/**
 * Genomic Testing Platform Integrations
 *
 * Connects to major genomic testing providers:
 * - Foundation Medicine (FoundationOne CDx, FoundationOne Liquid CDx)
 * - Guardant Health (Guardant360, GuardantOMNI)
 * - Tempus (xT, xF, xR panels)
 * - Caris Life Sciences (Caris Molecular Intelligence)
 * - NeoGenomics
 *
 * All data handling complies with HIPAA and CAP/CLIA requirements.
 */
import { EventEmitter } from 'events';
export interface GenomicTestOrder {
    orderId: string;
    patientId: string;
    testType: string;
    panelName: string;
    specimenType: 'tissue' | 'blood' | 'bone-marrow' | 'other';
    specimenId?: string;
    orderDate: Date;
    clinicalIndication: string;
    icdCodes: string[];
    orderingPhysician: {
        name: string;
        npi: string;
        facility: string;
    };
    status: 'ordered' | 'specimen-received' | 'in-process' | 'completed' | 'failed' | 'cancelled';
}
export interface GenomicTestResult {
    reportId: string;
    orderId: string;
    patientId: string;
    testType: string;
    panelName: string;
    specimenInfo: {
        type: 'tissue' | 'blood' | 'bone-marrow' | 'other';
        site?: string;
        collectionDate: Date;
        tumorPurity?: number;
        cellularity?: number;
    };
    reportDate: Date;
    variants: GenomicVariant[];
    copyNumberAlterations: CopyNumberAlteration[];
    fusions: GeneFusion[];
    biomarkers: GenomicBiomarker[];
    therapyMatches: TherapyMatch[];
    clinicalTrialMatches: ClinicalTrialMatch[];
    signatures?: {
        microsatelliteInstability?: MSIResult;
        tumorMutationalBurden?: TMBResult;
        homologousRecombinationDeficiency?: HRDResult;
        lossOfHeterozygosity?: LOHResult;
    };
    qualityMetrics: {
        meanCoverage?: number;
        percentBases100x?: number;
        tumorFraction?: number;
        contamination?: number;
        mappingRate?: number;
    };
    reportPdf?: string;
    rawData?: {
        vcfUrl?: string;
        bamUrl?: string;
        fastqUrl?: string;
    };
}
export interface GenomicVariant {
    gene: string;
    hgvsC?: string;
    hgvsP?: string;
    transcript?: string;
    chromosome?: string;
    position?: number;
    refAllele?: string;
    altAllele?: string;
    variantType: 'SNV' | 'insertion' | 'deletion' | 'indel' | 'MNV' | 'complex';
    variantAlleleFrequency: number;
    coverage?: number;
    zygosity?: 'heterozygous' | 'homozygous' | 'hemizygous';
    clinicalSignificance: 'pathogenic' | 'likely-pathogenic' | 'vus' | 'likely-benign' | 'benign';
    tier?: 'I' | 'II' | 'III' | 'IV';
    oncogenicity?: 'oncogenic' | 'likely-oncogenic' | 'vus' | 'likely-neutral' | 'neutral';
    functionalEffect?: 'loss-of-function' | 'gain-of-function' | 'switch-of-function' | 'unknown';
    somaticStatus?: 'somatic' | 'germline' | 'unknown';
    actionability?: {
        level: 'FDA-approved' | 'clinical-guideline' | 'clinical-evidence' | 'preclinical';
        therapies: string[];
        evidence: string[];
    };
    annotations?: {
        cosmic?: string;
        dbSNP?: string;
        clinVar?: string;
        gnomAD?: {
            frequency: number;
            popMax?: number;
        };
        oncokb?: {
            level: string;
            description: string;
        };
    };
}
export interface CopyNumberAlteration {
    gene: string;
    chromosome?: string;
    startPosition?: number;
    endPosition?: number;
    type: 'amplification' | 'gain' | 'loss' | 'deep-deletion';
    copyNumber?: number;
    logRatio?: number;
    clinicalSignificance: 'pathogenic' | 'likely-pathogenic' | 'vus' | 'likely-benign' | 'benign';
    actionability?: {
        level: 'FDA-approved' | 'clinical-guideline' | 'clinical-evidence' | 'preclinical';
        therapies: string[];
    };
}
export interface GeneFusion {
    gene5Prime: string;
    gene3Prime: string;
    fusionName: string;
    breakpoint5Prime?: string;
    breakpoint3Prime?: string;
    readsSupporting?: number;
    inFrame?: boolean;
    clinicalSignificance: 'pathogenic' | 'likely-pathogenic' | 'vus';
    actionability?: {
        level: 'FDA-approved' | 'clinical-guideline' | 'clinical-evidence' | 'preclinical';
        therapies: string[];
    };
}
export interface GenomicBiomarker {
    name: string;
    value: number | string;
    unit?: string;
    status: 'positive' | 'negative' | 'equivocal' | 'indeterminate';
    threshold?: number;
    method?: string;
    clinicalImplication?: string;
}
export interface MSIResult {
    status: 'MSI-H' | 'MSI-L' | 'MSS' | 'indeterminate';
    score?: number;
    markersAnalyzed?: number;
    markersUnstable?: number;
    method: 'NGS' | 'PCR' | 'IHC';
}
export interface TMBResult {
    value: number;
    unit: 'mutations/Mb';
    status: 'high' | 'intermediate' | 'low';
    threshold: number;
    percentile?: number;
}
export interface HRDResult {
    status: 'positive' | 'negative' | 'indeterminate';
    score?: number;
    components?: {
        loh?: number;
        tai?: number;
        lst?: number;
    };
    brcaStatus?: 'BRCA1-mut' | 'BRCA2-mut' | 'BRCA-wt';
}
export interface LOHResult {
    percentage: number;
    status: 'high' | 'intermediate' | 'low';
    genomeFraction?: number;
}
export interface TherapyMatch {
    therapy: string;
    drugs: string[];
    biomarkers: string[];
    evidenceLevel: 'FDA-approved' | 'NCCN-guideline' | 'clinical-evidence' | 'case-report' | 'preclinical';
    cancerType: string;
    approvalStatus?: string;
    clinicalTrials?: string[];
    responseRate?: number;
    references: string[];
}
export interface ClinicalTrialMatch {
    trialId: string;
    title: string;
    phase: 'I' | 'I/II' | 'II' | 'II/III' | 'III' | 'IV';
    matchingBiomarkers: string[];
    status: 'recruiting' | 'active-not-recruiting' | 'enrolling-by-invitation';
    locations?: {
        name: string;
        city: string;
        state: string;
        country: string;
    }[];
    sponsor?: string;
    drugs?: string[];
}
export interface GenomicPlatformConfig {
    platform: 'foundation-medicine' | 'guardant' | 'tempus' | 'caris' | 'neogenomics' | 'generic';
    apiBaseUrl: string;
    apiKey?: string;
    clientId?: string;
    clientSecret?: string;
    organizationId?: string;
    webhookUrl?: string;
    timeout?: number;
}
export declare abstract class GenomicPlatformClient extends EventEmitter {
    protected config: GenomicPlatformConfig;
    protected accessToken?: string;
    protected tokenExpiry?: Date;
    constructor(config: GenomicPlatformConfig);
    abstract authenticate(): Promise<void>;
    abstract submitOrder(order: GenomicTestOrder): Promise<{
        orderId: string;
        status: string;
    }>;
    abstract getOrderStatus(orderId: string): Promise<GenomicTestOrder>;
    abstract getResults(orderId: string): Promise<GenomicTestResult>;
    abstract listPatientResults(patientId: string): Promise<GenomicTestResult[]>;
    protected httpRequest(url: string, options: {
        method: string;
        headers?: Record<string, string>;
        body?: string;
    }): Promise<string>;
    protected getAuthHeaders(): Promise<Record<string, string>>;
}
export declare class FoundationMedicineClient extends GenomicPlatformClient {
    constructor(config: Omit<GenomicPlatformConfig, 'platform'>);
    authenticate(): Promise<void>;
    submitOrder(order: GenomicTestOrder): Promise<{
        orderId: string;
        status: string;
    }>;
    getOrderStatus(orderId: string): Promise<GenomicTestOrder>;
    getResults(orderId: string): Promise<GenomicTestResult>;
    listPatientResults(patientId: string): Promise<GenomicTestResult[]>;
    /**
     * Get FoundationOne CDx specific data
     */
    getFoundationOneCDxReport(orderId: string): Promise<{
        variants: GenomicVariant[];
        cnvs: CopyNumberAlteration[];
        fusions: GeneFusion[];
        msi: MSIResult;
        tmb: TMBResult;
        loh: LOHResult;
        therapies: TherapyMatch[];
    }>;
    private mapToFMIOrder;
    private mapPanelToFMICode;
    private mapFromFMIOrder;
    private mapFMICodeToPanel;
    private mapFMIStatus;
    private mapFromFMIReport;
    private mapVariantType;
    private mapPathogenicity;
    private mapTier;
}
export declare class GuardantHealthClient extends GenomicPlatformClient {
    constructor(config: Omit<GenomicPlatformConfig, 'platform'>);
    authenticate(): Promise<void>;
    submitOrder(order: GenomicTestOrder): Promise<{
        orderId: string;
        status: string;
    }>;
    getOrderStatus(orderId: string): Promise<GenomicTestOrder>;
    getResults(orderId: string): Promise<GenomicTestResult>;
    listPatientResults(patientId: string): Promise<GenomicTestResult[]>;
    /**
     * Get Guardant360 specific metrics including ctDNA fraction
     */
    getGuardant360Metrics(orderId: string): Promise<{
        ctDNAFraction: number;
        maxMAF: number;
        somatic: GenomicVariant[];
        clonalHematopoiesis: GenomicVariant[];
        msi: MSIResult;
    }>;
    private mapPanelToGuardantTest;
    private mapFromGuardantOrder;
    private mapGuardantStatus;
    private mapFromGuardantReport;
}
export declare class TempusClient extends GenomicPlatformClient {
    constructor(config: Omit<GenomicPlatformConfig, 'platform'>);
    authenticate(): Promise<void>;
    submitOrder(order: GenomicTestOrder): Promise<{
        orderId: string;
        status: string;
    }>;
    getOrderStatus(orderId: string): Promise<GenomicTestOrder>;
    getResults(orderId: string): Promise<GenomicTestResult>;
    listPatientResults(patientId: string): Promise<GenomicTestResult[]>;
    /**
     * Get Tempus xT/xF specific analysis including RNA expression
     */
    getTempusAnalysis(orderId: string): Promise<{
        dnaFindings: GenomicVariant[];
        rnaExpression?: {
            gene: string;
            zscore: number;
            percentile: number;
        }[];
        immuneProfile?: {
            pdl1: {
                score: number;
                method: string;
            };
            tils: number;
            immuneScore: number;
        };
        hrd: HRDResult;
    }>;
    private mapPanelToTempusCode;
    private mapFromTempusOrder;
    private mapTempusCodeToPanel;
    private mapTempusStatus;
    private mapFromTempusReport;
}
export declare class UnifiedGenomicsService {
    private clients;
    /**
     * Register a genomic platform client
     */
    registerClient(name: string, client: GenomicPlatformClient): void;
    /**
     * Get results from all platforms for a patient
     */
    getAllPatientResults(patientId: string): Promise<{
        platform: string;
        results: GenomicTestResult[];
    }[]>;
    /**
     * Aggregate and deduplicate variants across all platforms
     */
    getAggregatedVariants(patientId: string): Promise<{
        variants: GenomicVariant[];
        cnvs: CopyNumberAlteration[];
        fusions: GeneFusion[];
        biomarkers: {
            msi?: MSIResult;
            tmb?: TMBResult;
            hrd?: HRDResult;
            pdl1?: {
                score: number;
                scoreType: string;
            };
        };
    }>;
    /**
     * Match patient genomics to actionable therapies
     */
    matchToTherapies(patientId: string, cancerType: string): Promise<TherapyMatch[]>;
    private getFDAApprovedMatches;
    private getNCCNMatches;
}
export declare function createGenomicClient(config: GenomicPlatformConfig): GenomicPlatformClient;
export default UnifiedGenomicsService;
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