{"doi":"10.1371/journal.pcbi.1009484","title":"Experiment level curation of transcriptional regulatory interactions in neurodevelopment","abstract":"To facilitate the development of large-scale transcriptional regulatory networks (TRNs) that may enable in-silico analyses of disease mechanisms, a reliable catalogue of experimentally verified direct transcriptional regulatory interactions (DTRIs) is needed for training and validation. There has been a long history of using low-throughput experiments to validate single DTRIs. Therefore, we reason that a reliable set of DTRIs could be produced by curating the published literature for such evidence. In our survey of previous curation efforts, we identified the lack of details about the quantity and the types of experimental evidence to be a major gap, despite the theoretical importance of such details for the identification of bona fide DTRIs. We developed a curation protocol to inspect the published literature for support of DTRIs at the experiment level, focusing on genes important to the development of the mammalian nervous system. We sought to record three types of low-throughput experiments: Transcription factor (TF) perturbation, TF-DNA binding, and TF-reporter assays. Using this protocol, we examined a total of 1,310 papers to assemble a collection of 1,499 unique DTRIs, involving 251 TFs and 825 target genes, many of which were not reported in any other DTRI resource. The majority of DTRIs (965; 64%) were supported by two or more types of experimental evidence and 27% were supported by all three. Of the DTRIs with all three types of evidence, 170 had been tested using primary tissues or cells and 44 had been tested directly in the central nervous system. We used our resource to document research biases among reports towards a small number of well-studied TFs. To demonstrate a use case for this resource, we compared our curation to a previously published high-throughput perturbation screen and found significant enrichment of the curated targets among genes differentially expressed in the developing brain in response to Pax6 deletion. This study demonstrates a proof-of-concept for the assembly of a high resolution DTRI resource to support the development of large-scale TRNs.","journal":"PLoS Computational Biology","year":2021,"id":195799,"datarank":0.431441413661794,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.10185772706136101,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.10185772706136101,"corpus_percentile":56.803589386555274,"corpus_rank":5585,"citation_count":8,"citer_count":3,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.6261,"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":70.8333,"fair_percentile":91.99021705900336,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":745014,"name":"Alexander M. Morin","orcid":"0000-0002-6525-5800","position":1,"is_corresponding":false},{"id":767284,"name":"Tak Hou Calvin Chang","orcid":"0000-0003-0270-3490","position":2,"is_corresponding":false},{"id":767285,"name":"Tue Nguyen","orcid":"0000-0002-9685-7820","position":3,"is_corresponding":false},{"id":767286,"name":"Yi-Cheng Tsai","orcid":"0000-0003-0810-953X","position":4,"is_corresponding":false},{"id":767287,"name":"Aman Sharma","orcid":"0000-0002-8043-3804","position":5,"is_corresponding":false},{"id":767288,"name":"Chao Chun Liu","orcid":"0000-0002-8645-2598","position":6,"is_corresponding":false},{"id":660590,"name":"Paul Pavlidis","orcid":"0000-0002-0426-5028","position":7,"is_corresponding":false},{"id":767283,"name":"Eric Ching-Pan Chu","orcid":"0000-0002-8339-9277","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-18T23:50:07.691929Z","pmid":"34665801","pmcid":"PMC8565786","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":83.3333,"fair_a":68.75,"fair_i":60.0,"fair_r":41.6667,"fair_zscore":1.4401,"fair_rationale":{"fair_score":70.83,"has_llm":true,"taxonomy_version":"fair_taxonomy_v5","dimensions":{"F":{"name":"Findable","score":83.33,"criteria":[{"key":"f_dataset_pid","label":"Persistent identifier for the data","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"https://doi.org/10.5683/SP2/XLLWRL","grounded":true,"rationale":"The paper provides a DOI for its own dataset, which is a persistent identifier, in the Data Availability Statement.","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":"Scholars Portal Dataverse","grounded":true,"rationale":"The paper names Scholars Portal Dataverse as the repository holding the data; this is a repository listed 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 relevant data are within the manuscript and its Supporting Information files. The code for all data analyses and figures generation are available on GitHub ( https://github.com/PavlidisLab/dtri-curation ). An additional copy of the data has been deposited in Scholars Portal Dataverse ( https://doi.org/10.5683/SP2/XLLWRL )","grounded":true,"rationale":"The data-availability statement points to a repository record (Scholars Portal Dataverse with a DOI), which is Colavizza category 3.","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":"we established a collection of 1,499 unique DTRIs, involving 251 TFs and 825 targets","grounded":true,"rationale":"The dataset's content is described in running prose only, without an itemised inventory (section, table, or enumerated list) of files, variables, or samples. [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":"An additional copy of the data has been deposited in Scholars Portal Dataverse ( https://doi.org/10.5683/SP2/XLLWRL )","grounded":true,"rationale":"The dataset identifier (DOI) appears only in the body text (Data Availability Statement) and 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":68.75,"criteria":[{"key":"a_data_openly_accessible","label":"Access route free of preconditions","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"All relevant data are within the manuscript and its Supporting Information files. 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[majority verdict 'partial' (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":null,"grounded":false,"rationale":"The data are not sensitive or human-subject; no gatekeeper is mentioned and the criterion is not applicable.","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":"All relevant data are within the manuscript and its Supporting Information files","grounded":true,"rationale":"The paper states that the data are available now (within the manuscript and supporting information), but does not specify how long they will persist; no retention period or permanent archival claim is made. [majority verdict 'partial' (3/5 passes agreed)]","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":0.5,"verdict":"partial","evidence":"TSV","grounded":false,"rationale":"The data are provided in TSV (tab-separated values) format, which is an open, community-standard format. [downgraded to 'partial' — no verifiable quote from the paper]","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":"PSI-MI vocabulary","grounded":true,"rationale":"The paper uses the PSI-MI vocabulary (a community standard for molecular interactions) to annotate the curated records, and also uses standard ontologies such as UBERON. [majority verdict 'yes' (3/5 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 external resource identifier (accession, DOI, RRID, etc.) for data or code other than the paper's own dataset appears in the text; only bare names or citations are given. [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":41.67,"criteria":[{"key":"r_reuse_license","label":"Reuse licence","kind":"llm","weight":2.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No licence is named for the data itself; the CC BY licence applies only to the article, not to the dataset.","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":0.5,"verdict":"partial","evidence":"We developed a curation protocol to inspect the published literature for support of DTRIs at the experiment level","grounded":true,"rationale":"The data production (curation) is described in generic terms without naming specific instruments, kits, or software versions used for data generation. 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[majority verdict 'no' (4/5 passes agreed)]","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/PavlidisLab/dtri-curation","grounded":true,"rationale":"The paper provides a machine-resolvable locator (GitHub URL) for the study's own code.","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":"MH111099","grounded":true,"rationale":"The paper provides specific award/grant numbers for the funding sources. 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'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 licence is named for the data itself; the CC BY licence applies only to the article, not to the dataset.","gain":16.67,"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. Cite the social science repository accession (e.g. from ICPSR or the Harvard Dataverse) in the reference list.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"An additional copy of the data has been deposited in Scholars Portal Dataverse ( https://doi.org/10.5683/SP2/XLLWRL )","why":"The dataset identifier (DOI) appears only in the body text (Data Availability Statement) and not as a reference-list entry.","gain":4.17,"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. Prefer open social science formats such as CSV or SPSS/Stata with a codebook.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"TSV","why":"The data are provided in TSV (tab-separated values) format, which is an open, community-standard format. [downgraded to 'partial' — no verifiable quote from the paper]","gain":4.17,"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 provided for the released dataset; the paper does not identify which snapshot of the data is used or released. [majority verdict 'no' (4/5 passes agreed)]","gain":4.17,"priority":"useful","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":"we established a collection of 1,499 unique DTRIs, involving 251 TFs and 825 targets","why":"The dataset's content is described in running prose only, without an itemised inventory (section, table, or enumerated list) of files, variables, or samples. [majority verdict 'partial' (4/5 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":"partial","current":0.5,"evidence":"An additional copy of the data has been deposited in Scholars Portal Dataverse ( https://doi.org/10.5683/SP2/XLLWRL )","why":"The paper states that the data are deposited in a public repository and available within the manuscript, but does not explicitly label the access level using a standard vocabulary term. [majority verdict 'partial' (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":"partial","current":0.5,"evidence":"We developed a curation protocol to inspect the published literature for support of DTRIs at the experiment level","why":"The data production (curation) is described in generic terms without naming specific instruments, kits, or software versions used for data generation. [majority verdict 'partial' (2/5 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":"partial","current":0.5,"evidence":"Box 1. Experimental details recorded during curation","why":"The definitions of the recorded attributes (fields and variables) are provided inside the article in Box 1, not as a separate documentation object shipped with the data. [majority verdict 'partial' (4/5 passes agreed)]","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":null,"why":"The data are not sensitive or human-subject; no gatekeeper is mentioned and the criterion is not applicable.","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 external resource identifier (accession, DOI, RRID, etc.) for data or code other than the paper's own dataset appears in the text; only bare names or citations are given. [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":"partial","current":0.5,"evidence":"All relevant data are within the manuscript and its Supporting Information files","why":"The paper states that the data are available now (within the manuscript and supporting information), but does not specify how long they will persist; no retention period or permanent archival claim is made. [majority verdict 'partial' (3/5 passes agreed)]","gain":0.0,"priority":"useful","scored":false}],"suggestions":["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.","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 social science repository accession (e.g. from ICPSR or the Harvard Dataverse) in the reference list.","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 social science formats such as CSV or SPSS/Stata with a codebook.","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.","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":"2026-07-20T12:37:19.590785Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}