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 (WES) or OptiType for whole genome sequencing (WGS)
Publications
| Institution | Article | Comments |
|---|---|---|
| St. Jude Children’s Research Hospital | Comparison of Genome Sequencing and Clinical Genotyping for Pharmacogenes | WES and WGS can be used for PGx with in silico CNV calling and HLA calling |
| National Human Genome Research Institute | Assessing the capability of massively parallel sequencing for opportunistic pharmacogenetic screening | Suggests developing tools for PGx based on WES and WGS |
| University of Washington | PGRNseq: A Targeted Capture Sequencing Panel for Pharmacogenetic Research and Implementation | Targeted PGx panel with 84 genes |