{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40775242", "kind": "science-record", "revision": 3, "content_hash": "sha256:9c92f6d2c8245f8ea6e1f503f45dea9e9f75b3aa069871686ead7f94a6ce8af8", "created_at": "2026-11-01T20:30:52Z", "updated_at": "2026-11-01T22:14:30Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and experimental validation of mitochondrial and endoplasmic reticulum stress related gene in diabetic nephropathy.", "doi": "10.1038/s41598-025-11097-5", "pmid": "40775242", "authors": ["Ting Li", "Li Li", "Zijuan Sun", "Huijuan Zeng", "Guoyong He", "Zhong Tian", "Dong Chen", "Jun Li"], "journal": "Scientific reports", "year": 2025, "abstract": "Diabetic nephropathy (DN) is a kidney disease. Mitochondrial and endoplasmic reticulum stress (ERS) significantly contribute to diabetic nephropathy (DN), although the precise mechanisms involved have not yet been fully understood. The objective of this research was to explore the potential of mitochondrial and ERS genes as pivotal genetic elements in individuals with DN and to elucidate their fundamental molecular mechanisms. The datasets GSE30528 and GSE30122 were obtained from the Gene Expression Omnibus (GEO) database. Firstly, differentially expressed genes (DEGs) (DN and control samples) were identified by differential expression analysis. Candidate genes were obtained by intersecting the DEGs with mitochondria and endoplasmic reticulum stress-related genes. The key genes were identified through three machine learning methods, the receiver operating characteristic (ROC) curve analysis and expression validation. Subsequently, a nomogram model for DN was constructed. Moreover, gene set enrichment analysis (GSEA), immune infiltration, molecular regulatory networks of key genes were explored, Later, predicted their drugs. Finally, three key genes (GPX1, PPIF and VDAC1) were identified by expression validation and ROC validation and three key genes were all down-regulated in DN. Meanwhile, RT-qPCR analysis yielded the same results. In addition, the nomogram model of key genes was constructed, and the model had a good prediction effect. GSEA showed that the top 3 most prominent pathways shared by the 3 key genes included oxidative phosphorylation, glutathione metabolism, and ribosome. Immune cells, including gamma-delta T cells, activated mast cells, and M2 macrophages, exhibited differential infiltration between the DN group and the control group. A total of 23 lncRNAs targeting intersecting miRNAs of three key genes. There were 4 drugs associated with the three key genes. In this research, three key genes (GPX1, PPIF and VDAC1) mitochondrial and endoplasmic reticulum stress-related gene in DN were identified, providing a potential theoretical basis for DN treatment. However, this study still has certain limitations. This study only used a single dataset for analysis and validation, so the results of the study may not fully reflect the diversity of DN patients.", "claims": [{"id": "claim-method", "statement": "In GSE30528 and GSE30122, genes with consistent expression trends and significant differences (p < 0.05) between groups were obtained by Wilcoxon test for subsequent analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40775242", "locator": "sections[8] \"Expression validation and receiver operating characteristic (ROC) curve analysis\" paragraph 2", "quote": "In GSE30528 and GSE30122, genes with consistent expression trends and significant differences (p < 0.05) between groups were obtained by Wilcoxon test for subsequent analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analysed during the current study are available in the GEO repository （http://www.ncbi.nlm.nih.gov/geo/）, The Mitochondrial Protein Reference Set 3.0 (MitoCarta3.0) repository (http://www.broadinstitute.org/mitocarta), and The molecular signatures database (MSigDB, https://www.gsea-msigdb.org/gsea/msigdb/index.jsp).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40775242", "locator": "sections[33] \"Data availability\" paragraph 2", "quote": "The datasets analysed during the current study are available in the GEO repository （http://www.ncbi.nlm.nih.gov/geo/）, The Mitochondrial Protein Reference Set 3.0 (MitoCarta3.0) repository (http://www.broadinstitute.org/mitocarta), and The molecular signatures database (MSigDB, https://www.gsea-msigdb.org/gsea/msigdb/index.jsp)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Three genes (GPX1, PPIF, and VDAC1) with significant differences in expression and consistent trends between the DN and control groups were obtained by Wilcoxon test, and all three key genes were down-regulated in DN (p < 0.05).", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "In order to understand the distinctions in the expression of candidate characterized genes in GSE30528 and GSE30122, three genes (GPX1, PPIF, and VDAC1) with significant differences in expression and consistent trends between the DN and control groups were obtained by Wilcoxon test, and three key genes were all down-regulated in DN (p < 0.05) (Fig. 3e)."}, "evidence": [{"asset": "source:pmid:40775242", "locator": "sections[21] \"Identification of biomarker key genes\" paragraph 2", "quote": "In order to understand the distinctions in the expression of candidate characterized genes in GSE30528 and GSE30122, three genes (GPX1, PPIF, and VDAC1) with significant differences in expression and consistent trends between the DN and control groups were obtained by Wilcoxon test, and three key genes were all down-regulated in DN (p < 0.05) (Fig. 3e)."}, {"asset": "source:pmid:40775242", "locator": "sections[21] \"Identification of biomarker key genes\" paragraph 2", "quote": "Next, the ROC curves of the three genes were plotted, and the AUC values of the three genes in GSE30528 and GSE30122 were all exceeding 0.7, which were defined as the key genes (GPX1, PPIF, and VDAC1) to be used as the subsequent analyses (Fig. 3g)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Three genes (GPX1, PPIF, and VDAC1) with significant differences in expression and consistent trends between the DN and control groups were obtained by Wilcoxon test, and all three key genes were down-regulated in DN (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:40775242"], "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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A run that reproduces the effect is judged against this threshold."}], "gaps": ["method.group_comparison_wilcoxon"]}, "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": ["group_comparison_wilcoxon"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:40775242", "data:geo:GSE30122"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_wilcoxon", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE30122"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:58:48Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 16127, "completion_tokens": 2218, "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:40775242", "type": "paper", "label": "pmid:40775242"}, {"id": "source:pmid:40775242", "type": "manuscript", "label": "PMID 40775242 full text"}, {"id": "data:geo:GSE30122", "type": "dataset", "label": "GEO GSE30122"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40775242", "type": "paper", "label": "pmid:40775242"}, {"id": "source:pmid:40775242", "type": "manuscript", "label": "PMID 40775242 full text"}, {"id": "data:geo:GSE30122", "type": "dataset", "label": "GEO GSE30122"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40775242", "type": "extraction", "used": ["source:pmid:40775242"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE30122", "type": "accession_resolution", "used": ["data:geo:GSE30122"], "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:40775242", "parent_hash": "sha256:91349b3d138e7cdeaa7212ed2a19142ad9ad33a3b9d1bced775ed5cd484abf8c", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE30122 licence not read", "asset:data:geo:GSE30122 not downloaded", "asset:data:geo:GSE30528 licence not read", "asset:data:geo:GSE30528 not downloaded", "execution.not_run", "method.group_comparison_wilcoxon", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:group_comparison_wilcoxon"], "assays": [{"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": ["es were all down-regulated in DN. Meanwhile, RT-qPCR analysis yielded the same results. In additi", "were all down-regulated in DN. Meanwhile, RT-qPCR analysis yielded the same results. In additi"], "order_basis": "paper_text_order:1398", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["imer disease, amyotrophic lateral sclerosis, apoptosis, and so on (adj.p < 0.05) (Fig. 2b). 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Records without an assay match currently receive a zero-hour model value.","status":"unverified","severity":"high"},{"code":"signal_score_without_citations","basis":["5,529 of 5,529 records (100.0%) have no citation count from the source metadata."],"claim":"Signal score","gloss":"The signal score uses publication-type weight because the mirror supplied zero citation counts.","detail":"The source supplied no citation counts for any record in this run, so the signal score is publication-type weight only. The citation term of the ranking is inert here, and the shortlist is ordered by publication type alone.","status":"unverified","severity":"high"},{"code":"abstract_absent","basis":["1,667 of 5,529 records (30.2%) carry no abstract at all."],"claim":"Evidence base for classification","gloss":"Some records contain a title and publication type only, defining the available classification evidence.","detail":"Where the mirror contains a title and publication types only, those fields define the classifier evidence. A methods section is required for fuller automated and human review.","status":"unverified","severity":"medium"},{"code":"classifier_agreement_measured","basis":["Published two-way decision agreement 77.7% (310 of 399 decidable records) from a stratified hand-check of 438 real records.","Three-way diagnostic agreement 73.9% (288 of 390 decidable records).","data_only agreement 75.2% (100 of 133 decidable).","48 record(s) could not be decided from title and abstract and were excluded from the denominator.","56 analysis-only records were published under another work type, so the data_only share is not an upper bound."],"claim":"Published automatable decision","gloss":"This figure has been checked against a human reading the same papers, so we know how often it is right.","detail":"The published automatable / not-automatable distribution comes from a rule-based classifier that was hand-checked against a fixed ground-truth definition. The agreement rates below are measured, not estimated. The three-way work type remains a diagnostic and is reported separately.","status":"measured","severity":"high"},{"code":"llm_comparison_not_measured","basis":["rule_based_v1+lex99e1195c7d6f produced 5,529 of 5,529 classifications.","Measured on 438 labelled records; these are RULE-BASED figures, not model results."],"claim":"Rule-based versus LLM agreement","gloss":"Every number here is the rule engine’s own. Model comparison begins when a working API credential is connected and measured.","detail":"The published two-way decision agreed with a human reading on 310 of 399 decidable records (77.7%). The diagnostic three-way label agreed on 288 of 390 decidable records (73.9%). Every percentage in this run belongs to the rule engine. Model comparison begins when a working API credential is connected and measured.","status":"not_measured","severity":"high"},{"code":"confidence_is_a_band","basis":["low band: 135 of 210 hand-judged records were correct, 64.3% [57.6, 70.5] (95% CI).","medium band: 80 of 104 hand-judged records were correct, 76.9% [68.0, 84.0] (95% CI).","high band: 73 of 76 hand-judged records were correct, 96.0% [89.0, 98.7] (95% CI).","A fitted calibrated probability was built, measured and withdrawn: it overstated held-out accuracy and reorders nothing."],"claim":"Confidence band and evidence score","gloss":"The confidence band carries a measured accuracy interval; 0.85 represents relative rank strength.","detail":"Confidence on this run is a BAND plus its measured accuracy interval. The number stored alongside each record is a monotone evidence score that orders records; 0.85 represents relative rank strength. A fitted probability was withdrawn after it overstated held-out accuracy. Threshold on the band.","status":"measured","severity":"medium"},{"code":"three_way_split_is_diagnostic","basis":["The corpus is published at the two-way decision: automatable or not-automatable. The three-way split (data_only / physical / mixed) is published as a diagnostic with its measured reliability attached, not as a claim, because the rule engine's `mixed` call cannot be defended.","The engine called 22 record(s) mixed; 10 matched the human judgement (45.5%, 95% CI 26.9-65.3).","The engine's `mixed` call is right on 10/22 hand-judged records (45.5%, 95% CI 26.9%-65.3%); a constant `physical` guess scores 36.4%.","The engine's `mixed` call does not reliably beat a constant `physical` guess on the hand-judged records it labels mixed.","The sign of that difference flips between two independent samples, so the three-way refinement is not demonstrably informative.","The mixed stratum contributes a disproportionate share of errors relative to its size.","At title-only depth the physical/mixed split collapses: a title says that work was done, not whether it was also analysed."],"claim":"The published decision is two-way","gloss":"The three-way split is shown for diagnosis only. The published split is two ways.","detail":"Count and filter the corpus on automatable versus not-automatable. The data_only / physical / mixed split remains an internal engine diagnostic because the mixed call has lower measured reliability.","status":"measured","severity":"medium"},{"code":"automatable_flag_unproven","basis":["6 of 29 assay families are marked automatable now: meta_analysis, machine_learning, survival_analysis, pca, molecular_docking, differential_expression.","The flag is a rule over assay family and work type; validation begins with the first executed replication.","It inherits the 75.2% data_only agreement rate, because the flag requires the record to be analysis-only."],"claim":"Automatable now","gloss":"This flag marks assay families the rules classify as data-only. The first executed replication will validate it.","detail":"This flag marks families the rules consider replicable from data alone. Its validity depends on the analysis-only classification and will be measured through an executed replication.","status":"unverified","severity":"medium"}],"confidence_policy":"band_with_measured_interval","confidence_contract":{"policy":"band_with_measured_interval","summary":"Confidence is reported as a BAND with a measured accuracy interval. The raw evidence score supplies monotone ordering. A fitted point estimate was withdrawn after it overstated held-out accuracy.","evidence_score":"A monotone evidence score in [0,1] built from cue mass, axis separation and text coverage. Use it to order records. Interpret 0.85 as relative rank strength.","confidence_band":"low | medium | high. Consumers threshold on this value.","band_accuracy":"Wilson 95% interval on the measured agreement of the hand-judged records in this band.","calibrated_confidence":"WITHDRAWN. Reintroduction requires held-out evidence demonstrating reliable estimates across every bin."},"band_accuracy":{"low":{"n":210,"low":0.576,"band":"low","high":0.7046,"agree":135,"accuracy":0.6429},"high":{"n":76,"low":0.8903,"band":"high","high":0.9865,"agree":73,"accuracy":0.9605},"medium":{"n":104,"low":0.6795,"band":"medium","high":0.8397,"agree":80,"accuracy":0.7692}},"provider":"rule_based_v1+lex99e1195c7d6f","lexicon_id":"99e1195c7d6f","contract_published_at":"2026-10-23T12:25:29.022232+00:00","confidence_is_band":true,"confidence_is_probability":false,"decision_taxonomy":"two_way","decidable_fraction_two_way":0.8854,"decidable_fraction_two_way_low":0.8565,"decidable_fraction_two_way_high":0.9143,"decidable_fraction_three_way":0.8586,"decidable_fraction_three_way_low":0.8287,"decidable_fraction_three_way_high":0.8884,"decidable_population":5529,"validation_sample_size":438,"three_way_cost_fraction":0.0268,"three_way_cost_records":148,"decision_counts":{"automatable":230,"not_automatable":5299},"decision_split":{"automatable":{"count":230,"share":0.04159884246699222},"not_automatable":{"count":5299,"share":0.9584011575330078}},"diagnostic_work_type_counts":{"mixed":24,"physical":5275,"data_only":230}}}