{"doi":"10.1093/brain/awab327","title":"Assessing the landscape of <i>STXBP1</i>-related disorders in 534 individuals","abstract":"Disease-causing variants in STXBP1 are among the most common genetic causes of neurodevelopmental disorders. However, the phenotypic spectrum in STXBP1-related disorders is wide and clear correlations between variant type and clinical features have not been observed so far. Here, we harmonized clinical data across 534 individuals with STXBP1-related disorders and analysed 19 973 derived phenotypic terms, including phenotypes of 253 individuals previously unreported in the scientific literature. The overall phenotypic landscape in STXBP1-related disorders is characterized by neurodevelopmental abnormalities in 95% and seizures in 89% of individuals, including focal-onset seizures as the most common seizure type (47%). More than 88% of individuals with STXBP1-related disorders have seizure onset in the first year of life, including neonatal seizure onset in 47%. Individuals with protein-truncating variants and deletions in STXBP1 (n = 261) were almost twice as likely to present with West syndrome and were more phenotypically similar than expected by chance. Five genetic hotspots with recurrent variants were identified in more than 10 individuals, including p.Arg406Cys/His (n = 40), p.Arg292Cys/His/Leu/Pro (n = 30), p.Arg551Cys/Gly/His/Leu (n = 24), p.Pro139Leu (n = 12), and p.Arg190Trp (n = 11). None of the recurrent variants were significantly associated with distinct electroclinical syndromes, single phenotypic features, or showed overall clinical similarity, indicating that the baseline variability in STXBP1-related disorders is too high for discrete phenotypic subgroups to emerge. We then reconstructed the seizure history in 62 individuals with STXBP1-related disorders in detail, retrospectively assigning seizure type and seizure frequency monthly across 4433 time intervals, and retrieved 251 anti-seizure medication prescriptions from the electronic medical records. We demonstrate a dynamic pattern of seizure control and complex interplay with response to specific medications particularly in the first year of life when seizures in STXBP1-related disorders are the most prominent. Adrenocorticotropic hormone and phenobarbital were more likely to initially reduce seizure frequency in infantile spasms and focal seizures compared to other treatment options, while the ketogenic diet was most effective in maintaining seizure freedom. In summary, we demonstrate how the multidimensional spectrum of phenotypic features in STXBP1-related disorders can be assessed using a computational phenotype framework to facilitate the development of future precision-medicine approaches.","journal":"Brain","year":2021,"id":148534,"datarank":2.278626583942691,"base_score":4.836281906951478,"endowment":4.836281906951478,"self_citation_contribution":0.7254422860427218,"citation_network_contribution":1.5531842978999693,"self_endowment_contribution":0.7254422860427218,"citer_contribution":1.5531842978999693,"corpus_percentile":90.61653902684304,"corpus_rank":1214,"citation_count":125,"citer_count":59,"citers_with_citation_signal":46,"citers_with_endowment":46,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.8089,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":20.8333,"fair_percentile":36.38031183124427,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":632138,"name":"Shridhar Parthasarathy","orcid":"0000-0001-7415-801X","position":1,"is_corresponding":false},{"id":632139,"name":"Sarah M. Ruggiero","orcid":"0000-0002-0834-0750","position":2,"is_corresponding":false},{"id":106358,"name":"Ganna Balagura","orcid":"0000-0003-0212-8318","position":3,"is_corresponding":false},{"id":633446,"name":"Eryn Fitch","orcid":null,"position":4,"is_corresponding":false},{"id":282695,"name":"Katherine L. Helbig","orcid":"0000-0001-8249-0549","position":5,"is_corresponding":false},{"id":632140,"name":"Jing Gan","orcid":"0000-0001-5255-6324","position":6,"is_corresponding":false},{"id":106363,"name":"Shiva Ganesan","orcid":"0000-0002-2518-6505","position":7,"is_corresponding":false},{"id":632141,"name":"Michael C. Kaufman","orcid":"0000-0003-2718-296X","position":8,"is_corresponding":false},{"id":367694,"name":"Colin A. Ellis","orcid":"0000-0003-2152-8106","position":9,"is_corresponding":false},{"id":106356,"name":"David Lewis‐Smith","orcid":"0000-0002-1735-8178","position":10,"is_corresponding":false},{"id":106362,"name":"Peter D. Galer","orcid":"0000-0002-6408-0906","position":11,"is_corresponding":false},{"id":633447,"name":"Kristin Cunningham","orcid":null,"position":12,"is_corresponding":false},{"id":467263,"name":"Margaret O’Brien","orcid":"0000-0002-9306-6871","position":13,"is_corresponding":false},{"id":632142,"name":"Mahgenn Cosico","orcid":"0000-0001-5640-7473","position":14,"is_corresponding":false},{"id":632143,"name":"Kate Baker","orcid":"0000-0003-2986-0584","position":15,"is_corresponding":false},{"id":632144,"name":"Alejandra Darling","orcid":"0000-0003-0344-5809","position":16,"is_corresponding":false},{"id":632145,"name":"Fernanda Veiga de Góes","orcid":"0000-0001-9670-0631","position":17,"is_corresponding":false},{"id":632146,"name":"Christelle Moufawad El Achkar","orcid":"0000-0003-0497-8172","position":18,"is_corresponding":false},{"id":633448,"name":"Jan H Doering","orcid":null,"position":19,"is_corresponding":false},{"id":632147,"name":"Francesca Furia","orcid":"0000-0002-4893-9768","position":20,"is_corresponding":false},{"id":405503,"name":"Ángeles García‐Cazorla","orcid":null,"position":21,"is_corresponding":false},{"id":296373,"name":"Elena Gardella","orcid":"0000-0002-7138-6022","position":22,"is_corresponding":false},{"id":633449,"name":"Lisa Geertjens","orcid":null,"position":23,"is_corresponding":false},{"id":632148,"name":"Courtney Klein","orcid":"0000-0002-2762-4046","position":24,"is_corresponding":false},{"id":632149,"name":"Anna Kolesnik","orcid":"0000-0002-1395-0377","position":25,"is_corresponding":false},{"id":632150,"name":"Hanna C. A. Lammertse","orcid":"0000-0002-5452-5000","position":26,"is_corresponding":false},{"id":632151,"name":"Jeehun Lee","orcid":"0000-0002-8499-3307","position":27,"is_corresponding":false},{"id":633450,"name":"Alexandra T. Mackie","orcid":null,"position":28,"is_corresponding":false},{"id":632152,"name":"Mala Misra‐Isrie","orcid":"0000-0003-2104-2667","position":29,"is_corresponding":false},{"id":295015,"name":"Heather E. Olson","orcid":"0000-0002-5385-0119","position":30,"is_corresponding":false},{"id":311605,"name":"Emma Sexton","orcid":"0000-0003-4776-5230","position":31,"is_corresponding":false},{"id":311607,"name":"Beth Rosen Sheidley","orcid":"0000-0003-2317-177X","position":32,"is_corresponding":false},{"id":311606,"name":"Lacey Smith","orcid":"0000-0002-4456-0072","position":33,"is_corresponding":false},{"id":633451,"name":"Luiza Sotero","orcid":null,"position":34,"is_corresponding":false},{"id":297285,"name":"Hannah Stamberger","orcid":"0000-0001-8308-9511","position":35,"is_corresponding":false},{"id":632153,"name":"Steffen Syrbe","orcid":"0000-0003-2543-4844","position":36,"is_corresponding":false},{"id":632154,"name":"Kim Marie Thalwitzer","orcid":"0000-0002-6647-5864","position":37,"is_corresponding":false},{"id":632155,"name":"Annemiek A. van Berkel","orcid":"0000-0002-1046-8091","position":38,"is_corresponding":false},{"id":332569,"name":"Mieke M. van Haelst","orcid":"0000-0001-7126-2030","position":39,"is_corresponding":false},{"id":337310,"name":"Christopher J. Yuskaitis","orcid":"0000-0002-5643-9798","position":40,"is_corresponding":false},{"id":65647,"name":"Sarah Weckhuysen","orcid":"0000-0003-2878-1147","position":41,"is_corresponding":false},{"id":629645,"name":"Benjamin L. Prosser","orcid":"0000-0003-3696-9131","position":42,"is_corresponding":false},{"id":632156,"name":"Charlene Son Rigby","orcid":"0000-0001-8627-996X","position":43,"is_corresponding":false},{"id":632157,"name":"Scott Demarest","orcid":"0000-0002-4544-3724","position":44,"is_corresponding":false},{"id":275043,"name":"Samuel R. Pierce","orcid":"0000-0003-3215-4162","position":45,"is_corresponding":false},{"id":333965,"name":"Yuehua Zhang","orcid":"0000-0003-1432-5423","position":46,"is_corresponding":false},{"id":296376,"name":"Rikke S. Møller","orcid":"0000-0002-9664-1448","position":47,"is_corresponding":false},{"id":65565,"name":"Hilgo Bruining","orcid":"0000-0003-0660-1969","position":48,"is_corresponding":false},{"id":5709,"name":"Annapurna Poduri","orcid":"0000-0002-7350-5136","position":49,"is_corresponding":false},{"id":473779,"name":"Federico Zara","orcid":"0000-0001-9744-5222","position":50,"is_corresponding":false},{"id":52257,"name":"Pasquale Striano","orcid":null,"position":52,"is_corresponding":false},{"id":44516,"name":"Ingo Helbig","orcid":"0000-0001-8486-0558","position":53,"is_corresponding":false},{"id":106384,"name":"Julie Xian","orcid":"0000-0002-0205-0648","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-18T23:42:46.224799Z","pmid":"35190816","pmcid":"PMC9166568","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":22.2222,"fair_a":25.0,"fair_i":40.0,"fair_r":25.0,"fair_zscore":-0.5389,"fair_rationale":{"fair_score":20.83,"has_llm":true,"taxonomy_version":"fair_taxonomy_v5","dimensions":{"F":{"name":"Findable","score":22.22,"criteria":[{"key":"f_dataset_pid","label":"Persistent identifier for the data","kind":"llm","weight":2.0,"fraction":0.0,"verdict":"no","evidence":"Primary data for this analysis are available in the Supplementary material.","grounded":false,"rationale":"No persistent identifier scheme (DOI, Handle, ARK, repository accession) is given for the dataset; only supplementary material is mentioned.","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":0.0,"verdict":"no","evidence":"Primary data for this analysis are available in the Supplementary material.","grounded":false,"rationale":"No repository is named as the holder; the data are placed in the article's supplementary material, which is not a curated repository.","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":0.5,"verdict":"partial","evidence":"Primary data for this analysis are available in the Supplementary material . Computer code for HPO analysis, phenotypic similarity analysis, reconstruction of seizures and ASM history is available at github.com/helbig-lab/STXBP1.","grounded":true,"rationale":"The data-availability statement points to the article's supplementary material (Colavizza category 2), not to a repository record. [majority verdict 'partial' (3/5 passes agreed)]","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":"In the joint cohort of 534 individuals, we analysed a total of 5564 initially assigned (base) HPO terms, including 592 unique terms.","grounded":true,"rationale":"The paper describes the dataset's content in running prose (size, number of terms) but does not provide an itemised inventory (section, table, or list) of files or variables. [majority verdict 'partial' (3/5 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":0.0,"verdict":"no","evidence":"Primary data for this analysis are available in the Supplementary material.","grounded":false,"rationale":"The dataset identifier appears only in the body text (data-availability statement) and not as a reference-list entry. [downgraded to 'no' — no verifiable quote from the paper]","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":25.0,"criteria":[{"key":"a_data_openly_accessible","label":"Access route free of preconditions","kind":"llm","weight":2.0,"fraction":0.5,"verdict":"partial","evidence":"Primary data for this analysis are available in the Supplementary material.","grounded":false,"rationale":"The text gives a route (supplementary material) with no stated precondition; the data are freely available. [downgraded to 'partial' — no verifiable quote from the paper] [majority verdict 'partial' (3/5 passes agreed)]","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":0.0,"verdict":"no","evidence":"Primary data for this analysis are available in the Supplementary material.","grounded":false,"rationale":"The paper states where the data are available but does not apply an explicit access-level label (e.g., 'open access') to the data itself. [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (4/5 passes agreed)]","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":"Primary data for this analysis are available in the Supplementary material.","grounded":false,"rationale":"The data are openly available in the supplementary material; no gatekeeper is named, and the data are not described as sensitive or subject to controlled access.","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":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No sentence in the paper addresses how long the data will be available or any retention commitment.","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":40.0,"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; the paper only mentions 'Supplementary material' without specifying a format.","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":"Mapping of phenotypic features to Human Phenotype Ontology terms","grounded":true,"rationale":"The paper names and applies the Human Phenotype Ontology (HPO), a community-standard vocabulary, to its data. [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":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No identifier (accession, DOI, RRID, build ID) is given for any external resource that the data depend on or derive from. [majority verdict 'no' (3/5 passes agreed)]","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":25.0,"criteria":[{"key":"r_reuse_license","label":"Reuse licence","kind":"llm","weight":2.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"The paper states a CC BY license for the article but does not explicitly attach any license to the data itself. [majority verdict 'no' (3/5 passes agreed)]","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":0.0,"verdict":"no","evidence":"We then performed automatic reasoning (propagation) to infer higher-level clinical features based on the ontological structure of the HPO tree as previously reported.","grounded":false,"rationale":"The data production methods are described in generic terms without naming specific instruments, kits, or software versions. [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (4/5 passes agreed)]","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":"Primary data for this analysis are available in the Supplementary material.","grounded":false,"rationale":"No documentation object (README, data dictionary, codebook) is said to accompany the data; the paper does not describe a separate file defining variables.","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":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No version token or date is given for the released dataset; the data are referred to as a static snapshot without versioning information.","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":"Computer code for HPO analysis, phenotypic similarity analysis, reconstruction of seizures and ASM history is available at github.com/helbig-lab/STXBP1.","grounded":true,"rationale":"A machine-resolvable locator (GitHub URL) is provided for the study's own code. [majority verdict 'yes' (4/5 passes agreed)]","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":"National Institute for Neurological Disorders and Stroke K02 NS112600","grounded":true,"rationale":"A specific award number (K02 NS112600) is given, attached to a named funder. [majority verdict 'yes' (4/5 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":"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.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"Primary data for this analysis are available in the Supplementary material.","why":"No persistent identifier scheme (DOI, Handle, ARK, repository accession) is given for the dataset; only supplementary material is mentioned.","gain":16.67,"priority":"essential","scored":true},{"key":"f_repository_named","dimension":"F","label":"Named repository","action":"Deposit the data in a repository registered in re3data/FAIRsharing (a domain repository such as GEO, SRA, dbGaP, PRIDE, or a generalist such as Zenodo, Dryad, Dataverse) and name it explicitly in the paper. A lab website is not an archive: it has no retention commitment and no accession.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"Primary data for this analysis are available in the Supplementary material.","why":"No repository is named as the holder; the data are placed in the article's supplementary material, which is not a curated repository.","gain":16.67,"priority":"essential","scored":true},{"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":"The paper states a CC BY license for the article but does not explicitly attach any license to the data itself. [majority verdict 'no' (3/5 passes agreed)]","gain":16.67,"priority":"essential","scored":true},{"key":"a_data_openly_accessible","dimension":"A","label":"Access route free of preconditions","action":"Remove the precondition or justify it. Release the data at publication with no embargo, no registration wall, and no approval step — NIH's zero-embargo public- access rule (NOT-OD-25-101) has already made 'available at publication' the federal baseline for the article; the data should not lag behind it.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"Primary data for this analysis are available in the Supplementary material.","why":"The text gives a route (supplementary material) with no stated precondition; the data are freely available. [downgraded to 'partial' — no verifiable quote from the paper] [majority verdict 'partial' (3/5 passes agreed)]","gain":8.33,"priority":"essential","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.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"Primary data for this analysis are available in the Supplementary material.","why":"The dataset identifier appears only in the body text (data-availability statement) and not as a reference-list entry. [downgraded to 'no' — no verifiable quote from the paper]","gain":8.33,"priority":"important","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.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No file format is named for the released data; the paper only mentions 'Supplementary material' without specifying a format.","gain":8.33,"priority":"important","scored":true},{"key":"r_versioning","dimension":"R","label":"Snapshot identified","action":"Version the deposit and cite the exact version analysed (a version-specific DOI, or an accession with its version suffix). A reader reproducing your work against 'the current release' is reproducing it against a different dataset.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No version token or date is given for the released dataset; the data are referred to as a static snapshot without versioning information.","gain":4.17,"priority":"useful","scored":true},{"key":"f_data_availability_statement","dimension":"F","label":"Data-availability statement","action":"Replace the statement with the repository template: name the repository and give the accession or DOI (Colavizza category 3). This is the only DAS class associated with a measured citation advantage; 'available on reasonable request' and 'within the article' are not.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"Primary data for this analysis are available in the Supplementary material . Computer code for HPO analysis, phenotypic similarity analysis, reconstruction of seizures and ASM history is available at github.com/helbig-lab/STXBP1.","why":"The data-availability statement points to the article's supplementary material (Colavizza category 2), not to a repository record. [majority verdict 'partial' (3/5 passes agreed)]","gain":0.0,"priority":"essential","scored":false},{"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":"In the joint cohort of 534 individuals, we analysed a total of 5564 initially assigned (base) HPO terms, including 592 unique terms.","why":"The paper describes the dataset's content in running prose (size, number of terms) but does not provide an itemised inventory (section, table, or list) of files or variables. [majority verdict 'partial' (3/5 passes agreed)]","gain":0.0,"priority":"essential","scored":false},{"key":"a_access_conditions_stated","dimension":"A","label":"Access level labelled","action":"State the access level in words, using the standard vocabulary: 'These data are open access' / 'These data are controlled access'. A reader — and a harvester — should not have to infer the access level from the presence of a download link.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"Primary data for this analysis are available in the Supplementary material.","why":"The paper states where the data are available but does not apply an explicit access-level label (e.g., 'open access') to the data itself. [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (4/5 passes agreed)]","gain":0.0,"priority":"important","scored":false},{"key":"r_provenance_methods","dimension":"R","label":"Provenance of the data","action":"Name the instruments, kits, and software — with versions — that produced the data, not just the verbs. 'Reads were aligned' is not provenance; 'aligned with STAR v2.7.9a to GRCh38' is, because someone else can rerun it.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"We then performed automatic reasoning (propagation) to infer higher-level clinical features based on the ontological structure of the HPO tree as previously reported.","why":"The data production methods are described in generic terms without naming specific instruments, kits, or software versions. [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (4/5 passes agreed)]","gain":0.0,"priority":"important","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":"Primary data for this analysis are available in the Supplementary material.","why":"No documentation object (README, data dictionary, codebook) is said to accompany the data; the paper does not describe a separate file defining variables.","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. An author-gated dataset dies with the author's email address, and 'on reasonable request' has been shown repeatedly not to yield data.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"Primary data for this analysis are available in the Supplementary material.","why":"The data are openly available in the supplementary material; no gatekeeper is named, and the data are not described as sensitive or subject to controlled access.","gain":0.0,"priority":"useful","scored":false},{"key":"i_qualified_references","dimension":"I","label":"Identifiers for the resources the data depend on","action":"Cite by identifier every resource the data depend on — the source datasets' accessions, the reference build (GRCh38 / GCA_000001405.28), the cohort application number, the code DOI — and register those relations on the dataset record (IsDerivedFrom, IsSupplementTo). A name is not a link: it cannot be resolved, versioned, or followed by a machine.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No identifier (accession, DOI, RRID, build ID) is given for any external resource that the data depend on or derive from. [majority verdict 'no' (3/5 passes agreed)]","gain":0.0,"priority":"useful","scored":false},{"key":"a_timeline_retention","dimension":"A","label":"Availability timing & retention","action":"State when the data become available AND how long they will be retained — cite the repository's preservation policy. NIH DMS Element 4 asks for both; most papers give neither.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No sentence in the paper addresses how long the data will be available or any retention commitment.","gain":0.0,"priority":"useful","scored":false}],"suggestions":["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.","Deposit the data in a repository registered in re3data/FAIRsharing (a domain repository such as GEO, SRA, dbGaP, PRIDE, or a generalist such as Zenodo, Dryad, Dataverse) and name it explicitly in the paper. A lab website is not an archive: it has no retention commitment and no accession.","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.","Remove the precondition or justify it. Release the data at publication with no embargo, no registration wall, and no approval step — NIH's zero-embargo public- access rule (NOT-OD-25-101) has already made 'available at publication' the federal baseline for the article; the data should not lag behind it.","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."],"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":"2026-07-20T11:01:07.152124Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}