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pmid:37982752
Snapper: high-sensitive detection of methylation motifs based on Oxford Nanopore reads.
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
Bioinformatics (Oxford, England) · 2023 doi:10.1093/bioinformatics/btad702
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Experiment
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Complete file
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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). 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["PRJNA175046", "PXD038899", "SRP219538"], "resolved_accessions": ["PXD038899"], "statements": ["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)."], "basis": "The paper names PXD038899 in NCBI Sequence Read Archive and the accession resolves in the repository. 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"}]}