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! Technology !! Methods !! Comments
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| High density microarrays || HumanOmniExpress beadchip (OMNI, 8132 patients) and Global Screening Array (GSA, Illumina, 33157 patients), GenomeStudio (Illumina, genotyping, filtering for GSA), PLINK (filtering for all), [https://www.ncbi.nlm.nih.gov/pubmed/22843986 zCall ] (genotyping rare variants for GSA), Eagle2 (phasing), Beagle (impuation, population specific imputation panel from WGS) || 1308 of these patients were also Whole genome sequenced
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| Whole genome sequencing || TruSeq PCR-free prep, Illumina HiSeq X (150bp paired-end, 30x mean coverage), BWA-MEM (GRCh37 reference genome), Picard (mark PCR duplicates), GATK 3.4, bcftools (normalization and decomposition), Genome STRiP (CNV calls for CYP2D6, 2269 patients), Astrolabe (allele matching for CYP2D6, for comparison) || Quality filtering parameters are given in the article. The WGS samples (with some modifications) were also merged into a reference panel used for imputation (total 2279 Estonians and 1856 Finns)
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| Whole exome sequencing || Agilent SureSelect Human All Exon V5+UTRs target capture kit, HiSeq2500 (67x mean coverage) || Otherwise same bioinformatic pipeline as WGS
! [[NGS|Challenge]] !! Solution !! Comments
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| Example [[Allele definition]] || Example Pruning of allele definitions (removing variants from allele definitions (i.e. only keeping variants that destroys the protein), removing [[Unknown function|alleles with unknown function]]) | Example| The allele pruning also makes it more likely that patients are indeed normal, thus making the problem of [[Unknown function|alleles with unknown function]] less critical
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| Example [[NGS|HLA-typing]] | Example |SNP2HLA tool (WGS only) | Example| SNP2HLA is a fast and reasonably accurate tool, but it seems that in a clinical setting [https://www.ncbi.nlm.nih.gov/pubmed/27802932 other tools may be considered]
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| Example [[Allele definition|Multiple allele matches]] | Example |Made hierarchy of alleles based on the biochemical function (No function > Decreased Function > Other functional statuses) | Example| Probably this can be seen as a variant of the best solution to the [[Unknown function|unknown function problem]]: Look for the most serious consequence, and if not found, assume Normal function.
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| Example Haplotype calling || Example In case there were more than one star allele match per haplotype, they matched all possible star allele diplotypes || We suppose that they used haplotype estimation for WGS (Eagle2 as for microarrays?)|-| CYP2D6 calling || Combination of Genome STRiP and normal allele matching (favorable comparison to Astrolabe used by PharmCAT) || Example
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