{"doi":"10.1038/s41591-024-03215-z","title":"A multi-modal single-cell and spatial expression map of metastatic breast cancer biopsies across clinicopathological features","abstract":"Although metastatic disease is the leading cause of cancer-related deaths, its tumor microenvironment remains poorly characterized due to technical and biospecimen limitations. In this study, we assembled a multi-modal spatial and cellular map of 67 tumor biopsies from 60 patients with metastatic breast cancer across diverse clinicopathological features and nine anatomic sites with detailed clinical annotations. We combined single-cell or single-nucleus RNA sequencing for all biopsies with a panel of four spatial expression assays (Slide-seq, MERFISH, ExSeq and CODEX) and H&E staining of consecutive serial sections from up to 15 of these biopsies. We leveraged the coupled measurements to provide reference points for the utility and integration of different experimental techniques and used them to assess variability in cell type composition and expression as well as emerging spatial expression characteristics across clinicopathological and methodological diversity. Finally, we assessed spatial expression and co-localization features of macrophage populations, characterized three distinct spatial phenotypes of epithelial-to-mesenchymal transition and identified expression programs associated with local T cell infiltration versus exclusion, showcasing the potential of clinically relevant discovery in such maps.","journal":"Nature Medicine","year":2024,"id":6228,"datarank":1.3416350597857074,"base_score":4.5217885770490405,"endowment":4.5217885770490405,"self_citation_contribution":0.6782682865573562,"citation_network_contribution":0.6633667732283512,"self_endowment_contribution":0.6782682865573562,"citer_contribution":0.6633667732283512,"corpus_percentile":84.65227817745803,"corpus_rank":1985,"citation_count":91,"citer_count":85,"citers_with_citation_signal":36,"citers_with_endowment":36,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.7864,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-10-30","fair_score":66.6667,"fair_percentile":86.48731274839498,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":20801,"name":"Daniel L. 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Pfaff","orcid":"0000-0003-3311-5384","position":35,"is_corresponding":false},{"id":3727,"name":"Asaf Rotem","orcid":"0000-0002-6859-7435","position":37,"is_corresponding":false},{"id":56755,"name":"Sarah Strauss","orcid":null,"position":38,"is_corresponding":false},{"id":35221,"name":"Robert Strasser","orcid":null,"position":39,"is_corresponding":false},{"id":55261,"name":"Aaron R. 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Winer","orcid":"0000-0002-8819-1723","position":49,"is_corresponding":false},{"id":11617,"name":"Edward S. Boyden","orcid":"0000-0002-0419-3351","position":50,"is_corresponding":false},{"id":24055,"name":"Fei Chen","orcid":"0000-0003-2308-3649","position":51,"is_corresponding":false},{"id":35731,"name":"Garry P. Nolan","orcid":"0000-0002-8862-9043","position":52,"is_corresponding":false},{"id":3736,"name":"Scott J. Rodig","orcid":"0000-0003-1761-9769","position":53,"is_corresponding":false},{"id":3627,"name":"Xiaowei Zhuang","orcid":"0000-0002-6034-7853","position":54,"is_corresponding":false},{"id":2697,"name":"Orit Rozenblatt–Rosen","orcid":"0000-0001-6313-3570","position":55,"is_corresponding":false},{"id":5601,"name":"Bruce E. 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Porter","orcid":"0000-0001-8294-5232","position":61,"is_corresponding":false},{"id":56760,"name":"Sarah Strauß","orcid":"0000-0003-4451-2385","position":62,"is_corresponding":false},{"id":35225,"name":"Ralf Strasser","orcid":null,"position":63,"is_corresponding":false},{"id":3735,"name":"Orit Rozenblatt‐Rosen","orcid":null,"position":64,"is_corresponding":false},{"id":472,"name":"Johanna Klughammer","orcid":"0000-0002-3628-9278","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":"39478111","pmcid":"PMC11564109","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":"hybrid","license":"cc-by","views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":83.3333,"fair_a":62.5,"fair_i":60.0,"fair_r":50.0,"fair_zscore":1.2752,"fair_rationale":{"fair_score":66.67,"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":"phs002371","grounded":true,"rationale":"The paper provides a dbGaP accession number (phs002371), which is a persistent identifier scheme for the dataset.","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":"dbGaP","grounded":true,"rationale":"The paper names dbGaP (database of Genotypes and Phenotypes) as a repository holding the data.","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 data can be retrieved from Synapse or the database of Genotypes and Phenotypes (dbGaP) (accession number: phs002371 ) through the HTAN Portal at https://humantumoratlas.org and the associated HTAN Publication Page https://humantumoratlas.org/publications/htapp_mbc_klughammer_2024 . 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[majority verdict 'no' (3/5 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":"Supplementary Tables 1 and 2","why":"Variable and file definitions are provided in supplementary tables inside the article, but no documentation object is named as travelling with the deposited data. [majority verdict 'partial' (3/5 passes agreed)]","gain":0.0,"priority":"important","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 mention any retention period, permanent archival, or timing for data availability.","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. Prefer open genomics / sequencing formats such as FASTQ, BAM or VCF.","Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. Only a reference- list entry is machine-readable to Crossref/DataCite, and only a citation lets the data earn credit. Cite the genomics / sequencing repository accession (e.g. from GEO (GSE accession), SRA (SRP/SRR) or ENA/BioProject (PRJEB/PRJNA)) in the reference list.","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":"2026-07-20T11:06:18.640478Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}