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pmid:39697339
Machine learning-based diagnostic model of lymphatics-associated genes for new therapeutic target analysis in intervertebral disc degeneration.
Maoqiang Lin · Shaolong Li · Yabin Wang · Guan Zheng · Fukang Hu · Qiang Zhang · Pengjie Song · Haiyu Zhou
Frontiers in immunology · 2024 doi:10.3389/fimmu.2024.1441028
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Complete file
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There are notable differences in the distribution of lymphatic vessels (LV) in normal and pathological intervertebral discs. Nevertheless, the molecular mechanisms of lymphatics-associated genes (LAGs) in the development of IVDD remain unclear. An in-depth exploration of this area will help to reveal the biological and clinical significance of LAGs in IVDD and may lead to the search for new therapeutic targets for IVDD.\nMethods: Data sets were obtained from the Gene Expression Omnibus (GEO) database. Following quality control and normalization, the datasets (GSE153761, GSE147383, and GSE124272) were merged to form the training set, with GSE150408 serving as the validation set. LAGs from GeneCards, MSigDB, Gene Ontology, and KEGG database. The Venn diagram was employed to identify differentially expressed lymphatic-associated genes (DELAGs) that were differentially expressed in the normal and IVDD groups. Subsequently, four machine learning algorithms (SVM-RFE, Random Forest, XGB, and GLM) were used to select the method to construct the diagnostic model. The receiver operating characteristic (ROC) curve, nomogram, and Decision Curve Analysis (DCA) were used to evaluate the model effect. In addition, we constructed a potential drug regulatory network and competitive endogenous RNA (ceRNA) network for key LAGs.\nResults: A total of 15 differentially expressed LAGs were identified. By comparing four machine learning methods, the top five genes of importance in the XGB model (MET, HHIP, SPRY1, CSF1, TOX) were identified as lymphatics-associated gene diagnostic signatures. This signature was used to predict the diagnosis of IVDD with strong accuracy and an area under curve (AUC) value of 0.938. Furthermore, the diagnostic model was validated in an external dataset (GSE150408), with an AUC value of 0.772. The nomogram and DCA further prove that the diagnosis model has good performance and predictive value. Additionally, drug regulatory networks and ceRNA networks were constructed, revealing potential therapeutic drugs and post-transcriptional regulatory mechanisms.\nConclusion: We developed and validated a lymphatics-associated genes diagnostic model by machine learning algorithms that effectively identify IVDD patients. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE124272", "GSE147383", "GSE153761", "GSE150408"], "resolved_accessions": ["GSE124272", "GSE147383", "GSE153761", "GSE150408"], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material ."], "basis": "The paper names GSE124272, GSE147383, GSE153761, GSE150408 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:39697339", "data:geo:GSE124272"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "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": "2026-11-01T19:42:27Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 19908, "completion_tokens": 1766, "cached_tokens": 256}}, "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:39697339", "type": "paper", "label": "pmid:39697339"}, {"id": "source:pmid:39697339", "type": "manuscript", "label": "PMID 39697339 full text"}, {"id": "data:geo:GSE124272", "type": "dataset", "label": "GEO GSE124272"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39697339", "type": "paper", "label": "pmid:39697339"}, {"id": "source:pmid:39697339", "type": "manuscript", "label": "PMID 39697339 full text"}, {"id": "data:geo:GSE124272", "type": "dataset", "label": "GEO GSE124272"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39697339", "type": "extraction", "used": ["source:pmid:39697339"], "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:39697339", "parent_hash": "sha256:9832505247ca4869fbb453cad98ea9cabb53e9ecd309185aeaf089a7cab10c58", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE124272 licence not read", "asset:data:geo:GSE124272 not downloaded", "asset:data:geo:GSE147383 licence not read", "asset:data:geo:GSE147383 not downloaded", "asset:data:geo:GSE150408 licence not read", "asset:data:geo:GSE150408 not downloaded", "asset:data:geo:GSE153761 licence not read", "asset:data:geo:GSE153761 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["DEGs within the training set were identified using the “limma” package, with screening criteria set at |log fold change (FC)| > 0.5 and P value < 0.05."], "order_basis": "analysis_only", "id": "assay:1"}]}