Up-regulation of the interferon-related genes in BRCA2 knockout epithelial cells.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:25043256", "kind": "science-record", "revision": 2, "content_hash": "sha256:902962f199062630a007dc2b5127e1367159aa9ab0f17bda3946fd41a25e91f4", "created_at": "2026-11-01T15:40:05Z", "updated_at": "2026-11-01T18:47:06Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Up-regulation of the interferon-related genes in BRCA2 knockout epithelial cells.", "doi": "10.1002/path.4404", "pmid": "25043256", "authors": ["Hong Xu", "Jian Xian", "Emmanuelle Vire", "Steven McKinney", "Vivien Wei", "Jason Wong", "Rebecca Tong", "Tony Kouzarides", "Carlos Caldas", "Samuel Aparicio"], "journal": "The Journal of pathology", "year": 2014, "abstract": "BRCA2 mutations are significantly associated with early-onset breast cancer, and the tumour-suppressing function of BRCA2 has been attributed to its involvement in homologous recombination (HR)-mediated DNA repair. In order to identify additional functions of BRCA2, we generated BRCA2-knockout HCT116 human colorectal carcinoma cells. Using genome-wide microarray analyses, we have discovered a link between the loss of BRCA2 and the up-regulation of a subset of interferon (IFN)-related genes, including APOBEC3F and APOBEC3G. The over-expression of IFN-related genes was confirmed in different human BRCA2(-/-) and mouse Brca2(-/-) tumour cell lines, and was independent of senescence and apoptosis. In isogenic wild-type BRCA2 cells, we observed over-expression of IFN-related genes after treatment with DNA-damaging agents, and following ionizing radiation. Cells with endogenous DNA damage because of defective BRCA1 or RAD51 also exhibited over-expression of IFN-related genes. Transcriptional activity of the IFN-stimulated response element (ISRE) was increased in BRCA2 knockout cells, and the expression of BRCA2 greatly decreased IFNα-stimulated ISRE reporter activity, suggesting that BRCA2 directly represses the expression of IFN-related genes through the ISRE. Finally, the colony-forming capacity of BRCA2 knockout cells was significantly reduced in the presence of either IFNβ or IFNγ, suggesting that IFNs may have potential as therapeutic agents in cancer cells with BRCA2 mutations. The GEO Accession No. for microarray analysis is GSE54830.", "claims": [{"id": "claim-target-result", "statement": "Using genome-wide microarray analyses, the paper found that loss of BRCA2 is linked to up-regulation of a subset of interferon-related genes, including APOBEC3F and APOBEC3G.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:25043256", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Using genome-wide microarray analyses, we have discovered a link between the loss of BRCA2 and the up-regulation of a subset of interferon (IFN)-related genes, including APOBEC3F and APOBEC3G."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Using genome-wide microarray analyses, the paper found that loss of BRCA2 is linked to up-regulation of a subset of interferon-related genes, including APOBEC3F and APOBEC3G.", "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:25043256"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:25043256", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1002/path.4404", "sha256": "sha256:808d6a91bbe9794b5270473a9e9056b07956ca70a58e11cf59b6b94dab61a765", "bytes": 1519, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1002/path.4404", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC4882165", "source": "ncbi_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "absent", "methods": [], "targets": [], "gaps": ["method", "operations"]}, "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (not named), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible."}, "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": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": [], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:25043256"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:22:24Z", "independence": "single_reader"}, "evidence_check": {"method": null, "availability": null}, "calls": 2, "usage": {"prompt_tokens": 1606, "completion_tokens": 479, "cached_tokens": 529}}, "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:25043256", "type": "paper", "label": "pmid:25043256"}, {"id": "source:pmid:25043256", "type": "manuscript", "label": "PMID 25043256 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:25043256", "type": "paper", "label": "pmid:25043256"}, {"id": "source:pmid:25043256", "type": "manuscript", "label": "PMID 25043256 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-25043256", "type": "extraction", "used": ["source:pmid:25043256"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "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:25043256", "parent_hash": "sha256:f3da9c1c9fb9ce71b936a821e7f2cf549d491687c3a7eaa8b63025a09227afab", "fork_of": null, "generation": 1}, "gaps": ["execution.not_run", "method", "operations", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["olorectal carcinoma cells. Using genome-wide microarray analyses, we have discovered a link between", "h BRCA2 mutations. The GEO Accession No. for microarray analysis is GSE54830."], "order_basis": "paper_text_order:391", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["confirmed in different human BRCA2(-/-) and mouse Brca2(-/-) tumour cell lines, and was indepe"], "order_basis": "paper_text_order:656", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["lines, and was independent of senescence and apoptosis. In isogenic wild-type BRCA2 cells, we obser"], "order_basis": "paper_text_order:729", "id": "assay:3"}]}