{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37982752", "kind": "science-record", "revision": 3, "content_hash": "sha256:0cabf485af9b69f66deed93d35fb6fc9903bee0b6b5c2cbfb733606864e7751a", "created_at": "2026-11-01T19:02:54Z", "updated_at": "2026-11-01T21:31:59Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Snapper: high-sensitive detection of methylation motifs based on Oxford Nanopore reads.", "doi": "10.1093/bioinformatics/btad702", "pmid": "37982752", "authors": ["Dmitry N Konanov", "Vladislav V Babenko", "Aleksandra M Belova", "Arina G Madan", "Daria I Boldyreva", "Oksana E Glushenko", "Ivan O Butenko", "Dmitry E Fedorov", "Alexander I Manolov", "Danil V Krivonos", "Vassilii N Lazarev", "Vadim M Govorun", "Elena N Ilina"], "journal": "Bioinformatics (Oxford, England)", "year": 2023, "abstract": "MOTIVATION: The Oxford Nanopore technology has a great potential for the analysis of methylated motifs in genomes, including whole-genome methylome profiling. However, we found that there are no methylation motifs detection algorithms, which would be sensitive enough and return deterministic results. Thus, the MEME suit does not extract all Helicobacter pylori methylation sites de novo even using the iterative approach implemented in the most up-to-date methylation analysis tool Nanodisco.\nRESULTS: We present Snapper, a new highly sensitive approach, to extract methylation motif sequences based on a greedy motif selection algorithm. Snapper does not require manual control during the enrichment process and has enrichment sensitivity higher than MEME coupled with Tombo or Nanodisco instruments that was demonstrated on H.pylori strain J99 studied earlier by the PacBio technology and on four external datasets representing different bacterial species. We used Snapper to characterize the total methylome of a new H.pylori strain A45. At least four methylation sites that have not been described for H.pylori earlier were revealed. We experimentally confirmed the presence of a new CCAG-specific methyltransferase and inferred a gene encoding a new CCAAK-specific methyltransferase.\nAVAILABILITY AND IMPLEMENTATION: Snapper is implemented using Python and is freely available as a pip package named \"snapper-ont.\" Also, Snapper and the demo dataset are available in Zenodo (10.5281/zenodo.10117651).", "claims": [{"id": "claim-method", "statement": "Next, for each k-mer in the hash-table, the Kolmogorov–Smirnov test is performed to compare signal level distributions between native and WGA samples (or, more generally, between any two samples passed as the input).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37982752", "locator": "sections[12] \"2.4.3 Snapper\" paragraph 4", "quote": "Next, for each k-mer in the hash-table, the Kolmogorov–Smirnov test is performed to compare signal level distributions between native and WGA samples (or, more generally, between any two samples passed as the input)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All the source code is available on Github (https://github.com/DNKonanov/Snapper). Fastq files are available in SRA (NCBI Bioproject accession number PRJNA175046). The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (Perez-Riverol et al. 2019) partner repository with the dataset identifier PXD038899 (access for the reviewers: login reviewer pxd038899@ebi.ac.uk, password—xOuk64qK). All genome assemblies obtained during this study are available in GenBank (Helicobacter pylori A45 wild-type: GCA 000333835.2, hpy: GCA 013122115.1, hp1352: GCA 013122055.1, hp91/92: GCA 013122035.1). External fast5-files used in this study were downloaded from SRP219538. Additionally, we provide a small fast5 example dataset in order to demonstrate the tool capabilities. The demo-dataset includes 10 + 10 preprocessed multi-fast5 files containing 40 000 long reads for the hpy mutant and 40 000 reads for the wild A45 as a control (http://download.ripcm.com/snapper_test). Both Snapper tool and the demo dataset are available in Zenodo (10.5281/zenodo.10117651).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37982752", "locator": "sections[27] \"Data availability\" paragraph 2", "quote": "All the source code is available on Github (https://github.com/DNKonanov/Snapper). Fastq files are available in SRA (NCBI Bioproject accession number PRJNA175046). The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (Perez-Riverol et al. 2019) partner repository with the dataset identifier PXD038899 (access for the reviewers: login reviewer pxd038899@ebi.ac.uk, password—xOuk64qK). All genome assemblies obtained during this study are available in GenBank (Helicobacter pylori A45 wild-type: GCA 000333835.2, hpy: GCA 013122115.1, hp1352: GCA 013122055.1, hp91/92: GCA 013122035.1). External fast5-files used in this study were downloaded from SRP219538. Additionally, we provide a small fast5 example dataset in order to demonstrate the tool capabilities. The demo-dataset includes 10 + 10 preprocessed multi-fast5 files containing 40 000 long reads for the hpy mutant and 40 000 reads for the wild A45 as a control (http://download.ripcm.com/snapper_test). Both Snapper tool and the demo dataset are available in Zenodo (10.5281/zenodo.10117651)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Snapper has higher enrichment sensitivity than MEME coupled with Tombo or Nanodisco, and its use revealed at least four methylation sites not previously described for Helicobacter pylori.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37982752", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "We present Snapper, a new highly sensitive approach, to extract methylation motif sequences based on a greedy motif selection algorithm."}, {"asset": "source:pmid:37982752", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Snapper does not require manual control during the enrichment process and has enrichment sensitivity higher than MEME coupled with Tombo or Nanodisco instruments that was demonstrated on H.pylori strain J99 studied earlier by the PacBio technology and on four external datasets representing different bacterial species."}, {"asset": "source:pmid:37982752", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "We used Snapper to characterize the total methylome of a new H.pylori strain A45. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["chi_square_test"], "assets": ["source:pmid:37982752", "data:geo:PXD038899"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:PXD038899"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:59:28Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 12799, "completion_tokens": 3031, "cached_tokens": 256}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:37982752", "type": "paper", "label": "pmid:37982752"}, {"id": "source:pmid:37982752", "type": "manuscript", "label": "PMID 37982752 full text"}, {"id": "data:geo:PXD038899", "type": "dataset", "label": "GEO PXD038899"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37982752", "type": "paper", "label": "pmid:37982752"}, {"id": "source:pmid:37982752", "type": "manuscript", "label": "PMID 37982752 full text"}, {"id": "data:geo:PXD038899", "type": "dataset", "label": "GEO PXD038899"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37982752", "type": "extraction", "used": ["source:pmid:37982752"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-PXD038899", "type": "accession_resolution", "used": ["data:geo:PXD038899"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:37982752", "parent_hash": "sha256:42f715f57e6f37ccf8f36cdcb4b0a9012e7f15526df2c36dfc88d44673dd29f8", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:PRJNA175046 licence not read", "asset:data:geo:PRJNA175046 not downloaded", "asset:data:geo:PXD038899 licence not read", "asset:data:geo:PXD038899 not downloaded", "asset:data:geo:SRP219538 licence not read", "asset:data:geo:SRP219538 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "mass_spectrometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["or modification of CCAAK, we used non-target proteomics data that were obtained earlier for the wild"], "order_basis": "paper_text_order:8600", "id": "assay:1"}, {"role": "analysis", "definition_id": "contingency_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["chi_square_test"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Next, for each k-mer in the hash-table, the Kolmogorov–Smirnov test is performed to compare signal level distributions between native and WGA samples (or, more generally, between any two samples passed as the input)."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]},"meta":{"api_version":"v1","automation_ladder_snapshot":"ba34b49490d9bfaf","automation_ladder_caveats":["Method extraction is rule-based and has no hand-judged accuracy sample. 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. Resolving one blocker can leave another at the same tier."],"engine":"corpus_engine","engine_provider":"rule_based_v1+lex99e1195c7d6f","run_id":"run-20261023T122449232913","source":"esearch","source_detail":"PubMed mirror biomed_pubmed (read-only)","run_status":"complete","imported_at":"2026-11-03T20:16:52+00:00","generated_at":"2026-11-04T02:00:42+00:00","total_papers":5529,"total_assays_tracked":29,"automatable_assay_families":6,"validated":true,"caveat_count":9,"blocking_caveats":5,"caveats":[{"code":"low_evidence_dominates","basis":["4,152 of 5,529 classifications (75.1%) matched no cue evidence and sit at the 0.05 floor.","34 of 230 data_only calls (14.8%) are in that group."],"claim":"Work type and confidence bands","gloss":"Most records were classified from their title and framing alone, with assay-cue coverage at zero.","detail":"Most classifications in this run rest on no matched evidence at all. 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. Reintroduction requires held-out evidence demonstrating reliable estimates across every bin."},"band_accuracy":{"low":{"n":210,"low":0.576,"band":"low","high":0.7046,"agree":135,"accuracy":0.6429},"high":{"n":76,"low":0.8903,"band":"high","high":0.9865,"agree":73,"accuracy":0.9605},"medium":{"n":104,"low":0.6795,"band":"medium","high":0.8397,"agree":80,"accuracy":0.7692}},"provider":"rule_based_v1+lex99e1195c7d6f","lexicon_id":"99e1195c7d6f","contract_published_at":"2026-10-23T12:25:29.022232+00:00","confidence_is_band":true,"confidence_is_probability":false,"decision_taxonomy":"two_way","decidable_fraction_two_way":0.8854,"decidable_fraction_two_way_low":0.8565,"decidable_fraction_two_way_high":0.9143,"decidable_fraction_three_way":0.8586,"decidable_fraction_three_way_low":0.8287,"decidable_fraction_three_way_high":0.8884,"decidable_population":5529,"validation_sample_size":438,"three_way_cost_fraction":0.0268,"three_way_cost_records":148,"decision_counts":{"automatable":230,"not_automatable":5299},"decision_split":{"automatable":{"count":230,"share":0.04159884246699222},"not_automatable":{"count":5299,"share":0.9584011575330078}},"diagnostic_work_type_counts":{"mixed":24,"physical":5275,"data_only":230}}}