Integrative genomic analysis of N6-methyladenosine-single nucleotide polymorphisms (m6A-SNPs) associated with breast cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34151731", "kind": "science-record", "revision": 5, "content_hash": "sha256:1356d118a715e23b54d10da151abb11480268b093911d23fdcde4e2932a83b12", "created_at": "2026-11-01T15:41:39Z", "updated_at": "2026-11-01T21:25:34Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrative genomic analysis of N6-methyladenosine-single nucleotide polymorphisms (m6A-SNPs) associated with breast cancer.", "doi": "10.1080/21655979.2021.1935406", "pmid": "34151731", "authors": ["Zixue Xuan", "Yiwen Zhang", "Jinying Jiang", "Xiaowei Zheng", "Xiaoping Hu", "Xiuli Yang", "Yanfei Shao", "Guobing Zhang", "Ping Huang"], "journal": "Bioengineered", "year": 2021, "abstract": "Due to the important role of N6-methyladenosine (m6A) in breast cancer, single nucleotide polymorphisms (SNPs) in genes with m6A modification may also be involved in breast cancer pathogenesis. In this study, we used a public genome-wide association study dataset to identify m6A-SNPs associated with breast cancer and to further explore their potential functions. We found 113 m6A-SNPs associated with breast cancer that reached the genome-wide suggestive threshold (5.0E-05), and 86 m6A-SNPs had eQTL signals. Only six genes were differentially expressed between controls and breast cancer cases in GEO datasets (GSE15852, GSE115144, and GSE109169), and the SNPs rs4829 and rs9610915 were located next to the m6A modification sites in the 3'UTRs of TOM1L1 and MAFF, respectively. In addition, we found that polyadenylate-binding protein cytoplasmic 1 might have a potential interaction with rs4829 (TOM1L1) and rs9610915 (MAFF). In summary, these findings indicated that the SNPs rs4829 and rs9610915 are potentially associated with breast cancer because they had eQTL signals, altered gene expression, and were located next to the m6A modification sites in the 3'UTRs of their coding genes. However, further studies are still needed to clarify how genetic variation affects the epigenetic modification, m6A, and its subsequent functions in the pathogenesis of breast cancer.", "claims": [{"id": "claim-method", "statement": "Hence, eQTL analysis was performed to investigate the breast cancer-associated m6A-SNPs that could affect RNA modification using the HaploReg browser (https://www.encodeproject.org/software/haploreg/) [26,27]. To check whether these m6A-SNPs have eQTL effects, the HaploReg browser was used, finding that 86 of these breast cancer-associated m6A-SNPs had eQTL signals.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34151731", "locator": "sections[4] \"Expression quantitative trait loci (eQTL) analysis of m6A-SNPs\" paragraph 2", "quote": "Hence, eQTL analysis was performed to investigate the breast cancer-associated m6A-SNPs that could affect RNA modification using the HaploReg browser (https://www.encodeproject.org/software/haploreg/) [26,27]."}, {"asset": "source:pmid:34151731", "locator": "sections[9] \"Identification of m6A-SNPs associated with breast cancer\" paragraph 5", "quote": "To check whether these m6A-SNPs have eQTL effects, the HaploReg browser was used, finding that 86 of these breast cancer-associated m6A-SNPs had eQTL signals."}], "state": "complete"}, {"id": "claim-data-access", "statement": "In this study, breast cancer GWAS data were downloaded from the website (ftp://ftp.ebi.ac.uk/pub/databases/gwas/summary_statistics/MichailidouK_29059683_GCST004988/), and the m6A-SNP list was obtained from the m6Avar database (http://rmvar.renlab.org/download.html).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34151731", "locator": "sections[3] \"Screening for m6A -SNPs associated with breast cancer\" paragraph 3", "quote": "In this study, breast cancer GWAS data were downloaded from the website (ftp://ftp.ebi.ac.uk/pub/databases/gwas/summary_statistics/MichailidouK_29059683_GCST004988/), and the m6A-SNP list was obtained from the m6Avar database (http://rmvar.renlab.org/download.html)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:34151731"], "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:GSE109169"], "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:GSE109169"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34151731", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1080/21655979.2021.1935406", "sha256": 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"section_title": "Six corresponding genes of eight m6A-SNPs were differentially expressed in breast cancer", "row_count": 9, "column_count": 10}, "table": {"label": "Table 1.", "caption": "Six genes of eight m6A-SNPs associated with breast cancer were differentially expressed between controls and breast cancer in the GSE15852", "rows": [["SNP ID", "Chr", "Position", "m6A_ID", "Gene", "Gene_region", "eQTL Hit", "Confidence_level", "Modification_function", "Pvalue"], ["rs1802212", "17", "54961293", "RMVar_ID_782932", "TOM1L1", "3’UTR", "32", "m6A-Seal-seq:(Medium)", "Functional Loss", "3.20E-19"], ["rs2747655", "6", "152126186", "RMVar_ID_1369593", "ESR1", "3’UTR", "3", "Prediction:(Low)", "Functional Loss", "8.62E-14"], ["rs2267372", "22", "38202227", "RMVar_ID_520365", "MAFF", "exon", "35", "MeRIP-seq:(Medium)", "Functional Loss", "2.49E-10"], ["rs9610915", "22", "38215073", "RMVar_ID_778207", "MAFF", "3’UTR", "9", "MeRIP-seq:(Medium)", "Functional Loss", "1.05E-08"], ["rs1424916", "2", "217874577", "RMVar_ID_814993", "TNS1", "intron", "4", "m6A-Label-seq:(High)", "Functional Loss", "3.36E-08"], ["rs4829", "17", "54961954", "RMVar_ID_781699", "TOM1L1", "3’UTR", "14", "miCLIP:(High)", "Functional Loss", "1.00E-06"], ["rs2234458", "11", "65871903", "RMVar_ID_919384", "EFEMP2", "intron", "5", "Prediction:(Low)", "Functional Loss", "4.68E-06"], ["rs2023472", "6", "30108087", "RMVar_ID_1375857", "TRIM31", "CDS", "1", "Prediction:(Low)", "Functional Gain", "1.83E-05"]], "row_count": 9, "column_count": 10, "numeric_cells": 53, "header_rows": 1, "locator": "section[10]/table-wrap[1]#t0001"}}], "gaps": ["asset:data:geo:GSE109169 not downloaded", "asset:data:geo:GSE109169 licence not read", "asset:data:geo:GSE115144 not downloaded", "asset:data:geo:GSE115144 licence not read", "asset:data:geo:GSE15852 not downloaded", "asset:data:geo:GSE15852 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "genetic_association", "specific": 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To check whether these m6A-SNPs have eQTL effects, the HaploReg browser was used, finding that 86 of these breast cancer-associated m6A-SNPs had eQTL signals."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["gwas_locus_scan"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: gwas."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["gwas_locus_scan"], "assets": ["source:pmid:34151731", "data:geo:GSE109169", "asset:table:pmid:34151731:1"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE109169"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:31:14Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 21524, "completion_tokens": 2076, "cached_tokens": 776}}, "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:34151731", "type": "paper", "label": "pmid:34151731"}, {"id": "source:pmid:34151731", "type": "manuscript", "label": "PMID 34151731 full text"}, {"id": "data:geo:GSE109169", "type": "dataset", "label": "GEO GSE109169"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34151731", "type": "paper", "label": "pmid:34151731"}, {"id": "source:pmid:34151731", "type": "manuscript", "label": "PMID 34151731 full text"}, {"id": "data:geo:GSE109169", "type": "dataset", "label": "GEO GSE109169"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34151731", "type": "extraction", "used": ["source:pmid:34151731"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE109169", "type": "accession_resolution", "used": ["data:geo:GSE109169"], "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:34151731", "parent_hash": "sha256:d2403584550a975b09ef96421613b4a329dba514fe86875a65fce8aa2d8fba88", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE109169 licence not read", "asset:data:geo:GSE109169 not downloaded", "asset:data:geo:GSE115144 licence not read", "asset:data:geo:GSE115144 not downloaded", "asset:data:geo:GSE15852 licence not read", "asset:data:geo:GSE15852 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "genetic_association", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["gwas_locus_scan"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["genome-wide association study"], "order_basis": "analysis_only", "id": "assay:1"}]}