Role of lactylation and immune infiltration in atherosclerosis: novel insights from bioinformatics analyses.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40248193", "kind": "science-record", "revision": 4, "content_hash": "sha256:49c948c6af8d4843f35d81e48bf134a7252a1839f6dcf2fee954a6caa75914a9", "created_at": "2026-11-01T20:30:24Z", "updated_at": "2026-11-01T22:56:23Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Role of lactylation and immune infiltration in atherosclerosis: novel insights from bioinformatics analyses.", "doi": "10.3389/fgene.2025.1520325", "pmid": "40248193", "authors": ["Jintao Qian", "Qing Zhou"], "journal": "Frontiers in genetics", "year": 2025, "abstract": "Introduction: The existing evidence indicates that atherosclerosis (AS) plays a pivotal role in the progression and exacerbation of cardiovascular diseases and their associated complications. Current diagnostic and therapeutic strategies for atherosclerosis are limited in their ability to facilitate early detection and personalized treatment. This study employs a systems biology approach to investigate the role of lactylation-related genes (LRGs) in the pathogenesis of atherosclerosis, while considering the well-established correlation between inflammatory responses and atherosclerosis development.\nMethods: In this study, we utilized datasets obtained from the Gene Expression Omnibus (GEO) as well as data from previous studies on lactylation-related genes (LRGs). Following this, we identified 17 lactylation related genes associate with atherosclerosis (AS-LRGs) from the GSE100927 dataset. Subsequently, we employed the validation dataset (GSE43292) to assess these 17 AS-LRGs, resulting in the identification of 12 more reliable candidate genes. These genes were further analyzed for functional enrichment through Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). To elucidate the potential utility of AS-LRGs in diagnosing high-risk plaques, we assessed their expression in both early and late stages of atherosclerosis, as well as in high- and low-risk plaques. We then constructed interaction networks to elucidate the potential regulatory relationships among LRGs, miRNAs, transcription factors, and drugs. Finally, we utilized the single sample Gene Set Enrichment Analysis (ssGSEA) method to investigate immune infiltration in AS and evaluate the levels of immune cell infiltration.\nResults: We identified 12 lactylation-related genes that are more reliably associated with atherosclerosis: five upregulated genes (LSP1, IKZF1, MNDA, RCC2, and WAS) and seven downregulated genes (CSRP2, PPP1CB, CSRP1, HEXIM1, CALD1, PDLIM1, and RANBP2).\nDiscussion: This study elucidates the pivotal role of lactylation in atherosclerosis (AS) and establishes a robust foundation for future research into targeted therapies and clinical applications of the identified biomarkers.", "claims": [{"id": "claim-method", "statement": "The “limma (Ritchie et al., 2015)” R package was employed to normalize the data and identify differentially expressed genes (DEGs).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40248193", "locator": "sections[3] \"2.1 Identification of differentially expressed genes between atherosclerotic and healthy arteries\" paragraph 2", "quote": "The “limma (Ritchie et al., 2015)” R package was employed to normalize the data and identify differentially expressed genes (DEGs)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data and analyses presented in this study are sourced from public databases, with all references clearly cited in the text.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40248193", "locator": "sections[19] \"Data availability statement\" paragraph 2", "quote": "All data and analyses presented in this study are sourced from public databases, with all references clearly cited in the text."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 12 lactylation-related genes reliably associated with atherosclerosis: five upregulated genes (LSP1, IKZF1, MNDA, RCC2, and WAS) and seven downregulated genes (CSRP2, PPP1CB, CSRP1, HEXIM1, CALD1, PDLIM1, and RANBP2).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40248193", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We identified 12 lactylation-related genes that are more reliably associated with atherosclerosis: five upregulated genes (LSP1, IKZF1, MNDA, RCC2, and WAS) and seven downregulated genes (CSRP2, PPP1CB, CSRP1, HEXIM1, CALD1, PDLIM1, and RANBP2)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified 12 lactylation-related genes reliably associated with atherosclerosis: five upregulated genes (LSP1, IKZF1, MNDA, RCC2, and WAS) and seven downregulated genes (CSRP2, PPP1CB, CSRP1, HEXIM1, CALD1, PDLIM1, and RANBP2).", "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:40248193"], "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:GSE100927"], "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:GSE100927"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40248193", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2025.1520325", "sha256": "sha256:941f8d04475bedc5329e4bbe4c83640a6098d46ab8d6b6deee01dd27fd4dd1f0", "bytes": 29570, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2025.1520325", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12003320", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE100927", "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=GSE100927", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE100927", "version": null, "note": "All data and analyses presented in this study are sourced from public databases, with all references clearly cited in the text.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data and analyses presented in this study are sourced from public databases, with all references clearly cited in the text.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2696609", "GSM2696610", "GSM2696611", "GSM2696612", "GSM2696613", "GSM2696614", "GSM2696615", "GSM2696616", "GSM2696617", "GSM2696618", "GSM2696619", "GSM2696620", "GSM2696621", "GSM2696622", "GSM2696623", "GSM2696624", "GSM2696625", "GSM2696626", "GSM2696627", "GSM2696628", "GSM2696629", "GSM2696630", "GSM2696631", "GSM2696632", "GSM2696633", "GSM2696634", "GSM2696635", "GSM2696636", "GSM2696637", "GSM2696638", "GSM2696639", "GSM2696640", "GSM2696641", "GSM2696642", "GSM2696643", "GSM2696644", "GSM2696645", "GSM2696646", "GSM2696647", "GSM2696648", "GSM2696649", "GSM2696650", "GSM2696651", "GSM2696652", "GSM2696653", "GSM2696654", "GSM2696655", "GSM2696656", "GSM2696657", "GSM2696658", "GSM2696659", "GSM2696660", "GSM2696661", "GSM2696662", "GSM2696663", "GSM2696664", "GSM2696665", "GSM2696666", "GSM2696667", "GSM2696668", "GSM2696669", "GSM2696670", "GSM2696671", "GSM2696672", "GSM2696673", "GSM2696674", "GSM2696675", "GSM2696676", "GSM2696677", "GSM2696678", "GSM2696679", "GSM2696680", "GSM2696681", "GSM2696682", "GSM2696683", "GSM2696684", "GSM2696685", "GSM2696686", "GSM2696687", "GSM2696688", "GSM2696689", "GSM2696690", "GSM2696691", "GSM2696692", "GSM2696693", "GSM2696694", "GSM2696695", "GSM2696696", "GSM2696697", "GSM2696698", "GSM2696699", "GSM2696700", "GSM2696701", "GSM2696702", "GSM2696703", "GSM2696704", "GSM2696705", "GSM2696706", "GSM2696707", "GSM2696708", "GSM2696709", "GSM2696710", "GSM2696711", "GSM2696712"], "sample_count": 104, "group_sizes": null, "group_sizes_basis": null, "platform": "17077", "taxon": "Homo sapiens", "title": "Atherosclerotic and control peripheral artery gene expression", "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:GSE163154", "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=GSE163154", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE163154", "version": null, "note": "All data and analyses presented in this study are sourced from public databases, with all references clearly cited in the text.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data and analyses presented in this study are sourced from public databases, with all references clearly cited in the text.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4973394", "GSM4973395", "GSM4973397", "GSM4973398", "GSM4973400", "GSM4973401", "GSM4973403", "GSM4973404", "GSM4973406", "GSM4973408", "GSM4973409", "GSM4973411", "GSM4973412", "GSM4973414", "GSM4973415", "GSM4973417", "GSM4973418", "GSM4973419", "GSM4973421", "GSM4973422", "GSM4973424", "GSM4973425", "GSM4973427", "GSM4973429", "GSM4973430", "GSM4973432", "GSM4973433", "GSM4973435", "GSM4973436", "GSM4973438", "GSM4973439", "GSM4973440", "GSM4973441", "GSM4973443", "GSM4973444", "GSM4973445", "GSM4973446", "GSM4973448", "GSM4973449", "GSM4973451", "GSM4973452", "GSM4973454", "GSM4973456"], "sample_count": 43, "group_sizes": null, "group_sizes_basis": null, "platform": "6104", "taxon": "Homo sapiens", "title": "Maastricht Human Plaque Study (MaasHPS)", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"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": "All data and analyses presented in this study are sourced from public databases, with all references clearly cited in the text.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data and analyses presented in this study are sourced from public databases, with all references clearly cited in the text.", "access_statement_kind": "data_availability_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:GSE43292", "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=GSE43292", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE43292", "version": null, "note": "All data and analyses presented in this study are sourced from public databases, with all references clearly cited in the text.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data and analyses presented in this study are sourced from public databases, with all references clearly cited in the text.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1060117", "GSM1060118", "GSM1060119", "GSM1060120", "GSM1060121", "GSM1060122", "GSM1060123", "GSM1060124", "GSM1060125", "GSM1060126", "GSM1060127", "GSM1060128", "GSM1060129", "GSM1060130", "GSM1060131", "GSM1060132", "GSM1060133", "GSM1060134", "GSM1060135", "GSM1060136", "GSM1060137", "GSM1060138", "GSM1060139", "GSM1060140", "GSM1060141", "GSM1060142", "GSM1060143", "GSM1060144", "GSM1060145", "GSM1060146", "GSM1060147", "GSM1060148", "GSM1060149", "GSM1060150", "GSM1060151", "GSM1060152", "GSM1060153", "GSM1060154", "GSM1060155", "GSM1060156", "GSM1060157", "GSM1060158", "GSM1060159", "GSM1060160", "GSM1060161", "GSM1060162", "GSM1060163", "GSM1060164", "GSM1060165", "GSM1060166", "GSM1060167", "GSM1060168", "GSM1060169", "GSM1060170", "GSM1060171", "GSM1060172", "GSM1060173", "GSM1060174", "GSM1060175", "GSM1060176", "GSM1060177", "GSM1060178", "GSM1060179", "GSM1060180"], "sample_count": 64, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Genome-wide expression study of human carotid atheroma", "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:GSE100927 not downloaded", "asset:data:geo:GSE100927 licence not read", "asset:data:geo:GSE163154 not downloaded", "asset:data:geo:GSE163154 licence not read", "asset:data:geo:GSE28829 not downloaded", "asset:data:geo:GSE28829 licence not read", "asset:data:geo:GSE43292 not downloaded", "asset:data:geo:GSE43292 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "The “limma (Ritchie et al., 2015)” R package was employed to normalize the data and identify differentially expressed genes (DEGs)."}}, {"id": "method-2", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "pathway enrichment"}}, {"id": "method-4", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC analysis"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "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": ["GSE100927", "GSE43292", "GSE28829", "GSE163154"], "resolved_accessions": ["GSE100927", "GSE43292", "GSE28829", "GSE163154"], "statements": ["All data and analyses presented in this study are sourced from public databases, with all references clearly cited in the text."], "basis": "The paper names GSE100927, GSE43292, GSE28829, GSE163154 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:40248193", "data:geo:GSE100927"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE100927"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:50:27Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 8926, "completion_tokens": 1812, "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:40248193", "type": "paper", "label": "pmid:40248193"}, {"id": "source:pmid:40248193", "type": "manuscript", "label": "PMID 40248193 full text"}, {"id": "data:geo:GSE100927", "type": "dataset", "label": "GEO GSE100927"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40248193", "type": "paper", "label": "pmid:40248193"}, {"id": "source:pmid:40248193", "type": "manuscript", "label": "PMID 40248193 full text"}, {"id": "data:geo:GSE100927", "type": "dataset", "label": "GEO GSE100927"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40248193", "type": "extraction", "used": ["source:pmid:40248193"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE100927", "type": "accession_resolution", "used": ["data:geo:GSE100927"], "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:40248193", "parent_hash": "sha256:b18ad108deac56b5606170d0366cf9bbc95ca148d172ab1b0b20e55a72f9139b", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE100927 licence not read", "asset:data:geo:GSE100927 not downloaded", "asset:data:geo:GSE163154 licence not read", "asset:data:geo:GSE163154 not downloaded", "asset:data:geo:GSE28829 licence not read", "asset:data:geo:GSE28829 not downloaded", "asset:data:geo:GSE43292 licence not read", "asset:data:geo:GSE43292 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The “limma (Ritchie et al., 2015)” R package was employed to normalize the data and identify differentially expressed genes (DEGs)."], "order_basis": "analysis_only", "id": "assay:1"}]}