Development and Validation of Early Alert Model for Diabetes Mellitus-Tuberculosis Comorbidity.

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However, early risk prediction methods for DM patients complicated with TB (DM-TB) are lacking. This study mined transcriptome data of DM-TB patients from the GEO database (GSE181143 and GSE114192) and used differential analysis, weighted gene co-expression network analysis (WGCNA), intersecting immune databases, combined with ten machine learning algorithms, to identify immune biomarkers associated with DM-TB. An early alert model for DM-TB was constructed based on the identified core differentially expressed genes (DEGs) and validated through a prospective cohort study and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) for gene expression levels. Furthermore, we performed a detailed immune status analysis of DM-TB patients using the CIBERSORT algorithm. We identified 1090 DEGs associated with DM-TB and further pinpointed CETP (cholesteryl ester transfer protein) (AUC = 0.804, CI: 0.744-0.864), TYROBP (TYRO protein tyrosine kinase binding protein) (AUC = 0.810, CI: 0.752-0.867), and SECTM1 (secreted and transmembrane protein 1) (AUC = 0.811, CI: 0.757-0.864) as immune-related biomarkers for DM-TB patients. An early alert model was developed based on these three genes (AUC = 0.86, CI: 0.813-0.907), with a sensitivity of 0.80829 and a specificity of 0.75758 at a Youden index of 0.56587. External validation using the GSE114192 dataset showed an AUC of 0.901 (CI: 0.847-0.955). Population cohort research and RT-qPCR verified the expression levels of these three genes, demonstrating consistency with trends seen in the training set. KEGG enrichment analysis revealed that NF-κB and MAPK signaling pathways play crucial roles in the DM-TB pathogenic mechanism, and immune infiltration analysis showed significant suppression of certain adaptive immune cells and activation of inflammatory cells in DM-TB patients. This study identified three potential immune-related biomarkers for DM-TB, and the constructed risk assessment model demonstrated significant predictive efficiency, providing an early screening strategy for DM-TB.", "claims": [{"id": "claim-method", "statement": "This model, developed using binary logistic regression analysis, indicated that CETP (OR: 1.051, CI: 1.033–1.068; p < 0.0001), TYROBP (OR: 1.004, CI: 1.003–1.006; p < 0.0001), and SECTM1 (OR: 1.005, CI: 1.003–1.007; p < 0.0001) are important differential genes between DM–TB and diabetes (Table 4).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40284755", "locator": "sections[20] \"3.7. Logistic Regression Prediction of DM–TB Risk: Construction of a Nomogram\" paragraph 2", "quote": "This model, developed using binary logistic regression analysis, indicated that CETP (OR: 1.051, CI: 1.033–1.068; p < 0.0001), TYROBP (OR: 1.004, CI: 1.003–1.006; p < 0.0001), and SECTM1 (OR: 1.005, CI: 1.003–1.007; p < 0.0001) are important differential genes between DM–TB and diabetes (Table 4)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in this study are included in the article/Supplementary Materials. Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40284755", "locator": "sections[30] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in this study are included in the article/Supplementary Materials. Further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "An early alert model was developed based on these three genes (AUC = 0.86, CI: 0.813–0.907), with a sensitivity of 0.80829 and a specificity of 0.75758 at a Youden index of 0.56587.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40284755", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "An early alert model was developed based on these three genes (AUC = 0.86, CI: 0.813–0.907), with a sensitivity of 0.80829 and a specificity of 0.75758 at a Youden index of 0.56587."}, {"asset": "source:pmid:40284755", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "External validation using the GSE114192 dataset showed an AUC of 0.901 (CI: 0.847–0.955)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "An early alert model was developed based on these three genes (AUC = 0.86, CI: 0.813–0.907), with a sensitivity of 0.80829 and a specificity of 0.75758 at a Youden index of 0.56587.", "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:40284755"], "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. 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"GSM5491535", "GSM5491536"], "sample_count": 560, "group_sizes": null, "group_sizes_basis": null, "platform": "20795", "taxon": "Homo sapiens", "title": "Heterogeneous Gene Expression Patterns of Tuberculosis-Diabetes Interaction in Diverse Cohorts", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE114192 not downloaded", "asset:data:geo:GSE114192 licence not read", "asset:data:geo:GSE181143 not downloaded", "asset:data:geo:GSE181143 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "regression_modelling", "specific": "logistic", "label": "Regression modelling", "dsl_operations": ["glm_logit_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["predictors_and_outcome"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "This model, developed using binary logistic regression analysis, indicated that CETP (OR: 1.051, CI: 1.033–1.068; p < 0.0001), TYROBP (OR: 1.004, CI: 1.003–1.006; p < 0.0001), and SECTM1 (OR: 1.005, CI: 1.003–1.007; p < 0.0001) are important differential genes between DM–TB and diabetes (Table 4)."}}, {"id": "method-2", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "ANOVA"}}, {"id": "method-3", "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": "GO enrichment"}}], "targets": [], 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"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": ["GSE181143", "GSE114192"], "resolved_accessions": ["GSE181143", "GSE114192"], "statements": ["The original contributions presented in this study are included in the article/Supplementary Materials. Further inquiries can be directed to the corresponding authors."], "basis": "The paper names GSE181143, GSE114192 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": ["glm_logit_fit"], "assets": ["source:pmid:40284755", "data:geo:GSE114192"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE114192"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:51:05Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 21036, "completion_tokens": 1489, "cached_tokens": 264}}, "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:40284755", "type": "paper", "label": "pmid:40284755"}, {"id": "source:pmid:40284755", "type": "manuscript", "label": "PMID 40284755 full text"}, {"id": "data:geo:GSE114192", "type": "dataset", "label": "GEO GSE114192"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40284755", "type": "paper", "label": "pmid:40284755"}, {"id": "source:pmid:40284755", "type": "manuscript", "label": "PMID 40284755 full text"}, {"id": "data:geo:GSE114192", "type": "dataset", "label": "GEO GSE114192"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40284755", "type": "extraction", "used": ["source:pmid:40284755"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE114192", "type": "accession_resolution", "used": ["data:geo:GSE114192"], "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:40284755", "parent_hash": "sha256:2b4da3fafaeb69c54df7fd6e84837fe41372db29119746ebcecc151a9db7fbe2", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE114192 licence not read", "asset:data:geo:GSE114192 not downloaded", "asset:data:geo:GSE181143 licence not read", "asset:data:geo:GSE181143 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ith TB (DM-TB) are lacking. This study mined transcriptome data of DM-TB patients from the GEO database", "ence of immune cells in samples derived from RNA sequencing data [30,31]. By conducting an in-depth anal"], "order_basis": "paper_text_order:339", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["itative real-time polymerase chain reaction (RT-qPCR) for gene expression levels. Furthermore, we", "0.847-0.955). Population cohort research and RT-qPCR verified the expression levels of these thre", "tive real-time polymerase chain reaction (RT-qPCR) for gene expression levels. Furthermore, we", "47-0.955). Population cohort research and RT-qPCR verified the expression levels of these thre"], "order_basis": "paper_text_order:880", "id": "assay:2"}, {"role": "analysis", "definition_id": "regression_modelling", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["glm_logit_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["This model, developed using binary logistic regression analysis, indicated that CETP (OR: 1.051, CI: 1.033–1.068; p < 0.0001), TYROBP (OR: 1.004, CI: 1.003–1.006; p < 0.0001), and SECTM1 (OR: 1.005, CI: 1.003–1.007; p < 0.0001) are important differential genes between DM–TB and diabetes (Table 4)."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}