Identification and experimental validation of key extracellular proteins as potential targets in intervertebral disc degeneration.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37661086", "kind": "science-record", "revision": 4, "content_hash": "sha256:0f7da346e21ac3042d7475b383fd00c436775f404f0ad8d330f8aec2716a1d3a", "created_at": "2026-11-01T19:02:26Z", "updated_at": "2026-11-01T22:52:37Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and experimental validation of key extracellular proteins as potential targets in intervertebral disc degeneration.", "doi": "10.1302/2046-3758.129.BJR-2022-0369.R2", "pmid": "37661086", "authors": ["Guang-Zhi Zhang", "Lei Li", "Zhang-Bin Luo", "Cang-Yu Zhang", "Yong-Gang Wang", "Xue-Wen Kang"], "journal": "Bone & joint research", "year": 2023, "abstract": "Aims: This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).\nMethods: The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions.\nResults: A total of 56 EP-DEGs were identified in the differential expression analysis. EP-DEGs were enriched in the extracellular structure organization, ageing, collagen-activated signalling pathway, PI3K-Akt signalling pathway, and AGE-RAGE signalling pathway. PPI network analysis showed that the top ten hub EP-DEGs are closely related to IDD. Correlation analysis also demonstrated a significant correlation between the ten hub EP-DEGs (p＜0.05), which were selected to construct TF-gene interaction and TF-miRNA coregulatory networks. In addition, ten candidate drugs were screened for the treatment of IDD.\nConclusion: The findings clarify the roles of extracellular proteins in IDD and highlight their potential as promising novel therapeutic targets.", "claims": [{"id": "claim-method", "statement": "DEGs were screened out by the limma package22 using |log2 fold change (FC)| ≥ 1, p < 0.05 (independent-samples t-test) as the differential cut-off standard.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37661086", "locator": "sections[7] \"Screening of DEGs and extracellular protein-DEGs\" paragraph 2", "quote": "DEGs were screened out by the limma package22 using |log2 fold change (FC)| ≥ 1, p < 0.05 (independent-samples t-test) as the differential cut-off standard."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings for this study are available to other researchers from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37661086", "locator": "sections[30] \"fn-group\" paragraph 1", "quote": "The data that support the findings for this study are available to other researchers from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using the GSE23130 IDD tissue expression dataset, the study screened 428 differentially expressed genes between early and late intervertebral disc degeneration, identifying 400 upregulated and 28 downregulated genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37661086", "locator": "sections[4] \"Introduction\" paragraph 5", "quote": "We downloaded the IDD patient IVD tissue microarray gene expression profiling dataset (GSE23130) from the GEO database and used R software to screen for differentially expressed genes (DEGs) between IVD tissue samples of early and late IDD."}, {"asset": "source:pmid:37661086", "locator": "sections[20] \"Identification of DEGs\" paragraph 2", "quote": "A total of 428 DEGs were screened, among which 400 were highly expressed DEGs and 28 were low-expressed DEGs (Figure 2b)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using the GSE23130 IDD tissue expression dataset, the study screened 428 differentially expressed genes between early and late intervertebral disc degeneration, identifying 400 upregulated and 28 downregulated genes.", "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:37661086"], "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:GSE23130"], "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:GSE23130"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37661086", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1302/2046-3758.129.BJR-2022-0369.R2", "sha256": "sha256:fcbaea11746c7ad11429e5cddcf2353e9bb13c5f1530aa197748c3b18c85f7b4", "bytes": 43431, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1302/2046-3758.129.BJR-2022-0369.R2", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10475329", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE23130", "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=GSE23130", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE23130", "version": null, "note": "The data that support the findings for this study are available to other researchers from the corresponding author upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data that support the findings for this study are available to other researchers from the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM569830", "GSM569831", "GSM569832", "GSM569833", "GSM569834", "GSM569835", "GSM569836", "GSM569837", "GSM569838", "GSM569839", "GSM569840", "GSM569841", "GSM569842", "GSM569843", "GSM569844", "GSM569845", "GSM569846", "GSM569847", "GSM569848", "GSM569849", "GSM569850", "GSM569851", "GSM569852"], "sample_count": 23, "group_sizes": null, "group_sizes_basis": null, "platform": "1352", "taxon": "Homo sapiens", "title": "Gene Array Data from Human Annulus Disc Tissue", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE23130 not downloaded", "asset:data:geo:GSE23130 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "DEGs were screened out by the limma package22 using |log2 fold change (FC)| ≥ 1, p < 0.05 (independent-samples t-test) as the differential cut-off standard."}}, {"id": "method-2", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-3", "family": "network_analysis", "specific": "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-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": "pathway 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": ["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. 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