Predicting the Key Genes Involved in Aortic Valve Calcification Through Integrated Bioinformatics Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34046056", "kind": "science-record", "revision": 7, "content_hash": "sha256:b0ec069640c6a7b5c82b56e05ddf5ff2399723b7a244537e838f293074392466", "created_at": "2026-11-01T15:41:37Z", "updated_at": "2026-11-01T22:03:51Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Predicting the Key Genes Involved in Aortic Valve Calcification Through Integrated Bioinformatics Analysis.", "doi": "10.3389/fgene.2021.650213", "pmid": "34046056", "authors": ["Dinghui Wang", "Tianhua Xiong", "Wenlong Yu", "Bin Liu", "Jing Wang", "Kaihu Xiao", "Qiang She"], "journal": "Frontiers in genetics", "year": 2021, "abstract": "Background: Valvular heart disease is obtaining growing attention in the cardiovascular field and it is believed that calcific aortic valve disease (CAVD) is the most common valvular heart disease (VHD) in the world. CAVD does not have a fully effective treatment to delay its progression and the specific molecular mechanism of aortic valve calcification remains unclear. Materials and Methods: We obtained the gene expression datasets GSE12644 and GSE51472 from the public comprehensive free database GEO. Then, a series of bioinformatics methods, such as GO and KEGG analysis, STING online tool, Cytoscape software, were used to identify differentially expressed genes in CAVD and healthy controls, construct a PPI network, and then identify key genes. In addition, immune infiltration analysis was used via CIBERSORT to observe the expression of various immune cells in CAVD. Results: A total of 144 differential expression genes were identified in the CAVD samples in comparison with the control samples, including 49 up-regulated genes and 95 down-regulated genes. GO analysis of DEGs were most observably enriched in the immune response, signal transduction, inflammatory response, proteolysis, innate immune response, and apoptotic process. The KEGG analysis revealed that the enrichment of DEGs in CAVD were remarkably observed in the chemokine signaling pathway, cytokine-cytokine receptor interaction, and PI3K-Akt signaling pathway. Chemokines CXCL13, CCL19, CCL8, CXCL8, CXCL16, MMP9, CCL18, CXCL5, VCAM1, and PPBP were identified as the hub genes of CAVD. It was macrophages that accounted for the maximal proportion among these immune cells. The expression of macrophages M0, B cells memory, and Plasma cells were higher in the CAVD valves than in healthy valves, however, the expression of B cells naïve, NK cells activated, and macrophages M2 were lower. Conclusion: We detected that chemokines CXCL13, CXCL8, CXCL16, and CXCL5, and CCL19, CCL8, and CCL18 are the most important markers of aortic valve disease. The regulatory macrophages M0, plasma cells, B cells memory, B cells naïve, NK cells activated, and macrophages M2 are probably related to the occurrence and the advancement of aortic valve stenosis. These identified chemokines and these immune cells may interact with a subtle adjustment relationship in the development of calcification in CAVD.", "claims": [{"id": "claim-data-access", "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.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34046056", "locator": "sections[17] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s."}], "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:34046056"], "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:GSE12644"], "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:GSE12644"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34046056", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2021.650213", "sha256": 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"GSM663531", "GSM663532", "GSM663533", "GSM663534", "GSM663535", "GSM663536", "GSM663537", "GSM663538", "GSM663539", "GSM663540", "GSM663541", "GSM663542", "GSM663543", "GSM663544", "GSM663545", "GSM663546", "GSM663547", "GSM663548", "GSM663549", "GSM665514", "GSM665515", "GSM665516", "GSM665517", "GSM665518", "GSM665519", "GSM665520", "GSM665521", "GSM665522", "GSM665523", "GSM665524", "GSM665525", "GSM665526", "GSM665527", "GSM665528", "GSM665529", "GSM665530", "GSM665531", "GSM665532", "GSM665533", "GSM665534", "GSM665535", "GSM665536", "GSM665537"], "sample_count": 48, "group_sizes": null, "group_sizes_basis": null, "platform": "8179;6947", "taxon": "Homo sapiens", "title": "Discovery of Shear- and Side-specific mRNAs and miRNAs in Human Aortic Valvular Endothelial Cells", "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:GSE51472", "role": 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URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2203485", "GSM2203486", "GSM2203487", "GSM2203488", "GSM2203489", "GSM2203490", "GSM2203491", "GSM2203492", "GSM2203493", "GSM2203494", "GSM2203495", "GSM2203496", "GSM2203497", "GSM2203498", "GSM2203499", "GSM2203500", "GSM2203501", "GSM2203502", "GSM2203503", "GSM2203504", "GSM2203505", "GSM2203506", "GSM2203507", "GSM2203508", "GSM2203509", "GSM2203510", "GSM2203511"], "sample_count": 27, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Gene expression profile of calcified bicuspid, tricuspid and normal human aortic valves", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:34046056:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:10d85eb9a4bd1c2bb20d3097073a8aaf6baaf3df75a6ae6f65bebc286dbc1246", "bytes": 3806, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#T1", "version": null, "note": "The GO functional enrichment analyses of DEGs ranked by count.", "structure": {"pmcid": "PMC8144713", "section_index": 11, "section_title": "GO and KEGG Functional Analysis of DEGs in CAVD", "row_count": 22, "column_count": 4}, "table": {"label": "TABLE 1", "caption": "The GO functional enrichment analyses of DEGs ranked by count.", "rows": [["Term", "Count", "Genes", "P-value"], ["GO-BPs", "", "", ""], ["GO:0006955∼immune response", "23", "ADAMDEC1, CXCL8, GZMA, GPR65, AQP9, C5AR1, PRG4, PPBP, CXCL13, CXCL5, JCHAIN, FCGR3A, FCGR3B, CCL8, IGKC, TRBC1, CTSG, IGLC1, PKHD1L1, CCL19, IL7R, CCL18, and FCGR1B", "1.08E-12"], ["GO:0007165∼signal transduction", "17", "CXCL8, TNFAIP6, C5AR1, TRHDE, RASGRP1, CXCL5, ADRA2A, GREM1, CCL8, PLAU, WIF1, KIT, CLEC5A, NDP, IL7R, CCL18, and S100A9", "0.016322305"], ["GO:0006954∼inflammatory response", "16", "CXCL8, TNFAIP6, C5AR1, LY86, PPBP, CXCL13, CXCL5, CCL8, KIT, SPP1, CHI3L1, CCL19, CCL18, S100A9, SCG2, and S100A8", "2.20E-07"], ["GO:0006508∼proteolysis", "15", "FCN1, CPA3, ADAMDEC1, TPSB2, MMP1, TRHDE, MMP9, MMP12, GZMK, MMP13, RELN, IGKC, PLAU, CTSG, and IGLC1", "3.05E-05"], ["GO:0045087∼innate immune response", "11", "IGHM, C6, FCER1G, IGKC, CLEC5A, LY86, IGLC1, TREM1, S100A9, S100A8, and JCHAIN", "0.001788216"], ["GO:0006915∼apoptotic process", "11", "CD2, SHC4, GREM1, GZMA, GPR65, C5AR1, LY86, GZMB, CHI3L1, S100A9, and S100A8", "0.012113741"], ["GO-CCs", "", "", ""], ["GO:0005886∼plasma membrane", "48", "SHC4, GPM6A, IGHM, GPR65, C5AR1, AQP9, C2ORF88, GPR83, ATP1A2, GPR84, IFI30, TREM1, RASGRP1, CXCL16, FCGR3A, RELN, FCGR3B, IGKC, PRKAR2B, PLAU, LAMP3, TRBC1, CLEC5A, HMOX1, SCN7A, IGLC1, CTSG, FCGR1B, PRIMA1, FCER1G, VCAM1, CD93, ANXA3, LY86, SLC16A10, ADRA2A, VMP1, CD2, VNN2, KIT, GPR160, PCDHB5, PLPP3, IL7R, STEAP1, S100A9, S100A8, and CLEC4G", "8.05E-04"], ["GO:0005576∼extracellular region", "46", "FCN1, ADAMDEC1, TPSB2, CXCL8, COL11A1, TNC, NDNF, CXCL13, IFI30, THBS2, TREM1, PLA2G7, CHRDL1, CXCL5, CXCL16, JCHAIN, APELA, C6, IBSP, IGKC, PLAU, WIF1, SPP1, COL10A1, IGLC1, CTSG, CCL19, PLTP, CPA3, CHST9, MMP1, GZMA, ADIPOQ, PRG4, PPBP, MMP9, MFAP5, CD2, MMP12, GZMK, IGSF10, MMP13, COL6A6, IL7R, S100A9, and S100A8", "1.19E-15"], ["GO:0005615∼extracellular space", "41", "IGHM, CXCL8, TNFAIP6, TNC, CXCL13, CHRDL2, CXCL5, CXCL16, JCHAIN, APELA, RELN, CCL8, IBSP, IGKC, PLAU, SPP1, HMOX1, IGLC1, CTSG, NDP, CCL19, CCL18, PLTP, TIMP4, CTHRC1, CPA3, VCAM1, MYOC, ADIPOQ, LY86, PPBP, MMP9, GREM1, MMP13, KIT, CHI3L1, PKHD1L1, S100A9, SCG2, S100A8, and ANGPTL1", "1.04E-14"], ["GO:0070062∼extracellular exosome", "31", "GPM6A, IGHM, ITLN1, TRHDE, COCH, JCHAIN, FCGR3A, C6, FCGR3B, ALDH2, IGKC, TSPAN8, PRKAR2B, PLAU, SPP1, ACP5, IGLC1, CTSG, VCAM1, MYOC, ANXA3, ADIPOQ, MMP9, KRT18, KRT14, CHI3L1, MNDA, PLPP3, S100A9, S100A8, and ANGPTL1", "0.022687598"], ["GO:0005887∼integral component of plasma membrane", "17", "CD52, FCER1G, SCARA5, GPR65, AQP9, C5AR1, LAPTM5, GPR83, SLC16A10, GPR84, TRHDE, ADRA2A, CD2, TSPAN8, CLEC5A, PLPP3, and STEAP1", "0.059028895"], ["GO:0005578∼proteinaceous extracellular matrix", "14", "MYOC, MMP1, COL11A1, NDNF, MMP9, COCH, MMP12, MMP13, RELN, COL10A1, CHI3L1, COL6A6, TIMP4, and CTHRC1", "9.98E-08"], ["GO-MFs", "", "", ""], ["GO:0004252∼serine-type endopeptidase activity", "13", "FCN1, TPSB2, MMP1, GZMA, GZMB, MMP9, MMP12, GZMK, MMP13, IGKC, PLAU, CTSG, and IGLC1", "3.25E-07"], ["GO:0042803∼protein homodimerization activity", "11", "CD2, BCL2A1, GZMA, ID1, KIT, ADIPOQ, HMOX1, NDP, RASGRP1, ADRA2A, and JCHAIN", "0.038761584"], ["GO:0005509∼calcium ion binding", "10", "MMP12, MMP13, CD93, ANXA3, MMP1, PCDHB5, THBS2, S100A9, RASGRP1, and S100A8", "0.075449087"], ["GO:0008009∼chemokine activity", "8", "CCL8, CXCL8, PPBP, CCL19, CXCL13, CCL18, CXCL5, and CXCL16", "5.78E-08"], ["GO:0003823∼antigen binding", "5", "IGHM, IGKC, IGLC1, IL7R, and JCHAIN", "0.006624345"], ["GO:0004222∼metalloendopeptidase activity", "5", "MMP12, ADAMDEC1, MMP13, MMP1, and MMP9", "0.009131648"]], "row_count": 22, "column_count": 4, "numeric_cells": 70, "header_rows": 1, "locator": "section[11]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:34046056:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b7c902c1563aca90a8548d1f04b65fee973bfea9f4a1ae035cd11c9d98c917ec", "bytes": 1436, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[2]#T2", "version": null, "note": "The KEGG pathway analysis of DEGs ranked by count.", "structure": {"pmcid": "PMC8144713", "section_index": 11, "section_title": "GO and KEGG Functional Analysis of DEGs in CAVD", "row_count": 13, "column_count": 4}, "table": {"label": "TABLE 2", "caption": "The KEGG pathway analysis of DEGs ranked by count.", "rows": [["Term", "Count", "Genes", "P-value"], ["KEGG_PATHWAY", "", "", ""], ["hsa04062:Chemokine signaling pathway", "9", "SHC4, CCL8, CXCL8, PPBP, CCL19, CXCL13, CCL18, CXCL5, and CXCL16", "2.12E-04"], ["hsa04060:Cytokine-cytokine receptor interaction", "9", "CCL8, CXCL8, PPBP, CCL19, CXCL13, IL7R, CCL18, CXCL5, and CXCL16", "0.001258766"], ["hsa04151:PI3K-Akt signaling pathway", "9", "RELN, IBSP, COL11A1, KIT, SPP1, TNC, COL6A6, THBS2, and IL7R", "0.010615579"], ["hsa04510:Focal adhesion", "8", "SHC4, RELN, IBSP, COL11A1, SPP1, TNC, COL6A6, and THBS2", "0.002157992"], ["hsa04512:ECM-receptor interaction", "7", "RELN, IBSP, COL11A1, SPP1, TNC, COL6A6, and THBS2", "1.09E-04"], ["hsa04974:Protein digestion and absorption", "6", "CPA3, COL11A1, COL10A1, COL6A6, ATP1A2, and SLC16A10", "0.001034968"], ["hsa03320:PPAR signaling pathway", "5", "ACADL, MMP1, ADIPOQ, PLIN1, and PLTP", "0.002827573"], ["hsa04064:NF-kappa B signaling pathway", "5", "VCAM1, CXCL8, BCL2A1, PLAU, and CCL19", "0.007200464"], ["hsa04650:Natural killer cell mediated cytotoxicity", "5", "SHC4, FCGR3A, FCGR3B, FCER1G, and GZMB", "0.022607194"], ["hsa05323:Rheumatoid arthritis", "4", "CXCL8, MMP1, ACP5, and CXCL5", "0.042784539"], ["hsa00380:Tryptophan metabolism", "3", "TDO2, ALDH2, and MAOA", "0.048643268"]], "row_count": 13, "column_count": 4, "numeric_cells": 40, "header_rows": 1, "locator": "section[11]/table-wrap[2]#T2"}}, {"id": "asset:table:pmid:34046056:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:595ee946cbcd114053eebca3262837acf5faaf967fedd66a1610628f9183a904", "bytes": 6565, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#T3", "version": null, "note": "Summary of the function of 10 hub genes.", "structure": {"pmcid": "PMC8144713", "section_index": 12, "section_title": "Establishment of PPI Network and Module Analysis", "row_count": 12, "column_count": 3}, "table": {"label": "TABLE 3", "caption": "Summary of the function of 10 hub genes.", "rows": [["Top 10 in network string_interactions.tsv_MCC_top10 ranked by MCC method"], ["Gene symbol", "Full name", "Function"], ["CXCL13", "C-X-C motif chemokine ligand 13", "B lymphocyte chemoattractant, independently cloned and named Angie, is an antimicrobial peptide and CXC chemokine strongly expressed in the follicles of the spleen, lymph nodes, and Peyer’s patches. It preferentially promotes the migration of B lymphocytes (compared to T cells and macrophages), apparently by stimulating calcium influx into, and chemotaxis of, cells expressing Burkitt’s lymphoma receptor 1 (BLR-1). It may therefore function in the homing of B lymphocytes to follicles"], ["CCL19", "C-C motif chemokine ligand 19", "One of several CC cytokine genes clustered on the p-arm of chromosome 9. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The cytokine encoded by this gene may play a role in normal lymphocyte recirculation and homing. It also plays an important role in trafficking of T cells in thymus, and in T cell and B cell migration to secondary lymphoid organs. It specifically binds to chemokine receptor CCR"], ["CCL8", "C-C motif chemokine ligand 8", "One of several chemokine genes clustered on the q-arm of chromosome 17. Chemokines form a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of N-terminal cysteine residues of the mature peptide. This chemokine is a member of the CC subfamily which is characterized by two adjacent cysteine residues. This cytokine displays chemotactic activity for monocytes, lymphocytes, basophils, and eosinophils"], ["CXCL8", "C-X-C motif chemokine ligand 8", "A member of the CXC chemokine family and is a major mediator of the inflammatory response. The encoded protein is commonly referred to as interleukin-8 (IL-8). IL-8 is secreted by mononuclear macrophages, neutrophils, and eosinophils, T lymphocytes, epithelial cells, and fibroblasts. It functions as a chemotactic factor by guiding the neutrophils to the site of infection. Bacterial and viral products rapidly induce IL-8 expression. IL-8 also participates with other cytokines in the proinflammatory signaling cascade and plays a role in systemic inflammatory response syndrome (SIRS). This gene is believed to play a role in the pathogenesis of the lower respiratory tract infection bronchiolitis, a common respiratory tract disease caused by the respiratory syncytial virus (RSV). The overproduction of this proinflammatory protein is thought to cause the lung inflammation associated with csytic fibrosis. This proinflammatory protein is also suspected of playing a role in coronary artery disease and endothelial dysfunction. This protein is also secreted by tumor cells and promotes tumor migration, invasion, angiogenesis and metastasis."], ["CXCL16", "C-X-C motif chemokine ligand 16", "CXCL16 (C-X-C Motif Chemokine Ligand 16) is a Protein Coding gene. Diseases associated with CXCL16 include Xanthogranulomatous Cholecystitis and Systemic Lupus Erythematosus. Among its related pathways are Signaling by GPCR and PEDF Induced Signaling. Gene Ontology (GO) annotations related to this gene include chemokine activity and low-density lipoprotein particle receptor activity."], ["MMP9", "Matrix metallopeptidase 9", "The matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP’s are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The enzyme encoded by this gene degrades type IV and V collagens. Studies in rhesus monkeys suggest that the enzyme is involved in IL-8-induced mobilization of hematopoietic progenitor cells from bone marrow, and murine studies suggest a role in tumor-associated tissue remodeling"], ["CCL18", "C-C motif chemokine ligand 18", "One of several Cys-Cys (CC) cytokine genes clustered on the q arm of chromosome 17. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The cytokine encoded by this gene displays chemotactic activity for naive T cells, CD4+ and CD8+ T cells and nonactivated lymphocytes, but not for monocytes or granulocytes. This chemokine attracts naive T lymphocytes toward dendritic cells and activated macrophages in lymph nodes. It may play a role in both humoral and cell-mediated immunity responses"], ["CXCL5", "C-X-C motif chemokine ligand 5", "This gene encodes a protein that is a member of the CXC subfamily of chemokines. Chemokines, which recruit and activate leukocytes, are classified by function (inflammatory or homeostatic) or by structure. This protein is proposed to bind the G-protein coupled receptor chemokine (C-X-C motif) receptor 2 to recruit neutrophils, to promote angiogenesis and to remodel connective tissues. This protein is thought to play a role in cancer cell proliferation, migration, and invasion"], ["VCAM1", "Vascular cell adhesion molecule 1", "A member of the Ig superfamily and encodes a cell surface sialoglycoprotein expressed by cytokine-activated endothelium. This type I membrane protein mediates leukocyte-endothelial cell adhesion and signal transduction, and may play a role in the development of artherosclerosis and rheumatoid arthritis. Three alternatively spliced transcripts encoding different isoforms have been described for this gene."], ["PPBP", "Pro-platelet basic protein", "The protein encoded by this gene is a platelet-derived growth factor that belongs to the CXC chemokine family. This growth factor is a potent chemoattractant and activator of neutrophils. It has been shown to stimulate various cellular processes including DNA synthesis, mitosis, glycolysis, intracellular cAMP accumulation, prostaglandin E2 secretion, and synthesis of hyaluronic acid and sulfated glycosaminoglycan. It also stimulates the formation and secretion of plasminogen activator by synovial cells. The protein also is an antimicrobial protein with bactericidal and antifungal activity"]], "row_count": 12, "column_count": 3, "numeric_cells": 22, "header_rows": 2, "locator": "section[12]/table-wrap[1]#T3"}}], "gaps": ["asset:data:geo:GSE12644 not downloaded", "asset:data:geo:GSE12644 licence not read", "asset:data:geo:GSE26953 not downloaded", "asset:data:geo:GSE26953 licence not read", "asset:data:geo:GSE51472 not downloaded", "asset:data:geo:GSE51472 licence not read", "asset:data:geo:GSE83453 not downloaded", "asset:data:geo:GSE83453 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 1.0, "band": "reordered", "quote": "“Pearson correlation analysis shows that CCL8, CCL18, CCL19, CXCL16, and VCAM1 are positively correlated with fatty acid synthase (FAS) gene and hydroxymethylglutaryl coenzyme A reductase (HMGCR) gene among the 10 hub genes (Figures 7A,B), yet CXCL13, CXCL5, and CXCL8 have a strong negative correlation with the lecithin cholesterol acyltransferase (CAT) gene (Figure 7C).”"}}, {"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": 0.8, "band": "high", "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": 0.7, "band": "medium", "quote": "PPI"}}, {"id": "method-4", "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": "GO Enrichment"}}], "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": ["pearson_r"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pearson."}, "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": ["GSE12644", "GSE51472", "GSE83453", "GSE26953"], "resolved_accessions": ["GSE12644", "GSE51472", "GSE83453", "GSE26953"], "statements": ["The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s."], "basis": "The paper names GSE12644, GSE51472, GSE83453, GSE26953 in Expression Omnibus Gene (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["pearson_r"], "assets": ["source:pmid:34046056", "data:geo:GSE12644", "asset:table:pmid:34046056:1", "asset:table:pmid:34046056:2", "asset:table:pmid:34046056:3"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE12644"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:30:31Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 27944, "completion_tokens": 2506, "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:34046056", "type": "paper", "label": "pmid:34046056"}, {"id": "source:pmid:34046056", "type": "manuscript", "label": "PMID 34046056 full text"}, {"id": "data:geo:GSE12644", "type": "dataset", "label": "GEO GSE12644"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34046056", "type": "paper", "label": "pmid:34046056"}, {"id": "source:pmid:34046056", "type": "manuscript", "label": "PMID 34046056 full text"}, {"id": "data:geo:GSE12644", "type": "dataset", "label": "GEO GSE12644"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34046056", "type": "extraction", "used": ["source:pmid:34046056"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE12644", "type": "accession_resolution", "used": ["data:geo:GSE12644"], "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:34046056", "parent_hash": "sha256:a9dff4fc3184bd2da900b0da534a53a83c9f107e74baa4f3045f8f4811fa5257", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE12644 licence not read", "asset:data:geo:GSE12644 not downloaded", "asset:data:geo:GSE26953 licence not read", "asset:data:geo:GSE26953 not downloaded", "asset:data:geo:GSE51472 licence not read", "asset:data:geo:GSE51472 not downloaded", "asset:data:geo:GSE83453 licence not read", "asset:data:geo:GSE83453 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pearson_r"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["“Pearson correlation analysis shows that CCL8, CCL18, CCL19, CXCL16, and VCAM1 are positively correlated with fatty acid synthase (FAS) gene and hydroxymethylglutaryl coenzyme A reductase (HMGCR) gene among the 10 hub genes (Figures 7A,B), yet CXCL13, CXCL5, and CXCL8 have a strong negative correlation with the lecithin cholesterol acyltransferase (CAT) gene (Figure 7C).”"], "order_basis": "analysis_only", "id": "assay:1"}]}