https://w3id.org/np/RAfKB42E739cn7sWoTL4SM57vP9uFC_4O6U0CykcGu_nM/Head https://w3id.org/np/RAfKB42E739cn7sWoTL4SM57vP9uFC_4O6U0CykcGu_nM http://www.nanopub.org/nschema#hasAssertion https://w3id.org/np/RAfKB42E739cn7sWoTL4SM57vP9uFC_4O6U0CykcGu_nM/assertion https://w3id.org/np/RAfKB42E739cn7sWoTL4SM57vP9uFC_4O6U0CykcGu_nM http://www.nanopub.org/nschema#hasProvenance https://w3id.org/np/RAfKB42E739cn7sWoTL4SM57vP9uFC_4O6U0CykcGu_nM/provenance https://w3id.org/np/RAfKB42E739cn7sWoTL4SM57vP9uFC_4O6U0CykcGu_nM http://www.nanopub.org/nschema#hasPublicationInfo https://w3id.org/np/RAfKB42E739cn7sWoTL4SM57vP9uFC_4O6U0CykcGu_nM/pubinfo https://w3id.org/np/RAfKB42E739cn7sWoTL4SM57vP9uFC_4O6U0CykcGu_nM http://www.w3.org/1999/02/22-rdf-syntax-ns#type http://www.nanopub.org/nschema#Nanopublication https://w3id.org/np/RAfKB42E739cn7sWoTL4SM57vP9uFC_4O6U0CykcGu_nM/assertion https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test http://purl.org/dc/terms/description analysis.py fetches each Table S1 SBML file from BioModels and integrates it with libroadrunner 2.11.0 (CVODE, absolute and relative tolerance 1e-3, one retry at 1e-8 and 1e-6). An unstimulated run of 1010 time units sets the clamp (100 times the nonzero maximum, or the nonzero minimum divided by 100). Each floating species is then clamped up and down on six pulses of 50, 60, 70, 80, 90 and 100 time units, the stimulus reset every 0.1 time unit, with relaxations between pulses. A directed pair habituates when the first five stimulation-window means are at least 0.001 and each later mean is at most 1/1.5 of the previous. The pre-registered rule is applied to those counts. A second run reproduced the same counts. https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test http://www.w3.org/1999/02/22-rdf-syntax-ns#type https://w3id.org/delphi/ontology/Assessment https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test http://www.w3.org/2000/01/rdf-schema#comment Measured: 9 testable models with at least one habituating UCS-R pair (n = 30, deterministic given libroadrunner, the SBML files, and the tolerances recorded per model). Interpretation: The claim equates pharmacoresistance with habituation defined as a progressive 50% drop and, in the source sentence, as a ratio of 1:1.5. Section 4.5 states the operational ratio as 1/1.5 between successive stimulation-period means, across six stimulations whose lengths run from 5000 to 10000 steps of size 0.01, with relaxations equal to the following stimulation. This test uses that ratio, not a literal halving (1/2), and not the authors' MATLAB counter, which scores drug resistance when the first and last nonzero up/down labels differ. Nodes are the SBML floating species. The clamp is applied by resetting the stimulus after each 0.1 time unit, which is the restart interval in stimulateRelaxSingle.m and multiDrug.m. A stimulus direction whose clamped trajectory is non-finite is skipped and contributes no scored pairs. The unstimulated trajectory has to succeed. Parameters and reactions are never edited. The result is a property of these ODE models. It is not evidence that cells or patients habituate to drugs. https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test http://www.w3.org/2000/01/rdf-schema#label Claim test of levin-2022-grn-learning-14: refutes, confidence 0.45 https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test http://www.w3.org/2000/01/rdf-schema#seeAlso https://github.com/fractastical/delphisci/blob/bf2af6ee0a84e23ffa6414ad7a0a50a8c276506e/test-data/claim-tests/levin-papers/levin-2022-grn-learning-14/result.json https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test http://www.w3.org/ns/prov#wasAttributedTo https://w3id.org/delphi/resource/agent/delphisci-claim-tester-grok-4-7 https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/admissibleDatasets The 35 curated BioModels identifiers listed in Table S1 of Biswas, Clawson and Levin, Int. J. Mol. Sci. 2023, 24, 285 (doi:10.3390/ijms24010285), fetched as public SBML from the BioModels repository. No author-saved result matrix. Random synthetic circuits are outside this claim. A model that does not load or does not finish within the pre-registered time budget is not testable. https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/assessmentType claim-test/0.1.0 https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/dataKind computational https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/disconfirmingObservation A model that integrates has no such pair, or its share of such pairs is below 1% or above 50%. Either observation breaks the claim's universal statement about the testable BioModels set. Failure to integrate is not a counterexample; it removes the model from the testable set. https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/evidenceAgainst A longer averaging window can lower the mean of a short transient even when the peak does not fall. The test uses the mean because that is the quantity Section 4.5 names. https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/evidenceAgainst BIOMD0000000024 failed at load: libroadrunner reported that it cannot support delay differential equations. https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/evidenceAgainst Before this registration, Table S1 in the paper's supplementary PDF was read to copy the 35 BioModels identifiers. Result figures in that PDF were not used, and no SBML file had been downloaded. https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/evidenceAgainst Confidence stays at 0.45 because the pre-registered rule treats any testable model with fewer than two habituating pairs as single-pair fragile. Twenty-one models have zero, so the cap applies even though changing one pair would not change the verdict. https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/evidenceAgainst Eight of the 35 models were untestable in the paper. This registration treats a model that fails to load or exceeds 240 seconds of integration as untestable in the same sense, and does not count it as a failure of the claim. https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/evidenceAgainst Solver absolute tolerance is 1e-3 on the first attempt, matching the paper's Abstol, with one pre-registered retry at absolute 1e-8 and relative 1e-6 if the loose tolerance does not return a finite trajectory. The 0.001 floor on the first five window means is that same absolute tolerance, so a drop that is only visible below the tolerance does not count. https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/evidenceAgainst The authors' MATLAB sources on https://github.com/wesleypclawson/GRN_ODE (multiDrug.m, stimulateRelaxSingle.m, Find_DrugRes_Sensitize_SLURM1.m) were read to fix the pulse schedule. The repository's .mat result matrices were not downloaded. https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/evidenceAgainst The refutation is about this reimplementation of the published ratio on the public SBML. It is not a measurement of drug habituation in cells or patients. https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/evidenceAgainst Wall-clock seconds were left out of derived/measured.json so a later run can match the file. The pair counts were the same on the run that wrote this file and on the run before it. https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/expectedObservation Each ODE model that integrates under the six-pulse protocol has at least one UCS–R pair whose stimulation-window means fall by a factor of 1/1.5 at every successive pulse, and between 1% and 50% of the scored directed pairs in that model do so. https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/failCriterion Pre-registered. If fewer than 10 models are testable, the verdict is inconclusive (reason underpowered if at least one model was testable, otherwise data-unavailable). If at least 10 are testable and both clauses fail — some model has zero habituating pairs, and some model's fraction lies outside [0.01, 0.50] — the verdict is refutes. If exactly one of the two clauses fails, the verdict is mixed. A regulation-status flip counted by the authors' MATLAB is recorded as a descriptive statistic and does not decide the verdict. https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/hasConfidence 0.45 https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/hasEvidence https://w3id.org/delphi/resource/evidence/levin-2022-grn-learning-14--claim-test--dataset-1 https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/hasEvidence https://w3id.org/delphi/resource/evidence/levin-2022-grn-learning-14--claim-test--dataset-2 https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/hasVerdict refutes https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/hypothesis If pharmacoresistance-as-habituation holds in the published ODE pathway models, then in every BioModels entry from Table S1 of Biswas, Clawson and Levin (2022) that this protocol can integrate, at least one stimulus–response pair shows a progressive drop of the response mean by a factor of 1/1.5 at each of six lengthening stimulations, and the share of such pairs in that model is between 1% and 50%. https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/inferenceMethod Re-simulate each model from its SBML initial state. An unstimulated trajectory of 1010 time units sets the clamp levels (100 times the nonzero maximum, and the nonzero minimum divided by 100). Each other floating species is then clamped, up and down, on the paper's six lengthening pulses (50, 60, 70, 80, 90 and 100 time units) separated by relaxations equal to the next pulse. A directed pair habituates when the first five stimulation-window means are at least 0.001 and each later mean is at most 1/1.5 of the previous. The verdict is the rule in pass_criterion and fail_criterion. Confidence is 0.70 when at least 20 models are testable and reclassifying any one pair would not flip the verdict, 0.55 when fewer than 20 models are testable and the verdict is not single-pair fragile, 0.45 when it is single-pair fragile, and 0.60 when the verdict is inconclusive. Confidence is not raised above these values. https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/passCriterion Pre-registered (supports). Let a testable model be one of the 35 Table S1 BioModels whose SBML loads and for which every attempted unstimulated and clamped trajectory finishes inside the time budget with a finite sample, yielding at least one scored directed pair. Supports requires at least 10 testable models, every testable model has at least one habituating pair, and every testable model's habituating fraction (habituating pairs divided by scored directed pairs) lies in [0.01, 0.50] inclusive. https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/ontology/preregistered false https://w3id.org/delphi/resource/claim/levin-2022-grn-learning-14 https://w3id.org/delphi/ontology/hasAssessment https://w3id.org/delphi/resource/assessment/levin-2022-grn-learning-14--claim-test https://w3id.org/delphi/resource/evidence/levin-2022-grn-learning-14--claim-test--dataset-1 http://purl.org/dc/terms/description Source of the 35 BioModels identifiers. Result figures in the PDF were not used. The zip is over 1 MB and is not committed. analysis.py carries the identifiers copied from Table S1. https://w3id.org/delphi/resource/evidence/levin-2022-grn-learning-14--claim-test--dataset-1 http://purl.org/dc/terms/license CC BY (article) https://w3id.org/delphi/resource/evidence/levin-2022-grn-learning-14--claim-test--dataset-1 http://www.w3.org/1999/02/22-rdf-syntax-ns#type https://w3id.org/delphi/ontology/EvidenceItem https://w3id.org/delphi/resource/evidence/levin-2022-grn-learning-14--claim-test--dataset-1 http://www.w3.org/2000/01/rdf-schema#label Dataset: Supplementary PDF of Biswas, Clawson and Levin 2022, Table S1 (35 BioModels identifiers) https://w3id.org/delphi/resource/evidence/levin-2022-grn-learning-14--claim-test--dataset-1 http://www.w3.org/ns/prov#atLocation https://mdpi-res.com/d_attachment/ijms/ijms-24-00285/article_deploy/ijms-24-00285-s001.zip?version=1672829351 https://w3id.org/delphi/resource/evidence/levin-2022-grn-learning-14--claim-test--dataset-1 http://www.w3.org/ns/prov#wasDerivedFrom https://www.mdpi.com/article/10.3390/ijms24010285/s1 https://w3id.org/delphi/resource/evidence/levin-2022-grn-learning-14--claim-test--dataset-1 https://w3id.org/delphi/ontology/hasChecksum sha256:292a7f33bcb3a9589614507114de8c1a7a5f5d8bc11e382d546c3d08da381e39 https://w3id.org/delphi/resource/evidence/levin-2022-grn-learning-14--claim-test--dataset-2 http://purl.org/dc/terms/description ODE models integrated by analysis.py. Cached under cache/sbml/ and not committed. https://w3id.org/delphi/resource/evidence/levin-2022-grn-learning-14--claim-test--dataset-2 http://purl.org/dc/terms/license CC0 1.0 where the SBML says so (25 of 35 files). Ten files do not state a license in the XML: BIOMD0000000017, BIOMD0000000021, BIOMD0000000026, BIOMD0000000029, BIOMD0000000031, BIOMD0000000035, BIOMD0000000038, BIOMD0000000050, BIOMD0000000069, BIOMD0000000539. https://w3id.org/delphi/resource/evidence/levin-2022-grn-learning-14--claim-test--dataset-2 http://www.w3.org/1999/02/22-rdf-syntax-ns#type https://w3id.org/delphi/ontology/EvidenceItem https://w3id.org/delphi/resource/evidence/levin-2022-grn-learning-14--claim-test--dataset-2 http://www.w3.org/2000/01/rdf-schema#label Dataset: Curated SBML for the 35 BioModels identifiers in Table S1 https://w3id.org/delphi/resource/evidence/levin-2022-grn-learning-14--claim-test--dataset-2 http://www.w3.org/ns/prov#atLocation https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000001?filename=BIOMD0000000001_url.xml https://w3id.org/delphi/resource/evidence/levin-2022-grn-learning-14--claim-test--dataset-2 http://www.w3.org/ns/prov#atLocation 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