# Output Files
The primary output is the **HL7 FHIR** bundle, which integrates genomic typing, lineage assignment, and mutation findings with clinical metadata.

## FHIR Genomic Observations
Converts annotated genomic features into standardized FHIR **Observation** resources.
### Observation Resources
The pipeline generates specific Observation resources for:
*   **Dengue Classification**: 
    *   **Serotype**: The specific Dengue virus serotype (DENV-1, DENV-2, DENV-3, DENV-4).
    *   **Genotype**: The specific genotype within the serotype (e.g., Genotype I, Genotype II).
    *   **Lineage**: Major and Minor lineage assignments based on Nextclade analysis.
    *   **Confidence**: Confidence level of the assignment.
*   **Viral Consensus Genome**:
    *   **Sequence**: The full consensus nucleotide sequence.
    *   **Metrics**: Sequence length, coverage, GC Content, and completeness (N content).
*   **Genetic Variants**:
    *   **Gene ID**: Viral gene symbol (e.g., *E*, *NS1*, *NS5*).
    *   **Amino Acid Change**: The specific mutation in HGVS notation (e.g., `p.Val123Ile`).

## Clinical Data Integration & Reporting

### Generated Resources
*   **Patient**: uses `https://fhir.kemkes.go.id/r4/StructureDefinition/Patient` profile.
*   **Specimen**: Blood sample details.
*   **ServiceRequest**: Order for genetic assessment.
*   **Organization**: Testing facility details.
*   **Practitioner & PractitionerRole**: Medical staff details.
*   **DiagnosticReport**: 
    *   **Code**: LOINC `81247-9` (Master HL7 genetic variant reporting panel).
    *   **Conclusion**: A summary including the Serotype, Genotype, and Lineage.
    *   **Presentation**: Base64 encoded HTML report.

## Analysis Logic
### Serotyping
Determined by mapping reads against a database of reference sequences (DENV-1 through 4 and Sylvatic strains) using minimap2.
*   **Logic**: The serotype with the highest number of high-identity mapped reads is selected.

### Genotyping & Lineage
*   **Clade Assignment**: Assigns specific clades (e.g., `1I.A`, `3III_B.3.2`) which are parsed into Genotypes and Lineages.
*   **Mutation Calling**: Identifies amino acid substitutions relative to the serotype-specific reference.

## Output Directory Structure
```
results/
├── qc/
│   └── multiqc_report.html             # Aggregated QC report
├── consensus/
│   └── *.consensus.fasta               # Per-sample consensus sequences
├── serotyping/
│   └── *.serotype.json                 # Per-sample serotype results
├── genotyping/
│   └── *.genotype_lineage.json         # Per-sample genotype/lineage results
├── fhir/
│   └── *.fhir.json                     # FHIR genomics bundles
├── fhir_merged/
│   └── *.merged.fhir.json              # FHIR bundles with clinical data
├── fhir_validated/
│   └── *.validation.txt                # FHIR validation results
├── fhir_upload/
│   └── *.upload.json                   # FHIR upload results
├── reports/
│   └── *.summary_report.txt            # Per-sample summary reports
├── runningstat/
│   ├── execution.html                  # Nextflow execution report
│   ├── timeline.html                   # Timeline report
│   └── dag.html                        # Workflow DAG
└── software_versions.yml               # Software version manifest
```