{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35578687", "kind": "science-record", "revision": 3, "content_hash": "sha256:9e21912530d491e15d31f21c55151f0ed675a0273d4731cad54b85a43e0bcdb5", "created_at": "2026-11-01T18:14:28Z", "updated_at": "2026-11-01T21:27:52Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of SMIM1 and SEZ6L2 as Potential Biomarkers for Genes Associated with Intervertebral Disc Degeneration in Pyroptosis.", "doi": "10.1155/2022/9515571", "pmid": "35578687", "authors": ["Nan Wang", "Xiyu Liu", "Xiaoyang Fang", "Shuang Chen", "Zhipeng Xi", "Xiaoyu Zhang", "Congyang Xue", "Xin Liu", "Lin Xie"], "journal": "Disease markers", "year": 2022, "abstract": "Background: Inflammatory reactions and pyroptosis play an important role in the pathology of intervertebral disc degeneration (IDD). The aim of the present study was to investigate pyroptosis in the nucleus pulposus cells (NPCs) of inflammatory induced IDD by bioinformatic methods and to search for possible diagnostic biomarkers.\nMethods: Gene expression profiles related to IDD were downloaded from the GEO database to identify differentially expressed genes (DEGs) between inflammation-induced IDD and non-inflammatory intervention samples. Pyroptosis genes were then searched for, and their expression in IDD was analyzed. Weighted gene co-expression network analysis (WGCNA) was then used to search for modules of IDD genes associated with pyroptosis and intersected with DEGs to discover candidate genes that would be diagnostically valuable. A LASSO model was developed to screen for genes that met the requirements, and ROC curves were created to clarify the diagnostic value of the genetic markers. Ultimately, the screened genes were further validated, and their diagnostic value assessed by selecting gene sets from the GEO database. RT-PCR was used to assess the mRNA expression of diagnostic markers in the nucleus pulposus (NP). Pan-cancer analysis was applied to demonstrate the expression and prognostic value of the screened genes in various tumors.\nResults: A total of 733 DEGs were identified in GSE41883 and GSE27494, which were mainly enriched in transmembrane receptor protein serine/threonine, kinase signaling pathway, response to lipopolysaccharide, and other biological processes, and they were mainly related to TGF beta signaling pathway, toll-like receptor signaling pathway, and TNF signaling pathway. A total of 81 genes related to pyroptosis were identified in the literature, and eight genes related to IDD were identified in the Veen diagram, namely, IL1A, IL1B, NOD2, GBP1, IL6, AK1, EEF2K, and PYCARD. Eleven candidate genes were obtained after locating the intersection of pyroptosis-related module genes and DEGs according to WGCNA analysis. A total of six valid genes were obtained after constructing a machine learning model, and five key genes were finally identified after correlation analysis. GSE23132 and GSE56081 validated the candidate genes, and the final IDD-related diagnostic markers were obtained as SMIM1 and SEZ6L2. RT-PCR results indicated that the mRNA expression of both was significantly elevated in IDD. The pan-cancer analysis demonstrated that SMIM1 and SEZ6L2 have important roles in the expression and prognosis of various tumors.\nConclusion: In conclusion, this research identifies SMIM1 and SEZ6L2 as important biomarkers of IDD associated with pyroptosis, which will help to unravel the development and pathogenesis of IDD and determine potential therapeutic targets.", "claims": [{"id": "claim-method", "statement": "The Cox proportional hazards regression model was constructed by the coxph function of the survival package in R software to evaluate the prognostic relationship between SMIM1 and SEZ6L2 with pan-cancer [20].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35578687", "locator": "sections[11] \"2.9. Prognosis and Survival Analysis\" paragraph 2", "quote": "The Cox proportional hazards regression model was constructed by the coxph function of the survival package in R software to evaluate the prognostic relationship between SMIM1 and SEZ6L2 with pan-cancer [20]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data are available upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35578687", "locator": "sections[25] \"Data Availability\" paragraph 2", "quote": "All data are available upon request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "SMIM1 and SEZ6L2 showed significant prognostic value in the pan-cancer analysis, with survival-analysis P values of 4.3e − 6 and 1.8e − 9, respectively.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35578687", "locator": "sections[21] \"3.8. Prognostic Value of SMIM1 and SEZ6L2 in Pan-Cancer\" paragraph 2", "quote": "The best cutoff value obtained in the survival analysis was 0.3231, based on which the patients were divided into high and low groups, and we finally observed a significant prognostic difference (P = 4.3e − 6) (Figure 9(d))."}, {"asset": "source:pmid:35578687", "locator": "sections[21] \"3.8. Prognostic Value of SMIM1 and SEZ6L2 in Pan-Cancer\" paragraph 2", "quote": "Significant prognostic differences (P = 1.8e − 9) were observed in the results of the survival analysis (Figure 9(f))."}, {"asset": "source:pmid:35578687", "locator": "sections[21] \"3.8. Prognostic Value of SMIM1 and SEZ6L2 in Pan-Cancer\" paragraph 2", "quote": "SMIM1 and SEZ6L2 have an important prognostic value in the pan-cancer analysis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "SMIM1 and SEZ6L2 showed significant prognostic value in the pan-cancer analysis, with survival-analysis P values of 4.3e − 6 and 1.8e − 9, respectively.", "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:35578687"], "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:GSE124272"], "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:GSE124272"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35578687", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2022/9515571", "sha256": 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null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE23130", "version": null, "note": "All data are available upon request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data are available upon request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM569830", "GSM569831", "GSM569832", "GSM569833", "GSM569834", "GSM569835", "GSM569836", "GSM569837", "GSM569838", "GSM569839", "GSM569840", "GSM569841", "GSM569842", "GSM569843", "GSM569844", "GSM569845", "GSM569846", "GSM569847", "GSM569848", "GSM569849", "GSM569850", "GSM569851", "GSM569852"], "sample_count": 23, "group_sizes": null, "group_sizes_basis": null, "platform": "1352", "taxon": "Homo sapiens", "title": "Gene Array Data from Human Annulus Disc Tissue", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": 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expression of BDNF, NTF3 and NRP2 as well as NGF Production in Human Annulus Cells", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE41883", "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=GSE41883", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE41883", "version": null, "note": "All data are available upon request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data are available upon request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1026926", "GSM1026927", "GSM1026928", "GSM1026929", "GSM1026930", "GSM1026931", "GSM1026932", "GSM1026933"], "sample_count": 8, "group_sizes": null, "group_sizes_basis": null, "platform": "1352", "taxon": "Homo sapiens", "title": "Human annulus disc cells grown in a 3D collagen sponge and exposed to TNF-a", "resolution_checked_at": "2026-11-01T18:06:44Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE56081", "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=GSE56081", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE56081", "version": null, "note": "All data are available upon request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data are available upon request.", "access_statement_kind": "data_availability_statement", "sample_accessions": 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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": ["GSE41883", "GSE27494", "GSE124272", "GSE23130", "GSE56081"], "resolved_accessions": ["GSE41883", "GSE27494", "GSE124272", "GSE23130", "GSE56081"], "statements": ["All data are available upon request."], "basis": "The paper names GSE41883, GSE27494, GSE124272, GSE23130, GSE56081 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:35578687", "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": "2026-11-01T17:46:29Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 8968, "completion_tokens": 2879, "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:35578687", "type": "paper", "label": "pmid:35578687"}, {"id": "source:pmid:35578687", "type": "manuscript", "label": "PMID 35578687 full text"}, {"id": "data:geo:GSE124272", "type": "dataset", "label": "GEO GSE124272"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35578687", "type": "paper", "label": "pmid:35578687"}, {"id": "source:pmid:35578687", "type": "manuscript", "label": "PMID 35578687 full text"}, {"id": "data:geo:GSE124272", "type": "dataset", "label": "GEO GSE124272"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35578687", "type": "extraction", "used": ["source:pmid:35578687"], "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:35578687", "parent_hash": "sha256:911672b704347dfb5968eb14115f4fa8bc82ce43853654d2608c28831d08917c", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE124272 licence not read", "asset:data:geo:GSE124272 not downloaded", "asset:data:geo:GSE23130 licence not read", "asset:data:geo:GSE23130 not downloaded", "asset:data:geo:GSE27494 licence not read", "asset:data:geo:GSE27494 not downloaded", "asset:data:geo:GSE41883 licence not read", "asset:data:geo:GSE41883 not downloaded", "asset:data:geo:GSE56081 licence not read", "asset:data:geo:GSE56081 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The Cox proportional hazards regression model was constructed by the coxph function of the survival package in R software to evaluate the prognostic relationship between SMIM1 and SEZ6L2 with pan-cancer [20]."], "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. Evidence bands order textual support; method agreement intervals are null (n=0), never probabilities. Work-type validation does not validate methods.","Operation coverage describes only explicitly named methods. It does not prove a complete protocol, compatible parameters, successful compilation or re-execution. Unrecognised or ambiguous methods require review.","Data reachability is a textual accession or public-data statement. No dataset was downloaded or checked for access, completeness or licence.","Capabilities are planning states seeded from the dated equipment register. No bench ownership, completed quote or partner booking is inferred. Procurement counts are dependencies, not guaranteed replications or financial returns.","Tier and blocker counts are deterministic assessments of this corpus, not measured agreement. R3 is reserved for procurement; unresolved methods and data require human work (R4). The most restrictive axis wins, with capability, method, data as tie-breaks. Resolving one blocker can leave another at the same tier."],"engine":"corpus_engine","engine_provider":"rule_based_v1+lex99e1195c7d6f","run_id":"run-20261023T122449232913","source":"esearch","source_detail":"PubMed mirror biomed_pubmed (read-only)","run_status":"complete","imported_at":"2026-11-03T20:16:52+00:00","generated_at":"2026-11-04T00:46:16+00:00","total_papers":5529,"total_assays_tracked":29,"automatable_assay_families":6,"validated":true,"caveat_count":9,"blocking_caveats":5,"caveats":[{"code":"low_evidence_dominates","basis":["4,152 of 5,529 classifications (75.1%) matched no cue evidence and sit at the 0.05 floor.","34 of 230 data_only calls (14.8%) are in that group."],"claim":"Work type and confidence bands","gloss":"Most records were classified from their title and framing alone, with assay-cue coverage at zero.","detail":"Most classifications in this run rest on no matched evidence at all. 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}}}