/**
 * Precision Medicine and Genomic Interpretation Module
 *
 * ╔═══════════════════════════════════════════════════════════════════════════════╗
 * ║  PRECISION ONCOLOGY - BIOMARKER-DRIVEN TREATMENT SELECTION                  ║
 * ╠═══════════════════════════════════════════════════════════════════════════════╣
 * ║  This module provides:                                                        ║
 * ║  - Comprehensive genomic interpretation                                      ║
 * ║  - Actionable mutation databases                                             ║
 * ║  - Pharmacogenomics for toxicity prediction                                  ║
 * ║  - Tumor microenvironment analysis                                           ║
 * ║  - ctDNA/liquid biopsy interpretation                                        ║
 * ║  - Variant actionability scoring                                             ║
 * ╚═══════════════════════════════════════════════════════════════════════════════╝
 */
export interface GenomicAlteration {
    gene: string;
    alteration: string;
    alterationType: AlterationType;
    frequency: string;
    cancerTypes: string[];
    actionability: ActionabilityLevel;
    therapies: TargetedTherapy[];
    clinicalTrials: string[];
    resistance: ResistanceMutation[];
    prognosticValue: PrognosticValue;
}
export type AlterationType = 'Missense Mutation' | 'Nonsense Mutation' | 'Frameshift' | 'In-frame Deletion' | 'In-frame Insertion' | 'Splice Site' | 'Amplification' | 'Deletion' | 'Fusion' | 'Rearrangement' | 'Copy Number Gain' | 'Copy Number Loss';
export interface ActionabilityLevel {
    level: 'Level 1' | 'Level 2' | 'Level 3A' | 'Level 3B' | 'Level 4' | 'Not Actionable';
    description: string;
    source: string;
}
export interface TargetedTherapy {
    drug: string;
    class: string;
    approvalStatus: 'FDA-Approved' | 'EMA-Approved' | 'Off-Label' | 'Clinical Trial';
    indication: string;
    responseRate: string;
    medianPFS: string;
    keyTrial: string;
}
export interface ResistanceMutation {
    mutation: string;
    frequency: string;
    overcomingStrategy: string[];
}
export interface PrognosticValue {
    impact: 'Favorable' | 'Unfavorable' | 'Neutral' | 'Context-Dependent';
    description: string;
}
export declare const ACTIONABLE_GENOMIC_DATABASE: GenomicAlteration[];
export interface PharmacogenomicMarker {
    gene: string;
    variant: string;
    affectedDrugs: DrugPGx[];
    testingRecommendation: 'Required' | 'Strongly Recommended' | 'Consider' | 'Optional';
    guidelineSource: string;
}
export interface DrugPGx {
    drug: string;
    effect: string;
    recommendation: string;
    doseAdjustment?: string;
}
export declare const PHARMACOGENOMIC_MARKERS: PharmacogenomicMarker[];
export interface TumorMicroenvironment {
    immuneInfiltration: ImmuneInfiltration;
    stromalPhenotype: StromalPhenotype;
    vascularization: VascularStatus;
    immunePhenotype: 'Inflamed' | 'Excluded' | 'Desert';
    therapeuticImplications: TherapeuticImplication[];
}
export interface ImmuneInfiltration {
    cd8TILs: 'High' | 'Intermediate' | 'Low' | 'Absent';
    cd4TILs: 'High' | 'Intermediate' | 'Low';
    tregs: 'High' | 'Low';
    myeloidCells: MDSCStatus;
    nkCells: 'Present' | 'Absent';
    bCells: 'Present' | 'Absent' | 'TLS Present';
}
export interface MDSCStatus {
    mdscLevel: 'High' | 'Low';
    m1m2Ratio: 'M1-predominant' | 'M2-predominant' | 'Mixed';
}
export interface StromalPhenotype {
    cafPresence: 'High' | 'Low';
    ecmDensity: 'Dense' | 'Moderate' | 'Loose';
    fibrosis: boolean;
}
export interface VascularStatus {
    vascularDensity: 'High' | 'Moderate' | 'Low';
    vascularNormalization: boolean;
    hypoxia: boolean;
}
export interface TherapeuticImplication {
    finding: string;
    implication: string;
    recommendation: string;
}
export declare const TME_THERAPEUTIC_IMPLICATIONS: Record<string, TherapeuticImplication[]>;
export interface LiquidBiopsyResult {
    sampleDate: string;
    ctdnaFraction: number;
    alterationsDetected: CtDNAAlteration[];
    clinicalInterpretation: CtDNAInterpretation;
}
export interface CtDNAAlteration {
    gene: string;
    alteration: string;
    vaf: number;
    clinicalSignificance: 'Actionable' | 'Resistance' | 'Prognostic' | 'VUS' | 'Benign';
}
export interface CtDNAInterpretation {
    summary: string;
    actionableFindings: string[];
    resistanceMutations: string[];
    monitoringRecommendation: string;
    tissueConfirmationNeeded: boolean;
}
export declare function interpretCtDNA(result: LiquidBiopsyResult): CtDNAInterpretation;
export declare class PrecisionMedicineEngine {
    getActionableAlterations(gene: string): GenomicAlteration[];
    getAlterationByType(alteration: string): GenomicAlteration | undefined;
    getTherapiesForAlteration(gene: string, alteration: string): TargetedTherapy[];
    getPharmacogenomicRecommendation(drug: string): PharmacogenomicMarker | undefined;
    assessActionability(alterations: {
        gene: string;
        alteration: string;
    }[]): {
        level1: GenomicAlteration[];
        level2: GenomicAlteration[];
        level3: GenomicAlteration[];
        notActionable: string[];
    };
    getTMEImplications(phenotype: TumorMicroenvironment['immunePhenotype']): TherapeuticImplication[];
    interpretLiquidBiopsy(result: LiquidBiopsyResult): CtDNAInterpretation;
    generatePrecisionReport(patientId: string, genomicProfile: {
        gene: string;
        alteration: string;
        type: string;
    }[], pharmacogenomics: string[], tmeIfAvailable?: TumorMicroenvironment): {
        actionableTargets: GenomicAlteration[];
        pgxRecommendations: PharmacogenomicMarker[];
        tmeImplications: TherapeuticImplication[];
        clinicalTrialTargets: string[];
        summary: string;
    };
}
export declare const precisionMedicineEngine: PrecisionMedicineEngine;
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