Changes

* Haplotype calling is challenging due to short reads. 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 GATK haplotype caller since version 3.3]phasing of the reads. Haplotype calling phasing can also be performed obtained by Trio analysis, or estimated by various 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]* Difficult variant calling in homologous regions, such as CYP2D6. I.e. regions with copy number variations (CNV) or pseudogenes. The CYP2D6 genotyping tool that was used by [https://github.com/PharmGKB/PharmCAT/wiki PharmCAT] is [https://www.nature.com/articles/npjgenmed201639 Astrolabe]. Recently, a (seemingly) vastly improved We intend to use the more recent program [https://github.com/inumanag/aldy Aldy], has been published.* 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. Recently, a (seemingly) vastly improved program The candidate that we are investigating closer is [https://github.com/humanlongevity/HLA xHLA] has been published.