{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40703651", "kind": "science-record", "revision": 4, "content_hash": "sha256:573f7c1088b46fe6475645b12e0132c7ab81c19e990994aea1228b9d54de3215", "created_at": "2026-11-01T20:30:48Z", "updated_at": "2026-11-01T22:56:53Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Mitochondrial insights: key biomarkers and potential treatments for diabetic nephropathy and sarcopenia.", "doi": "10.3389/fcell.2025.1596204", "pmid": "40703651", "authors": ["Yi Wei Chen", "Shan He", "Yu Wang", "Lian Ying Hu", "Qin Kai Chen", "Si Yi Liu"], "journal": "Frontiers in cell and developmental biology", "year": 2025, "abstract": "Introduction: Clinical studies reveal bidirectional links between sarcopenia (SP) and diabetic nephropathy (DN). Damage to mitochondria in DN may result in diminished energy production, which consequently triggers SP. Consequently, mitochondria seem to function as critical nodes connecting DN with SP. The objective of this research was to pinpoint biomarkers associated with mitochondrial dysfunction in DN and SP.\nMethods: By analyzing the Gene Expression Omnibus (GEO) repository, we identified shared differentially expressed genes (DEGs) in the DN (GSE96804, GSE30528) and SP (GSE1428, GSE136344) datasets that displayed similar expression trends in mitochondrial genes. Using Least Absolute Shrinkage and Selection Operator (LASSO), Support Vector Machine (SVM), Extreme Gradient Boosting (XGB), and Random Forest (RF) algorithms, we identified three key mitochondrial hub genes. Diagnostic nomograms were created to predict DN and SP risk. We assessed immune infiltration using CIBERSORT and built a drug-gene network with Cytoscape. Molecular docking determined binding affinities between potential drugs and hub genes, which were validated in the datasets.\nResults: Analysis of GEO datasets identified 80 shared DEGs between DN and SP, including 10 mitochondria-related genes. Utilizing four machine learning algorithms (LASSO, SVM, XGBoost, RF), we pinpointed three mitochondrial hub genes. Subsequent validation confirmed two key mitochondria-related genes - HTT and TTC19 - as shared diagnostic biomarkers for both DN and SP. These biomarkers demonstrated strong diagnostic power (AUC >0.8), leading to the construction of diagnostic nomograms. Immune infiltration analysis revealed elevated M1 macrophages in DN and increased M2 macrophages in SP, with both biomarkers showing significant correlations with various immune cells. Gene set enrichment analysis linked HTT and TTC19 to mitochondrial metabolic processes. Crucially, in silico drug prediction identified 156 potential drugs, and molecular docking confirmed a high binding affinity between acetaminophen and the HTT protein.\nConclusion: Our study identifies HTT and TTC19 as novel mitochondria-immune related biomarkers common to both DN and SP, providing insights into their shared pathogenesis involving mitochondrial dysfunction and immune dysregulation. The computational prediction of acetaminophen interaction highlights a potential avenue for therapeutic exploration. Further clinical and mechanistic studies are warranted to validate these findings and elucidate the underlying pathways.", "claims": [{"id": "claim-method", "statement": "We used the “limma” package in R software to perform differential analysis on the expression profile data of the DN - Datasets and SP - Datasets respectively, and screened the genes with the criteria of |logFC| > 0.25 and p. value <0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40703651", "locator": "sections[4] \"2.2 Differential expression gene analysis\" paragraph 2", "quote": "We used the “limma” package in R software to perform differential analysis on the expression profile data of the DN - Datasets and SP - Datasets respectively, and screened the genes with the criteria of |logFC| > 0.25 and p. value <0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40703651", "locator": "sections[23] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "HTT and TTC19 were validated as shared diagnostic biomarkers for both diabetic nephropathy and sarcopenia.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40703651", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Subsequent validation confirmed two key mitochondria-related genes - HTT and TTC19 - as shared diagnostic biomarkers for both DN and SP."}, {"asset": "source:pmid:40703651", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "These biomarkers demonstrated strong diagnostic power (AUC >0.8), leading to the construction of diagnostic nomograms."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "HTT and TTC19 were validated as shared diagnostic biomarkers for both diabetic nephropathy and sarcopenia.", "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:40703651"], "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:GSE136344"], "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:GSE136344"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40703651", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcell.2025.1596204", "sha256": 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"identifier": "GSE30528", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM756992", "GSM756993", "GSM756994", "GSM756995", "GSM756996", "GSM756997", "GSM756998", "GSM756999", "GSM757000", "GSM757001", "GSM757002", "GSM757003", "GSM757004", "GSM757005", "GSM757006", "GSM757007", "GSM757008", "GSM757009", "GSM757010", "GSM757011", "GSM757012", "GSM757013"], "sample_count": 22, "group_sizes": null, "group_sizes_basis": null, "platform": "571", "taxon": "Homo sapiens", "title": "Transcriptome Analysis 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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": ["GSE96804", "GSE30528", "GSE1428", "GSE136344"], "resolved_accessions": ["GSE96804", "GSE30528", "GSE1428", "GSE136344"], "statements": ["The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors."], "basis": "The paper names GSE96804, GSE30528, GSE1428, GSE136344 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:40703651", "data:geo:GSE136344"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE136344"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:57:43Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 12197, "completion_tokens": 2228, "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:40703651", "type": "paper", "label": "pmid:40703651"}, {"id": "source:pmid:40703651", "type": "manuscript", "label": "PMID 40703651 full text"}, {"id": "data:geo:GSE136344", "type": "dataset", "label": "GEO GSE136344"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40703651", "type": "paper", "label": "pmid:40703651"}, {"id": "source:pmid:40703651", "type": "manuscript", "label": "PMID 40703651 full text"}, {"id": "data:geo:GSE136344", "type": "dataset", "label": "GEO GSE136344"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40703651", "type": "extraction", "used": ["source:pmid:40703651"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE136344", "type": "accession_resolution", "used": ["data:geo:GSE136344"], "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:40703651", "parent_hash": "sha256:e6ce4f3c50f54e36969f31c0b73b08eb4dba292623776cefa2ef839da9c3da3b", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE136344 licence not read", "asset:data:geo:GSE136344 not downloaded", "asset:data:geo:GSE1428 licence not read", "asset:data:geo:GSE1428 not downloaded", "asset:data:geo:GSE30528 licence not read", "asset:data:geo:GSE30528 not downloaded", "asset:data:geo:GSE96804 licence not read", "asset:data:geo:GSE96804 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": ["We used the “limma” package in R software to perform differential analysis on the expression profile data of the DN - Datasets and SP - Datasets respectively, and screened the genes with the criteria of |logFC| > 0.25 and p. value <0.05."], "order_basis": "analysis_only", "id": "assay:1"}]},"meta":{"api_version":"v1","automation_ladder_snapshot":"ba34b49490d9bfaf","automation_ladder_caveats":["Method extraction is rule-based and has no hand-judged accuracy sample. 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At the evidence floor the work type comes from title framing and a fixed prior, not from anything in the paper, so the published work-type split should be read as a rough triage signal rather than a measured distribution. The impact is bounded but not removed: since 2026-10-23 the engine excludes floor-confidence records from the shortlist entirely and publishes them separately as held out, so the recommendation is unaffected even though the census is.","status":"unverified","severity":"high"},{"code":"runtime_is_modelled","basis":["Runtime is summed from published per-assay hour figures. Timing awaits the first executed replication.","4,407 of 5,529 records (79.7%) model to 0.00 hours because no assay was matched, which the ranking then reads as \"cheapest\".","0 of 10 shortlisted records carry a 0.00-hour estimate."],"claim":"Estimated replication runtime","gloss":"The hour figures are estimates built from assay mentions; timing awaits the first executed replication.","detail":"The hour figures are a cost model derived from the bench steps implied by each matched assay family. The first executed replication will supply measured timing. 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}}}