296
edits
Changes
→Challenges and solutions
| [[Allele definition]] || 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]]) || The allele pruning also makes it more likely that patients have normal phenotype (instead of unknown phenotype), removing most sources to [[Unknown function|alleles with unknown function]]
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| [[NGS|HLA-typing]] || [https://www.ncbi.nlm.nih.gov/pubmed/23762245 SNP2HLA] tool (WGS only) || A review of HLA-typing methods [https://www.ncbi.nlm.nih.gov/pubmed/27802932 from Bauer ''et al.''] does not mention this tool, but SNP2HLA is provided by the Broad Institute, so it should be good.
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| [[Allele definition|Multiple allele matches]] || Made hierarchy of alleles based on the biochemical function (No function > Decreased Function > Other functional statuses) || 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 no allele with serious consequence was found, assume Normal function.
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| Haplotype calling || Haplotype estimation for WGS was performed, but it is unclear which method was used. Probably the methodology is similar to that used in [https://www.nature.com/articles/ejhg201751 ''Mitt et al.''], in which case they used SHAPEIT2. Otherwise Eagle2 which is 6 times faster (cf. speed advantage of [https://www.ncbi.nlm.nih.gov/pubmed/27802932 SNP2HLA vs OptiType]). || In general, the difference between haplotyping and PGx allele matching it not clear (maybe right to say that PGx allele matching is a subset of general haplotyping?). In case there were more than one star allele match per haplotype, they matched all possible star allele diplotypes, and picked the diplotype with the most serious clinical consequence
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| CYP2D6 calling || Combination of Genome STRiP and normal allele matching (favorable comparison to Astrolabe used by PharmCAT) || Did not understand exactly how they did it (maybe check out reference by [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292679/ ''Gaedigk et al.''])
