{"doi":"10.1167/iovs.65.13.60","title":"Novel Uveal Melanoma Patient-Derived Organoid Models Recapitulate Human Disease to Support Translational Research","abstract":"Purpose: A lack of representative human disease models has limited the translation of new and more effective treatments in uveal melanoma (UM), the most common primary adult intraocular malignancy. To fill this critical need, we developed and characterized a multicenter biobank of UM patient-derived organoids (PDOs). Methods: UM patients requiring enucleation from 2019 to 2024 donated tumor tissue for PDO generation. PDOs were cultured in Cultrex and compared to donor primary tumor using exome sequencing, RNA sequencing, and immunohistochemistry. The ability of PDOs to maintain the transformed phenotype was evaluated in an orthotopic xenograft model and monitored with fundus imaging. ATAC sequencing and drug response assays were done in a subset of PDOs to explore the feasibility of their use for mechanistic and translational studies. Results: PDOs were successfully established in 40 of 44 cases (91%), retained clinically relevant mutations and molecular markers from the primary tumor, and displayed similar gene expression profiles and well-validated clinical prognostic markers of the disease. PDOs retained tumorigenic capacity in an in vivo model resembling human disease progression. Finally, we demonstrated that PDOs were a feasible platform to identify and evaluate novel therapeutic targets and investigate differential, personalized drug response. Conclusions: PDO models offer a new platform with improved representation of human UM to aid in translational research for this dismal condition.","journal":"Investigative Ophthalmology & Visual Science","year":2024,"id":443768,"datarank":0.3512374433654116,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.021653756764978608,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.021653756764978608,"corpus_percentile":49.81047420128414,"corpus_rank":6489,"citation_count":8,"citer_count":5,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.8278,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":58.3333,"fair_percentile":72.8829104249465,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1258946,"name":"Cynthia Andrews‐Pfannkoch","orcid":null,"position":1,"is_corresponding":false},{"id":1258425,"name":"David R. Miley","orcid":"0000-0002-7668-7465","position":2,"is_corresponding":false},{"id":323354,"name":"Tara L. Hogenson","orcid":"0000-0002-6246-6987","position":3,"is_corresponding":false},{"id":1258947,"name":"Samantha A. Erickson","orcid":null,"position":4,"is_corresponding":false},{"id":1258426,"name":"Shivani Malpotra","orcid":"0000-0003-3524-4219","position":5,"is_corresponding":false},{"id":1258427,"name":"Kjersten J. Anderson","orcid":"0009-0001-0743-7729","position":6,"is_corresponding":false},{"id":1258948,"name":"Mohammed E. Omer","orcid":null,"position":7,"is_corresponding":false},{"id":454535,"name":"Luciana L. Almada","orcid":"0000-0002-5651-1585","position":8,"is_corresponding":false},{"id":280869,"name":"Cheng Zhang","orcid":"0000-0003-3843-1562","position":9,"is_corresponding":false},{"id":1258428,"name":"Hu Li","orcid":"0000-0001-8590-1753","position":10,"is_corresponding":false},{"id":1132701,"name":"Diva R. Salomão","orcid":"0000-0001-5066-9667","position":11,"is_corresponding":false},{"id":413363,"name":"Carol L. Shields","orcid":"0000-0002-3288-3632","position":12,"is_corresponding":false},{"id":1051423,"name":"Sara E. Lally","orcid":null,"position":13,"is_corresponding":false},{"id":1258949,"name":"Rachel M. Malsch","orcid":null,"position":14,"is_corresponding":false},{"id":1258429,"name":"James A. Armitage","orcid":"0000-0002-3762-0911","position":15,"is_corresponding":false},{"id":701290,"name":"Heather L. Holmes","orcid":null,"position":16,"is_corresponding":false},{"id":470102,"name":"Michael F. Romero","orcid":"0000-0002-1555-7835","position":17,"is_corresponding":false},{"id":528702,"name":"Michael P. Fautsch","orcid":"0000-0002-9115-2485","position":18,"is_corresponding":false},{"id":514671,"name":"Svetomir N. Markovic","orcid":"0000-0002-9238-4325","position":19,"is_corresponding":false},{"id":323368,"name":"Martín E. Fernández-Zapico","orcid":"0000-0002-8089-3907","position":20,"is_corresponding":false},{"id":889036,"name":"Lauren A. Dalvin","orcid":"0000-0001-9710-4284","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T02:01:29.001453Z","pmid":"39601636","pmcid":"PMC11605663","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":62.5,"fair_i":0.0,"fair_r":25.0,"fair_zscore":0.9454,"fair_rationale":{"fair_score":58.33,"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":"Data described in this report have been deposited in a Sequence Read Archive (BioProject accession no. 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[majority verdict 'no' (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":0.0,"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 that data were deposited in SRA without specifying formats.","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":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No data or metadata community standard (e.g., MIAME, ontology) is named in the text.","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 for an external resource (e.g., another dataset, reference genome) is provided; the paper mentions TCGA but without an identifier.","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":"No license is explicitly stated for the data; the CC BY-NC-ND license applies to the article, not the data.","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":"Cells were dissociated using a gentleMACS Octo Dissociator (130-096-427; Miltenyi Biotec).","grounded":true,"rationale":"A specific instrument (gentleMACS Octo Dissociator) is named for data production. 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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 license is explicitly stated for the data; the CC BY-NC-ND license applies to the article, not the data.","gain":16.67,"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.","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 that data were deposited in SRA without specifying formats.","gain":8.33,"priority":"important","scored":true},{"key":"x_code_availability","dimension":"R","label":"Analysis code available","action":"Publish the analysis code in a public forge, archive a tagged release with a DOI (Zenodo/Software Heritage), and cite that DOI in the paper. NIH DMS Element 2 asks for the tools and code, not only the data — and 'available on request' is not a locator. Archive the analysis code in a versioned repository (GitHub + a Zenodo release DOI).","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No code availability statement is provided; the paper does not mention any code release.","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 clinical / human-subjects repository accession (e.g. from dbGaP or the European Genome-phenome Archive (EGA)) in the reference list.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"Data described in this report have been deposited in a Sequence Read Archive (BioProject accession no. 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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":"Data described in this report have been deposited in a Sequence Read Archive (BioProject accession no. PRJNA1068520).","why":"The paper does not explicitly label the access level, but the deposit in a public repository (SRA) implies open access, which is an action from which the level can be inferred.","gain":0.0,"priority":"important","scored":false},{"key":"i_community_standard_vocabulary","dimension":"I","label":"Community standard / vocabulary","action":"Adopt and NAME your domain's data standard — the minimum-information checklist, metadata schema, or ontology your community uses (MIAME/MINSEQE, ISA-Tab, BIDS, an OBO ontology, HL7 FHIR/OMOP) — and say which one you followed. A reporting checklist standardises your paper; it does nothing for your data. In clinical / human-subjects, describe the data with OMOP CDM, CDISC SDTM or HL7 FHIR.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No data or metadata community standard (e.g., MIAME, ontology) is named in the text.","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. 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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 for an external resource (e.g., another dataset, reference genome) is provided; the paper mentions TCGA but without an identifier.","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 states when the data are available or how long they will persist. [majority verdict 'no' (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.","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.","Publish the analysis code in a public forge, archive a tagged release with a DOI (Zenodo/Software Heritage), and cite that DOI in the paper. NIH DMS Element 2 asks for the tools and code, not only the data — and 'available on request' is not a locator. Archive the analysis code in a versioned repository (GitHub + a Zenodo release DOI).","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 clinical / human-subjects repository accession (e.g. from dbGaP or the European Genome-phenome Archive (EGA)) in the reference list.","Version the deposit and cite the exact version analysed (a version-specific DOI, or an accession with its version suffix). 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