Methylation of Immune-Related Genes in Peripheral Blood Leukocytes and Breast Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35223499", "kind": "science-record", "revision": 4, "content_hash": "sha256:c1b07a427e6a23343bafab4bcf2fbda074e9c26f3a1b81c4f13a49f684a4b04b", "created_at": "2026-11-01T17:36:59Z", "updated_at": "2026-11-01T21:27:20Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Methylation of Immune-Related Genes in Peripheral Blood Leukocytes and Breast Cancer.", "doi": "10.3389/fonc.2022.817565", "pmid": "35223499", "authors": ["Tian Tian", "JinMing Fu", "DaPeng Li", "YuPeng Liu", "HongRu Sun", "Xuan Wang", "XianYu Zhang", "Ding Zhang", "Ting Zheng", "Yashuang Zhao", "Da Pang"], "journal": "Frontiers in oncology", "year": 2022, "abstract": "Abnormal DNA methylation contributes to breast cancer (BC). Immune-related genes play crucial roles in BC development and progression. This study aims to investigate the effect of methylation of immune-related genes in peripheral blood leukocytes (PBLs) on BC risk. GSE51032 and GSE104942 datasets were used to identify significantly differentially methylated CpG sites (DMCs) of immune-related genes. A case-control study was conducted using MethylTarget sequencing to validate the relationship between the methylation levels of the screened genes and BC risk. We also evaluated the association between methylation haplotypes of screened genes and BC risk. Moreover, we sorted the blood leukocytes into T cells, B cells, and monocytes to detect the difference of DNA methylation in different cell subtypes. A total of five DMCs were screened from GEO datasets, including cg01760846 (PSMC1), cg07141527 (SPPL3), cg15658543 (CARD11), cg21568368 (PSMB8), and cg24045276 (NCF2). In the case-control study, there were significant associations between methylation of the CpG sites in the five genes and BC risk. Methylation haplotype burdens of PSMC1, CARD11, and PSMB8 were associated with reduced BC risk. Moreover, there were heterogeneities in the methylation levels of the genes in different cell subtypes. In conclusion, methylation of PSMC1, SPPL3, CARD11, PSMB8, and NCF2 in PBLs were associated with BC risk. The five-gene methylation could be the potential biomarkers for predicting BC risk.", "claims": [{"id": "claim-method", "statement": "DMCs related to BC were identified using t-test with p-value less than 0.05 and the absolute value of the average methylation difference between cases and controls (|Δβ|) greater than 0.015.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35223499", "locator": "sections[5] \"Data Preprocessing and DMC Selection\" paragraph 2", "quote": "DMCs related to BC were identified using t-test with p-value less than 0.05 and the absolute value of the average methylation difference between cases and controls (|Δβ|) greater than 0.015."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data presented in the study are deposited in the Figshare repository. Dataset: https://doi.org/10.6084/m9.figshare.17450303.v1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35223499", "locator": "sections[30] \"Data Availability Statement\" paragraph 2", "quote": "The data presented in the study are deposited in the Figshare repository. Dataset: https://doi.org/10.6084/m9.figshare.17450303.v1."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In conclusion, methylation of PSMC1, SPPL3, CARD11, PSMB8, and NCF2 in PBLs were associated with BC risk.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35223499", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In conclusion, methylation of PSMC1, SPPL3, CARD11, PSMB8, and NCF2 in PBLs were associated with BC risk."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In conclusion, methylation of PSMC1, SPPL3, CARD11, PSMB8, and NCF2 in PBLs were associated with BC risk.", "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:35223499"], "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:GSE104942"], "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:GSE104942"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35223499", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2022.817565", "sha256": "sha256:83f975296cce47923020d3027ecacaac7064c91871f506bb47b3db36dfc04c40", "bytes": 36612, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fonc.2022.817565", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8867609", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE104942", "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=GSE104942", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE104942", "version": null, "note": "The data presented in the study are deposited in the Figshare repository. 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"GSM1236376", "GSM1236377", "GSM1236378"], "sample_count": 845, "group_sizes": null, "group_sizes_basis": null, "platform": "13534", "taxon": "Homo sapiens", "title": "EPIC-Italy at HuGeF", "resolution_checked_at": "2026-11-01T18:06:44Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE104942 not downloaded", "asset:data:geo:GSE104942 licence not read", "asset:data:geo:GSE51032 not downloaded", "asset:data:geo:GSE51032 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "regression_modelling", "specific": "logistic", "label": "Regression modelling", "dsl_operations": ["glm_logit_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["predictors_and_outcome"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "DMCs related to BC were identified using t-test with p-value less than 0.05 and the absolute value of the average methylation difference between cases and controls (|Δβ|) greater than 0.015."}}, {"id": "method-2", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "Chi-square"}}], "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": 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE51032", "GSE104942"], "resolved_accessions": ["GSE51032", "GSE104942"], "statements": ["The data presented in the study are deposited in the Figshare repository. Dataset: https://doi.org/10.6084/m9.figshare.17450303.v1."], "basis": "The paper names GSE51032, GSE104942 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["glm_logit_fit"], "assets": ["source:pmid:35223499", "data:geo:GSE104942"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE104942"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:36:10Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10610, "completion_tokens": 2792, "cached_tokens": 128}}, "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:35223499", "type": "paper", "label": "pmid:35223499"}, {"id": "source:pmid:35223499", "type": "manuscript", "label": "PMID 35223499 full text"}, {"id": "data:geo:GSE104942", "type": "dataset", "label": "GEO GSE104942"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35223499", "type": "paper", "label": "pmid:35223499"}, {"id": "source:pmid:35223499", "type": "manuscript", "label": "PMID 35223499 full text"}, {"id": "data:geo:GSE104942", "type": "dataset", "label": "GEO GSE104942"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35223499", "type": "extraction", "used": ["source:pmid:35223499"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE104942", "type": "accession_resolution", "used": ["data:geo:GSE104942"], "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:35223499", "parent_hash": "sha256:550ffce1feb28e3958817673747815fa9f8fda4207e5595c8ec886b8d83d302b", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE104942 licence not read", "asset:data:geo:GSE104942 not downloaded", "asset:data:geo:GSE51032 licence not read", "asset:data:geo:GSE51032 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "regression_modelling", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["glm_logit_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["DMCs related to BC were identified using t-test with p-value less than 0.05 and the absolute value of the average methylation difference between cases and controls (|Δβ|) greater than 0.015."], "order_basis": "analysis_only", "id": "assay:1"}]}