{ "updates": [ { "date": "2026-09-08", "type": "plain_language_and_evidence_links", "humanReviewed": false, "note": "Replaced metaphorical introduction and labels with practical wording. Corrected GenCC HGNC identifier links and replaced the unavailable FDA belzutifan announcement with its official approval letter. External request failures recorded separately from confirmed broken links; generated CGC URLs validated against record identifiers. Scientific records and counts unchanged." }, { "date": "2026-09-08", "type": "all_cgc_tiers_included", "humanReviewed": false, "counts": { "all": { "diseaseTFs": 395, "cgcTFs": 146 }, "nonNR": { "diseaseTFs": 372, "cgcTFs": 139 } }, "note": "Included all CGC-attributed direct associations via Open Targets 26.06 without tier restrictions. ClinGen/GenCC still require Strong or Definitive. GWAS and other excluded evidence remain excluded. Binder, clinical, first-report and census records unchanged. Existing weekly task updated." }, { "date": "2026-09-08", "type": "strict_disease_evidence", "humanReviewed": false, "associationsBefore": 44461, "associationsAfter": 535, "TFsWithQualifyingDiseaseEvidence": 321, "nonNuclearReceptorTFsWithQualifyingDiseaseEvidence": 302, "note": "Only ClinGen/GenCC Strong or Definitive assessments retained. GWAS, weaker genetic, experimental and literature evidence removed from current data and filters. CGC Tier 1 import pending authorized verified export; previous unverified driver records excluded. Binder, clinical, timeline and census data identical. Existing weekly task updated." }, { "date": "2026-09-08", "type": "disease_scope_narrowed", "humanReviewed": false, "removedEvidenceTypes": [ "Automated literature association", "Clinical feature / trait" ], "associationsBefore": 280389, "associationsAfter": 44461, "note": "Removed automated literature and clinical feature/trait attributes and their sources, filters and details. Manually literature-curated associations retained. Binder, clinical, timeline and census records unchanged." }, { "date": "2026-09-08", "type": "disease_annotations_and_filters", "humanReviewed": false, "coverage": "All TFs queried; source coverage incomplete", "addedTFs": [], "note": "Added source-linked disease and clinical-feature annotations, independent disease/evidence filters across map, list and timeline, and disease-filtered binder coverage. Existing weekly task extended. All binder, clinical, historical date and roster records unchanged. Without nuclear receptors: 17/1593 TFs, 7/52 classes; including receptors: 45/1640 TFs, 8/53 classes.", "diseaseAudit": { "checkedAt": "2026-09-08", "humanReviewed": false, "assessedGenes": 1637, "unmappedOrFailedGenes": [ "DUX1", "DUX3", "HOMEZ" ], "sources": [ { "name": "Open Targets", "url": "https://platform.opentargets.org/", "version": "26.06", "status": "Imported direct associations", "note": "Animal-model-only, pathway-only and clinical-precedence-only records excluded. Literature text mining remains a separate evidence label." }, { "name": "ClinGen", "url": "https://search.clinicalgenome.org/kb/gene-validity", "version": "Export 2026-09-08", "status": "Imported 282 TF assessments" }, { "name": "GenCC", "url": "https://thegencc.org/", "version": "Export 2026-09-08", "status": "Imported 2349 TF assessments", "note": "ClinGen submissions deduplicated in favor of direct ClinGen. Moderate, Strong and Definitive qualify for expert-reviewed filter; limited and disputed relationships are separate." }, { "name": "COSMIC Cancer Gene Census", "url": "https://cancer.sanger.ac.uk/census", "version": "As integrated in Open Targets 26.06", "status": "Imported via Open Targets", "note": "Direct COSMIC release not independently downloaded; original tiers not assigned." }, { "name": "IntOGen", "url": "https://www.intogen.org/", "version": "As integrated in Open Targets 26.06", "status": "Imported as genetic association evidence" }, { "name": "HPO", "url": "https://hpo.jax.org/", "version": "Download 2026-09-08", "status": "Imported clinical features; excluded from disease-association counts" }, { "name": "TFcancer", "url": "https://lcbb.swjtu.edu.cn/tfcancer/download.html", "version": "2021 publication; download 2026-09-08", "status": "Imported 1269 unambiguously mapped source rows", "note": "577 rows unresolved or outside the atlas; not assigned by guesswork." }, { "name": "Lambert et al.", "url": "https://humantfs.ccbr.utoronto.ca/download.php", "version": "2018 / catalogue v1.01", "status": "Census baseline retained; historical disease workbook not imported", "note": "Direct download timed out. Updated HPO annotations imported; historical workbook retained as a linked reference." }, { "name": "DISGENET", "url": "https://www.disgenet.com/", "status": "Optional supplementary source; not imported", "note": "Access and reuse arrangements not established." } ], "definition": "Positive disease association means a non-feature record with evidence other than disputed/refuted only. No source score cutoff or causal inference. Expert-reviewed filter requires direct ClinGen/GenCC Moderate, Strong or Definitive classification.", "sourceRecordCounts": { "eva": 3250, "genomics_england": 1190, "uniprot_literature": 595, "gene2phenotype": 473, "europepmc": 219889, "orphanet": 671, "crispr_screen": 1298, "gwas_credible_sets": 21444, "gene_burden": 261, "expression_atlas": 10609, "uniprot_variants": 428, "crispr": 98, "eva_somatic": 220, "cancer_gene_census": 16583, "intogen": 400, "cancer_biomarkers": 29 }, "tfcancerUnmappedLabels": { "CREB": 8, "SF-1": 1, "ERR\u4f2a": 1, "COUP-TFI": 3, "ER-\u5c3e": 1, "NF-kappaB": 74, "HIF-1alpha": 22, "NRF1": 2, "PR": 9, "AP-1": 29, "c-fos": 6, "Brn-3b": 5, "ER": 10, "Twist": 10, "TRP": 1, "Snail1": 13, "Nrf1": 1, "c-Myc": 18, "cJun": 2, "cFos": 2, "FOXO3a": 10, "AP-2alpha": 5, "PDEF": 6, "ZER6": 1, "NF\u9b4fB": 2, "deltaEF1": 1, "OCT1": 4, "PPARalpha": 2, "hXBP-1": 1, "mtp53": 2, "FoxO3a": 8, "c-Jun": 11, "YB-1": 3, "TRF2": 1, "TRF1": 1, "DeltaNp63alpha": 2, "PEA3": 6, "AP-2": 8, "Kaiso": 3, "tGLI1": 1, "OCT2": 2, "NF-kappa B": 4, "ER alpha": 5, "SRC-1": 9, "c-Fos": 9, "ER\u4f2a": 1, "TCF4": 2, "FRA-1": 2, "TWIST": 1, "LRH-1": 3, "AP-4": 1, "Smad2/3": 1, "Fra-1": 9, "ER-alpha": 1, "STAT5": 6, "AIB1": 4, "C/EBPalpha": 5, "c-myc": 7, "Ap-1": 3, "AP2-alpha": 2, "SAF-1": 1, "NF-I": 1, "PPAR\u7eac": 1, "Eralpha": 4, "SUZ12": 1, "NFAT3": 4, "ERalpha": 1, "Fra-2": 4, "AP2-gamma": 2, "ERRalpha": 1, "DeltaEF1": 2, "C-ets-1": 1, "T-bet": 3, "OCT4": 14, "C/EBP alpha": 2, "ER\u4f2a36": 1, "c-jun": 4, "PPARgamma": 5, "ER81": 3, "ACTR": 1, "p65": 11, "CBFbeta": 1, "Pit-1": 1, "FKHR": 1, "GR": 2, "EVI1": 5, "AP-2alphal": 1, "LIP": 1, "Stat5": 1, "ER-beta": 1, "SAP1": 1, "DEC1": 2, "ESX": 1, "Pokemon": 1, "C/EBPbeta": 1, "DEC2": 1, "sLZIP": 1, "ITF2": 1, "DeltaNp63": 1, "HNF6": 1, "PPAR gamma": 1, "c-FOS": 2, "CHOP": 5, "ZBP-99": 2, "ESE3": 1, "GKLF": 1, "WIG-1": 2, "NF-\u9b4fB": 6, "RAR-beta": 1, "2021-10-04 00:00:00": 3, "fra-1": 1, "NFkappaB": 4, "HIF-1 alpha": 1, "Pouf1": 1, "PPAR-Delta": 1, "HIF-1\u4f2a": 3, "HIF": 2, "PLZF": 1, "HLTF": 1, "AML1": 2, "BSAP": 1, "N-Myc": 1, "FXR": 2, "pokemon": 1, "Bclaf1": 2, "HNF-4alpha": 3, "NF-kB": 1, "Zbtb7": 1, "p73-isoform": 2, "c-JUN": 1, "hTcf-4": 1, "p53mt249": 1, "FOXA": 1, "ICER": 1, "PPAR-alpha": 1, "HNF-1alpha": 4, "c-Myb": 1, "mutp53": 1, "LSF": 3, "GADD153": 1, "NKX3.1": 1, "ELK": 1, "C/EBP-beta": 3, "Gli": 1, "CREBH": 1, "HNF4\u4f2a": 2, "NRF-1": 1, "PREP1": 2, "BLIMP1": 1, "HNF-3": 1, "FOG2": 1, "FOXO3A": 2, "HNF4alpha": 2, "PPAR-gamma": 2, "p63": 1, "C/EBP-alpha": 1, "Tel": 1, "Ptf1-p48": 1, "DPC4": 2, "Ikaros": 1, "Atf": 1, "TULP3": 1, "Id2": 2, "GLI2A": 1, "ETS": 1, "TCF-4": 1, "CREB silencing": 1, "c-MYC": 1, "HASH1": 1, "Foxo3a": 1, "ERM": 1, "NFI": 1 } } }, { "date": "2026-09-07", "type": "patent_preprint_coverage_correction", "coverage": "partial", "humanReviewed": false, "addedTFs": [], "note": "Updated existing unified workflow and recurring task to explicitly require nuclear-receptor patent and preprint coverage, including genes already supported by published papers. Reran24 gene-batch web queries covering47 NR symbols, supplemental alias searches and Elicit paper searches. Existing combined report completed with80sources,46fulltexts; omissions and outdated clinical statements not imported. No new reports/tasks/workflows created. No newly verified qualifying affinity entries. Counts unchanged:17/1593and7/52 withoutNR;45/1640and8/53 withNR.", "sourceLimitations": [ "Search batches are discovery only, not exhaustive review.", "Several preprint full texts inaccessible (403/429); quantitative figure values not inferred.", "Patent activity claims, antibody affinities and unresolved compound-specific measurements not admitted." ] }, { "date": "2026-09-07", "type": "unified_workflow_and_display", "humanReviewed": false, "addedTFs": [], "note": "Unified all-TF Elicit review launched; earlier receptor/non-receptor reports retained as provenance, not separate recurring workflows. Review processing; no extraction imported. Canonical dataset byte-for-byte unchanged. Without NRs:17/1593 TFs and7/52 classes; with NRs:45/1640 TFs and8/53 classes. Scope starts closed; timeline initially scrolls to recent years.", "reviewUrl": "https://elicit.com/review/551fd09c-d044-41e2-b0db-08839566c36c", "reviewStatus": "processing", "coverage": "pending reconciliation" }, { "date": "2026-09-07", "type": "clinical_translation_and_timeline", "coverage": "partial", "humanReviewed": false, "addedTFs": [], "clinicalTFCounts": { "approved": 18, "clinical": 9, "secondary": 3, "historical": 1, "none": 14 }, "note": "Assessed all 45 affinity-supported TFs for representative approved and clinical small-molecule programs. Added clinical filter, source-linked details and earliest-identified report timeline from 1980 to present. No affinity evidence or first-report dates changed. Weekly protocol now refreshes clinical status.", "sourceLimitations": [ "Elicit review completed but its mostly review-based corpus missed several current programs; reconciled with regulatory, registry and primary sources.", "Clinical annotation does not transfer submicromolar affinity to a different compound or imply a subtype-selective approval.", "No program identified is not proof of absence; historical dates remain provisional." ] }, { "date": "2026-09-07", "type": "nuclear_receptor_scope_expansion", "coverage": "partial", "humanReviewed": false, "addedTFs": [ "AR", "ESR1", "ESR2", "ESRRG", "NR1D2", "NR1H2", "NR1H3", "NR1I2", "NR2E1", "NR3C1", "NR3C2", "NR4A2", "NR5A1", "NR5A2", "PGR", "PPARD", "PPARG", "RARA", "RARB", "RARG", "RORA", "RORB", "RORC", "RXRA", "RXRB", "THRA", "THRB", "VDR" ], "note": "Nuclear receptors now included in collection and weekly queries; display toggle defaults on and controls TF/class counts, map, finder and recent summary. Added 28 nuclear receptors with affinity reports; original report years retained. Elicit audit completed; supplemented by IUPHAR/BPS and primary source metadata. No claim of exhaustive coverage.", "sourceLimitations": [ "Elicit retrieved 46 sources with 14 full texts; many classic binding studies absent from that corpus.", "Database human assignments cross-checked where possible; unresolved construct and reversibility caveats retained. Known nonhuman records excluded.", "Google Patents expansion used broad discovery queries, not an exhaustive receptor-by-receptor patent review. Patent leads require assay-level verification before affinity admission.", "Historical priority and full-text extraction remain incomplete." ] }, { "date": "2026-09-07", "type": "setup_and_historical_backfill", "coverage": "partial", "humanReviewed": false, "addedTFs": [], "historicalEvidenceAdded": [ "AHR", "STAT3", "STAT5B", "TP53" ], "note": "Automatic weekly publishing enabled. Date metadata from Crossref, Europe PMC, Elicit and Google Patents. Source metadata checks and targeted historical searches only; not a complete new literature/patent screen.", "sourceLimitations": [ "Some publisher/PubMed pages inaccessible; used primary abstract records through Europe PMC/Elicit where available.", "Several Crossref lookups rate-limited; alternate metadata used.", "Exact day unavailable for some historical records; these cannot trigger recent-discovery badges." ] } ] }