In Silico Identification of a BRCA1:miR-29:DNMT3 Axis Involved in the Control of Hormone Receptors in BRCA1-Associated Breast Cancers.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37373065", "kind": "science-record", "revision": 3, "content_hash": "sha256:e34510ce4ff1c96367bc829a12dceaaca9274caa057af392f1191642ec29e91a", "created_at": "2026-11-01T19:02:07Z", "updated_at": "2026-11-01T22:52:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "In Silico Identification of a BRCA1:miR-29:DNMT3 Axis Involved in the Control of Hormone Receptors in BRCA1-Associated Breast Cancers.", "doi": "10.3390/ijms24129916", "pmid": "37373065", "authors": ["Manuela Santarosa", "Davide Baldazzi", "Michela Armellin", "Roberta Maestro"], "journal": "International journal of molecular sciences", "year": 2023, "abstract": "Germline inactivating mutations in the BRCA1 gene lead to an increased lifetime risk of ovarian and breast cancer (BC). Most BRCA1-associated BC are triple-negative tumors (TNBC), aggressive forms of BC characterized by a lack of expression of estrogen and progesterone hormone receptors (HR) and HER2. How BRCA1 inactivation may favor the development of such a specific BC phenotype remains to be elucidated. To address this question, we focused on the role of miRNAs and their networks in mediating BRCA1 functions. miRNA, mRNA, and methylation data were retrieved from the BRCA cohort of the TCGA project. The cohort was divided into a discovery set (Hi-TCGA) and a validation set (GA-TCGA) based on the platform used for miRNA analyses. The METABRIC, GSE81002, and GSE59248 studies were used as additional validation data sets. BCs were differentiated into BRCA1-like and non-BRCA1-like based on an established signature of BRCA1 pathway inactivation. Differential expression of miRNAs, gene enrichment analysis, functional annotation, and methylation correlation analyses were performed. The miRNAs downregulated in BRCA1-associated BC were identified by comparing the miRNome of BRCA1-like with non-BRCA1-like tumors from the Hi-TCGA discovery cohort. miRNAs:gene-target anticorrelation analyses were then performed. The target genes of miRNAs downregulated in the Hi-TCGA series were enriched in the BRCA1-like tumors from the GA-TCGA and METABRIC validation data sets. Functional annotation of these genes revealed an over-representation of several biological processes ascribable to BRCA1 activity. The enrichment of genes related to DNA methylation was particularly intriguing, as this is an aspect of BRCA1 functions that has been poorly explored. We then focused on the miR-29:DNA methyltransferase network and showed that the miR-29 family, which was downregulated in BRCA1-like tumors, was associated with poor prognosis in these BCs and inversely correlated with the expression of the DNA methyltransferases DNMT3A and DNMT3B. This, in turn, correlated with the methylation extent of the promoter of HR genes. These results suggest that BRCA1 may control the expression of HR via a miR-29:DNMT3:HR axis and that disruption of this network may contribute to the receptor negative phenotype of tumors with dysfunctional BRCA1.", "claims": [{"id": "claim-method", "statement": "Spearman rank order correlation coefficients were computed between the normalized miRNA expression levels from the Hi-TCGA data set and the corresponding log2 RSEM-normalized counts of the putative targets. Statistical differences between groups were evaluated using the Welch t-test or a Mann–Whitney rank sum test, depending on the normal distribution of the variables considered. Survival was estimated using the Kaplan–Meier method, and differences between groups were evaluated with the log-rank test using the Survival and Survminer R packages [78,79].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37373065", "locator": "sections[14] \"4.4. Disease-Free Survival and Statistical Analysis\" paragraph 2", "quote": "Spearman rank order correlation coefficients were computed between the normalized miRNA expression levels from the Hi-TCGA data set and the corresponding log2 RSEM-normalized counts of the putative targets."}, {"asset": "source:pmid:37373065", "locator": "sections[14] \"4.4. Disease-Free Survival and Statistical Analysis\" paragraph 2", "quote": "Statistical differences between groups were evaluated using the Welch t-test or a Mann–Whitney rank sum test, depending on the normal distribution of the variables considered."}, {"asset": "source:pmid:37373065", "locator": "sections[14] \"4.4. Disease-Free Survival and Statistical Analysis\" paragraph 2", "quote": "Survival was estimated using the Kaplan–Meier method, and differences between groups were evaluated with the log-rank test using the Survival and Survminer R packages [78,79]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data sets analyzed in the current study are publicly available from TCGA Research Network: TCGA-BRCA project, https://www.cancer.gov/tcga; from the METABRIC project (information at https://ega-archive.org/studies/EGAS00000000098); and from Gene Expression Omnibus database (GEO; https://www.ncbi.nlm.nih.gov/gds) for the GSE81002 and GSE59248 series.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37373065", "locator": "sections[20] \"notes\" paragraph 1", "quote": "The data sets analyzed in the current study are publicly available from TCGA Research Network: TCGA-BRCA project, https://www.cancer.gov/tcga; from the METABRIC project (information at https://ega-archive.org/studies/EGAS00000000098); and from Gene Expression Omnibus database (GEO; https://www.ncbi.nlm.nih.gov/gds) for the GSE81002 and GSE59248 series."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37373065"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE59248"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE59248"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37373065", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/ijms24129916", "sha256": "sha256:4cffc95aa837dacdd81e39ae9deed4b9165ac935f8c8d8bd5e8a779a49b11d3c", "bytes": 31082, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/ijms24129916", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10298721", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE59248", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE59248", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE59248", "version": null, "note": "The data sets analyzed in the current study are publicly available from TCGA Research Network: TCGA-BRCA project, https://www.cancer.gov/tcga; from the METABRIC project (information at https://ega-archive.org/studies/EGAS00000000098); and from Gene Expression Omnibus database (GEO; https://www.ncbi.nlm.nih.gov/gds) for the GSE81002 and GSE59248 series.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data sets analyzed in the current study are publicly available from TCGA Research Network: TCGA-BRCA project, https://www.cancer.gov/tcga; from the METABRIC project (information at https://ega-archive.org/studies/EGAS00000000098); and from Gene Expression Omnibus database (GEO; https://www.ncbi.nlm.nih.gov/gds) for the GSE81002 and GSE59248 series.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1431259", "GSM1431260", "GSM1431261", "GSM1431262", "GSM1431263", "GSM1431264", "GSM1431265", "GSM1431266", "GSM1431267", "GSM1431268", "GSM1431269", "GSM1431270", "GSM1431271", "GSM1431272", "GSM1431273", "GSM1431274", "GSM1431275", "GSM1431276", "GSM1431277", "GSM1431278", "GSM1431279", "GSM1431280", "GSM1431281", "GSM1431282", "GSM1431283", "GSM1431284", "GSM1431285", "GSM1431286", "GSM1431287", "GSM1431288", "GSM1431289", "GSM1431290", "GSM1431291", "GSM1431292", "GSM1431293", "GSM1431294", "GSM1431295", "GSM1431296", "GSM1431297", "GSM1431298", "GSM1431299", "GSM1431300", "GSM1431301", "GSM1431302", "GSM1431303", "GSM1431304", "GSM1431305", "GSM1431306", "GSM1431307", "GSM1431308", "GSM1431309", "GSM1431310", "GSM1431311", "GSM1431312", "GSM1431313", "GSM1431314", "GSM1431315", "GSM1431316", "GSM1431317", "GSM1431318", "GSM1431319", "GSM1431320", "GSM1431321", "GSM1431322", "GSM1431323", "GSM1431324", "GSM1431325", "GSM1431326", "GSM1431327", "GSM1431328", "GSM1431329", "GSM1431330", "GSM1431331", "GSM1431332", "GSM1431333", "GSM1431334", "GSM1431335", "GSM1431336", "GSM1431337", "GSM1431338", "GSM1431339", "GSM1431340", "GSM1431341", "GSM1431342", "GSM1431343", "GSM1431344", "GSM1431345", "GSM1431346", "GSM1431347", "GSM1431348", "GSM1431349", "GSM1431350", "GSM1431351", "GSM1431352", "GSM1431353", "GSM1431354", "GSM1431355", "GSM1431356", "GSM1431357", "GSM1431358", "GSM1431359", "GSM1431360", "GSM1431361", "GSM1431362", "GSM1431363", "GSM1431364", "GSM1431365", "GSM1431366", "GSM1431367", "GSM1431368", "GSM1431369", "GSM1431370", "GSM1431371", "GSM1431372", "GSM1431373", "GSM1431374", "GSM1431375", "GSM1431376", "GSM1431377", "GSM1431378", "GSM1431379", "GSM1431380", "GSM1431381", "GSM1431382", "GSM1431383", "GSM1431384", "GSM1431385", "GSM1431386", "GSM1431387", "GSM1431388", "GSM1431389", "GSM1431390", "GSM1431391", "GSM1431392", "GSM1431393", "GSM1431394", "GSM1431395", "GSM1431396", "GSM1431397", "GSM1431398", "GSM1431399", "GSM1431400", "GSM1431401", "GSM1431402", "GSM1431403", "GSM1431404", "GSM1431405", "GSM1431406", "GSM1431407", "GSM1431408", "GSM1431409", "GSM1431410", "GSM1431411"], "sample_count": 153, "group_sizes": null, "group_sizes_basis": null, "platform": "13607;15019", "taxon": "Homo sapiens", "title": "Molecular features of subtype-specific progression from ductal carcinoma in situ to invasive breast cancer", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE81002", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE81002", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE81002", "version": null, "note": "The data sets analyzed in the current study are publicly available from TCGA Research Network: TCGA-BRCA project, https://www.cancer.gov/tcga; from the METABRIC project (information at https://ega-archive.org/studies/EGAS00000000098); and from Gene Expression Omnibus database (GEO; https://www.ncbi.nlm.nih.gov/gds) for the GSE81002 and GSE59248 series.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data sets analyzed in the current study are publicly available from TCGA Research Network: TCGA-BRCA project, https://www.cancer.gov/tcga; from the METABRIC project (information at https://ega-archive.org/studies/EGAS00000000098); and from Gene Expression Omnibus database (GEO; https://www.ncbi.nlm.nih.gov/gds) for the GSE81002 and GSE59248 series.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1403342", "GSM1403343", "GSM1403344", "GSM1403345", "GSM1403346", "GSM1403347", "GSM1403348", "GSM1403349", "GSM1403350", "GSM1403351", "GSM1403352", "GSM1403353", "GSM1403354", "GSM1403355", "GSM1403356", "GSM1403357", "GSM1403358", "GSM1403359", "GSM1403360", "GSM1403361", "GSM1403362", "GSM1403363", "GSM1403364", "GSM1403365", "GSM1403366", "GSM1403367", "GSM1403368", "GSM1403369", "GSM1403370", "GSM1403371", "GSM1403372", "GSM1403373", "GSM1403374", "GSM1403375", "GSM1403376", "GSM1403377", "GSM1403378", "GSM1403379", "GSM1403380", "GSM1403381", "GSM1403382", "GSM1403383", "GSM1403384", "GSM1403385", "GSM1403386", "GSM1403387", "GSM1403388", "GSM1403389", "GSM1403390", "GSM1403391", "GSM1403392", "GSM1403393", "GSM1403394", "GSM1403395", "GSM1403396", "GSM1403397", "GSM1403398", "GSM1403399", "GSM1403400", "GSM1403401", "GSM1403402", "GSM1403403", "GSM1403404", "GSM1403405", "GSM1403406", "GSM1403407", "GSM1403408", "GSM1403409", "GSM1403410", "GSM1403411", "GSM1403412", "GSM1403413", "GSM1403414", "GSM1403415", "GSM1403416", "GSM1403417", "GSM1403418", "GSM1403419", "GSM1403420", "GSM1403421", "GSM1403422", "GSM1403423", "GSM1403424", "GSM1403425", "GSM1403426", "GSM1403427", "GSM1403428", "GSM1403429", "GSM1403430", "GSM1403431", "GSM1403432", "GSM1403433", "GSM1403434", "GSM1403435", "GSM1403436", "GSM1403437", "GSM1403438", "GSM1403439", "GSM1403440", "GSM1403441", "GSM1403442", "GSM1403443", "GSM1403444", "GSM1403445", "GSM1403446", "GSM1403447", "GSM1403448", "GSM1403449", "GSM1403450", "GSM1403451", "GSM1403452", "GSM1403453", "GSM1403454", "GSM1403455", "GSM1403456", "GSM1403457", "GSM1403458", "GSM1403459", "GSM1403460", "GSM1403461", "GSM1403462", "GSM1403463", "GSM1403464", "GSM1403465", "GSM1403466", "GSM1403467", "GSM1403468", "GSM1403469", "GSM1403470", "GSM1403471", "GSM1403472", "GSM1403473", "GSM1403474", "GSM1403475", "GSM1403476", "GSM1403477", "GSM1403478", "GSM1403479", "GSM1403480", "GSM1403481", "GSM1403482", "GSM1403483", "GSM1403484", "GSM1403485", "GSM1403486", "GSM1403487", "GSM1403488", "GSM1403489", "GSM1403490", "GSM1403491", "GSM1403492", "GSM1403493", "GSM1403494", "GSM1403495", "GSM1403496", "GSM1403497", "GSM1403498", "GSM1403499", "GSM1403500", "GSM1403501", "GSM1403502", "GSM1403503", "GSM1403504", "GSM1403505", "GSM1403506", "GSM1403507", "GSM1403508", "GSM1403509", "GSM1403510", "GSM1403511", "GSM1403512", "GSM1403513", "GSM1403514", "GSM1403515", "GSM1403516", "GSM1403517", "GSM1403518", "GSM1403519", "GSM1403520", "GSM1403521", "GSM1403522", "GSM1403523", "GSM1403524", "GSM1403525", "GSM1403526", "GSM1403527", "GSM1403528", "GSM1403529", "GSM1403530", "GSM1403531", "GSM1403532", "GSM1403533", "GSM1403534", "GSM1403535", "GSM1403536", "GSM1403537", "GSM1403538", "GSM1403539", "GSM1403540", "GSM1403541", "GSM1403542", "GSM1403543", "GSM1403544", "GSM1403545", "GSM1403546", "GSM1403547", "GSM1403548", "GSM1403549", "GSM1403550", "GSM1403551", "GSM1403552", "GSM1403553", "GSM1403554", "GSM1403555", "GSM1403556", "GSM1403557", "GSM1403558", "GSM1403559", "GSM1403560", "GSM1403561", "GSM1403562", "GSM1403563", "GSM1403564", "GSM1403565", "GSM1403566", "GSM1403567", "GSM1403568", "GSM1403569", "GSM1403570", "GSM1403571", "GSM1403572", "GSM1403573", "GSM1403574", "GSM1403575", "GSM1403576", "GSM1403577", "GSM1403578", "GSM1403579", "GSM1403580", "GSM1403581", "GSM1403582", "GSM1403583", "GSM1403584", "GSM1403585", "GSM1403586", "GSM1403587", "GSM1403588", "GSM1403589", "GSM1403590", "GSM1403591", "GSM1403592", "GSM1403593", "GSM1403594", "GSM1403595", "GSM1403596", "GSM1403597", "GSM1403598", "GSM1403599", "GSM1403600", "GSM1403601", "GSM1403602", "GSM1403603", "GSM1403604", "GSM1403605", "GSM1403606", "GSM1403607", "GSM1403608", "GSM1403609", "GSM1403610", "GSM1403611", "GSM1403612", "GSM1403613", "GSM1403614", "GSM1403615", "GSM1403616", "GSM1403617", "GSM1403618", "GSM1403619", "GSM1403620", "GSM1403621", "GSM1403622", "GSM1403623", "GSM1403624", "GSM1403625", "GSM1403626", "GSM1403627", "GSM1403628", "GSM1403629", "GSM1403630", "GSM1403631", "GSM1403632", "GSM1403633", "GSM1403634", "GSM1403635", "GSM1403636", "GSM1403637", "GSM1403638", "GSM1403639", "GSM1403640", "GSM1403641", "GSM1403642", "GSM1403643", "GSM1403644", "GSM1403645", "GSM1403646", "GSM1403647", "GSM1403648", "GSM1403649", "GSM1403650", "GSM1403651", "GSM1403652", "GSM1403653", "GSM1403654", "GSM1403655", "GSM1403656", "GSM1403657", "GSM1403658", "GSM1403659", "GSM1403660", "GSM1403661", "GSM1403662", "GSM1403663", "GSM1403664", "GSM1403665", "GSM1403666", "GSM1403667", "GSM1403668", "GSM1403669", "GSM1403670", "GSM1403671", "GSM1403672", "GSM1403673", "GSM1403674", "GSM1403675", "GSM1403676", "GSM1403677", "GSM1403678", "GSM1403679", "GSM1403680", "GSM1403681", "GSM1403682", "GSM1403683", "GSM1403684", "GSM1403685", "GSM1403686", "GSM1403687", "GSM1403688", "GSM1403689", "GSM1403690", "GSM1403691", "GSM1403692", "GSM1403693", "GSM1403694", "GSM1403695", "GSM1403696", "GSM1403697", "GSM1403698", "GSM1403699", "GSM1403700", "GSM1403701", "GSM1403702", "GSM1403703", "GSM1403704", "GSM1403705", "GSM1403706", "GSM1403707", "GSM1403708", "GSM1403709", "GSM1403710", "GSM1403711", "GSM1403712", "GSM1403713", "GSM1403714", "GSM1403715", "GSM1403716", "GSM1403717", "GSM1403718", "GSM1403719", "GSM1403720", "GSM1403721", "GSM1403722", "GSM1403723", "GSM1403724", "GSM1403725", "GSM1403726", "GSM1403727", "GSM1403728", "GSM1403729", "GSM1403730", "GSM1403731", "GSM1403732", "GSM1403733", "GSM1403734", "GSM1403735", "GSM1403736", "GSM1403737", "GSM1403738", "GSM1403739", "GSM1403740", "GSM1403741", "GSM1403742", "GSM1403743", "GSM1403744", "GSM1403745", "GSM1403746", "GSM1403747", "GSM1403748", "GSM1403749", "GSM1403750", "GSM1403751", "GSM1403752", "GSM1403753", "GSM1403754", "GSM1403755", "GSM1403756", "GSM1403757", "GSM1403758", "GSM1403759", "GSM1403760", "GSM1403761", "GSM1403762", "GSM1403763", "GSM1403764", "GSM1403765", "GSM1403766", "GSM1403767", "GSM1403768", "GSM1403769", "GSM1403770", "GSM1403771", "GSM1403772", "GSM1403773", "GSM1403774", "GSM1403775", "GSM1403776", "GSM1403777", "GSM1403778", "GSM1403779", "GSM1403780", "GSM1403781", "GSM1403782", "GSM1403783", "GSM1403784", "GSM1403785", "GSM1403786", "GSM1403787", "GSM1403788", "GSM1403789", "GSM1403790", "GSM1403791", "GSM1403792", "GSM1403793", "GSM1403794", "GSM1403795", "GSM1403796", "GSM1403797", "GSM1403798", "GSM1403799", "GSM1403800", "GSM1403801", "GSM1403802", "GSM1403803", "GSM1403804", "GSM1403805", "GSM1403806", "GSM1403807", "GSM1403808", "GSM1403809", "GSM1403810", "GSM1403811", "GSM1403812", "GSM1403813", "GSM1403814", "GSM1403815", "GSM1403816", "GSM1403817", "GSM1403818", "GSM1403819", "GSM1403820", "GSM1403821", "GSM1403822", "GSM1403823", "GSM1403824", "GSM1403825", "GSM1403826", "GSM1403827", "GSM1403828", "GSM1403829", "GSM1403830", "GSM1403831", "GSM1403832", "GSM1403833", "GSM1403834", "GSM1403835", "GSM1403836", "GSM1403837", "GSM1403838", "GSM1403839", "GSM1403840", "GSM1403841", "GSM1403842", "GSM1403843", "GSM1403844", "GSM1403845", "GSM1403846", "GSM1403847", "GSM1403848", "GSM1403849", "GSM1403850", "GSM1403851", "GSM1403852", "GSM1403853", "GSM1403854", "GSM1403855", "GSM1403856", "GSM1403857", "GSM1403858", "GSM1403859", "GSM1403860", "GSM1403861", "GSM1403862", "GSM1403863", "GSM1403864", "GSM1403865", "GSM1403866", "GSM1403867", "GSM1403868", "GSM1403869", "GSM1403870", "GSM1403871", "GSM1403872", "GSM1403873", "GSM1403874", "GSM1403875", "GSM1403876", "GSM1403877", "GSM1403878", "GSM1403879", "GSM1403880", "GSM1403881", "GSM1403882", "GSM1403883", "GSM1403884", "GSM1403885", "GSM1403886", "GSM1403887", "GSM1403888", "GSM1403889", "GSM1403890", "GSM1403891", "GSM1403892", "GSM1403893", "GSM1403894", "GSM1403895", "GSM1403896", "GSM1403897", "GSM1403898", "GSM1403899", "GSM1403900", "GSM1403901", "GSM1403902", "GSM1403903", "GSM1403904", "GSM1403905", "GSM1403906", "GSM1403907", "GSM2140316", "GSM2140317", "GSM2140318", "GSM2140319", "GSM2140320", "GSM2140321", "GSM2140322", "GSM2140323", "GSM2140324", "GSM2140325", "GSM2140326", "GSM2140327", "GSM2140328", "GSM2140329", "GSM2140330", "GSM2140331", "GSM2140332", "GSM2140333", "GSM2140334", "GSM2140335", "GSM2140336", "GSM2140337", "GSM2140338", "GSM2140339", "GSM2140340", "GSM2140341", "GSM2140342", "GSM2140343", "GSM2140344", "GSM2140345", "GSM2140346", "GSM2140347", "GSM2140348", "GSM2140349", "GSM2140350", "GSM2140351", "GSM2140352", "GSM2140353", "GSM2140354", "GSM2140355", "GSM2140356", "GSM2140357", "GSM2140358", "GSM2140359", "GSM2140360", "GSM2140361", "GSM2140362", "GSM2140363", "GSM2140364", "GSM2140365", "GSM2140366", "GSM2140367", "GSM2140368", "GSM2140369", "GSM2140370", "GSM2140371", "GSM2140372", "GSM2140373", "GSM2140374", "GSM2140375", "GSM2140376", "GSM2140377", "GSM2140378", "GSM2140379", "GSM2140380", "GSM2140381", "GSM2140382", "GSM2140383", "GSM2140384", "GSM2140385", "GSM2140386", "GSM2140387", "GSM2140388", "GSM2140389", "GSM2140390", "GSM2140391", "GSM2140392", "GSM2140393", "GSM2140394", "GSM2140395", "GSM2140396", "GSM2140397", "GSM2140398", "GSM2140399", "GSM2140400", "GSM2140401", "GSM2140402", "GSM2140403", "GSM2140404", "GSM2140405", "GSM2140406", "GSM2140407", "GSM2140408", "GSM2140409", "GSM2140410", "GSM2140411", "GSM2140412", "GSM2140413", "GSM2140414", "GSM2140415", "GSM2140416", "GSM2140417", "GSM2140418", "GSM2140419", "GSM2140420", "GSM2140421", "GSM2140422", "GSM2140423", "GSM2140424", "GSM2140425", "GSM2140426", "GSM2140427", "GSM2140428", "GSM2140429", "GSM2140430", "GSM2140431", "GSM2140432", "GSM2140433", "GSM2140434", "GSM2140435", "GSM2140436", "GSM2140437", "GSM2140438", "GSM2140439", "GSM2140440", "GSM2140441", "GSM2140442", "GSM2140443", "GSM2140444", "GSM2140445", "GSM2140446", "GSM2140447", "GSM2140448", "GSM2140449", "GSM2140450", "GSM2140451", "GSM2140452", "GSM2140453", "GSM2140454", "GSM2140455", "GSM2140456", "GSM2140457", "GSM2140458", "GSM2140459", "GSM2140460", "GSM2140461", "GSM2140462", "GSM2140463", "GSM2140464", "GSM2140465", "GSM2140466", "GSM2140467", "GSM2140468", "GSM2140469", "GSM2140470", "GSM2140471", "GSM2140472", "GSM2140473", "GSM2140474", "GSM2140475", "GSM2140476", "GSM2140477", "GSM2140478", "GSM2140479", "GSM2140480", "GSM2140481", "GSM2140482", "GSM2140483", "GSM2140484", "GSM2140485", "GSM2140486", "GSM2140487", "GSM2140488", "GSM2140489", "GSM2140490", "GSM2140491", "GSM2140492", "GSM2140493", "GSM2140494", "GSM2140495", "GSM2140496", "GSM2140497", "GSM2140498", "GSM2140499", "GSM2140500", "GSM2140501", "GSM2140502", "GSM2140503", "GSM2140504", "GSM2140505", "GSM2140506", "GSM2140507", "GSM2140508", "GSM2140509", "GSM2140510", "GSM2140511", "GSM2140512", "GSM2140513", "GSM2140514", "GSM2140515", "GSM2140516", "GSM2140517", "GSM2140518", "GSM2140519", "GSM2140520", "GSM2140521", "GSM2140522", "GSM2140523", "GSM2140524", "GSM2140525", "GSM2140526", "GSM2140527", "GSM2140528", "GSM2140529", "GSM2140530", "GSM2140531", "GSM2140532", "GSM2140533", "GSM2140534", "GSM2140535", "GSM2140536", "GSM2140537", "GSM2140538", "GSM2140539", "GSM2140540", "GSM2140541", "GSM2140542", "GSM2140543", "GSM2140544", "GSM2140545", "GSM2140546", "GSM2140547", "GSM2140548", "GSM2140549", "GSM2140550", "GSM2140551", "GSM2140552", "GSM2140553", "GSM2140554", "GSM2140555"], "sample_count": 806, "group_sizes": null, "group_sizes_basis": null, "platform": "10656;14550", "taxon": "Homo sapiens", "title": "Integrative clustering reveals a novel split in the luminal A subtype of breast cancer with impact on outcome", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE59248 not downloaded", "asset:data:geo:GSE59248 licence not read", "asset:data:geo:GSE81002 not downloaded", "asset:data:geo:GSE81002 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "welch_t_test", "label": "Group comparison", "dsl_operations": ["welch_t"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "reordered", "quote": "Spearman rank order correlation coefficients were computed between the normalized miRNA expression levels from the Hi-TCGA data set and the corresponding log2 RSEM-normalized counts of the putative targets. Statistical differences between groups were evaluated using the Welch t-test or a Mann–Whitney rank sum test, depending on the normal distribution of the variables considered. Survival was estimated using the Kaplan–Meier method, and differences between groups were evaluated with the log-rank test using the Survival and Survminer R packages [78,79]."}}, {"id": "method-2", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log-rank"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["welch_t"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: welch_t_test."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE81002", "GSE59248"], "resolved_accessions": ["GSE81002", "GSE59248"], "statements": ["The data sets analyzed in the current study are publicly available from TCGA Research Network: TCGA-BRCA project, https://www.cancer.gov/tcga; from the METABRIC project (information at https://ega-archive.org/studies/EGAS00000000098); and from Gene Expression Omnibus database (GEO; https://www.ncbi.nlm.nih.gov/gds) for the GSE81002 and GSE59248 series."], "basis": "The paper names GSE81002, GSE59248 in Gene Expression Omnibus database (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["welch_t"], "assets": ["source:pmid:37373065", "data:geo:GSE59248"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE59248"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:45:07Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9685, "completion_tokens": 2680, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:37373065", "type": "paper", "label": "pmid:37373065"}, {"id": "source:pmid:37373065", "type": "manuscript", "label": "PMID 37373065 full text"}, {"id": "data:geo:GSE59248", "type": "dataset", "label": "GEO GSE59248"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37373065", "type": "paper", "label": "pmid:37373065"}, {"id": "source:pmid:37373065", "type": "manuscript", "label": "PMID 37373065 full text"}, {"id": "data:geo:GSE59248", "type": "dataset", "label": "GEO GSE59248"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37373065", "type": "extraction", "used": ["source:pmid:37373065"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE59248", "type": "accession_resolution", "used": ["data:geo:GSE59248"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:37373065", "parent_hash": "sha256:55e8cfc491c45577b1e198ecbe7f7f0434e38067ac1518cfff4c266864f6ef0f", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE59248 licence not read", "asset:data:geo:GSE59248 not downloaded", "asset:data:geo:GSE81002 licence not read", "asset:data:geo:GSE81002 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["welch_t"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Spearman rank order correlation coefficients were computed between the normalized miRNA expression levels from the Hi-TCGA data set and the corresponding log2 RSEM-normalized counts of the putative targets. Statistical differences between groups were evaluated using the Welch t-test or a Mann–Whitney rank sum test, depending on the normal distribution of the variables considered. Survival was estimated using the Kaplan–Meier method, and differences between groups were evaluated with the log-rank test using the Survival and Survminer R packages [78,79]."], "order_basis": "analysis_only", "id": "assay:1"}]}