Identification and validation of diagnostic markers of atherosclerosis progression via bioinformatics strategies.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41348730", "kind": "science-record", "revision": 3, "content_hash": "sha256:98c8684e1c96446b9b0c8e50ed0e648a178730fdc2e47fc42d3dd98faba7c5e7", "created_at": "2026-11-01T20:31:21Z", "updated_at": "2026-11-01T22:15:07Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of diagnostic markers of atherosclerosis progression via bioinformatics strategies.", "doi": "10.1371/journal.pone.0336139", "pmid": "41348730", "authors": ["Yun Mao", "Yang Xiao", "Xia Hu"], "journal": "PloS one", "year": 2025, "abstract": "BACKGROUND: Arteriosclerosis (AS) is a leading cause of cardiovascular disease, imposing significant burdens on families and society. However, the underlying mechanisms remain unclear. This study aims to elucidate these mechanisms and explore potential pharmacological treatments through the integration of bioinformatics.\nMETHODS: The GSE28829 dataset was retrieved from the GEO database. Differential gene expression between early- and late-stage AS plaques in GSE28829 was identified via the limma package. We focused on the intersecting genes associated with endoplasmic reticulum stress and mitochondrial damage. LASSO regression analysis was applied to pinpoint potential core genes associated with AS. An protein interaction network was constructed, with a focus on the hub genes within this network. Assessment of immune cell infiltration levels was achieved via the ssGSEA method and confirmed via CIBERSORT. We used the DrugBank database to predict small molecule drugs that could intervene in AS progression.\nRESULTS: In this study, DEGs associated with AS were identified, and hub genes, including FCGR3A, ITGB2, TYROBP, FCGR2B, CTSS, FCER1G, CD86, TLR2, C1QB, and C1QA, were identified. We also found a strong correlation between the hub genes and immune processes, indicating that ER stress and mitochondrial damage were correlated with the activation of immune processes. Additionally, a diagnostic model for AS was established, demonstrating the substantial predictive value of these hub genes.\nCONCLUSIONS: This study reveals the involvement of genes related to endoplasmic reticulum stress and mitochondrial damage in the pathogenesis of AS. These hub genes offer new directions for further research and the development of pharmacological treatments.", "claims": [{"id": "claim-method", "statement": "Here, we first screened all cellular genes via LASSO regression for DEGs associated with ER stress and mitochondrial damage via the R package glmnet (v4.1-2) to implement the method and select the best lambda value.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41348730", "locator": "sections[7] \"2.5. Construction of the diagnostic model\" paragraph 3", "quote": "Here, we first screened all cellular genes via LASSO regression for DEGs associated with ER stress and mitochondrial damage via the R package glmnet (v4.1-2) to implement the method and select the best lambda value."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GSE28829 dataset from human AS patients was downloaded from the GEO database [6]. This dataset contained a total of 29 patients, 13 in early-stage and 16 in advanced-stage. Microarray sequencing data in raw CEL format were read using the R package affy (v1.70.0), and the background correction was performed using the RMA method [7].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41348730", "locator": "sections[3] \"2.1. Data and preprocessing\" paragraph 2", "quote": "The GSE28829 dataset from human AS patients was downloaded from the GEO database [6]. This dataset contained a total of 29 patients, 13 in early-stage and 16 in advanced-stage. Microarray sequencing data in raw CEL format were read using the R package affy (v1.70.0), and the background correction was performed using the RMA method [7]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The seven-gene diagnostic model showed areas under the ROC curve of 0.9952, 1, and 1 in GSE28829, GSE41571, and GSE120521, respectively.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41348730", "locator": "sections[15] \"3.4. Diagnostic model based on ER stress and mitochondrial damage genes\" paragraph 3", "quote": "To verify the evaluation efficacy of the diagnostic model, the predicted ROC curves were drawn on the basis of the original datasets GSE 28829 and the external datasets GSE41571 and GSE120521, revealing that the predictive model in both datasets had areas under the curve of 0.9952, 1 and 1 (Fig 6D-F)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The seven-gene diagnostic model showed areas under the ROC curve of 0.9952, 1, and 1 in GSE28829, GSE41571, and GSE120521, respectively.", "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:41348730"], "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:GSE28829"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {"p_value": "he Wilcoxon test, and a P value <0"}, "inputs": ["data:geo:GSE28829"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41348730", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0336139", "sha256": "sha256:cdaa62a5fbb3413bdc5f0d758d75093ad370a8cc12fa3215f0fd4abd946e72ef", "bytes": 44518, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1371/journal.pone.0336139", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12680236", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE28829", "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=GSE28829", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE28829", "version": null, "note": "The GSE28829 dataset from human AS patients was downloaded from the GEO database [6]. This dataset contained a total of 29 patients, 13 in early-stage and 16 in advanced-stage. Microarray sequencing data in raw CEL format were read using the R package affy (v1.70.0), and the background correction was performed using the RMA method [7].", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The GSE28829 dataset from human AS patients was downloaded from the GEO database [6]. This dataset contained a total of 29 patients, 13 in early-stage and 16 in advanced-stage. Microarray sequencing data in raw CEL format were read using the R package affy (v1.70.0), and the background correction was performed using the RMA method [7].", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM714070", "GSM714071", "GSM714072", "GSM714073", "GSM714074", "GSM714075", "GSM714076", "GSM714077", "GSM714078", "GSM714079", "GSM714080", "GSM714081", "GSM714082", "GSM714083", "GSM714084", "GSM714085", "GSM714086", "GSM714087", "GSM714088", "GSM714089", "GSM714090", "GSM714091", "GSM714092", "GSM714093", "GSM714094", "GSM714095", "GSM714096", "GSM714097", "GSM714098"], "sample_count": 29, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene Expression in early and advanced atherosclerotic plaque from human carotid", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE41571", "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=GSE41571", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE41571", "version": null, "note": "The GSE28829 dataset from human AS patients was downloaded from the GEO database [6]. This dataset contained a total of 29 patients, 13 in early-stage and 16 in advanced-stage. Microarray sequencing data in raw CEL format were read using the R package affy (v1.70.0), and the background correction was performed using the RMA method [7].", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The GSE28829 dataset from human AS patients was downloaded from the GEO database [6]. This dataset contained a total of 29 patients, 13 in early-stage and 16 in advanced-stage. Microarray sequencing data in raw CEL format were read using the R package affy (v1.70.0), and the background correction was performed using the RMA method [7].", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM1019539", "GSM1019540", "GSM1019541", "GSM1019542", "GSM1019543", "GSM1019544", "GSM1019545", "GSM1019546", "GSM1019547", "GSM1019548", "GSM1019549"], "sample_count": 11, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Genome-wide expression profiling of laser micro-dissected macrophages from ruptured and stable atherosclerotic human plaques", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE28829 not downloaded", "asset:data:geo:GSE28829 licence not read", "asset:data:geo:GSE41571 not downloaded", "asset:data:geo:GSE41571 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {"p_value": "he Wilcoxon test, and a P value <0"}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-2", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.7, "band": "medium", "quote": "limma"}}, {"id": "method-3", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "PPI"}}, {"id": "method-4", "family": null, "specific": null, "label": "LASSO regression", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Here, we first screened all cellular genes via LASSO regression for DEGs associated with ER stress and mitochondrial damage via the R package glmnet (v4.1-2) to implement the method and select the best lambda value."}}], "targets": [], "gaps": ["method.reader_named_unmapped", "method.group_comparison_wilcoxon"]}, "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": false, "required_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon."}, "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": ["GSE28829", "GSE41571"], "resolved_accessions": ["GSE28829", "GSE41571"], "statements": ["The GSE28829 dataset from human AS patients was downloaded from the GEO database [6]. This dataset contained a total of 29 patients, 13 in early-stage and 16 in advanced-stage. Microarray sequencing data in raw CEL format were read using the R package affy (v1.70.0), and the background correction was performed using the RMA method [7]."], "basis": "The paper names GSE28829, GSE41571 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:41348730", "data:geo:GSE28829"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_wilcoxon", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE28829"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T20:07:22Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 11532, "completion_tokens": 1778, "cached_tokens": 256}}, "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:41348730", "type": "paper", "label": "pmid:41348730"}, {"id": "source:pmid:41348730", "type": "manuscript", "label": "PMID 41348730 full text"}, {"id": "data:geo:GSE28829", "type": "dataset", "label": "GEO GSE28829"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:41348730", "type": "paper", "label": "pmid:41348730"}, {"id": "source:pmid:41348730", "type": "manuscript", "label": "PMID 41348730 full text"}, {"id": "data:geo:GSE28829", "type": "dataset", "label": "GEO GSE28829"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-41348730", "type": "extraction", "used": ["source:pmid:41348730"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE28829", "type": "accession_resolution", "used": ["data:geo:GSE28829"], "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:41348730", "parent_hash": "sha256:33b8ffab875f6a616db3f8fd704ca08e57db5330e7373adef20999fa75411d1d", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE28829 licence not read", "asset:data:geo:GSE28829 not downloaded", "asset:data:geo:GSE41571 licence not read", "asset:data:geo:GSE41571 not downloaded", "execution.not_run", "method.group_comparison_wilcoxon", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:group_comparison_wilcoxon"], "assays": [{"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Wilcoxon"], "order_basis": "analysis_only", "id": "assay:1"}]}