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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

Paper

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Experiment

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Data

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Snapper: high-sensitive detection of methylation motifs based on Oxford Nanopore reads.
doi
10.1093/bioinformatics/btad702
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Dmitry N Konanov
[1]
Vladislav V Babenko
[2]
Aleksandra M Belova
[3]
Arina G Madan
[4]
Daria I Boldyreva
[5]
Oksana E Glushenko
[6]
Ivan O Butenko
[7]
Dmitry E Fedorov
[8]
Alexander I Manolov
[9]
Danil V Krivonos
[10]
Vassilii N Lazarev
[11]
Vadim M Govorun
[12]
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. RESULTS: 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. AVAILABILITY 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).
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capability_table_fingerprint
2cb3e42f047d2ecf
snapshot_id
ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:37982752
parent_hash
sha256:42f715f57e6f37ccf8f36cdcb4b0a9012e7f15526df2c36dfc88d44673dd29f8
fork_of
null
gaps array · 10 items
[0]
asset:data:geo:PRJNA175046 licence not read
[1]
asset:data:geo:PRJNA175046 not downloaded
[2]
asset:data:geo:PXD038899 licence not read
[3]
asset:data:geo:PXD038899 not downloaded
[4]
asset:data:geo:SRP219538 licence not read
[5]
asset:data:geo:SRP219538 not downloaded
[6]
execution.not_run
[7]
review.human_critique
[8]
review.independent_reader
[9]
review.machine_critique
assays array · 2 items
[0] object · 11 fields
role
data_generation
definition_id
mass_spectrometry
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.69
evidence array · 1 item
[0]
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
[1] object · 11 fields
role
analysis
definition_id
contingency_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
[0]
chi_square_test
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
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
Complete file
{"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. At least four methylation sites that have not been described for H.pylori earlier were revealed."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "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.", "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:37982752"], "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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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"}]}