Stargazer

Stargazer performs genotyping of polymorphic pharmacogenes from next-generation sequencing (NGS) data to detect single nucleotide variants (SNVs), insertion‑deletion variants (indels), and structural variants in CYP2D6 to inform precision drug therapy.

Key Features:

• Target gene focus: Primary focus on CYP2D6 with explicit handling of the highly homologous paralog CYP2D7.
• Variant types detected: Calls SNVs and indels from NGS data.
• Structural variant detection: Identifies gene deletions, duplications, and conversions from NGS data.
• Paralog‑specific copy‑number analysis: Calculates paralog‑specific copy numbers from read depths to resolve copy‑number changes.
• Hybrid detection: Detects CYP2D6/CYP2D7 hybrids and other conversion events.
• Star‑allele assignment: Assigns CYP2D6 star alleles based on combined SNV/indel and structural variant calls.
• Data input: Operates on next‑generation sequencing (NGS) data.
• Validation and performance: Validated on 32 ethnically diverse HapMap trios with 99.0% concordance versus established methods (TaqMan, long‑range PCR, quantitative multiplex PCR, high‑resolution melting analysis, and Sanger sequencing).
• Observed structural variation frequency: Identified structural variants in 28.1% of validated samples, including hybrids.
• Extensibility: Implementation reported to be extended to additional pharmacogenes.

Scientific Applications:

• Clinical pharmacogenetics: Genotyping CYP2D6 to support drug dosing and metabolizer phenotype prediction for precision drug therapy.
• Pharmacogene research: Characterizing SNVs, indels, and complex structural variation in CYP2D6 and related paralogs.
• Population and cohort studies: Applying NGS-based genotyping to ethnically diverse cohorts such as HapMap trios to assess allele and structural variant frequencies.
• Method benchmarking: Comparing NGS genotyping results against established assays (TaqMan, long‑range PCR, quantitative multiplex PCR, high‑resolution melting analysis, Sanger sequencing).

Methodology:

Processes NGS data to call SNVs and indels and calculates paralog‑specific copy numbers from read depths to detect deletions, duplications, conversions and CYP2D6/CYP2D7 hybrids and assign star alleles.