{"doi":"10.1126/sciadv.abo6764","title":"Unified epigenomic, transcriptomic, proteomic, and metabolomic taxonomy of Alzheimer’s disease progression and heterogeneity","abstract":"Alzheimer’s disease (AD) is a heterogeneous disorder with abnormalities in multiple biological domains. In an advanced machine learning analysis of postmortem brain and in vivo blood multi-omics molecular data ( N = 1863), we integrated epigenomic, transcriptomic, proteomic, and metabolomic profiles into a multilevel biological AD taxonomy. We obtained a personalized multilevel molecular index of AD dementia progression that predicts severity of neuropathologies, and identified three robust molecular-based subtypes that explain much of the pathologic and clinical heterogeneity of AD. These subtypes present distinct patterns of alteration in DNA methylation, RNA, proteins, and metabolites, identifiable in the brain and subsequently in blood. In addition, the genetic variations that predispose to the various AD subtypes in brain predict distinct spatial patterns of alteration in cell types, suggesting a unique influence of each putative AD variant on neuropathological mechanisms. These observations support that an individually tailored multi-omics molecular taxonomy of AD may represent distinct targets for preventive or treatment interventions.","journal":"Science Advances","year":2022,"id":234458,"datarank":1.6666609697879957,"base_score":4.59511985013459,"endowment":4.59511985013459,"self_citation_contribution":0.6892679775201885,"citation_network_contribution":0.9773929922678072,"self_endowment_contribution":0.6892679775201885,"citer_contribution":0.9773929922678072,"corpus_percentile":87.47582579098012,"corpus_rank":1620,"citation_count":98,"citer_count":80,"citers_with_citation_signal":53,"citers_with_endowment":53,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.651,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":29.1667,"fair_percentile":43.01436869458881,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":656988,"name":"Quadri Adewale","orcid":"0000-0001-5090-6140","position":1,"is_corresponding":false},{"id":656987,"name":"Ahmed Faraz Khan","orcid":"0009-0006-7233-8416","position":2,"is_corresponding":false},{"id":233774,"name":"Simon Ducharme","orcid":"0000-0002-7309-1113","position":3,"is_corresponding":false},{"id":272076,"name":"Pedro Rosa‐Neto","orcid":"0000-0001-9116-1376","position":4,"is_corresponding":false},{"id":5171,"name":"Kieran J. O’Donnell","orcid":"0000-0002-3935-1014","position":5,"is_corresponding":false},{"id":60409,"name":"Vladislav Petyuk","orcid":"0000-0003-4076-151X","position":6,"is_corresponding":false},{"id":264345,"name":"Serge Gauthier","orcid":"0000-0003-4272-3330","position":7,"is_corresponding":false},{"id":771,"name":"Philip L. De Jager","orcid":"0000-0002-8057-2505","position":8,"is_corresponding":false},{"id":561488,"name":"John C.S. Breitner","orcid":"0000-0003-4229-4687","position":9,"is_corresponding":false},{"id":778,"name":"David A. Bennett","orcid":"0000-0003-3689-554X","position":10,"is_corresponding":false},{"id":226047,"name":"Yasser Iturria‐Medina","orcid":"0000-0002-9345-0347","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T00:21:36.529874Z","pmid":"36399579","pmcid":"PMC9674284","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":50.0,"fair_i":20.0,"fair_r":25.0,"fair_zscore":-0.2091,"fair_rationale":{"fair_score":29.17,"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":null,"grounded":false,"rationale":"The paper does not provide a persistent identifier (DOI, accession, etc.) for its own dataset. [majority verdict 'no' (4/5 passes agreed)]","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":0.5,"verdict":"partial","evidence":"All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.","grounded":true,"rationale":"The data are stated to be within the article and supplementary materials, which is a non-repository host. [majority verdict 'partial' (3/5 passes agreed)]","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":"All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.","grounded":true,"rationale":"The statement points to the article and supplementary materials (Colavizza category 2), not to a repository record.","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":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"The paper contains no itemised inventory (section, table, or list) describing the dataset's files, records, or variables.","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":null,"grounded":false,"rationale":"No identifier for the dataset appears in the reference list or body text.","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":50.0,"criteria":[{"key":"a_data_openly_accessible","label":"Access route free of preconditions","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.","grounded":true,"rationale":"The data-availability statement specifies that the data are contained within the article and supplementary materials, which are publicly accessible without precondition. [majority verdict 'yes' (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":null,"grounded":false,"rationale":"The paper does not label the access level of the data. 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[majority verdict 'no' (3/5 passes agreed)]","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":"The paper does not state how long the data will remain available. [majority verdict 'no' (4/5 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":20.0,"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":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No data or metadata community standard (e.g., MIAME, MINSEQE, an OBO ontology) is named as applied to the data.","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":"downloaded from the AMP-AD knowledge portal (www.synapse.org), using the following Synapse IDs: syn3157275 (for epigenomic data), syn3800853 (transcriptomic), syn10468856 (proteomic), and syn10235595 and syn10235594 (metabolomic).","grounded":true,"rationale":"The paper references Synapse identifiers for the source datasets used in the study, which are external resources. [majority verdict 'yes' (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":"No license is explicitly attached to the data; the CC BY-NC license applies to the article, not to the data as a separate entity. [majority verdict 'no' (4/5 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":1.0,"verdict":"yes","evidence":"For each molecular data type, data exploration and visualization were performed via cPCA (43).","grounded":true,"rationale":"The paper names the specific algorithm (cPCA) used to produce the data. 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[downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (3/5 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":"Funding: This project was undertaken thanks, in part, to the following funding awards to Y.I.-M.: the Canada Research Chair tier-2, the CIHR Project Grant 2020, the Weston Family Foundation’s Transformational Research in AD 2020, and the New Investigator start-up grant from McGill University’s Healthy Brains for Healthy Lives Initiative (Canada First Research Excellence Fund).","grounded":true,"rationale":"Award numbers are stated for the named funders. 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[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. 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Prefer open proteomics formats such as mzML or mzIdentML.","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":"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. 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[majority verdict 'no' (4/5 passes agreed)]","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 proteomics, describe the data with mzML or MIAPE.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No data or metadata community standard (e.g., MIAME, MINSEQE, an OBO ontology) is named as applied to the data.","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":null,"why":"No documentation object (e.g., codebook, README) is named as accompanying the data; variable definitions are not provided in 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. 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 study's own data are aggregated results presented in the paper and supplementary materials, not individual-level sensitive data requiring a gatekeeper. [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":"The paper does not state how long the data will remain available. [majority verdict 'no' (4/5 passes agreed)]","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. For proteomics data, deposit in PRIDE (PXD accession) or ProteomeXchange.","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.","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. For proteomics data, deposit in PRIDE (PXD accession) or ProteomeXchange.","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 proteomics repository accession (e.g. from PRIDE (PXD accession) or ProteomeXchange) 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 proteomics formats such as mzML or mzIdentML."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v8","fulltext_source":"unpaywall_pdf"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v8","fair_fulltext_source":"unpaywall_pdf","fair_has_llm":true,"fair_computed_at":"2026-07-20T11:04:45.121345Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}