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pmid:41158309

Metabolic-immune crosstalk in myocardial infarction: RLF and SMCHD1 identified as causal therapeutic targets via integrated lactylation-MR analysis.

Juli Tang · Lingyan Yuan · Yong-Li Han

Frontiers in cell and developmental biology · 2025 doi:10.3389/fcell.2025.1653551

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Experiment

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Data

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Metabolic-immune crosstalk in myocardial infarction: RLF and SMCHD1 identified as causal therapeutic targets via integrated lactylation-MR analysis.
doi
10.3389/fcell.2025.1653551
pmid
41158309
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Juli Tang
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Lingyan Yuan
[2]
Yong-Li Han
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Frontiers in cell and developmental biology
year
2025
abstract
Background: The diagnosis of Myocardial Infarction (MI) requires the discovery of specific diagnostic biomarkers beyond high-sensitivity cardiac troponins. To identify causal MI-associated genes regulated by lactylation modification and elucidate their roles in metabolic-immune dysregulation. Methods: This multi-omics study combined bioinformatic analyses of human MI datasets (GSE60993/GSE61144/GSE66360) with experimental validation to investigate lactylation-related genes (LRGs). Differential expression analysis (limma, P < 0.05, |log2FC|>0.585) identified 571 Differentially Expressed Genes (DEGs), which intersected with 2,051 curated lactylation-related genes (LRGs) (PubMed/GeneCards) yielding 56 lactylation-associated DEGs. Mendelian randomization (MR) utilized genetic instruments (P < 5 × 10-6) from Gene eQTL and three MI-GWAS cohorts (43,676 cases/128,199 controls), employing inverse-variance weighted (IVW) regression with sensitivity analyses (MR-Egger/weighted median). Functional enrichment (clusterProfiler) of the 56 DEGs examined GO/KEGG terms (FDR P < 0.05), supplemented by Gene Set Variation Analysis (GSVA) of Rearranged L-myc fusion (RLF) and Structural Maintenance of Chromosomes Hinge Domain Containing 1 (SMCHD1) expression strata and CIBERSORT-based immune infiltration assessment. Experimental validation involved LAD ligation-induced MI modeling in C57BL/6 mice, with RLF/SMCHD1 expression quantified via qPCR and Western blot. Results: Integrated transcriptomic analysis of three GEO datasets (73 MI patients, 67 controls) identified 571 DEGs. Cross-referencing these DEGs with 2,051 LRGs yielded 56 Lactylation-associated DEGs. MR analysis using 42,699 instrumental SNPs established RLF (AUC = 0.823) and SMCHD1 (AUC = 0.809) as causal risk genes that were significantly elevated in MI patients. Functional enrichment implicated both genes in metabolic dysregulation (nucleotide metabolism, HIF-1/MAPK signaling) and necroptosis. Immune profiling revealed increased monocytes, neutrophils, and activated CD4+ T cells within MI tissues, all positively correlated with RLF and SMCHD1 expression. Conversely, reduced CD8+ T cell infiltration correlated negatively with RLF expression. Independent validation confirmed significant RLF upregulation in MI. Quantitative analyses revealed significant increases in RLF and SMCHD1 expression-at both transcriptional (mRNA) and translational (protein) levels-in MI-induced mice relative to sham controls. Conclusion: This study pioneers the integration of lactylation modification with MR analysis for MI, establishing RLF and SMCHD1 as causal diagnostic biomarkers. Their dual roles in promoting metabolic dysregulation and pro-inflammatory immune infiltration position them as promising therapeutic targets for MI intervention.
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Primary analysis used IVW regression. Sensitivity analyses employed MR-Egger, weighted median, and simple mode methods.
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sections[6] "2.4 MR analysis" paragraph 2
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Primary analysis used IVW regression. Sensitivity analyses employed MR-Egger, weighted median, and simple mode methods.
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Data availability statement The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author(s). The publicly available datasets analyzed in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: (1) Gene Expression Omnibus (GEO): GSE60993: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60993 GSE61144: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61144 GSE66360: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66360 (2) GWAS summary statistics were obtained from the IEU OpenGWAS and GWAS Catalog platforms:ebi-a-GCST011365: https://opengwas.io/datasets/ebi-a-GCST011365ieu-a-798: https://opengwas.io/datasets/ieu-a-798ebi-a-GCST90018877: https://opengwas.io/datasets/ebi-a-GCST90018877 (3) The list of lactylation-related genes (LRGs) was curated from published literature and the GeneCards database (https://www.genecards.org/).
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Data availability statement The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author(s). The publicly available datasets analyzed in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: (1) Gene Expression Omnibus (GEO): GSE60993: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60993 GSE61144: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61144 GSE66360: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66360 (2) GWAS summary statistics were obtained from the IEU OpenGWAS and GWAS Catalog platforms:ebi-a-GCST011365: https://opengwas.io/datasets/ebi-a-GCST011365ieu-a-798: https://opengwas.io/datasets/ieu-a-798ebi-a-GCST90018877: https://opengwas.io/datasets/ebi-a-GCST90018877 (3) The list of lactylation-related genes (LRGs) was curated from published literature and the GeneCards database (https://www.genecards.org/).
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MR analysis identified RLF and SMCHD1 as causal MI-risk genes with high diagnostic accuracy, achieving AUCs of 0.823 and 0.809, respectively.
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sections[15] "3.2 Identification of Lactylation-associated" paragraph 2
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Through MR analysis under three predefined screening criteria (Supplementary Table S7), we established RLF and SMCHD1 as causal risk genes significantly elevated in MI patients
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Receiver operating characteristic (ROC) curves demonstrated high diagnostic accuracy for both genes (RLF: AUC = 0.823, Figure 2C; SMCHD1: AUC = 0.809; Figure 2F) in discriminating MI patients from controls.
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MR analysis identified RLF and SMCHD1 as causal MI-risk genes with high diagnostic accuracy, achieving AUCs of 0.823 and 0.809, respectively.
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Data availability statement The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author(s). The publicly available datasets analyzed in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: (1) Gene Expression Omnibus (GEO): GSE60993: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60993 GSE61144: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61144 GSE66360: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66360 (2) GWAS summary statistics were obtained from the IEU OpenGWAS and GWAS Catalog platforms:ebi-a-GCST011365: https://opengwas.io/datasets/ebi-a-GCST011365ieu-a-798: https://opengwas.io/datasets/ieu-a-798ebi-a-GCST90018877: https://opengwas.io/datasets/ebi-a-GCST90018877 (3) The list of lactylation-related genes (LRGs) was curated from published literature and the GeneCards database (https://www.genecards.org/).
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title
A Whole Blood Molecular Signature for the Identification of Acute Myocardial Infarction Without Relying Upon Myonecrosis (microarray)
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Data availability statement The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author(s). The publicly available datasets analyzed in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: (1) Gene Expression Omnibus (GEO): GSE60993: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60993 GSE61144: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61144 GSE66360: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66360 (2) GWAS summary statistics were obtained from the IEU OpenGWAS and GWAS Catalog platforms:ebi-a-GCST011365: https://opengwas.io/datasets/ebi-a-GCST011365ieu-a-798: https://opengwas.io/datasets/ieu-a-798ebi-a-GCST90018877: https://opengwas.io/datasets/ebi-a-GCST90018877 (3) The list of lactylation-related genes (LRGs) was curated from published literature and the GeneCards database (https://www.genecards.org/).
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e, with RLF/SMCHD1 expression quantified via qPCR and Western blot. Results: Integrated transc
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LF/SMCHD1 expression quantified via qPCR and Western blot. Results: Integrated transcriptomic analysis
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41158309", "kind": "science-record", "revision": 3, "content_hash": "sha256:763067fdcb84f340334e96a7cbba4696d8ae337d8e1ded889e2cf29a7d15fa0a", "created_at": "2026-11-01T20:31:12Z", "updated_at": "2026-11-01T22:14:54Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Metabolic-immune crosstalk in myocardial infarction: RLF and SMCHD1 identified as causal therapeutic targets via integrated lactylation-MR analysis.", "doi": "10.3389/fcell.2025.1653551", "pmid": "41158309", "authors": ["Juli Tang", "Lingyan Yuan", "Yong-Li Han"], "journal": "Frontiers in cell and developmental biology", "year": 2025, "abstract": "Background: The diagnosis of Myocardial Infarction (MI) requires the discovery of specific diagnostic biomarkers beyond high-sensitivity cardiac troponins. To identify causal MI-associated genes regulated by lactylation modification and elucidate their roles in metabolic-immune dysregulation.\nMethods: This multi-omics study combined bioinformatic analyses of human MI datasets (GSE60993/GSE61144/GSE66360) with experimental validation to investigate lactylation-related genes (LRGs). Differential expression analysis (limma, P < 0.05, |log2FC|>0.585) identified 571 Differentially Expressed Genes (DEGs), which intersected with 2,051 curated lactylation-related genes (LRGs) (PubMed/GeneCards) yielding 56 lactylation-associated DEGs. Mendelian randomization (MR) utilized genetic instruments (P < 5 × 10-6) from Gene eQTL and three MI-GWAS cohorts (43,676 cases/128,199 controls), employing inverse-variance weighted (IVW) regression with sensitivity analyses (MR-Egger/weighted median). Functional enrichment (clusterProfiler) of the 56 DEGs examined GO/KEGG terms (FDR P < 0.05), supplemented by Gene Set Variation Analysis (GSVA) of Rearranged L-myc fusion (RLF) and Structural Maintenance of Chromosomes Hinge Domain Containing 1 (SMCHD1) expression strata and CIBERSORT-based immune infiltration assessment. Experimental validation involved LAD ligation-induced MI modeling in C57BL/6 mice, with RLF/SMCHD1 expression quantified via qPCR and Western blot.\nResults: Integrated transcriptomic analysis of three GEO datasets (73 MI patients, 67 controls) identified 571 DEGs. Cross-referencing these DEGs with 2,051 LRGs yielded 56 Lactylation-associated DEGs. MR analysis using 42,699 instrumental SNPs established RLF (AUC = 0.823) and SMCHD1 (AUC = 0.809) as causal risk genes that were significantly elevated in MI patients. Functional enrichment implicated both genes in metabolic dysregulation (nucleotide metabolism, HIF-1/MAPK signaling) and necroptosis. Immune profiling revealed increased monocytes, neutrophils, and activated CD4+ T cells within MI tissues, all positively correlated with RLF and SMCHD1 expression. Conversely, reduced CD8+ T cell infiltration correlated negatively with RLF expression. Independent validation confirmed significant RLF upregulation in MI. Quantitative analyses revealed significant increases in RLF and SMCHD1 expression-at both transcriptional (mRNA) and translational (protein) levels-in MI-induced mice relative to sham controls.\nConclusion: This study pioneers the integration of lactylation modification with MR analysis for MI, establishing RLF and SMCHD1 as causal diagnostic biomarkers. Their dual roles in promoting metabolic dysregulation and pro-inflammatory immune infiltration position them as promising therapeutic targets for MI intervention.", "claims": [{"id": "claim-method", "statement": "Primary analysis used IVW regression. Sensitivity analyses employed MR-Egger, weighted median, and simple mode methods.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41158309", "locator": "sections[6] \"2.4 MR analysis\" paragraph 2", "quote": "Primary analysis used IVW regression. Sensitivity analyses employed MR-Egger, weighted median, and simple mode methods."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data availability statement\nThe original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author(s). The publicly available datasets analyzed in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: (1) Gene Expression Omnibus (GEO): GSE60993: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60993 GSE61144: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61144 GSE66360: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66360 (2) GWAS summary statistics were obtained from the IEU OpenGWAS and GWAS Catalog platforms:ebi-a-GCST011365: https://opengwas.io/datasets/ebi-a-GCST011365ieu-a-798: https://opengwas.io/datasets/ieu-a-798ebi-a-GCST90018877: https://opengwas.io/datasets/ebi-a-GCST90018877 (3) The list of lactylation-related genes (LRGs) was curated from published literature and the GeneCards database (https://www.genecards.org/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41158309", "locator": "sections[28] \"Data availability statement\" paragraphs 1-2", "quote": "Data availability statement\nThe original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author(s). The publicly available datasets analyzed in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: (1) Gene Expression Omnibus (GEO): GSE60993: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60993 GSE61144: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61144 GSE66360: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66360 (2) GWAS summary statistics were obtained from the IEU OpenGWAS and GWAS Catalog platforms:ebi-a-GCST011365: https://opengwas.io/datasets/ebi-a-GCST011365ieu-a-798: https://opengwas.io/datasets/ieu-a-798ebi-a-GCST90018877: https://opengwas.io/datasets/ebi-a-GCST90018877 (3) The list of lactylation-related genes (LRGs) was curated from published literature and the GeneCards database (https://www.genecards.org/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "MR analysis identified RLF and SMCHD1 as causal MI-risk genes with high diagnostic accuracy, achieving AUCs of 0.823 and 0.809, respectively.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41158309", "locator": "sections[15] \"3.2 Identification of Lactylation-associated\" paragraph 2", "quote": "Through MR analysis under three predefined screening criteria (Supplementary Table S7), we established RLF and SMCHD1 as causal risk genes significantly elevated in MI patients"}, {"asset": "source:pmid:41158309", "locator": "sections[15] \"3.2 Identification of Lactylation-associated\" paragraph 2", "quote": "Receiver operating characteristic (ROC) curves demonstrated high diagnostic accuracy for both genes (RLF: AUC = 0.823, Figure 2C; SMCHD1: AUC = 0.809; Figure 2F) in discriminating MI patients from controls."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "MR analysis identified RLF and SMCHD1 as causal MI-risk genes with high diagnostic accuracy, achieving AUCs of 0.823 and 0.809, 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:41158309"], "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:GSE60993"], "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_mann_whitney", "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:GSE60993"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_mann_whitney"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41158309", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcell.2025.1653551", "sha256": "sha256:3aa29ad4ba15767b2b43b95fd71f0d481faedd6493c0f145f5e3cb05432b4390", "bytes": 45858, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcell.2025.1653551", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12554677", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE60993", "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=GSE60993", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE60993", "version": null, "note": "Data availability statement\nThe original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author(s). The publicly available datasets analyzed in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: (1) Gene Expression Omnibus (GEO): GSE60993: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60993 GSE61144: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61144 GSE66360: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66360 (2) GWAS summary statistics were obtained from the IEU OpenGWAS and GWAS Catalog platforms:ebi-a-GCST011365: https://opengwas.io/datasets/ebi-a-GCST011365ieu-a-798: https://opengwas.io/datasets/ieu-a-798ebi-a-GCST90018877: https://opengwas.io/datasets/ebi-a-GCST90018877 (3) The list of lactylation-related genes (LRGs) was curated from published literature and the GeneCards database (https://www.genecards.org/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data availability statement\nThe original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author(s). The publicly available datasets analyzed in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: (1) Gene Expression Omnibus (GEO): GSE60993: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60993 GSE61144: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61144 GSE66360: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66360 (2) GWAS summary statistics were obtained from the IEU OpenGWAS and GWAS Catalog platforms:ebi-a-GCST011365: https://opengwas.io/datasets/ebi-a-GCST011365ieu-a-798: https://opengwas.io/datasets/ieu-a-798ebi-a-GCST90018877: https://opengwas.io/datasets/ebi-a-GCST90018877 (3) The list of lactylation-related genes (LRGs) was curated from published literature and the GeneCards database (https://www.genecards.org/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1495313", "GSM1495314", "GSM1495315", "GSM1495316", "GSM1495317", "GSM1495318", "GSM1495319", "GSM1495320", "GSM1495321", "GSM1495322", "GSM1495323", "GSM1495324", "GSM1495325", "GSM1495326", "GSM1495327", "GSM1495328", "GSM1495329", "GSM1495330", "GSM1495331", "GSM1495332", "GSM1495333", "GSM1495334", "GSM1495335", "GSM1495336", "GSM1495337", "GSM1495338", "GSM1495339", "GSM1495340", "GSM1495341", "GSM1495342", "GSM1495343", "GSM1495344", "GSM1495345"], "sample_count": 33, "group_sizes": null, "group_sizes_basis": null, "platform": "6884", "taxon": "Homo sapiens", "title": "Assessment and Diagnostic Relevance of Novel Serum Biomarkers for Early Decision of ST-elevation Myocardial Infarction", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE61144", "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=GSE61144", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE61144", "version": null, "note": "Data availability statement\nThe original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author(s). The publicly available datasets analyzed in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: (1) Gene Expression Omnibus (GEO): GSE60993: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60993 GSE61144: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61144 GSE66360: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66360 (2) GWAS summary statistics were obtained from the IEU OpenGWAS and GWAS Catalog platforms:ebi-a-GCST011365: https://opengwas.io/datasets/ebi-a-GCST011365ieu-a-798: https://opengwas.io/datasets/ieu-a-798ebi-a-GCST90018877: https://opengwas.io/datasets/ebi-a-GCST90018877 (3) The list of lactylation-related genes (LRGs) was curated from published literature and the GeneCards database (https://www.genecards.org/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data availability statement\nThe original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author(s). The publicly available datasets analyzed in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: (1) Gene Expression Omnibus (GEO): GSE60993: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60993 GSE61144: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61144 GSE66360: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66360 (2) GWAS summary statistics were obtained from the IEU OpenGWAS and GWAS Catalog platforms:ebi-a-GCST011365: https://opengwas.io/datasets/ebi-a-GCST011365ieu-a-798: https://opengwas.io/datasets/ieu-a-798ebi-a-GCST90018877: https://opengwas.io/datasets/ebi-a-GCST90018877 (3) The list of lactylation-related genes (LRGs) was curated from published literature and the GeneCards database (https://www.genecards.org/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1498369", "GSM1498370", "GSM1498371", "GSM1498372", "GSM1498373", "GSM1498374", "GSM1498375", "GSM1498376", "GSM1498377", "GSM1498378", "GSM1498379", "GSM1498380", "GSM1498381", "GSM1498382", "GSM1498383", "GSM1498384", "GSM1498385", "GSM1498386", "GSM1498387", "GSM1498388", "GSM1498389", "GSM1498390", "GSM1498391", "GSM1498392"], "sample_count": 24, "group_sizes": null, "group_sizes_basis": null, "platform": "6106", "taxon": "Homo sapiens", "title": "Expression data from blood samples of STEMI and Same STEMI patients after PIC", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE61145", "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=GSE61145", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE61145", "version": null, "note": "Data availability statement\nThe original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author(s). The publicly available datasets analyzed in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: (1) Gene Expression Omnibus (GEO): GSE60993: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60993 GSE61144: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61144 GSE66360: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66360 (2) GWAS summary statistics were obtained from the IEU OpenGWAS and GWAS Catalog platforms:ebi-a-GCST011365: https://opengwas.io/datasets/ebi-a-GCST011365ieu-a-798: https://opengwas.io/datasets/ieu-a-798ebi-a-GCST90018877: https://opengwas.io/datasets/ebi-a-GCST90018877 (3) The list of lactylation-related genes (LRGs) was curated from published literature and the GeneCards database (https://www.genecards.org/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data availability statement\nThe original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author(s). The publicly available datasets analyzed in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: (1) Gene Expression Omnibus (GEO): GSE60993: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60993 GSE61144: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61144 GSE66360: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66360 (2) GWAS summary statistics were obtained from the IEU OpenGWAS and GWAS Catalog platforms:ebi-a-GCST011365: https://opengwas.io/datasets/ebi-a-GCST011365ieu-a-798: https://opengwas.io/datasets/ieu-a-798ebi-a-GCST90018877: https://opengwas.io/datasets/ebi-a-GCST90018877 (3) The list of lactylation-related genes (LRGs) was curated from published literature and the GeneCards database (https://www.genecards.org/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1495313", "GSM1495314", "GSM1495315", "GSM1495316", "GSM1495317", "GSM1495318", "GSM1495319", "GSM1495320", "GSM1495321", "GSM1495322", "GSM1495323", "GSM1495324", "GSM1495325", "GSM1495326", "GSM1495327", "GSM1495328", "GSM1495329", "GSM1495330", "GSM1495331", "GSM1495332", "GSM1495333", "GSM1495334", "GSM1495335", "GSM1495336", "GSM1495337", "GSM1495338", "GSM1495339", "GSM1495340", "GSM1495341", "GSM1495342", "GSM1495343", "GSM1495344", "GSM1495345", "GSM1498369", "GSM1498370", "GSM1498371", "GSM1498372", "GSM1498373", "GSM1498374", "GSM1498375", "GSM1498376", "GSM1498377", "GSM1498378", "GSM1498379", "GSM1498380", "GSM1498381", "GSM1498382", "GSM1498383", "GSM1498384", "GSM1498385", "GSM1498386", "GSM1498387", "GSM1498388", "GSM1498389", "GSM1498390", "GSM1498391", "GSM1498392"], "sample_count": 57, "group_sizes": null, "group_sizes_basis": null, "platform": "6106;6884", "taxon": "Homo sapiens", "title": "Identification of Novel Serum Biomarkers for Early Decision of ST-elevation Myocardial Infarction", "resolution_checked_at": "2026-11-01T18:06:44Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE66360", "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=GSE66360", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE66360", "version": null, "note": "Data availability statement\nThe original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author(s). The publicly available datasets analyzed in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: (1) Gene Expression Omnibus (GEO): GSE60993: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60993 GSE61144: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61144 GSE66360: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66360 (2) GWAS summary statistics were obtained from the IEU OpenGWAS and GWAS Catalog platforms:ebi-a-GCST011365: https://opengwas.io/datasets/ebi-a-GCST011365ieu-a-798: https://opengwas.io/datasets/ieu-a-798ebi-a-GCST90018877: https://opengwas.io/datasets/ebi-a-GCST90018877 (3) The list of lactylation-related genes (LRGs) was curated from published literature and the GeneCards database (https://www.genecards.org/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data availability statement\nThe original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author(s). The publicly available datasets analyzed in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: (1) Gene Expression Omnibus (GEO): GSE60993: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60993 GSE61144: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61144 GSE66360: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66360 (2) GWAS summary statistics were obtained from the IEU OpenGWAS and GWAS Catalog platforms:ebi-a-GCST011365: https://opengwas.io/datasets/ebi-a-GCST011365ieu-a-798: https://opengwas.io/datasets/ieu-a-798ebi-a-GCST90018877: https://opengwas.io/datasets/ebi-a-GCST90018877 (3) The list of lactylation-related genes (LRGs) was curated from published literature and the GeneCards database (https://www.genecards.org/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1620819", "GSM1620820", "GSM1620821", "GSM1620822", "GSM1620823", "GSM1620824", "GSM1620825", "GSM1620826", "GSM1620827", "GSM1620828", "GSM1620829", "GSM1620830", "GSM1620831", "GSM1620832", "GSM1620833", "GSM1620834", "GSM1620835", "GSM1620836", "GSM1620837", "GSM1620838", "GSM1620839", "GSM1620840", "GSM1620841", "GSM1620842", "GSM1620843", "GSM1620844", "GSM1620845", "GSM1620846", "GSM1620847", "GSM1620848", "GSM1620849", "GSM1620850", "GSM1620851", "GSM1620852", "GSM1620853", "GSM1620854", "GSM1620855", "GSM1620856", "GSM1620857", "GSM1620858", "GSM1620859", "GSM1620860", "GSM1620861", "GSM1620862", "GSM1620863", "GSM1620864", "GSM1620865", "GSM1620866", "GSM1620867", "GSM1620868", "GSM1620869", "GSM1620870", "GSM1620871", "GSM1620872", "GSM1620873", "GSM1620874", "GSM1620875", "GSM1620876", "GSM1620877", "GSM1620878", "GSM1620879", "GSM1620880", "GSM1620881", "GSM1620882", "GSM1620883", "GSM1620884", "GSM1620885", "GSM1620886", "GSM1620887", "GSM1620888", "GSM1620889", "GSM1620890", "GSM1620891", "GSM1620892", "GSM1620893", "GSM1620894", "GSM1620895", "GSM1620896", "GSM1620897", "GSM1620898", "GSM1620899", "GSM1620900", "GSM1620901", "GSM1620902", "GSM1620903", "GSM1620904", "GSM1620905", "GSM1620906", "GSM1620907", "GSM1620908", "GSM1620909", "GSM1620910", "GSM1620911", "GSM1620912", "GSM1620913", "GSM1620914", "GSM1620915", "GSM1620916", "GSM1620917"], "sample_count": 99, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "A Whole Blood Molecular Signature for the Identification of Acute Myocardial Infarction Without Relying Upon Myonecrosis (microarray)", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE60993 not downloaded", "asset:data:geo:GSE60993 licence not read", "asset:data:geo:GSE61144 not downloaded", "asset:data:geo:GSE61144 licence not read", "asset:data:geo:GSE61145 not downloaded", "asset:data:geo:GSE61145 licence not read", "asset:data:geo:GSE66360 not downloaded", "asset:data:geo:GSE66360 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "mann_whitney", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_mann_whitney"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Mann-Whitney"}}, {"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": "genetic_association", "specific": "gwas", "label": "Genetic association (GWAS / linkage / MR)", "dsl_operations": ["gwas_locus_scan"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["genotype_phenotype_table"], "evidence": {"score": 0.7, "band": "medium", "quote": "GWAS"}}, {"id": "method-4", "family": "genetic_association", "specific": "mendelian_randomisation", "label": "Genetic association (GWAS / linkage / MR)", "dsl_operations": ["mr_estimate"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["genotype_phenotype_table"], "evidence": {"score": 0.7, "band": "medium", "quote": "Mendelian randomization"}}, {"id": "method-5", "family": null, "specific": null, "label": "Inverse-variance weighted regression, with MR-Egger, weighted median, and simple mode sensitivity analyses", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Primary analysis used IVW regression. Sensitivity analyses employed MR-Egger, weighted median, and simple mode methods."}}], "targets": [], "gaps": ["method.reader_named_unmapped", "method.group_comparison_mann_whitney"]}, "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_mann_whitney"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: mann_whitney."}, "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": ["GSE60993", "GSE61144", "GSE66360", "GSE61145"], "resolved_accessions": ["GSE60993", "GSE61144", "GSE66360", "GSE61145"], "statements": ["Data availability statement\nThe original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author(s). The publicly available datasets analyzed in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: (1) Gene Expression Omnibus (GEO): GSE60993: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60993 GSE61144: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61144 GSE66360: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66360 (2) GWAS summary statistics were obtained from the IEU OpenGWAS and GWAS Catalog platforms:ebi-a-GCST011365: https://opengwas.io/datasets/ebi-a-GCST011365ieu-a-798: https://opengwas.io/datasets/ieu-a-798ebi-a-GCST90018877: https://opengwas.io/datasets/ebi-a-GCST90018877 (3) The list of lactylation-related genes (LRGs) was curated from published literature and the GeneCards database (https://www.genecards.org/)."], "basis": "The paper names GSE60993, GSE61144, GSE66360, GSE61145 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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