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pmid:31667013
Identification of hub genes and small-molecule compounds related to intracerebral hemorrhage with bioinformatics analysis.
Zhendong Liu · Ruotian Zhang · Xin Chen · Penglei Yao · Tao Yan · Wenwu Liu · Jiawei Yao · Andrei Sokhatskii · Ilgiz Gareev · Shiguang Zhao
PeerJ · 2019 doi:10.7717/peerj.7782
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Complete file
{"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", 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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/ 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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. 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