* Bad coverage of pharmacogenes. This most seriously affects Notably, the lack of intronic variants in WES.* Haplotype calling is challenging due to short readreads. NGS requires ''in silico'' haplotype estimation. There is support for basic haplotype estimation in Since GATK 3.3, the [https://software.broadinstitute.org/gatk/documentation/tooldocs/3.8-0/org_broadinstitute_gatk_tools_walkers_haplotypecaller_HaplotypeCaller.php Haplotype Caller] assemble contigs of 300 base pairs, but it does not consider the phasing of the GATK haplotype caller since version 3.3]reads. Haplotype calling phasing can e.g. be performed obtained by Trio analysis, or estimated by imputation methods [http://faculty.washington.edu/browning/beagle/beagle.html Beagle] or [http://dx.doi.org/10.1038/ng.3679 Eagle2] or [https://doi.org/10.1371/journal.pgen.1004234 SHAPEIT].Other possible options at Oslo University Hospital are long read technology from [https://www.sequencing.uio.no/services/pacbio.html PacBio] or synthetic long reads from [https://www.sequencing.uio.no/news/2019/10x%20Genomics%20is%20here%21 10x Genomics]* Variants Difficult variant calling in homologous regions are hard to capture (, such as CYP2D6. I.e. regions with copy number variations (CNV)). Notably, the genes CYP2D6 and CYP2A6 are challengingor pseudogenes. The CYP2D6 genotyping tool that was used by [https://github.com/PharmGKB/PharmCAT/wiki PharmCAT] is [https://www.nature.com/articles/npjgenmed201639 Astrolabe]. We intend to use the more recent program [https://github.com/inumanag/aldy Aldy].* HLA-typing require special software. There are many options. [https://doi.org/10.1002/cpt.411 Yang et al.] proposed to use [https://software.broadinstitute.org/cancer/cga/polysolver Polysolver] for whole exome sequencing (WES) or [https://github.com/FRED-2/OptiType OptiType] for whole genome sequencing (WGS). [https://doi.org/10.1101/356204 Reisberg et al.] proposed [https://doi.org/10.1371/journal.pone.0064683 SNP2HLA] for WGS. The candidate that we are investigating closer is [https://github.com/humanlongevity/HLA xHLA].

[[PGx in Estonia|Solutions A solution for PGx on NGS genotyping biobank data]] are given has been investigated by ''Reisberg et al.'' in their article [https://doi.org/10.1101/356204 Translating genotype data of 44,000 biobank participants into clinical pharmacogenetic recommendations: challenges and solutions]. An excellent solution for genotyping a collection of ADME (absorption, distribution, metabolism and elimination) genes for individual patients is Aldy, which is fast, accurate and relatively simple to use.