Identification and validation of NAD+ metabolism-related biomarkers in patients with diabetic peripheral neuropathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38464965", "kind": "science-record", "revision": 5, "content_hash": "sha256:83eaea776c3fdae300095a5bd24b27ad857933ed7262971fc9a356685544d8d9", "created_at": "2026-11-01T19:20:24Z", "updated_at": "2026-11-01T22:53:50Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of NAD+ metabolism-related biomarkers in patients with diabetic peripheral neuropathy.", "doi": "10.3389/fendo.2024.1309917", "pmid": "38464965", "authors": ["Chenhao Ye", "Yuedong Fu", "Xijie Zhou", "Feiya Zhou", "Xuwei Zhu", "Yiheng Chen"], "journal": "Frontiers in endocrinology", "year": 2024, "abstract": "Background: The mechanism of Nicotinamide Adenine Dinucleotide (NAD+) metabolism-related genes (NMRGs) in diabetic peripheral neuropathy (DPN) is unclear. This study aimed to find new NMRGs biomarkers in DPN.\nMethods: DPN related datasets GSE95849 and GSE185011 were acquired from the Gene Expression Omnibus (GEO) database. 51 NMRGs were collected from a previous article. To explore NMRGs expression in DPN and control samples, differential expression analysis was completed in GSE95849 to obtain differentially expressed genes (DEGs), and the intersection of DEGs and NMRGs was regarded as DE-NMRGs. Next, a protein-protein interaction (PPI) network based on DE-NMRGs was constructed and biomarkers were screened by eight algorithms. Additionally, Gene Set Enrichment Analysis (GSEA) enrichment analysis was completed, biomarker-based column line graphs were constructed, lncRNA-miRNA-mRNA and competing endogenouse (ce) RNA networks were constructed, and drug prediction was completed. Finally, biomarkers expression validation was completed in GSE95849 and GSE185011.\nResults: 5217 DEGs were obtained from GSE95849 and 21 overlapping genes of DEGs and NMRGs were DE-NMRGs. Functional enrichment analysis revealed that DE-NMRGs were associated with glycosyl compound metabolic process. The PPI network contained 93 protein-interaction pairs and 21 nodes, with strong interactions between NMNAT1 and NAMPT, NADK and NMNAT3, ENPP3 and NUDT12 as biomarkers based on 8 algorithms. Expression validation suggested that ENPP3 and NUDT12 were upregulated in DPN samples (P < 0.05). Moreover, an alignment diagram with good diagnostic efficacy based on ENPP3 and NUDT12 were identified was constructed. GSEA suggested that ENPP3 was enriched in Toll like receptor (TLR) pathway, NUDT12 was enriched in maturity onset diabetes of the young and insulin pathway. Furthermore, 18 potential miRNAs and 36 Transcription factors (TFs) were predicted and the miRNA-mRNA-TF networks were constructed, suggesting that ENPP3 might regulate hsa-miR-34a-5p by affecting MYNN. The ceRNA network suggested that XLOC_013024 might regulate hsa-let-7b-5p by affecting NUDT12. 15 drugs were predicted, with 8 drugs affecting NUDT12 such as resveratrol, and 13 drugs affecting ENPP3 such as troglitazone.\nConclusion: ENPP3 and NUDT12 might play key roles in DPN, which provides reference for further research on DPN.", "claims": [{"id": "claim-method", "statement": "Limma was used to identify DEGs. The Benjamini & Hochberg (BH) test was used for multiple test correction screening of DEGs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38464965", "locator": "sections[8] \"Statistical analysis\" paragraph 2", "quote": "Limma was used to identify DEGs. The Benjamini & Hochberg (BH) test was used for multiple test correction screening of DEGs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: GEO database (https://www.ncbi.nlm.nih.gov/gds) STRING (https://string-db.org) database GeneMANIA database (http://genemania.org). Comparative Toxicogenomics Database (CTD, http://ctdbase.org/) miRNet database (https://www.mirnet.ca/) NetworkAnalyst database (https://www.networkanalyst.ca/) lncBaseV2 database (http://carolina.imis.athena-innovation.gr/diana_tools/web/index.php).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38464965", "locator": "sections[16] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: GEO database (https://www.ncbi.nlm.nih.gov/gds) STRING (https://string-db.org) database GeneMANIA database (http://genemania.org). Comparative Toxicogenomics Database (CTD, http://ctdbase.org/) miRNet database (https://www.mirnet.ca/) NetworkAnalyst database (https://www.networkanalyst.ca/) lncBaseV2 database (http://carolina.imis.athena-innovation.gr/diana_tools/web/index.php)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Expression validation suggested that ENPP3 and NUDT12 were upregulated in DPN samples (P < 0.05).", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "Expression validation suggested that ENPP3 and NUDT12 were upregulated in DPN samples (P < 0.05)."}, "evidence": [{"asset": "source:pmid:38464965", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Expression validation suggested that ENPP3 and NUDT12 were upregulated in DPN samples (P < 0.05)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Expression validation suggested that ENPP3 and NUDT12 were upregulated in DPN samples (P < 0.05).", "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:38464965"], "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:GSE185011"], "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:GSE185011"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38464965", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fendo.2024.1309917", "sha256": "sha256:c4b91774449e915a01e8b1159afa2f690f17f2edfb3a3e0adf0c1cbee789e68e", "bytes": 41269, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fendo.2024.1309917", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10920259", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE185011", "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=GSE185011", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE185011", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: GEO database (https://www.ncbi.nlm.nih.gov/gds) STRING (https://string-db.org) database GeneMANIA database (http://genemania.org). Comparative Toxicogenomics Database (CTD, http://ctdbase.org/) miRNet database (https://www.mirnet.ca/) NetworkAnalyst database (https://www.networkanalyst.ca/) lncBaseV2 database (http://carolina.imis.athena-innovation.gr/diana_tools/web/index.php).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found here: GEO database (https://www.ncbi.nlm.nih.gov/gds) STRING (https://string-db.org) database GeneMANIA database (http://genemania.org). Comparative Toxicogenomics Database (CTD, http://ctdbase.org/) miRNet database (https://www.mirnet.ca/) NetworkAnalyst database (https://www.networkanalyst.ca/) lncBaseV2 database (http://carolina.imis.athena-innovation.gr/diana_tools/web/index.php).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM5603427", "GSM5603428", "GSM5603429", "GSM5603430", "GSM5603431", "GSM5603432", "GSM5603433", "GSM5603434", "GSM5603435", "GSM5603436", "GSM5603437", "GSM5603438", "GSM5603439", "GSM5603440", "GSM5603441", "GSM5603442", "GSM5603443", "GSM5603444", "GSM5603445", "GSM5603446", "GSM5603447", "GSM5603448", "GSM5603449", "GSM5603450", "GSM5603451"], "sample_count": 25, "group_sizes": null, "group_sizes_basis": null, "platform": "24676", "taxon": "Homo sapiens", "title": "The expression of mRNA and lncRNA in peripheral blood mononuclear cells (PBMCs) of diabetes mellitus, diabetic retinopathy (DR), diabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN) patients", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE95849", "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=GSE95849", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE95849", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: GEO database (https://www.ncbi.nlm.nih.gov/gds) STRING (https://string-db.org) database GeneMANIA database (http://genemania.org). Comparative Toxicogenomics Database (CTD, http://ctdbase.org/) miRNet database (https://www.mirnet.ca/) NetworkAnalyst database (https://www.networkanalyst.ca/) lncBaseV2 database (http://carolina.imis.athena-innovation.gr/diana_tools/web/index.php).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found here: GEO database (https://www.ncbi.nlm.nih.gov/gds) STRING (https://string-db.org) database GeneMANIA database (http://genemania.org). Comparative Toxicogenomics Database (CTD, http://ctdbase.org/) miRNet database (https://www.mirnet.ca/) NetworkAnalyst database (https://www.networkanalyst.ca/) lncBaseV2 database (http://carolina.imis.athena-innovation.gr/diana_tools/web/index.php).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2527022", "GSM2527023", "GSM2527024", "GSM2527025", "GSM2527026", "GSM2527027", "GSM2527028", "GSM2527029", "GSM2527030", "GSM2527031", "GSM2527032", "GSM2527033", "GSM2527034", "GSM2527035", "GSM2527036", "GSM2527037", "GSM2527038", "GSM2527039"], "sample_count": 18, "group_sizes": null, "group_sizes_basis": null, "platform": "22448", "taxon": "Homo sapiens", "title": "Transcriptional profiling of diabetic peripheral neuropathy patients, diabetic patients, and healthy participants", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE185011 not downloaded", "asset:data:geo:GSE185011 licence not read", "asset:data:geo:GSE95849 not downloaded", "asset:data:geo:GSE95849 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": "Limma was used to identify DEGs. The Benjamini & Hochberg (BH) test was used for multiple test correction screening of DEGs."}}, {"id": "method-2", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "spearman correlation"}}, {"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"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "build_graph", "expected_value": 0.05, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "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. 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