{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31649062", "kind": "science-record", "revision": 7, "content_hash": "sha256:acc591090375ce85c17b5d1692f0fb17da9cb0c866018b567f4248c0653f40ba", "created_at": "2026-11-01T15:40:50Z", "updated_at": "2026-11-01T22:00:56Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "PACAP and Other Neuropeptide Targets Link Chronic Migraine and Opioid-induced Hyperalgesia in Mouse Models.", "doi": "10.1074/mcp.RA119.001767", "pmid": "31649062", "authors": ["Krishna D. B. Anapindi", "Ning Yang", "Elena V Romanova", "Stanislav S Rubakhin", "Alycia Tipton", "Isaac Dripps", "Zoie Sheets", "Jonathan V Sweedler", "Amynah A Pradhan"], "journal": "Molecular & cellular proteomics : MCP", "year": 2019, "abstract": "Chronic use of opioids can produce opioid-induced hyperalgesia (OIH), and when used to treat migraine, these drugs can result in increased pain and headache chronicity. We hypothesized that overlapping mechanisms between OIH and chronic migraine occur through neuropeptide dysregulation. Using label-free, non-biased liquid chromatography-mass spectrometry to identify and measure changes in more than 1500 neuropeptides under these two conditions, we observed only 16 neuropeptides that were altered between the two conditions. The known pro-migraine molecule, calcitonin-gene related peptide, was among seven peptides associated with chronic migraine, with several pain-processing neuropeptides among the nine other peptides affected in OIH. Further, composite peptide complements Pituitary adenylate cyclase-activating polypeptide (PACAP), Vasoactive intestinal peptide (VIP) and Secretogranin (SCG) showed significant changes in both chronic migraine and OIH. In a follow-up pharmacological study, we confirmed the role of PACAP in models of these two disorders, validating the effectiveness of our peptidomic approach, and identifying PACAP as a mechanistic link between chronic migraine and OIH. Data are available via ProteomeXchange with identifier PXD013362.", "claims": [{"id": "claim-method", "statement": "An unpaired, 2-tailed Student's t test with equal variance was used to identify the significantly different peptide levels in the control and test groups for both conditions (supplemental Table S2 and on ProteomeXchange Consortium via the PRIDE).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31649062", "locator": "sections[11] \"Statistical Rationale for Peptide Quantitation and Behavioral Analysis\" paragraph 2", "quote": "An unpaired, 2-tailed Student's t test with equal variance was used to identify the significantly different peptide levels in the control and test groups for both conditions (supplemental Table S2 and on ProteomeXchange Consortium via the PRIDE)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry peptidomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [1] partner repository with the dataset identifier PXD013362 and 10.6019/PXD013362.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31649062", "locator": "sections[21] \"DATA AVAILABILITY\" paragraph 2", "quote": "The mass spectrometry peptidomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [1] partner repository with the dataset identifier PXD013362 and 10.6019/PXD013362."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:31649062"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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For this analysis, the list of precursor proteins that are common to both cohort 1 and cohort 2 only were considered. Gene expression validation (from Allen Brain Atlas) of the same proteins is included in Supplementary Table IV", "structure": {"pmcid": "PMC6885698", "section_index": 16, "section_title": "Functional Classification of Migraine and OIH-relevant Precursor Proteins", "row_count": 39, "column_count": 3}, "table": {"label": "Table I", "caption": "Precursor proteins that correspond to the significantly changed peptides for the migraine and OIH models. For this analysis, the list of precursor proteins that are common to both cohort 1 and cohort 2 only were considered. Gene expression validation (from Allen Brain Atlas) of the same proteins is included in Supplementary Table IV", "rows": [["Region", "Protein name (Migraine)", "Protein name (OIH)"], ["DH", "Secretogranin I", "Secretogranin II"], ["", "Pro-Enkephalin A/B", "Secretogranin I"], ["", "Calcitonin gene-related peptide", "Pro-Enkephalin A/B"], ["", "Macrophage migration inhibitory factor", "Calcitonin gene-related peptide"], ["", "Phosphatidylethanolamine-binding protein", "Pro-Neuropeptide Y"], ["", "", "Protachykinin-1"], ["H", "Secretogranin I", "Secretogranin II"], ["", "Eukaryotic translation initiation factor", "Neuro VGF"], ["", "", "Neuroendocrine protein 7B2"], ["", "", "ProSAAS"], ["NAC", "Macrophage migration inhibitory factor", "Peptidyl-prolyl cis-trans isomerase Aa"], ["", "Phosphatidylethanolamine-binding protein", "Neuro VGF"], ["", "Clathrin light chaina", "Acidic leucine-rich nuclear phosphoprotein 32 family member A"], ["", "Serine/arginine-rich splicing factor", "Vasoactive intestinal peptides"], ["", "Tubulin beta-2A chaina", "Peptidyl-prolyl cis-trans isomerasea"], ["", "Tubulin beta-2B chain a", ""], ["", "Tubulin beta-6 chain", ""], ["", "Tubulin beta-5 chaina", ""], ["", "Tubulin beta-4B chaina", ""], ["", "Clathrin light chaina", ""], ["", "Clathrin light chaina", ""], ["", "Calcitonin gene-related peptidea", ""], ["", "Clathrin light chaina", ""], ["", "Clathrin light chaina", ""], ["PAG", "Pituitary adenylate cyclase-activating polypeptide", "ProSAAS"], ["", "Pro-Enkephalin A/B", "Secretogranin I"], ["", "Neuro VGF", ""], ["", "Secretogranin II", ""], ["TG", "40S ribosomal protein S12a", "Thymosin beta-10"], ["", "Mast cell protease 4", "Apolipoprotein A"], ["", "Alpha Globin", ""], ["", "Peptidyl-prolyl cis-trans isomerase A", ""], ["", "Hemoglobin Aa", ""], ["TN", "Calcitonin gene-related peptide", "Pro-Enkephalin A/B"], ["", "", "Neuro VGF"], ["", "", "Secretogranin I"], ["", "", "ProSAAS"], ["", "", "Pro-Dynorphin"]], "row_count": 39, "column_count": 3, "numeric_cells": 11, "header_rows": 1, "locator": "section[16]/table-wrap[1]#tbl1"}}], "gaps": ["asset:data:geo:PXD013362 not downloaded", "asset:data:geo:PXD013362 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "An unpaired, 2-tailed Student's t test with equal variance was used to identify the significantly different peptide levels in the control and test groups for both conditions (supplemental Table S2 and on ProteomeXchange Consortium via the PRIDE)."}}], "targets": [], "gaps": ["method.student_t"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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Evidence bands order textual support; method agreement intervals are null (n=0), never probabilities. Work-type validation does not validate methods.","Operation coverage describes only explicitly named methods. It does not prove a complete protocol, compatible parameters, successful compilation or re-execution. Unrecognised or ambiguous methods require review.","Data reachability is a textual accession or public-data statement. No dataset was downloaded or checked for access, completeness or licence.","Capabilities are planning states seeded from the dated equipment register. No bench ownership, completed quote or partner booking is inferred. Procurement counts are dependencies, not guaranteed replications or financial returns.","Tier and blocker counts are deterministic assessments of this corpus, not measured agreement. R3 is reserved for procurement; unresolved methods and data require human work (R4). The most restrictive axis wins, with capability, method, data as tie-breaks. 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At the evidence floor the work type comes from title framing and a fixed prior, not from anything in the paper, so the published work-type split should be read as a rough triage signal rather than a measured distribution. The impact is bounded but not removed: since 2026-10-23 the engine excludes floor-confidence records from the shortlist entirely and publishes them separately as held out, so the recommendation is unaffected even though the census is.","status":"unverified","severity":"high"},{"code":"runtime_is_modelled","basis":["Runtime is summed from published per-assay hour figures. Timing awaits the first executed replication.","4,407 of 5,529 records (79.7%) model to 0.00 hours because no assay was matched, which the ranking then reads as \"cheapest\".","0 of 10 shortlisted records carry a 0.00-hour estimate."],"claim":"Estimated replication runtime","gloss":"The hour figures are estimates built from assay mentions; timing awaits the first executed replication.","detail":"The hour figures are a cost model derived from the bench steps implied by each matched assay family. The first executed replication will supply measured timing. Records without an assay match currently receive a zero-hour model value.","status":"unverified","severity":"high"},{"code":"signal_score_without_citations","basis":["5,529 of 5,529 records (100.0%) have no citation count from the source metadata."],"claim":"Signal score","gloss":"The signal score uses publication-type weight because the mirror supplied zero citation counts.","detail":"The source supplied no citation counts for any record in this run, so the signal score is publication-type weight only. The citation term of the ranking is inert here, and the shortlist is ordered by publication type alone.","status":"unverified","severity":"high"},{"code":"abstract_absent","basis":["1,667 of 5,529 records (30.2%) carry no abstract at all."],"claim":"Evidence base for classification","gloss":"Some records contain a title and publication type only, defining the available classification evidence.","detail":"Where the mirror contains a title and publication types only, those fields define the classifier evidence. A methods section is required for fuller automated and human review.","status":"unverified","severity":"medium"},{"code":"classifier_agreement_measured","basis":["Published two-way decision agreement 77.7% (310 of 399 decidable records) from a stratified hand-check of 438 real records.","Three-way diagnostic agreement 73.9% (288 of 390 decidable records).","data_only agreement 75.2% (100 of 133 decidable).","48 record(s) could not be decided from title and abstract and were excluded from the denominator.","56 analysis-only records were published under another work type, so the data_only share is not an upper bound."],"claim":"Published automatable decision","gloss":"This figure has been checked against a human reading the same papers, so we know how often it is right.","detail":"The published automatable / not-automatable distribution comes from a rule-based classifier that was hand-checked against a fixed ground-truth definition. The agreement rates below are measured, not estimated. The three-way work type remains a diagnostic and is reported separately.","status":"measured","severity":"high"},{"code":"llm_comparison_not_measured","basis":["rule_based_v1+lex99e1195c7d6f produced 5,529 of 5,529 classifications.","Measured on 438 labelled records; these are RULE-BASED figures, not model results."],"claim":"Rule-based versus LLM agreement","gloss":"Every number here is the rule engine’s own. Model comparison begins when a working API credential is connected and measured.","detail":"The published two-way decision agreed with a human reading on 310 of 399 decidable records (77.7%). The diagnostic three-way label agreed on 288 of 390 decidable records (73.9%). Every percentage in this run belongs to the rule engine. Model comparison begins when a working API credential is connected and measured.","status":"not_measured","severity":"high"},{"code":"confidence_is_a_band","basis":["low band: 135 of 210 hand-judged records were correct, 64.3% [57.6, 70.5] (95% CI).","medium band: 80 of 104 hand-judged records were correct, 76.9% [68.0, 84.0] (95% CI).","high band: 73 of 76 hand-judged records were correct, 96.0% [89.0, 98.7] (95% CI).","A fitted calibrated probability was built, measured and withdrawn: it overstated held-out accuracy and reorders nothing."],"claim":"Confidence band and evidence score","gloss":"The confidence band carries a measured accuracy interval; 0.85 represents relative rank strength.","detail":"Confidence on this run is a BAND plus its measured accuracy interval. The number stored alongside each record is a monotone evidence score that orders records; 0.85 represents relative rank strength. A fitted probability was withdrawn after it overstated held-out accuracy. Threshold on the band.","status":"measured","severity":"medium"},{"code":"three_way_split_is_diagnostic","basis":["The corpus is published at the two-way decision: automatable or not-automatable. The three-way split (data_only / physical / mixed) is published as a diagnostic with its measured reliability attached, not as a claim, because the rule engine's `mixed` call cannot be defended.","The engine called 22 record(s) mixed; 10 matched the human judgement (45.5%, 95% CI 26.9-65.3).","The engine's `mixed` call is right on 10/22 hand-judged records (45.5%, 95% CI 26.9%-65.3%); a constant `physical` guess scores 36.4%.","The engine's `mixed` call does not reliably beat a constant `physical` guess on the hand-judged records it labels mixed.","The sign of that difference flips between two independent samples, so the three-way refinement is not demonstrably informative.","The mixed stratum contributes a disproportionate share of errors relative to its size.","At title-only depth the physical/mixed split collapses: a title says that work was done, not whether it was also analysed."],"claim":"The published decision is two-way","gloss":"The three-way split is shown for diagnosis only. The published split is two ways.","detail":"Count and filter the corpus on automatable versus not-automatable. The data_only / physical / mixed split remains an internal engine diagnostic because the mixed call has lower measured reliability.","status":"measured","severity":"medium"},{"code":"automatable_flag_unproven","basis":["6 of 29 assay families are marked automatable now: meta_analysis, machine_learning, survival_analysis, pca, molecular_docking, differential_expression.","The flag is a rule over assay family and work type; validation begins with the first executed replication.","It inherits the 75.2% data_only agreement rate, because the flag requires the record to be analysis-only."],"claim":"Automatable now","gloss":"This flag marks assay families the rules classify as data-only. The first executed replication will validate it.","detail":"This flag marks families the rules consider replicable from data alone. Its validity depends on the analysis-only classification and will be measured through an executed replication.","status":"unverified","severity":"medium"}],"confidence_policy":"band_with_measured_interval","confidence_contract":{"policy":"band_with_measured_interval","summary":"Confidence is reported as a BAND with a measured accuracy interval. The raw evidence score supplies monotone ordering. A fitted point estimate was withdrawn after it overstated held-out accuracy.","evidence_score":"A monotone evidence score in [0,1] built from cue mass, axis separation and text coverage. Use it to order records. Interpret 0.85 as relative rank strength.","confidence_band":"low | medium | high. Consumers threshold on this value.","band_accuracy":"Wilson 95% interval on the measured agreement of the hand-judged records in this band.","calibrated_confidence":"WITHDRAWN. 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