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Automates ACMG/AMP 2015 classification using a Bayesian point-based framework (Tavtigian et al. 2018) with BayesDel ClinGen SVI-calibrated thresholds (Pejaver et al. 2022). Integrates 8 reference databases (gnomAD v4.1, ClinVar, dbNSFP 4.9c, SpliceAI, gnomAD Constraint, HPO, ClinGen, Ensembl VEP). Analyzes nuclear and mtDNA variants, structural and copy-number variants (SV/CNV), with trio/family and cohort analysis. Supports HPO-based phenotype matching, biomedical literature mining across 2M+ PubMed publications, and structured clinical report generation. AI assists in evidence synthesis but does not make classification decisions. 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Excludes proprietary clinical interpretation logic, private data, credentials and operational infrastructure.", "version": "1.2.2" } ], "documentation": [ { "url": "https://folklore.helena.bio/docs", "type": [ "General" ], "note": "Complete production documentation covering every threshold, database version, and classification rule. Intended for clinical geneticists, laboratory directors, accreditation auditors, and bioinformaticians." }, { "url": "https://folklore.helena.bio/how-it-works", "type": [ "General" ], "note": "Seven-stage analysis pipeline (quality control, annotation, classification, phenotype matching, literature, screening, interpretation) transforming a raw VCF into a clinician-ready report, each stage producing traceable, auditable output." }, { "url": "https://folklore.helena.bio/methodology", "type": [ "General" ], "note": "ACMG/AMP 2015 classification methodology (Richards et al. 2015) via Bayesian point-based system (Tavtigian et al. 2018), BayesDel ClinGen SVI-calibrated thresholds (Pejaver et al. 2022), and SpliceAI aligned to ClinGen SVI 2023 (Walker et al. 2023). Optional ClinGen VCEP overlay for ~50-60 genes. Strictly evidence-based, no ML determines pathogenicity." }, { "url": "https://folklore.helena.bio/methodology/mtdna", "type": [ "General" ], "note": "Mitochondrial DNA variant classification under the ClinGen Mitochondrial Disease Working Group (MMDWG) 2020 specification (McCormick et al. 2020). Operates as an independent module from the nuclear ACMG/AMP pipeline; every variant carries an explicit framework provenance label. Strength tiers follow ClinGen mtDNA VCEP v1.0.0." }, { "url": "https://folklore.helena.bio/methodology/family-analysis", "type": [ "General" ], "note": "Inheritance-aware evidence from trio (proband + both parents), duo, and proband-plus-sibling analyses. Implements ClinGen SVI 2018 de novo PS2/PM6 (PMID 29543229), Jarvik & Browning 2016 LOD segregation framework (PMID 27236918), and ClinGen SVI 2021 PP1 strength bands. Augments the existing ACMG/AMP classification without re-calling variants." }, { "url": "https://folklore.helena.bio/methodology/sv", "type": [ "General" ], "note": "Structural and copy-number variant evaluation under the Riggs 2020 joint ACMG/ClinGen technical standard. Documents the point-based loss and gain metrics, dosage-sensitivity evidence, and five-tier classification, with reference data and documented limitations." }, { "url": "https://folklore.helena.bio/screening-methodology", "type": [ "General" ], "note": "Prioritizes classified variants for clinical review. After ACMG classification determines what each variant is, screening determines which to review first based on patient-specific clinical relevance. Evaluates seven independent dimensions, applies clinical profile boosts, and produces a four-tier priority ranking with transparent, visible score components." }, { "url": "https://folklore.helena.bio/docs/folklore-connector", "type": [ "API documentation" ], "note": "Canonical connector guide for Folklore Clinical Variant Interpretation MCP (io.github.helena-bioinformatics/folklore), version 1.2.2." }, { "url": "https://github.com/helena-bioinformatics/folklore-mcp#readme", "type": [ "General" ], "note": "Public Apache-2.0 MCP protocol adapter README. The Folklore SaaS platform and clinical interpretation backend remain proprietary." }, { "url": "https://github.com/helena-bioinformatics/folklore-mcp/blob/main/CHANGELOG.md", "type": [ "Release notes" ], "note": "Release history for the public Folklore MCP protocol adapter." } ], "publication": [ { "doi": "10.5281/zenodo.21105027", "pmid": null, "pmcid": null, "type": [ "Preprint" ], "version": "1.0", "note": "Methodological framework for real-world performance studies of the platform's variant classification, demonstrated on three internal validation cohorts.", "metadata": null }, { "doi": "10.5281/zenodo.21189571", "pmid": null, "pmcid": null, "type": [ "Preprint" ], "version": "1.0", "note": "A Deterministic Classification Core with an Agentic Interpretation Layer: An Architecture for Auditable, Human-Gated Clinical Variant Analysis", "metadata": null }, { "doi": "10.5281/zenodo.21763096", "pmid": null, "pmcid": null, "type": [ "Preprint" ], "version": null, "note": "Robustness and cross-cohort concordance of developmental regulons in endometrial carcinoma. Authors: Draga Toncheva, Vasil Sgurev and Vladimir Mitev.", "metadata": null }, { "doi": "10.5281/zenodo.21922952", "pmid": null, "pmcid": null, "type": [ "Other" ], "version": "1.2.2", "note": "Archived public Apache-2.0 Folklore MCP adapter release. All-version DOI: 10.5281/zenodo.21922951.", "metadata": null }, { "doi": "10.5281/zenodo.22093164", "pmid": null, "pmcid": null, "type": [ "Other" ], "version": "1.3.1", "note": "Archived public Apache-2.0 Folklore MCP adapter release with four read-only tools, including semantic Literature Corpus search. 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