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