{"doi":"10.1016/j.celrep.2023.112930","title":"Topography of mutational signatures in human cancer","abstract":"The somatic mutations found in a cancer genome are imprinted by different mutational processes. Each process exhibits a characteristic mutational signature, which can be affected by the genome architecture. However, the interplay between mutational signatures and topographical genomic features has not been extensively explored. Here, we integrate mutations from 5,120 whole-genome-sequenced tumors from 40 cancer types with 516 topographical features from ENCODE to evaluate the effect of nucleosome occupancy, histone modifications, CTCF binding, replication timing, and transcription/replication strand asymmetries on the cancer-specific accumulation of mutations from distinct mutagenic processes. Most mutational signatures are affected by topographical features, with signatures of related etiologies being similarly affected. Certain signatures exhibit periodic behaviors or cancer-type-specific enrichments/depletions near topographical features, revealing further information about the processes that imprinted them. Our findings, disseminated via the COSMIC (Catalog of Somatic Mutations in Cancer) signatures database, provide a comprehensive online resource for exploring the interactions between mutational signatures and topographical features across human cancer.","journal":"Cell Reports","year":2023,"id":321053,"datarank":0.9294721027403563,"base_score":3.8501476017100584,"endowment":3.8501476017100584,"self_citation_contribution":0.5775221402565088,"citation_network_contribution":0.3519499624838475,"self_endowment_contribution":0.5775221402565088,"citer_contribution":0.3519499624838475,"corpus_percentile":78.23934400866403,"corpus_rank":2814,"citation_count":46,"citer_count":36,"citers_with_citation_signal":20,"citers_with_endowment":20,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.5855,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":62.5,"fair_percentile":81.0149801284011,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":839788,"name":"Marcos Díaz‐Gay","orcid":"0000-0003-0658-0467","position":1,"is_corresponding":false},{"id":1032939,"name":"Ian Vermes","orcid":null,"position":2,"is_corresponding":false},{"id":13254,"name":"Erik N. Bergstrom","orcid":"0000-0001-7740-022X","position":3,"is_corresponding":false},{"id":1032500,"name":"Maria Zhivagui","orcid":"0000-0002-3410-4014","position":4,"is_corresponding":false},{"id":839790,"name":"Mark Barnes","orcid":"0000-0002-5650-780X","position":5,"is_corresponding":false},{"id":13201,"name":"Ludmil B. Alexandrov","orcid":"0000-0003-3596-4515","position":6,"is_corresponding":false},{"id":471842,"name":"Burçak Otlu","orcid":"0000-0002-4931-7979","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-19T01:07:27.434133Z","pmid":"37540596","pmcid":"PMC10507738","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":72.2222,"fair_a":81.25,"fair_i":60.0,"fair_r":50.0,"fair_zscore":1.1103,"fair_rationale":{"fair_score":62.5,"has_llm":true,"taxonomy_version":"fair_taxonomy_v5","dimensions":{"F":{"name":"Findable","score":72.22,"criteria":[{"key":"f_dataset_pid","label":"Persistent identifier for the data","kind":"llm","weight":2.0,"fraction":0.5,"verdict":"partial","evidence":"All topographical data and figures regarding topography of mutational signatures in human cancer generated in this study have been deposited at COSMIC, Catalog of Somatic Mutations in Cancer ( https://cancer.sanger.ac.uk/signatures/ ), through COSMIC Signatures v3.3, released on May 27 th , 2022 and are currently publicly available.","grounded":true,"rationale":"The only identifier given is a URL (https://cancer.sanger.ac.uk/signatures/) which is not a persistent identifier scheme (DOI, Handle, ARK, URN, or repository accession pattern).","anchors":["RDA-F1-01D — FAIR Data Maturity Model: 'Data is identified by a persistent identifier' (priorit","RDA-F1-02D — FAIR Data Maturity Model: 'Data is identified by a globally unique identifier'","FsF-F1-02D — F-UJI/FAIRsFAIR: 'Data is assigned a persistent identifier'"],"scored":true,"signal":null},{"key":"f_repository_named","label":"Named repository","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"All topographical data and figures regarding topography of mutational signatures in human cancer generated in this study have been deposited at COSMIC, Catalog of Somatic Mutations in Cancer","grounded":true,"rationale":"COSMIC is a well-known data repository registered in re3data/FAIRsharing.","anchors":["RDA-F4-01M — FAIR Data Maturity Model: metadata is offered so it can be harvested and indexed (","NIH DMS Policy Element 4 (NOT-OD-21-014) — name the repository where data will be archived","NSTC Desirable Characteristics of Data Repositories (2022) — 'Long-Term Sustainability', 'Reten"],"scored":true,"signal":null},{"key":"f_data_availability_statement","label":"Data-availability statement","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"All topographical data and figures regarding topography of mutational signatures in human cancer generated in this study have been deposited at COSMIC, Catalog of Somatic Mutations in Cancer ( https://cancer.sanger.ac.uk/signatures/ ), through COSMIC Signatures v3.3, released on May 27 th , 2022 and are currently publicly available.","grounded":true,"rationale":"The statement points to a repository (COSMIC) with a link, which is a Colavizza category 3 link to archived data.","anchors":["Colavizza, Hrynaszkiewicz, Staden, Whitaker & McGillivray (2020), 'The citation advantage of li","Springer Nature research data policy — Data Availability Statements: standard statement templat","RDA-F3-01M — metadata clearly and explicitly includes the identifier of the data it describes"],"scored":false,"signal":null},{"key":"f_discovery_metadata","label":"Description of the dataset as an object","kind":"llm","weight":2.0,"fraction":0.5,"verdict":"partial","evidence":"Our evaluation encompassed examining the effects of nucleosome occupancy, histone modifications, CTCF binding sites, replication timing, transcription strand asymmetry, and replication strand asymmetry on the accumulation of somatic mutations from more than 70 distinct mutational signatures.","grounded":true,"rationale":"The dataset content is described in running prose but not itemised in a section, table, or enumerated list. [majority verdict 'partial' (4/5 passes agreed)]","anchors":["RDA-F2-01M — 'Rich metadata is provided to allow discovery' (priority Essential)","FsF-F2-01M — F-UJI: 'Metadata includes descriptive core elements to support data findability'","FsF-R1-01MD — F-UJI: 'Metadata specifies the content of the data'"],"scored":false,"signal":null},{"key":"f_dataset_cited","label":"Dataset formally cited","kind":"llm","weight":1.0,"fraction":0.5,"verdict":"partial","evidence":"All topographical data and figures regarding topography of mutational signatures in human cancer generated in this study have been deposited at COSMIC, Catalog of Somatic Mutations in Cancer ( https://cancer.sanger.ac.uk/signatures/ ), through COSMIC Signatures v3.3, released on May 27 th , 2022 and are currently publicly available.","grounded":true,"rationale":"The dataset's identifier (URL and version) appears only in the body text, not as a reference-list entry.","anchors":["FORCE11 Joint Declaration of Data Citation Principles (2014) — data should be cited as a first-","RDA-F3-01M — metadata clearly and explicitly includes the identifier of the data it describes","FsF-F3-01M — F-UJI: 'Metadata includes the identifier of the data it describes'"],"scored":true,"signal":null}]},"A":{"name":"Accessible","score":81.25,"criteria":[{"key":"a_data_openly_accessible","label":"Access route free of preconditions","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"All topographical data and figures regarding topography of mutational signatures in human cancer generated in this study have been deposited at COSMIC, Catalog of Somatic Mutations in Cancer ( https://cancer.sanger.ac.uk/signatures/ ), through COSMIC Signatures v3.3, released on May 27 th , 2022 and are currently publicly available.","grounded":true,"rationale":"The text gives a route (COSMIC) with no stated precondition; the data are 'publicly available' immediately.","anchors":["RDA-A1.1-01D — 'Data is accessible through a free access protocol'","FsF-A1-01M — F-UJI: 'Metadata contains access level and access conditions of the data'","NSTC Desirable Characteristics of Data Repositories (2022) — 'Free and Easy Access'"],"scored":true,"signal":null},{"key":"a_access_conditions_stated","label":"Access level labelled","kind":"llm","weight":1.0,"fraction":1.0,"verdict":"yes","evidence":"are currently publicly available","grounded":true,"rationale":"The paper states that the data are 'publicly available', which is an explicit access-level label.","anchors":["FsF-A1-01M — F-UJI: 'Metadata contains access level and access conditions of the data'","RDA-A1-01M — metadata contains information to enable the user to get access to the data","COAR Controlled Vocabularies — Access Rights v1.0 (open / embargoed / restricted / metadata-onl"],"scored":false,"signal":null},{"key":"a_controlled_access_for_sensitive","label":"Gatekeeper for sensitive data","kind":"llm","weight":0.5,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"The data are not sensitive human-subject data requiring controlled access, and no gatekeeper is named.","anchors":["NIH Genomic Data Sharing Policy (NOT-OD-14-124) — controlled-access via a Data Access Committee","RDA-A1.2-01D — 'Data is accessible through an access protocol that supports authentication and ","NIH DMS Policy Element 5 (NOT-OD-21-014) — Access, Distribution, or Reuse Considerations (conse"],"scored":false,"signal":null},{"key":"a_timeline_retention","label":"Availability timing & retention","kind":"llm","weight":0.5,"fraction":0.5,"verdict":"partial","evidence":"released on May 27 th , 2022 and are currently publicly available","grounded":true,"rationale":"The paper states the release date and current availability but does not commit to any retention period or permanent archiving.","anchors":["NIH DMS Plan Element 4 (NOT-OD-21-014) — Data Preservation, Access, and Associated Timelines","NSTC Desirable Characteristics (2022), Organizational Infrastructure: 'Retention Policy'","RDA-A2-01M — 'Metadata is guaranteed to remain available after data is no longer available'"],"scored":false,"signal":null}]},"I":{"name":"Interoperable","score":60.0,"criteria":[{"key":"i_open_nonproprietary_format","label":"Open file format","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No file format is named for the released data.","anchors":["FsF-R1.3-02D — F-UJI: 'Data is available in a file format recommended by the target research co","RDA-R1.3-02D — data is expressed in a machine-understandable community standard","RDA-I1-01D — data uses a knowledge representation expressed in a standardised format"],"scored":true,"signal":null},{"key":"i_community_standard_vocabulary","label":"Community standard / vocabulary","kind":"llm","weight":1.0,"fraction":1.0,"verdict":"yes","evidence":"SBS-96, DBS-78, and ID-83 mutational classification schemas","grounded":true,"rationale":"The paper names standard mutational classification schemas (SBS-96, DBS-78, ID-83) which are community data standards. [majority verdict 'yes' (4/5 passes agreed)]","anchors":["RDA-R1.3-01M — 'Metadata complies with a community standard' (priority Essential)","RDA-R1.3-01D — 'Data complies with a community standard'","RDA-I2-01M — '(Meta)data use vocabularies that follow FAIR principles'"],"scored":false,"signal":null},{"key":"i_qualified_references","label":"Identifiers for the resources the data depend on","kind":"llm","weight":0.5,"fraction":1.0,"verdict":"yes","evidence":"https://doi.org/10.6084/m9.figshare.22744733","grounded":true,"rationale":"The paper provides a DOI for the MUTOGRAPHS project dataset, which is an external resource used by the study.","anchors":["RDA-I3-01M — '(meta)data include references to other (meta)data'","RDA-I3-03M — 'metadata includes qualified references to other metadata'","FsF-I3-01M — F-UJI: 'Metadata includes links between the data and its related entities'"],"scored":false,"signal":null}]},"R":{"name":"Reusable","score":50.0,"criteria":[{"key":"r_reuse_license","label":"Reuse licence","kind":"llm","weight":2.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No license is stated for the data; the CC BY license applies to the article only.","anchors":["RDA-R1.1-01M — 'Metadata includes information about the licence under which the data can be reu","RDA-R1.1-02M — 'Metadata refers to a standard reuse licence'","RDA-R1.1-03M — 'Metadata refers to a machine-understandable reuse licence'"],"scored":true,"signal":null},{"key":"r_provenance_methods","label":"Provenance of the data","kind":"llm","weight":1.0,"fraction":1.0,"verdict":"yes","evidence":"SigProfilerExtractor was utilized for de novo extraction of mutational signatures","grounded":true,"rationale":"The paper names specific software tools (SigProfilerExtractor, SigProfilerSimulator) used to produce the data.","anchors":["RDA-R1.2-01M — 'Metadata includes provenance information according to community- specific standa","FsF-R1.2-01M — F-UJI: 'Metadata includes provenance information about data creation or generati","W3C PROV-O (W3C Recommendation, 2013) — the entity/activity/agent model of provenance"],"scored":false,"signal":null},{"key":"r_documentation_codebook","label":"Documentation / codebook","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":"our analysis leverages 516 unique tissue-matched topographical features from the ENCODE project ( Table S1 )","grounded":false,"rationale":"Supplementary Table S1 lists the topographical features, providing variable-level documentation inside the article. [downgraded to 'no' — no verifiable quote from the paper]","anchors":["RDA-R1-01M — '(Meta)data are richly described with a plurality of accurate and relevant attribu","FsF-R1-01MD — F-UJI: 'Metadata specifies the content of the data'","NIH DMS Policy Element 3 (NOT-OD-21-014) — Standards (documentation and metadata to accompany t"],"scored":false,"signal":null},{"key":"r_versioning","label":"Snapshot identified","kind":"llm","weight":0.5,"fraction":1.0,"verdict":"yes","evidence":"COSMIC Signatures v3.3","grounded":true,"rationale":"The data release is identified by a version token: 'v3.3'.","anchors":["DataCite Metadata Schema 4.6 — the 'Version' property","RDA-R1.2-01M — provenance information (which version was used is provenance)","NSTC Desirable Characteristics of Data Repositories (2022) — 'Provenance', 'Retention Policy'"],"scored":true,"signal":null},{"key":"x_code_availability","label":"Analysis code available","kind":"llm","weight":1.0,"fraction":1.0,"verdict":"yes","evidence":"https://github.com/AlexandrovLab/SigProfilerTopography","grounded":true,"rationale":"The paper provides a GitHub URL for the custom code, which is a machine-resolvable locator.","anchors":["NIH DMS Policy Element 2 (NOT-OD-21-014) — 'Related Tools, Software and/or Code'","FAIR4RS Principles v1.0 (Chue Hong et al., 2022; RDA/FORCE11/ReSA) — FAIR Principles for Resear","FORCE11 Software Citation Principles (Smith, Katz & Niemeyer, 2016, PeerJ CS 2:e86)"],"scored":true,"signal":null},{"key":"x_funding_attribution","label":"Funder and award number","kind":"llm","weight":0.5,"fraction":1.0,"verdict":"yes","evidence":"R01ES030993","grounded":true,"rationale":"Specific grant numbers (e.g., R01ES030993) are given for the funding. [majority verdict 'yes' (3/5 passes agreed)]","anchors":["DataCite Metadata Schema 4.6 — 'FundingReference' property (funderName, funderIdentifier, award","Crossref Funder Registry — canonical funder identifiers for funding metadata","RDA-F2-01M — rich metadata provided to allow discovery (funding is part of the descriptive reco"],"scored":true,"signal":null}]}},"actions":[{"key":"r_reuse_license","dimension":"R","label":"Reuse licence","action":"Attach a standard, machine-readable open licence to the deposit — CC0 or CC BY, which is what Horizon Europe and most funders expect — and print the licence identifier in the paper. 'Free to use' is not a licence: it grants nothing a reuser's institution can rely on.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No license is stated for the data; the CC BY license applies to the article only.","gain":16.67,"priority":"essential","scored":true},{"key":"f_dataset_pid","dimension":"F","label":"Persistent identifier for the data","action":"Mint or cite a persistent identifier for the dataset — a repository DOI or an accession from a registered repository — and print it in the paper. A bare URL is not persistent: it is the single most common cause of a dead data link five years after publication. For genomics / sequencing data, deposit in GEO (GSE accession), SRA (SRP/SRR) or ENA/BioProject (PRJEB/PRJNA).","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"All topographical data and figures regarding topography of mutational signatures in human cancer generated in this study have been deposited at COSMIC, Catalog of Somatic Mutations in Cancer ( https://cancer.sanger.ac.uk/signatures/ ), through COSMIC Signatures v3.3, released on May 27 th , 2022 and are currently publicly available.","why":"The only identifier given is a URL (https://cancer.sanger.ac.uk/signatures/) which is not a persistent identifier scheme (DOI, Handle, ARK, URN, or repository accession pattern).","gain":8.33,"priority":"essential","scored":true},{"key":"i_open_nonproprietary_format","dimension":"I","label":"Open file format","action":"Release the data in an open, community-standard format (CSV/TSV, JSON, HDF5, NetCDF, FASTQ, VCF, NIfTI…) instead of — or alongside — any proprietary or instrument-native format, and name the format in the paper. A dataset that needs a €2,000 licence to open is not reusable. Prefer open genomics / sequencing formats such as FASTQ, BAM or VCF.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No file format is named for the released data.","gain":8.33,"priority":"important","scored":true},{"key":"f_dataset_cited","dimension":"F","label":"Dataset formally cited","action":"Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. Only a reference- list entry is machine-readable to Crossref/DataCite, and only a citation lets the data earn credit. Cite the genomics / sequencing repository accession (e.g. from GEO (GSE accession), SRA (SRP/SRR) or ENA/BioProject (PRJEB/PRJNA)) in the reference list.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"All topographical data and figures regarding topography of mutational signatures in human cancer generated in this study have been deposited at COSMIC, Catalog of Somatic Mutations in Cancer ( https://cancer.sanger.ac.uk/signatures/ ), through COSMIC Signatures v3.3, released on May 27 th , 2022 and are currently publicly available.","why":"The dataset's identifier (URL and version) appears only in the body text, not as a reference-list entry.","gain":4.17,"priority":"important","scored":true},{"key":"f_discovery_metadata","dimension":"F","label":"Description of the dataset as an object","action":"Add a 'Data Records' section: itemise every file in the deposit and every variable or sample it holds, with counts and units. Describe the dataset as an object in its own right, not as a by-product of the findings — this is what makes it discoverable to someone who is not looking for your paper.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"Our evaluation encompassed examining the effects of nucleosome occupancy, histone modifications, CTCF binding sites, replication timing, transcription strand asymmetry, and replication strand asymmetry on the accumulation of somatic mutations from more than 70 distinct mutational signatures.","why":"The dataset content is described in running prose but not itemised in a section, table, or enumerated list. [majority verdict 'partial' (4/5 passes agreed)]","gain":0.0,"priority":"essential","scored":false},{"key":"r_documentation_codebook","dimension":"R","label":"Documentation / codebook","action":"Ship a README and a data dictionary IN the deposit — every file, every variable, its units, its allowed values, its missing-value codes. It is the cheapest single thing that makes a dataset usable by someone who was not in the lab, and a table buried in the article does not travel with the data.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"our analysis leverages 516 unique tissue-matched topographical features from the ENCODE project ( Table S1 )","why":"Supplementary Table S1 lists the topographical features, providing variable-level documentation inside the article. [downgraded to 'no' — no verifiable quote from the paper]","gain":0.0,"priority":"important","scored":false},{"key":"a_controlled_access_for_sensitive","dimension":"A","label":"Gatekeeper for sensitive data","action":"Route sensitive data through an institutional gatekeeper — deposit in a controlled- access repository (dbGaP, EGA) with a Data Access Committee and a published DUA — rather than through the corresponding author's inbox. 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For genomics / sequencing data, deposit in GEO (GSE accession), SRA (SRP/SRR) or ENA/BioProject (PRJEB/PRJNA).","Release the data in an open, community-standard format (CSV/TSV, JSON, HDF5, NetCDF, FASTQ, VCF, NIfTI…) instead of — or alongside — any proprietary or instrument-native format, and name the format in the paper. A dataset that needs a €2,000 licence to open is not reusable. Prefer open genomics / sequencing formats such as FASTQ, BAM or VCF.","Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. Only a reference- list entry is machine-readable to Crossref/DataCite, and only a citation lets the data earn credit. Cite the genomics / sequencing repository accession (e.g. from GEO (GSE accession), SRA (SRP/SRR) or ENA/BioProject (PRJEB/PRJNA)) in the reference list.","Add a 'Data Records' section: itemise every file in the deposit and every variable or sample it holds, with counts and units. Describe the dataset as an object in its own right, not as a by-product of the findings — this is what makes it discoverable to someone who is not looking for your paper."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v8","fulltext_source":"epmc_xml"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v8","fair_fulltext_source":"epmc_xml","fair_has_llm":true,"fair_computed_at":"2026-07-20T11:22:19.284906Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}