{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31667013", "kind": "science-record", "revision": 8, "content_hash": "sha256:699fa92289778a7dc052f0e5b2c2e6043ebf83bace0ce95342066d32a8a496fa", "created_at": "2026-11-01T15:40:51Z", "updated_at": "2026-11-01T22:44:17Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of hub genes and small-molecule compounds related to intracerebral hemorrhage with bioinformatics analysis.", "doi": "10.7717/peerj.7782", "pmid": "31667013", "authors": ["Zhendong Liu", "Ruotian Zhang", "Xin Chen", "Penglei Yao", "Tao Yan", "Wenwu Liu", "Jiawei Yao", "Andrei Sokhatskii", "Ilgiz Gareev", "Shiguang Zhao"], "journal": "PeerJ", "year": 2019, "abstract": "BACKGROUND: Because of the complex mechanisms of injury, conventional surgical treatment and early blood pressure control does not significantly reduce mortality or improve patient prognosis in cases of intracerebral hemorrhage (ICH). We aimed to identify the hub genes associated with intracerebral hemorrhage, to act as therapeutic targets, and to identify potential small-molecule compounds for treating ICH.\nMETHODS: The GSE24265 dataset, consisting of data from four perihematomal brain tissues and seven contralateral brain tissues, was downloaded from the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (DEGs) in ICH, with a fold change (FC) value of (|log2FC|) > 2 and a P-value of <0.05 set as cut-offs. The functional annotation of DEGs was performed using Gene Ontology (GO) resources, and the cell signaling pathway analysis of DEGs was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), with a P-value of <0.05 set as the cut-off. We constructed a protein-protein interaction (PPI) network to clarify the interrelationships between the different DEGs and to select the hub genes with significant interactions. Next, the DEGs were analyzed using the CMap tool to identify small-molecule compounds with potential therapeutic effects. Finally, we verified the expression levels of the hub genes by RT-qPCR on the rat ICH model.\nRESULT: A total of 59 up-regulated genes and eight down-regulated genes associated with ICH were identified. The biological functions of DEGs associated with ICH are mainly involved in the inflammatory response, chemokine activity, and immune response. The KEGG analysis identified several pathways significantly associated with ICH, including but not limited to HIF-1, TNF, toll-like receptor, cytokine-cytokine receptor interaction, and chemokine molecules. A PPI network consisting of 57 nodes and 373 edges was constructed using STRING, and 10 hub genes were identified with Cytoscape software. These hub genes are closely related to secondary brain injury induced by ICH. RT-qPCR results showed that the expression of ten hub genes was significantly increased in the rat model of ICH. In addition, a CMap analysis of three small-molecule compounds revealed their therapeutic potential.\nCONCLUSION: In this study we obtained ten hub genes, such as IL6, TLR2, CXCL1, TIMP1, PLAUR, SERPINE1, SELE, CCL4, CCL20, and CD163, which play an important role in the pathology of ICH. At the same time, the ten hub genes obtained through PPI network analysis were verified in the rat model of ICH. In addition, we obtained three small molecule compounds that will have therapeutic effects on ICH, including Hecogenin, Lidocaine, and NU-1025.", "claims": [{"id": "claim-method", "statement": "Both the normalization of the data and screening of the DEGs were performed using the limma package in the R language (version 3.5.1) (Guo et al., 2017).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31667013", "locator": "sections[4] \"Screening results of DEGs\" paragraph 2", "quote": "Both the normalization of the data and screening of the DEGs were performed using the limma package in the R language (version 3.5.1) (Guo et al., 2017)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data is available in the Gene Expression Omnibus: GSE24265.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31667013", "locator": "sections[25] \"Data Availability\" paragraph 2", "quote": "The data is available in the Gene Expression Omnibus: GSE24265."}], "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:31667013"], "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:GSE24265"], "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:GSE24265"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31667013", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.7782", "sha256": "sha256:e766602ecaf398934d8b9aa198682022c8e957fa2707ae055e0b27044b5cbf69", "bytes": 43478, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7717/peerj.7782", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6816389", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE24265", "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=GSE24265", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE24265", "version": null, "note": "The data is available in the Gene Expression Omnibus: GSE24265.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data is available in the Gene Expression Omnibus: GSE24265.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM596842", "GSM596843", "GSM596844", "GSM596845", "GSM596846", "GSM596847", "GSM596848", "GSM596849", "GSM596850", "GSM596851", "GSM596852"], "sample_count": 11, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Expression data from human brain samples", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:31667013:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ea9f09ff824b3fd88d6f80c8332c4ccb07458ec2fdb5e909eb49b811698e9390", "bytes": 297, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#table-1", "version": null, "note": "Details for GEO ICH data.", "structure": {"pmcid": "PMC6816389", "section_index": 11, "section_title": "Identification of DEGs in ICH", "row_count": 2, "column_count": 7}, "table": {"label": "Table 1", "caption": "Details for GEO ICH data.", "rows": [["Reference", "Sample", "GEO", "Platform", "PH", "CW", "CG"], ["Rosell et al. (2011)", "Brain", "GSE24265", "GPL570", "4", "4", "3"]], "row_count": 2, "column_count": 7, "numeric_cells": 6, "header_rows": 1, "locator": "section[11]/table-wrap[1]#table-1"}}, {"id": "asset:table:pmid:31667013:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:a643ad17cca87b31499178549ccd55ecdce71f156cffca2efa2e2229794f35ea", "bytes": 733, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[2]#table-2", "version": null, "note": "Screening DEGs in ICH by integrated microarray.", "structure": {"pmcid": "PMC6816389", "section_index": 11, "section_title": "Identification of DEGs in ICH", "row_count": 3, "column_count": 2}, "table": {"label": "Table 2", "caption": "Screening DEGs in ICH by integrated microarray.", "rows": [["DEGs", "Gene terms"], ["Upregulated", "CXCL8, CCL20, C15orf48, CXCL1, VMP1, AGPAT9, G0S2, CXCL3, PTX3, TFPI2, CYTIP, TNFAIP3, PPBP, HSPA6, BCL2A1, TREM1, CCL4, IL18RAP, PMAIP1, SERPINE1, HBD, TGFBI, PNP, SELE, TIMP1, IL6, NCF2, PLAUR, LAPTM5, TCIRG1, OLR1, HBB, DUSP5, ISG20,S100P, PROK2, METRNL, CTGF, CD93,HCAR3, ANXA2P2, C5AR1, TLR2, FGR,MARCO, HMOX1, TUBB6, CYB5R2 ADM, UPP1, SLC2A3, CD163, BCAT1,CLEC5A, CCL8, HLA-DRA, TNFRSF12A,ANXA2, S100A11."], ["Downregulated", "NXPH1, PRRT2, SLITRK5, SOWAHA, CNTN3, CACNA2D3, MUM1L1, ZNRF3."]], "row_count": 3, "column_count": 2, "numeric_cells": 1, "header_rows": 1, "locator": "section[11]/table-wrap[2]#table-2"}}, {"id": "asset:table:pmid:31667013:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f6e45cb3bc72bc77ed1ac87e5d8fc2314fd2ec4feb80585312e93cb2f2308d7e", "bytes": 2085, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#table-3", "version": null, "note": "Top 10 of the most significantly enriched GO terms.", "structure": {"pmcid": "PMC6816389", "section_index": 12, "section_title": "Functional annotation analysis of DEGs using GO", "row_count": 34, "column_count": 4}, "table": {"label": "Table 3", "caption": "Top 10 of the most significantly enriched GO terms.", "rows": [["Pathway ID", "Terms", "Gene count", "P-value"], ["BP", "", "", ""], ["GO:0006954", "Inflammatory response", "16", "5.41E−12"], ["GO:0030593", "Neutrophil chemotaxis", "8", "4.33E−09"], ["GO:0006955", "Immune response", "13", "3.67E−08"], ["GO:0070098", "Chemokine-mediated signaling pathway", "7", "2.35E−07"], ["GO:0006935", "Chemotaxis", "7", "5.73E−06"], ["GO:0001525", "Angiogenesis", "8", "1.75E−05"], ["GO:0032496", "Response to lipopolysaccharide", "7", "3.10E−05"], ["GO:0090023", "Positive regulation of neutrophil chemotaxis", "4", "7.02E−05"], ["GO:0071347", "Cellular response to interleukin-1", "5", "1.36E−04"], ["GO:0045765", "Regulation of angiogenesis", "4", "2.00E−04"], ["CC", "", "", ""], ["GO:0005615", "Extracellular space", "19", "5.27E−07"], ["GO:0005576", "Extracellular region", "19", "6.79E−06"], ["GO:0005886", "Plasma membrane", "27", "9.38E−04"], ["GO:0005604", "Basement membrane", "4", "2.70E−03"], ["GO:0005887", "Integral component of plasma membrane", "13", "3.43E−03"], ["GO:0070062", "Extracellular exosome", "19", "6.75E−03"], ["GO:0009986", "Cell surface", "7", "1.18E−02"], ["GO:0031093", "Platelet alpha granule lumen", "3", "1.60E−02"], ["GO:0031012", "Extracellular matrix", "5", "2.02E−02"], ["GO:0030666", "Endocytic vesicle membrane", "3", "2.25E−02"], ["MF", "", "", ""], ["GO:0008009", "Chemokine activity", "7", "2.25E−02"], ["GO:0045236", "CXCR chemokine receptor binding", "3", "2.25E−02"], ["GO:0008083", "Growth factor activity", "5", "2.25E−02"], ["GO:0002020", "Protease binding", "4", "2.25E−02"], ["GO:0004872", "Receptor activity", "5", "2.25E−02"], ["GO:0048306", "Calcpium-dependent protein binding", "3", "2.25E−02"], ["GO:0008329", "Signaling pattern recognition receptor activity", "2", "2.25E−02"], ["GO:0001849", "Complement component C1q binding", "2", "2.25E−02"], ["GO:0005102", "Receptor binding", "5", "2.25E−02"], ["GO:0004859", "Phospholipase inhibitor activity", "2", "2.25E−02"]], "row_count": 34, "column_count": 4, "numeric_cells": 91, "header_rows": 1, "locator": "section[12]/table-wrap[1]#table-3"}}, {"id": "asset:table:pmid:31667013:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:8b97292bc0269a4b9613006c39a753185ab84ce77cbf759ba40370a5956f3b9a", "bytes": 2816, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#table-4", "version": null, "note": "Significantly enriched KEGG pathway.", "structure": {"pmcid": "PMC6816389", "section_index": 13, "section_title": "KEGG pathway analysis of DEGs", "row_count": 30, "column_count": 5}, "table": {"label": "Table 4", "caption": "Significantly enriched KEGG pathway.", "rows": [["Pathway ID", "Terms", "Gene count", "P-Value", "Genes"], ["hsa04060", "Cytokine-cytokine receptor interaction", "10", "1.59E−09", "CCL4, CCL8, CXCL8, CCL20, TNFRSF12A, IL18RAP, CXCL3, PPBP, CXCL1, IL6"], ["hsa05323", "Rheumatoid arthritis", "7", "3.50E−09", "TCIRG1, CXCL8, CCL20, TLR2, CXCL1, HLA-DRA, IL6"], ["hsa05134", "Legionellosis", "6", "9.62E−09", "CXCL8, TLR2, CXCL3, CXCL1, IL6, HSPA6"], ["hsa04062", "Chemokine signaling pathway", "8", "3.28E−08", "CCL4, CCL8, CXCL8, CCL20, FGR, CXCL3, PPBP, CXCL1"], ["hsa04145", "Phagosome", "7", "1.45E−07", "TCIRG1, OLR1, NCF2, TLR2, TUBB6, HLA-DRA, MARCO"], ["hsa05144", "Malaria", "5", "2.19E−07", "IL6, CXCL8, HBB, SELE, TLR2"], ["hsa04668", "TNF signaling pathway", "6", "5.37E−07", "TNFAIP3, CCL20, CXCL3, SELE, CXCL1, IL6"], ["hsa05132", "Salmonella infection", "5", "3.30E−06", "CXCL1, CCL4, IL6, CXCL3, CXCL8"], ["hsa04621", "NOD-like receptor signaling pathway", "4", "1.78E−05", "CXCL1, IL6, TNFAIP3, UPP1"], ["hsa05321", "Inflammatory bowel disease (IBD)", "4", "2.43E−05", "HLA-DRA, IL6, IL18RAP, TLR2,"], ["hsa04064", "NF-kappa B signaling pathway", "4", "1.04E−04", "CCL4, TNFAIP3, BCL2A1, CXCL8"], ["hsa05143", "African trypanosomiasis", "3", "1.09E−04", "IL6, HBB, SELE"], ["hsa05146", "Amoebiasis", "4", "1.36E−04", "CXCL1, IL6, CXCL8, TLR2"], ["hsa04933", "AGE-RAGE signaling pathway in diabetic complications", "4", "1.52E−04", "IL6, SERPINE1, SELE, CXCL8"], ["hsa04066", "HIF-1 signaling pathway", "4", "1.63E−04", "IL6, SERPINE1, TIMP1, HMOX1"], ["hsa05142", "Chagas disease (American trypanosomiasis)", "4", "1.69E−04", "IL6, CXCL8, SERPINE1, TLR2"], ["hsa04620", "Toll-like receptor signaling pathway", "4", "1.81E−04", "CCL4, IL6, CXCL8, TLR2"], ["hsa05162", "Measles", "4", "4.47E−04", "IL6, TNFAIP3, HSPA6, TLR2"], ["hsa05120", "Epithelial cell signaling in Helicobacter pylori infection", "3", "7.57E−04", "CXCL1, TCIRG1, CXCL8"], ["hsa05140", "Leishmaniasis", "3", "8.21E−04", "HLA-DRA, NCF2, TLR2"], ["hsa05152", "Tuberculosis", "4", "1.04E−03", "TCIRG1, IL6, HLA-DRA, TLR2"], ["hsa05164", "Influenza A", "4", "1.06E−03", "HLA-DRA, IL6, HSPA6, CXCL8"], ["hsa04610", "Complement and coagulation cascades", "3", "1.15E−03", "C5AR1, PLAUR, SERPINE1"], ["hsa05169", "Epstein-Barr virus infection", "4", "1.85E−03", "HLA-DRA, FGR, TNFAIP3, HSPA6"], ["hsa05145", "Toxoplasmosis", "3", "3.57E−03", "HLA-DRA, HSPA6, TLR2"], ["hsa05332", "Graft-versus-host disease", "2", "4.53E−03", "HLA-DRA, IL6"], ["hsa04672", "Intestinal immune network for IgA production", "2", "6.46E−03", "HLA-DRA, IL6"], ["hsa05161", "Hepatitis B", "3", "6.47E−03", "IL6, CXCL8, TLR2"], ["hsa05150", "Staphylococcus aureus infection", "2", "8.12E−03", "HLA-DRA, C5AR1"]], "row_count": 30, "column_count": 5, "numeric_cells": 93, "header_rows": 1, "locator": "section[13]/table-wrap[1]#table-4"}}, {"id": "asset:table:pmid:31667013:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ec3f73777e8807c510ac4a9076c43b9d42a29a0a4e9682db72a479b9c1a0e95e", "bytes": 3185, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#table-5", "version": null, "note": "Significantly enriched GO of hub genes.", "structure": {"pmcid": "PMC6816389", "section_index": 14, "section_title": "PPI network construction and hub gene identification", "row_count": 38, "column_count": 5}, "table": {"label": "Table 5", "caption": "Significantly enriched GO of hub genes.", "rows": [["ID", "Description", "P-value", "Count", "Gene names"], ["BP", "", "", "", ""], ["GO:0009611", "Response to wounding", "4.58E−11", "9", "CXCL1/ IL6/ CCL20/ SERPINE1/ TLR2/ SELE/ CCL4/ PLAUR/ CD163."], ["GO:0006954", "Inflammatory response", "1.45E−08", "7", "CXCL1/ IL6/ CCL20/ TLR2/ SELE/ CCL4/ CD163."], ["GO:0006952", "Defense response", "6.44E−07", "7", "CXCL1/ IL6/ CCL20/ TLR2/ SELE/ CCL4/ CD163."], ["GO:0042330", "Taxis", "2.27E−06", "5", "CXCL1/ IL6/ CCL20/ CCL4/ PLAUR."], ["GO:0006935", "Chemotaxis", "2.27E−06", "5", "CXCL1/ IL6/ CCL20/ CCL4/ PLAUR."], ["GO:0006955", "Immune response", "2.25E−04", "4", "CXCL1/ IL6/ CCL20/ TLR2/ CCL4."], ["GO:0007596", "Blood coagulation", "6.88E−04", "5", "IL6/ SERPINE1/ PLAUR."], ["GO:0050817", "Coagulation", "0.001396979", "3", "IL6/ SERPINE1/ PLAUR."], ["GO:0007599", "Hemostasis", "0.001957914", "3", "IL6/ SERPINE1/ PLAUR."], ["GO:0042742", "Defense response to bacterium", "0.001957914", "3", "IL6/ CCL20/ TLR2."], ["GO:0006928", "Cell motion", "0.002191691", "3", "IL6/ SELE/ CCL4/ PLAUR."], ["GO:0050878", "Regulation of body fluid levels", "0.002354575", "3", "IL6/ SERPINE1/ PLAUR."], ["GO:0032101", "Regulation of response to external stimulus", "0.003084628", "4", "IL6/ SERPINE1/ SELE."], ["GO:0042060", "Wound healing", "0.003701403", "3", "IL6/ SERPINE1/ PLAUR."], ["GO:0032755", "Positive regulation of interleukin-6 production", "0.004681351", "3", "IL6/ TLR2."], ["GO:0042127", "Regulation of cell proliferation", "0.006688038", "3", "CXCL1/ IL6/ SERPINE1/ TIMP1."], ["GO:0042246", "Tissue regeneration", "0.012573365", "2", "SERPINE1/ PLAUR."], ["GO:0032675", "Regulation of interleukin-6 production", "0.012647695", "4", "IL6/ TLR2."], ["GO:0006953", "Acute-phase response", "0.02109503", "2", "IL6/ CD163."], ["GO:0030162", "Regulation of proteolysis", "0.023703896", "2", "PLAUR/ TIMP1."], ["GO:0050900", "Leukocyte migration", "0.02630658", "2", "IL6/ SELE."], ["GO:0051091", "Positive regulation of transcription factor activity", "0.034722761", "2", "IL6/ TLR2."], ["GO:0045765", "Regulation of angiogenesis", "0.037299313", "2", "IL6/ SERPINE1."], ["GO:0031099", "Regeneration", "0.039227714", "2", "SERPINE1/ PLAUR."], ["GO:0043388", "Positive regulation of DNA binding", "0.04115268", "2", "IL6/ TLR2."], ["GO:0031349", "Positive regulation of defense response", "0.044992331", "2", "IL6/ TLR2."], ["GO:0050727", "Regulation of inflammatory response", "0.049454644", "2", "IL6/ SELE."], ["CC", "", "", "", ""], ["GO:0009611", "Extracellular region", "2.86E−06", "9", "CXCL1/ IL6/ CCL20/ SERPINE1/ SELE/ CCL4/ PLAUR/ CD163/ TIMP1."], ["GO:0006954", "Extracellular region part", "2.31E−04", "6", "CXCL1/ IL6/ CCL20/ SELE/ CCL4/ TIMP1."], ["GO:0006952", "Extracellular space", "8.30E−04", "5", "CXCL1/ IL6/ CCL20/ SELE/ CCL4."], ["MF", "", "", "", ""], ["GO:0005125", "Cytokine activity", "2.62E−04", "4", "CXCL1/ IL6/ CCL20/ CCL4."], ["GO:0008009", "Chemokine activity", "4.35E−04", "3", "CXCL1/ CCL20/ CCL4."], ["GO:0042379", "Chemokine receptor binding", "4.94E−04", "3", "CXCL1/ CCL20/ CCL4."], ["GO:0019899", "Enzyme binding", "0.048323907", "3", "SERPINE1/ SELE/ PLAUR."]], "row_count": 38, "column_count": 5, "numeric_cells": 118, "header_rows": 1, "locator": "section[14]/table-wrap[1]#table-5"}}, {"id": "asset:table:pmid:31667013:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ac1f5f61fc235fdde9c5ec43bc16f030b19564d2ada5c0132f740e7bb46fcb86", "bytes": 1269, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[2]#table-6", "version": null, "note": "Significantly enriched KEGG pathway of hub genes.", "structure": {"pmcid": "PMC6816389", "section_index": 14, "section_title": "PPI network construction and hub gene identification", "row_count": 14, "column_count": 5}, "table": {"label": "Table 6", "caption": "Significantly enriched KEGG pathway of hub genes.", "rows": [["Pathway ID", "Terms", "Gene count", "P-Value", "Genes"], ["hsa04668", "TNF signaling pathway", "4", "5.54E−08", "CXCL1, CCL20, IL6, SELE."], ["hsa04066", "HIF-1 signaling pathway", "3", "6.38E−06", "IL6, SERPINE1, TIMP1."], ["hsa04060", "Cytokine-cytokine receptor interaction", "3", "9.63E−05", "CXCL1, CCL20, IL6."], ["hsa04621", "NOD-like receptor signaling pathway", "2", "0.000199993", "CXCL1,IL6."], ["hsa04610", "Complement and coagulation cascades", "2", "0.000364662", "SERPINE1,PLAUR."], ["hsa04620", "Toll-like receptor signaling pathway", "2", "0.000671108", "IL6,TLR2."], ["hsa04062", "Chemokine signaling pathway", "2", "0.00200085", "CXCL1,CCL20."], ["hsa04151", "PI3K-Akt signaling pathway", "2", "0.006358451", "IL6,TLR2."], ["hsa04672", "Intestinal immune network for IgA production", "1", "0.016724268", "IL6"], ["hsa04623", "Cytosolic DNA-sensing pathway", "1", "0.022711959", "IL6"], ["hsa04115", "p53 signaling pathway", "1", "0.02481751", "SERPINE1"], ["hsa01521", "EGFR tyrosine kinase inhibitor resistance", "1", "0.029714789", "IL6"], ["hsa04068", "FoxO signaling pathway", "1", "0.047713858", "IL6"]], "row_count": 14, "column_count": 5, "numeric_cells": 44, "header_rows": 1, "locator": "section[14]/table-wrap[2]#table-6"}}, {"id": "asset:table:pmid:31667013:7", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:69545480f490ec046c51ab20d70513b0ba45a5bb6fb9920df82c00dbe7bbea63", "bytes": 731, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#table-7", "version": null, "note": "Results of CMap analysis.", "structure": {"pmcid": "PMC6816389", "section_index": 15, "section_title": "CMap analysis", "row_count": 10, "column_count": 6}, "table": {"label": "Table 7", "caption": "Results of CMap analysis.", "rows": [["Rank", "CMap name", "Mean", "N", "Enrichment", "P-value"], ["1", "Hecogenin", "−0.613", "4", "−0.931", "0.00002"], ["2", "Pralidoxime", "−0.529", "4", "−0.872", "0.00056"], ["3", "Metolazone", "−0.282", "5", "−0.779", "0.00096"], ["4", "Lidocaine", "−0.258", "5", "−0.766", "0.0013"], ["5", "NU-1025", "−0.579", "2", "−0.956", "0.00414"], ["6", "Ambroxol", "−0.269", "4", "−0.774", "0.00527"], ["7", "Pipemidic acid", "−0.336", "3", "−0.846", "0.00735"], ["8", "Yohimbic acid", "−0.345", "3", "−0.845", "0.00747"], ["9", "Chlorphenesin", "−0.354", "4", "−0.74", "0.00899"]], "row_count": 10, "column_count": 6, "numeric_cells": 46, "header_rows": 1, "locator": "section[15]/table-wrap[1]#table-7"}}], "gaps": ["asset:data:geo:GSE24265 not downloaded", "asset:data:geo:GSE24265 licence not read"]}, "analysis": {"state": "complete", "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": "Both the normalization of the data and screening of the DEGs were performed using the limma package in the R language (version 3.5.1) (Guo et al., 2017)."}}, {"id": "method-2", "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": "protein-protein interaction"}}, {"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": "GO enrichment"}}], "targets": [], "gaps": []}, "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": ["GSE24265"], "resolved_accessions": ["GSE24265"], "statements": ["The data is available in the Gene Expression Omnibus: GSE24265."], "basis": "The paper names GSE24265 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:31667013", "data:geo:GSE24265", "asset:table:pmid:31667013:1", "asset:table:pmid:31667013:2", "asset:table:pmid:31667013:3", "asset:table:pmid:31667013:4", "asset:table:pmid:31667013:5", "asset:table:pmid:31667013:6", "asset:table:pmid:31667013:7"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE24265"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:16:39Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 34604, "completion_tokens": 1253, "cached_tokens": 792}}, "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:31667013", "type": "paper", "label": "pmid:31667013"}, {"id": "source:pmid:31667013", "type": "manuscript", "label": "PMID 31667013 full text"}, {"id": "data:geo:GSE24265", "type": "dataset", "label": "GEO GSE24265"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:31667013", "type": "paper", "label": "pmid:31667013"}, {"id": "source:pmid:31667013", "type": "manuscript", "label": "PMID 31667013 full text"}, {"id": "data:geo:GSE24265", "type": "dataset", "label": "GEO GSE24265"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-31667013", "type": "extraction", "used": ["source:pmid:31667013"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE24265", "type": "accession_resolution", "used": ["data:geo:GSE24265"], "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:31667013", "parent_hash": "sha256:cdf9852fd58bbe7dd5ca883f3f6bc57aa291a20ea7b3beb1f14f49da2a2e678a", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE24265 licence not read", "asset:data:geo:GSE24265 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ed the expression levels of the hub genes by RT-qPCR on the rat ICH model. RESULT: A total of 59", "ed to secondary brain injury induced by ICH. RT-qPCR results showed that the expression of ten hu", "the expression levels of the hub genes by RT-qPCR on the rat ICH model. RESULT: A total of 59", "to secondary brain injury induced by ICH. RT-qPCR results showed that the expression of ten hu"], "order_basis": "paper_text_order:1443", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["of ten hub genes was significantly increased in the rat model of ICH. In addition, a CMap analysis o", "d through PPI network analysis were verified in the rat model of ICH. In addition, we obtained three", "on levels of the hub genes by RT-qPCR on the rat ICH model. RESULT: A total of 59 up-regulate", "hub genes was significantly increased in the rat model of ICH. In addition, a CMap analysis o"], "order_basis": "paper_text_order:1458", "id": "assay:2"}, {"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": ["Both the normalization of the data and screening of the DEGs were performed using the limma package in the R language (version 3.5.1) (Guo et al., 2017)."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]},"meta":{"api_version":"v1","automation_ladder_snapshot":"ba34b49490d9bfaf","automation_ladder_caveats":["Method extraction is rule-based and has no hand-judged accuracy sample. Evidence bands order textual support; method agreement intervals are null (n=0), never probabilities. Work-type validation does not validate methods.","Operation coverage describes only explicitly named methods. It does not prove a complete protocol, compatible parameters, successful compilation or re-execution. Unrecognised or ambiguous methods require review.","Data reachability is a textual accession or public-data statement. No dataset was downloaded or checked for access, completeness or licence.","Capabilities are planning states seeded from the dated equipment register. No bench ownership, completed quote or partner booking is inferred. Procurement counts are dependencies, not guaranteed replications or financial returns.","Tier and blocker counts are deterministic assessments of this corpus, not measured agreement. R3 is reserved for procurement; unresolved methods and data require human work (R4). The most restrictive axis wins, with capability, method, data as tie-breaks. Resolving one blocker can leave another at the same tier."],"engine":"corpus_engine","engine_provider":"rule_based_v1+lex99e1195c7d6f","run_id":"run-20261023T122449232913","source":"esearch","source_detail":"PubMed mirror biomed_pubmed (read-only)","run_status":"complete","imported_at":"2026-11-03T20:16:52+00:00","generated_at":"2026-11-04T01:34:39+00:00","total_papers":5529,"total_assays_tracked":29,"automatable_assay_families":6,"validated":true,"caveat_count":9,"blocking_caveats":5,"caveats":[{"code":"low_evidence_dominates","basis":["4,152 of 5,529 classifications (75.1%) matched no cue evidence and sit at the 0.05 floor.","34 of 230 data_only calls (14.8%) are in that group."],"claim":"Work type and confidence bands","gloss":"Most records were classified from their title and framing alone, with assay-cue coverage at zero.","detail":"Most classifications in this run rest on no matched evidence at all. At the evidence floor the work type comes from title framing and a fixed prior, not from anything in the paper, so the published work-type split should be read as a rough triage signal rather than a measured distribution. The impact is bounded but not removed: since 2026-10-23 the engine excludes floor-confidence records from the shortlist entirely and publishes them separately as held out, so the recommendation is unaffected even though the census is.","status":"unverified","severity":"high"},{"code":"runtime_is_modelled","basis":["Runtime is summed from published per-assay hour figures. Timing awaits the first executed replication.","4,407 of 5,529 records (79.7%) model to 0.00 hours because no assay was matched, which the ranking then reads as \"cheapest\".","0 of 10 shortlisted records carry a 0.00-hour estimate."],"claim":"Estimated replication runtime","gloss":"The hour figures are estimates built from assay mentions; timing awaits the first executed replication.","detail":"The hour figures are a cost model derived from the bench steps implied by each matched assay family. The first executed replication will supply measured timing. Records without an assay match currently receive a zero-hour model value.","status":"unverified","severity":"high"},{"code":"signal_score_without_citations","basis":["5,529 of 5,529 records (100.0%) have no citation count from the source metadata."],"claim":"Signal score","gloss":"The signal score uses publication-type weight because the mirror supplied zero citation counts.","detail":"The source supplied no citation counts for any record in this run, so the signal score is publication-type weight only. The citation term of the ranking is inert here, and the shortlist is ordered by publication type alone.","status":"unverified","severity":"high"},{"code":"abstract_absent","basis":["1,667 of 5,529 records (30.2%) carry no abstract at all."],"claim":"Evidence base for classification","gloss":"Some records contain a title and publication type only, defining the available classification evidence.","detail":"Where the mirror contains a title and publication types only, those fields define the classifier evidence. A methods section is required for fuller automated and human review.","status":"unverified","severity":"medium"},{"code":"classifier_agreement_measured","basis":["Published two-way decision agreement 77.7% (310 of 399 decidable records) from a stratified hand-check of 438 real records.","Three-way diagnostic agreement 73.9% (288 of 390 decidable records).","data_only agreement 75.2% (100 of 133 decidable).","48 record(s) could not be decided from title and abstract and were excluded from the denominator.","56 analysis-only records were published under another work type, so the data_only share is not an upper bound."],"claim":"Published automatable decision","gloss":"This figure has been checked against a human reading the same papers, so we know how often it is right.","detail":"The published automatable / not-automatable distribution comes from a rule-based classifier that was hand-checked against a fixed ground-truth definition. The agreement rates below are measured, not estimated. The three-way work type remains a diagnostic and is reported separately.","status":"measured","severity":"high"},{"code":"llm_comparison_not_measured","basis":["rule_based_v1+lex99e1195c7d6f produced 5,529 of 5,529 classifications.","Measured on 438 labelled records; these are RULE-BASED figures, not model results."],"claim":"Rule-based versus LLM agreement","gloss":"Every number here is the rule engine’s own. Model comparison begins when a working API credential is connected and measured.","detail":"The published two-way decision agreed with a human reading on 310 of 399 decidable records (77.7%). The diagnostic three-way label agreed on 288 of 390 decidable records (73.9%). Every percentage in this run belongs to the rule engine. Model comparison begins when a working API credential is connected and measured.","status":"not_measured","severity":"high"},{"code":"confidence_is_a_band","basis":["low band: 135 of 210 hand-judged records were correct, 64.3% [57.6, 70.5] (95% CI).","medium band: 80 of 104 hand-judged records were correct, 76.9% [68.0, 84.0] (95% CI).","high band: 73 of 76 hand-judged records were correct, 96.0% [89.0, 98.7] (95% CI).","A fitted calibrated probability was built, measured and withdrawn: it overstated held-out accuracy and reorders nothing."],"claim":"Confidence band and evidence score","gloss":"The confidence band carries a measured accuracy interval; 0.85 represents relative rank strength.","detail":"Confidence on this run is a BAND plus its measured accuracy interval. The number stored alongside each record is a monotone evidence score that orders records; 0.85 represents relative rank strength. A fitted probability was withdrawn after it overstated held-out accuracy. Threshold on the band.","status":"measured","severity":"medium"},{"code":"three_way_split_is_diagnostic","basis":["The corpus is published at the two-way decision: automatable or not-automatable. The three-way split (data_only / physical / mixed) is published as a diagnostic with its measured reliability attached, not as a claim, because the rule engine's `mixed` call cannot be defended.","The engine called 22 record(s) mixed; 10 matched the human judgement (45.5%, 95% CI 26.9-65.3).","The engine's `mixed` call is right on 10/22 hand-judged records (45.5%, 95% CI 26.9%-65.3%); a constant `physical` guess scores 36.4%.","The engine's `mixed` call does not reliably beat a constant `physical` guess on the hand-judged records it labels mixed.","The sign of that difference flips between two independent samples, so the three-way refinement is not demonstrably informative.","The mixed stratum contributes a disproportionate share of errors relative to its size.","At title-only depth the physical/mixed split collapses: a title says that work was done, not whether it was also analysed."],"claim":"The published decision is two-way","gloss":"The three-way split is shown for diagnosis only. The published split is two ways.","detail":"Count and filter the corpus on automatable versus not-automatable. The data_only / physical / mixed split remains an internal engine diagnostic because the mixed call has lower measured reliability.","status":"measured","severity":"medium"},{"code":"automatable_flag_unproven","basis":["6 of 29 assay families are marked automatable now: meta_analysis, machine_learning, survival_analysis, pca, molecular_docking, differential_expression.","The flag is a rule over assay family and work type; validation begins with the first executed replication.","It inherits the 75.2% data_only agreement rate, because the flag requires the record to be analysis-only."],"claim":"Automatable now","gloss":"This flag marks assay families the rules classify as data-only. The first executed replication will validate it.","detail":"This flag marks families the rules consider replicable from data alone. Its validity depends on the analysis-only classification and will be measured through an executed replication.","status":"unverified","severity":"medium"}],"confidence_policy":"band_with_measured_interval","confidence_contract":{"policy":"band_with_measured_interval","summary":"Confidence is reported as a BAND with a measured accuracy interval. The raw evidence score supplies monotone ordering. A fitted point estimate was withdrawn after it overstated held-out accuracy.","evidence_score":"A monotone evidence score in [0,1] built from cue mass, axis separation and text coverage. Use it to order records. Interpret 0.85 as relative rank strength.","confidence_band":"low | medium | high. Consumers threshold on this value.","band_accuracy":"Wilson 95% interval on the measured agreement of the hand-judged records in this band.","calibrated_confidence":"WITHDRAWN. Reintroduction requires held-out evidence demonstrating reliable estimates across every bin."},"band_accuracy":{"low":{"n":210,"low":0.576,"band":"low","high":0.7046,"agree":135,"accuracy":0.6429},"high":{"n":76,"low":0.8903,"band":"high","high":0.9865,"agree":73,"accuracy":0.9605},"medium":{"n":104,"low":0.6795,"band":"medium","high":0.8397,"agree":80,"accuracy":0.7692}},"provider":"rule_based_v1+lex99e1195c7d6f","lexicon_id":"99e1195c7d6f","contract_published_at":"2026-10-23T12:25:29.022232+00:00","confidence_is_band":true,"confidence_is_probability":false,"decision_taxonomy":"two_way","decidable_fraction_two_way":0.8854,"decidable_fraction_two_way_low":0.8565,"decidable_fraction_two_way_high":0.9143,"decidable_fraction_three_way":0.8586,"decidable_fraction_three_way_low":0.8287,"decidable_fraction_three_way_high":0.8884,"decidable_population":5529,"validation_sample_size":438,"three_way_cost_fraction":0.0268,"three_way_cost_records":148,"decision_counts":{"automatable":230,"not_automatable":5299},"decision_split":{"automatable":{"count":230,"share":0.04159884246699222},"not_automatable":{"count":5299,"share":0.9584011575330078}},"diagnostic_work_type_counts":{"mixed":24,"physical":5275,"data_only":230}}}