Hub Genes and Key Pathways of Intervertebral Disc Degeneration: Bioinformatics Analysis and Validation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34545328", "kind": "science-record", "revision": 7, "content_hash": "sha256:76b70f509846fbd825f3e28b2f2e1ec844cb1aaf8e7f09d53c9f8e1a240dfc40", "created_at": "2026-11-01T15:41:53Z", "updated_at": "2026-11-01T22:04:46Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Hub Genes and Key Pathways of Intervertebral Disc Degeneration: Bioinformatics Analysis and Validation.", "doi": "10.1155/2021/5340449", "pmid": "34545328", "authors": ["Zhiwen Zhang", "Qiong Wang", "Yang Li", "Bangzhi Li", "Liming Zheng", "Chengjian He"], "journal": "BioMed research international", "year": 2021, "abstract": "OBJECTIVE: To identify significant pathways and genes in intervertebral disc degeneration (IDD) based on bioinformatics analysis.\nDESIGN: The GEO database was used to download the GSE124272 dataset. Differentially expressed genes (DEGs) were analyzed using Limma package in R language. Then, gene ontologies (GO), Kyoto encyclopedia of genes and genomes (KEGG), and protein-protein interaction (PPI) networks were used to further identify hub genes. The mRNA expression levels of top six hub genes were verified.\nRESULTS: We found 563 DEGs, of which 214 were upregulated and 349 were downregulated. The top 5 GO terms and pathways were shown including immune response, cell cycle, and p53 pathway. Based on the PPI analysis, we verified the mRNA expression levels of 6 hub genes. The mRNA levels of CHEK1, CDCA2, SKA3, and KIF20A were upregulated in degenerative NP tissue than in healthy NP tissue. However, the mRNA level of BUB1 and SPC25 was downregulated.\nCONCLUSIONS: This study may provide new biomarkers for the IDD and treatments to repair IDD related to CHEK1, CDCA2, SKA3, BUB1, KIF20A, and SPC25.", "claims": [{"id": "claim-method", "statement": "These data were analyzed using Student's t-test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34545328", "locator": "sections[9] \"2.7. Statistical Analysis\" paragraph 2", "quote": "These data were analyzed using Student's t-test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Our data can be found in the GEO database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34545328", "locator": "sections[17] \"Data Availability\" paragraph 2", "quote": "Our data can be found in the GEO database."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "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:34545328"], "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:GSE124272"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:student_t", "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:GSE124272"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:student_t"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34545328", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2021/5340449", "sha256": "sha256:d74b46d6a05ecc1e95c1a466e949db5225bd35504962afae17064f3ee1d154c0", "bytes": 34146, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2021/5340449", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8449732", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE124272", "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=GSE124272", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE124272", "version": null, "note": "Our data can be found in the GEO database.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Our data can be found in the GEO database.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3526782", "GSM3526783", "GSM3526784", "GSM3526785", "GSM3526786", "GSM3526787", "GSM3526788", "GSM3526789", "GSM3526790", "GSM3526791", "GSM3526792", "GSM3526793", "GSM3526794", "GSM3526795", "GSM3526796", "GSM3526797"], "sample_count": 16, "group_sizes": null, "group_sizes_basis": null, "platform": "21185", "taxon": "Homo sapiens", "title": "Transcriptome signatures reveal candidate key genes in the whole blood of patients with lumbar disc prolapse", "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:34545328:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:08ee3fbb3136da2d93c7bdfba4b40a197426b9c4827469f5a1cce8218cdc7b9e", "bytes": 903, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[1]#tab1", "version": null, "note": "Primer sequences.", "structure": {"pmcid": "PMC8449732", "section_index": 8, "section_title": "2.6. RNA Extraction and Quantitative Real-Time- (qRT-) PCR", "row_count": 9, "column_count": 3}, "table": {"label": "Table 1", "caption": "Primer sequences.", "rows": [["Gene", "Sequence", "Size"], ["CDCA2", "Forward: 5′-TGTGGGCAGCTCTGTAGAAA-3′Reverse: 5′-GGGAAGTGGAAGGAAGTGGA-3′", "185 bp"], ["KIF20A", "Forward: 5′-CGCAGTCACAGCATCTTCTC-3′Reverse: 5′-GACGAAGGGCAGCAATACAG-3′", "202 bp"], ["SPC25", "Forward: 5′-TGCAGAGAGGTTGAAAAGGC-3′Reverse: 5′-TGAGGGGCACTATCTGACAC-3′", "198 bp"], ["CHEK1", "Forward: 5′-TCAGGTGGTGTGTCAGAGTC-3′Reverse: 5′-GACATGTGGGCTGGGAAAAG-3′", "211 bp"], ["SKA3", "Forward: 5′-AGCCCGTAATTGTAACCCCA-3′Reverse: 5′-TCTGTATCTATGGCCTCCTCAC-3′", "211 bp"], ["BUB1", "Forward: 5′-TCCCCTCTGTACATTGCCTG-3′", "168 bp"], ["Reverse: 5′-AGCTGGCAAATGGGTTTCAG-3′", ""], ["GAPDH", "Forward: 5′-TCAAGAAGGTGGTGAAGCAGG-3′Reverse: 5′-TCAAAGGTGGAGGAGTGGGT-3′", "115 bp"]], "row_count": 9, "column_count": 3, "numeric_cells": 17, "header_rows": 1, "locator": "section[8]/table-wrap[1]#tab1"}}, {"id": "asset:table:pmid:34545328:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:20273942b8a078e359497f2ee0fb7cba81b9d8e34e9ce4558407c029bfd53a07", "bytes": 1535, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#tab2", "version": null, "note": "Functional and pathway enrichment analysis of DEGs.", "structure": {"pmcid": "PMC8449732", "section_index": 12, "section_title": "3.2. GO and KEGG Functional Enrichment Analysis of DEGs", "row_count": 21, "column_count": 5}, "table": {"label": "Table 2", "caption": "Functional and pathway enrichment analysis of DEGs.", "rows": [["Category", "Term", "Count", "Gene ratio (%)", "P value"], ["GOTERM_BP", "Defense response to gram-negative bacterium", "7", "1.75%", "2.00E − 04"], ["GOTERM_BP", "Mitotic nuclear division", "13", "3.24%", "5.04E − 04"], ["GOTERM_BP", "Chromosome segregation", "7", "1.75%", "6.38E − 04"], ["GOTERM_BP", "Response to yeast", "4", "1.00%", "9.36E − 04"], ["GOTERM_BP", "Cell division", "15", "3.74%", "1.16E − 03"], ["GOTERM_CC", "Plasma membrane", "95", "23.71%", "2.95E − 05"], ["GOTERM_CC", "Specific granule", "5", "1.25%", "3.70E − 05"], ["GOTERM_CC", "Neuronal cell body", "17", "4.24%", "3.75E − 05"], ["GOTERM_CC", "Extracellular space", "40", "9.98%", "1.29E − 04"], ["GOTERM_CC", "Cell surface", "20", "4.99%", "8.98E − 04"], ["GOTERM_MF", "Carbohydrate binding", "9", "2.25%", "1.09E − 02"], ["GOTERM_MF", "Peptidase activity", "6", "1.50%", "1.25E − 02"], ["GOTERM_MF", "Iron ion binding", "7", "1.75%", "3.08E − 02"], ["GOTERM_MF", "Galactosyltransferase activity", "3", "0.75%", "3.38E − 02"], ["GOTERM_MF", "Cytokine binding", "3", "0.75%", "3.38E − 02"], ["KEGG_pathway", "Cell cycle", "7", "1.75%", "1.05E − 02"], ["KEGG_PATHWAY", "p53 signaling pathway", "5", "1.25%", "1.77E − 02"], ["KEGG_PATHWAY", "Amoebiasis", "5", "1.25%", "7.41E − 02"], ["KEGG_PATHWAY", "PPAR signaling pathway", "4", "1.00%", "7.86E − 02"], ["KEGG_PATHWAY", "Oocyte meiosis", "5", "1.25%", "8.45E − 02"]], "row_count": 21, "column_count": 5, "numeric_cells": 61, "header_rows": 1, "locator": "section[12]/table-wrap[1]#tab2"}}], "gaps": ["asset:data:geo:GSE124272 not downloaded", "asset:data:geo:GSE124272 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "These data were analyzed using Student's t-test."}}, {"id": "method-2", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.7, "band": "medium", "quote": "Limma"}}, {"id": "method-3", "family": "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.student_t"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test."}, "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": ["GSE124272"], "resolved_accessions": ["GSE124272"], "statements": ["Our data can be found in the GEO database."], "basis": "The paper names GSE124272 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:34545328", "data:geo:GSE124272", "asset:table:pmid:34545328:1", "asset:table:pmid:34545328:2"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "student_t", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE124272"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:34:56Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 29708, "completion_tokens": 814, "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:34545328", "type": "paper", "label": "pmid:34545328"}, {"id": "source:pmid:34545328", "type": "manuscript", "label": "PMID 34545328 full text"}, {"id": "data:geo:GSE124272", "type": "dataset", "label": "GEO GSE124272"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34545328", "type": "paper", "label": "pmid:34545328"}, {"id": "source:pmid:34545328", "type": "manuscript", "label": "PMID 34545328 full text"}, {"id": "data:geo:GSE124272", "type": "dataset", "label": "GEO GSE124272"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34545328", "type": "extraction", "used": ["source:pmid:34545328"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE124272", "type": "accession_resolution", "used": ["data:geo:GSE124272"], "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:34545328", "parent_hash": "sha256:45dec3dbe985e2e706f8a133f9b28ce4d2fd822d4a21b1db62eec72016109115", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE124272 licence not read", "asset:data:geo:GSE124272 not downloaded", "execution.not_run", "method.student_t", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:student_t"], "assays": [{"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["These data were analyzed using Student's t-test."], "order_basis": "analysis_only", "id": "assay:1"}]}