{
  "schemaVersion": "cathedral.malaria-resistance.result.v1",
  "generatedAt": "2026-10-29T21:31:14.038Z",
  "outcomeClass": "Original experiment partially reproduced",
  "scientificQuestion": "Among source-reported Ugandan Plasmodium falciparum isolates carrying high-major-allele PIN or LMD PX1 calls, do ex-vivo antimalarial susceptibility measurements differ, overall and within K13 wild type?",
  "data": {
    "px1Source": {
      "doi": "10.1038/s41591-026-04590-5",
      "source": "Nature Medicine article Source Data workbook, Source_dataset1",
      "release": "published 2026 article source data",
      "sha256": "7f08b7218fe7c0eb4741a003fd298b6656598030a0165653d9f736ce364b9c31",
      "license": "CC BY-NC-ND 4.0 (article license; confirm dataset-specific reuse before redistribution)",
      "rawRows": 1346,
      "uniqueSampleIds": 1346,
      "rawSampleIdsWrittenToResults": false
    },
    "whoMarkerSource": {
      "title": "WHO Compendium of molecular markers for antimalarial drug resistance, version 2.0 (July 2026)",
      "sha256": "6e7ac3d7d395920153712f983d9a352b64369b487c14e46bf3a08430cd3cd0f3",
      "license": "WHO source; retained locally for analysis only, no redistribution"
    },
    "filters": {
      "primary": [
        "px1_haplotype is PIN or LMD",
        "wsaf > 0.9",
        "K13 genotype is one of the values used by the authors' analysis script",
        "outcome is present for the assay"
      ],
      "readDepth": "The source workbook does not contain row-level numeric depth, so the article's >=25x criterion could not be independently applied."
    },
    "accounting": {
      "rawRows": 1346,
      "blankOrDuplicateIds": 0,
      "pinOrLmdRows": 1084,
      "wsafOverPointNineRows": 820,
      "authorK13EligibleRows": 772,
      "excludedNonPinLmd": 262,
      "excludedWsafMissingOrNotOverPointNine": 264,
      "excludedK13OutsideAuthorSet": 48
    },
    "articleComparison": {
      "articleReportedSequenceDepthQualifiedSamples": 465,
      "articleReadDepthThreshold": "at least 25x",
      "sourceWorkbookReadDepthAvailable": false,
      "articleReportedK13WildTypeDha": {
        "pinN": 110,
        "pinMedian": 3.7,
        "lmdN": 240,
        "lmdMedian": 1.8
      },
      "thisReanalysisK13WildTypeDha": {
        "pinN": 115,
        "pinMedian": 3.7,
        "lmdN": 236,
        "lmdMedian": 1.77
      }
    },
    "perAssay": {
      "DHA": {
        "nWithOutcome": 409,
        "nMissingOutcome": 363
      },
      "Lumefantrine": {
        "nWithOutcome": 415,
        "nMissingOutcome": 357
      },
      "Mefloquine": {
        "nWithOutcome": 408,
        "nMissingOutcome": 364
      },
      "RSA": {
        "nWithOutcome": 179,
        "nMissingOutcome": 593
      }
    }
  },
  "markerReference": [
    {
      "gene": "Pfk13",
      "alteration": "C469Y",
      "classification": "Validated marker (Epi., Lab. & Clin.)",
      "references": "34551228, 35388682, 36289202, 37611122, 38837973, 39028193, 39540797, 40112841"
    },
    {
      "gene": "Pfk13",
      "alteration": "A675V",
      "classification": "Validated marker (Epi., Lab. & Clin.)",
      "references": "30651111, 34551228, 35388682, 37611122, 38837973, 40112841"
    }
  ],
  "methods": {
    "mainComparison": "Two-sided Mann–Whitney U / Wilcoxon rank-sum, tie-corrected normal approximation with continuity correction; effect summary is PIN-minus-LMD median difference.",
    "uncertainty": "Deterministic nonparametric bootstrap percentile 95% interval, 4,000 resamples within each group; seed 20261029.",
    "multiplicity": "Benjamini–Hochberg q-values within each four-assay analysis family.",
    "secondaryStratum": "K13 wild type only, matching a reported paper stratum.",
    "interpretations": "Observational association only. No causation or clinical outcome inference."
  },
  "results": [
    {
      "assay": "DHA",
      "label": "Dihydroartemisinin (DHA)",
      "unit": "nM IC50",
      "subset": "All eligible PIN/LMD records",
      "n": 409,
      "pin": {
        "n": 156,
        "median": 3.71,
        "q1": 2.43575,
        "q3": 5.525
      },
      "lmd": {
        "n": 253,
        "median": 1.8,
        "q1": 1.2,
        "q3": 2.8
      },
      "medianDifferencePinMinusLmd": 1.91,
      "bootstrap95MedianDifference": [
        1.5900000000000003,
        2.4644999999999997
      ],
      "pValue": 2.138206011624937e-19,
      "uStatistic": 30192,
      "test": "Mann–Whitney U, tie-corrected normal approximation with continuity correction",
      "missingOutcomeExcluded": 363,
      "qValue": 4.276412023249874e-19
    },
    {
      "assay": "Lumefantrine",
      "label": "Lumefantrine",
      "unit": "nM IC50",
      "subset": "All eligible PIN/LMD records",
      "n": 415,
      "pin": {
        "n": 157,
        "median": 15.14,
        "q1": 9.84,
        "q3": 23.99
      },
      "lmd": {
        "n": 258,
        "median": 6.25,
        "q1": 4.4,
        "q3": 10.5225
      },
      "medianDifferencePinMinusLmd": 8.89,
      "bootstrap95MedianDifference": [
        7.3999999999999995,
        11.61
      ],
      "pValue": 1.0535427099481053e-20,
      "uStatistic": 31310,
      "test": "Mann–Whitney U, tie-corrected normal approximation with continuity correction",
      "missingOutcomeExcluded": 357,
      "qValue": 4.2141708397924213e-20
    },
    {
      "assay": "Mefloquine",
      "label": "Mefloquine",
      "unit": "nM IC50",
      "subset": "All eligible PIN/LMD records",
      "n": 408,
      "pin": {
        "n": 154,
        "median": 16.95,
        "q1": 11,
        "q3": 26.6575
      },
      "lmd": {
        "n": 254,
        "median": 11.125,
        "q1": 7.7,
        "q3": 16.075000000000003
      },
      "medianDifferencePinMinusLmd": 5.824999999999999,
      "bootstrap95MedianDifference": [
        3.5,
        8.969999999999999
      ],
      "pValue": 9.815693304388377e-11,
      "uStatistic": 27028.5,
      "test": "Mann–Whitney U, tie-corrected normal approximation with continuity correction",
      "missingOutcomeExcluded": 364,
      "qValue": 1.3087591072517836e-10
    },
    {
      "assay": "RSA",
      "label": "Ring-stage survival assay",
      "unit": "% survival",
      "subset": "All eligible PIN/LMD records",
      "n": 179,
      "pin": {
        "n": 115,
        "median": 4.07,
        "q1": 1.42734723,
        "q3": 11.00534206
      },
      "lmd": {
        "n": 64,
        "median": 3.0965986395,
        "q1": 0.8052056289999999,
        "q3": 7.1830168555
      },
      "medianDifferencePinMinusLmd": 0.9734013605000005,
      "bootstrap95MedianDifference": [
        -1.079619456,
        2.717987165
      ],
      "pValue": 0.26279976082370815,
      "uStatistic": 4052,
      "test": "Mann–Whitney U, tie-corrected normal approximation with continuity correction",
      "missingOutcomeExcluded": 593,
      "qValue": 0.26279976082370815
    },
    {
      "assay": "DHA",
      "label": "Dihydroartemisinin (DHA)",
      "unit": "nM IC50",
      "subset": "K13 wild type",
      "n": 351,
      "pin": {
        "n": 115,
        "median": 3.7,
        "q1": 2.4215,
        "q3": 5.484999999999999
      },
      "lmd": {
        "n": 236,
        "median": 1.77,
        "q1": 1.2,
        "q3": 2.6
      },
      "medianDifferencePinMinusLmd": 1.9300000000000002,
      "bootstrap95MedianDifference": [
        1.5559999999999998,
        2.5300000000000002
      ],
      "pValue": 5.602284753823697e-16,
      "uStatistic": 20795,
      "test": "Mann–Whitney U, tie-corrected normal approximation with continuity correction",
      "missingOutcomeExcluded": 297,
      "qValue": 1.1204569507647393e-15
    },
    {
      "assay": "Lumefantrine",
      "label": "Lumefantrine",
      "unit": "nM IC50",
      "subset": "K13 wild type",
      "n": 356,
      "pin": {
        "n": 115,
        "median": 14.46,
        "q1": 9.82,
        "q3": 23.985
      },
      "lmd": {
        "n": 241,
        "median": 6.1,
        "q1": 4.38,
        "q3": 10.44
      },
      "medianDifferencePinMinusLmd": 8.360000000000001,
      "bootstrap95MedianDifference": [
        6.859999999999999,
        11.43
      ],
      "pValue": 1.0368993536669118e-16,
      "uStatistic": 21395,
      "test": "Mann–Whitney U, tie-corrected normal approximation with continuity correction",
      "missingOutcomeExcluded": 292,
      "qValue": 4.1475974146676473e-16
    },
    {
      "assay": "Mefloquine",
      "label": "Mefloquine",
      "unit": "nM IC50",
      "subset": "K13 wild type",
      "n": 351,
      "pin": {
        "n": 114,
        "median": 16.715,
        "q1": 10.5275,
        "q3": 26.4375
      },
      "lmd": {
        "n": 237,
        "median": 11,
        "q1": 7.7,
        "q3": 16
      },
      "medianDifferencePinMinusLmd": 5.715,
      "bootstrap95MedianDifference": [
        3.2347499999999996,
        9.32
      ],
      "pValue": 1.1258962137633986e-8,
      "uStatistic": 18593,
      "test": "Mann–Whitney U, tie-corrected normal approximation with continuity correction",
      "missingOutcomeExcluded": 297,
      "qValue": 1.5011949516845316e-8
    },
    {
      "assay": "RSA",
      "label": "Ring-stage survival assay",
      "unit": "% survival",
      "subset": "K13 wild type",
      "n": 134,
      "pin": {
        "n": 80,
        "median": 3.8141421214999998,
        "q1": 1.28603862575,
        "q3": 9.521841769
      },
      "lmd": {
        "n": 54,
        "median": 3.0965986395,
        "q1": 0.8228677449999999,
        "q3": 7.884335055999999
      },
      "medianDifferencePinMinusLmd": 0.717543482,
      "bootstrap95MedianDifference": [
        -1.6770576389500003,
        2.8891400737
      ],
      "pValue": 0.5716096803146004,
      "uStatistic": 2285,
      "test": "Mann–Whitney U, tie-corrected normal approximation with continuity correction",
      "missingOutcomeExcluded": 514,
      "qValue": 0.5716096803146004
    }
  ],
  "limits": [
    "The paper's mixed-effects model is not reproduced: the retrieved source workbook lacks COI (complexity-of-infection) values, and row-level numeric read-depth data are not present. The original model included site, parasitemia, COI, year and K13.",
    "The author's R script also consumes separate phenotype, parasitemia and COI files; this analysis uses only the article's published Source_dataset1 table and cannot recreate undocumented joins or full model provenance.",
    "The article's data are observational ex-vivo susceptibility measurements, not randomized clinical treatment outcomes.",
    "Applying the accessible source workbook with available filters does not reproduce the article's exact analytic sample: K13-wild-type DHA counts are 115 PIN and 236 LMD here, versus 110 and 240 reported. Numeric read depth is absent, so the paper's >=25x inclusion rule cannot be verified. Treat this as an independent partial reanalysis, not exact sample-level reproduction.",
    "This is a partial reproduction of already published comparisons, not a novel discovery or independent biological replication.",
    "Source workbook reuse and redistribution are constrained by the article's stated CC BY-NC-ND license; obtain dataset-specific permission before using these artifacts commercially or redistributing the workbook or adapted content."
  ],
  "provenance": {
    "analysisVersion": "1.0.0",
    "seed": 20261029,
    "bootstrapReplicates": 4000,
    "scriptSha256": "7fe762fb695b39a35467bab55a69c93c1442e648cd4431d5555432f0ffb59abb",
    "sourceRetrievalDate": "2026-10-29",
    "execution": "Local Node.js; no Supabase, cloud compute or author R scripts used"
  }
}