362,
      "method": "two-sided Clopper-Pearson exact binomial interval",
      "numerator": 28,
      "upper": 1.0
    },
    "query_total": 28,
    "query_true_positives": 28,
    "scope_limitations": [
      "not_a_replacement_for_hap.py_or_vcfeval",
      "indel_equivalence_requires_repeat_aware_normalization_and_exact_match",
      "ambiguous_or_overlapping_component_sets_are_not_matched"
    ],
    "truth_callable": 28,
    "truth_recall_callable_only": {
      "confidence": 0.95,
      "denominator": 28,
      "estimate": 1.0,
      "lower": 0.8765638814997362,
      "method": "two-sided Clopper-Pearson exact binomial interval",
      "numerator": 28,
      "upper": 1.0
    },
    "truth_recall_intention_to_test": {
      "confidence": 0.95,
      "denominator": 29,
      "estimate": 0.9655172413793104,
      "lower": 0.822355704511277,
      "method": "two-sided Clopper-Pearson exact binomial interval",
      "numerator": 28,
      "upper": 0.9991273531164201
    },
    "truth_total": 29,
    "truth_true_positives": 28,
    "truth_true_positives_callable": 28
  },
  "sample_count": 8,
  "sample_evaluations": [
    {
      "calls_matching_non_callable_truth": [],
      "confidence_interval_method": "two-sided Clopper-Pearson exact",
      "decision_rule": "non_reject",
      "false_positives": [],
      "matches": [],
      "matching_method": "one-to-one exact normalized CHROM/POS/REF/ALT",
      "metrics": {
        "ALL": {
          "callability": {
            "confidence": 0.95,
            "denominator": 0,
            "estimate": null,
            "lower": 0.0,
            "method": "two-sided Clopper-Pearson exact binomial interval",
            "numerator": 0,
            "upper": 1.0
          },
          "callable_bases": 8000,
          "called_total": 0,
          "false_negatives_callable": 0,
          "false_negatives_intention_to_test": 0,
          "false_positives": 0,
          "false_positives_per_callable_mb": 0.0,
          "ppa_callable_only": {
            "confidence": 0.95,
            "denominator": 0,
            "estimate": null,
            "lower": 0.0,
            "method": "two-sided Clopper-Pearson exact binomial interval",
            "numerator": 0,
            "upper": 1.0
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}