Next Generation Sequencing (NGS) is an interesting technology for PGx
A nice overview of the Requirements for comprehensive pharmacogenetic genotyping platforms was published by Volker Lauschke et al. They claim that rare variants account for 30-40% of functional variability in PGx. However they argue that pre-emptive PGx should only include validated variants, and rare variants should be investigated only when the patient experience unexpected drug response.
Challenges
- Short read NGS requires a priori knowledge of likelihood of particular haplotypes. In silico haplotype estimation can e.g. be performed by Beagle.
- Variants in homologous regions are hard to capture. Notably, the genes CYP2D6 and CYP2A6 are challenging.
- HLA-typing require special software, e.g. Polysolver for whole exome sequencing or OptiType for whole genome sequencing