TABLE 3.

Key features of the PGx dedicated variant functional prediction tools.

Tool/Algorithm	Main features	Reference
Stargazer	Stargazer calls the star alleles from the NGS data by detecting SNVs, InDels, and structural variants. Stargazer detects variations with structural changes including gene duplications, deletions, and conversions by calculating the paralog-specific copy numbers from read depth	Lee et al. (2019)
PharmCAT	Pharmacogenomics Clinical Annotation Tool (PharmCAT) captures the variants indicated in guidelines from a genomic data set derived from sequencing or genotyping technologies (i.e., VCF), infers haplotypes and diplotypes, and generates a report containing genotype/diplotype-based annotations, as well as guidelines and recommendations according to CPIC guidelines	Sangkuhl et al. (2020)
Aldy	Aldy is a computational tool that performs allelic decomposition of highly polymorphic, multi-copy genes through the use of the whole or targeted genome sequencing data and identifies multiple rare and novel alleles for several important pharmacogenes	Numanagić et al. (2018)
Astrolabe	Astrolabe (former Constellation) is a computational method and probabilistic scoring system that enables automated ascertainment of CYP2D6 and CYP2D19 activity scores from the unphased NGS data, aligned with the catalog of pharmacogenetic alleles with high percentage of analytic sensitivity and specificity	Twist et al. (2017)
Cypripi	Cypripi is an algorithm that computationally assumes CYP2D6 genotype at base-pair resolution from the high throughput sequencing data. It can resolve complex genotypes, including the alleles that are the product of the duplication, deletion, and fusion events involving CYP2D6 and its related pseudogene, CYP2D7	Numanagić et al. (2015)
g-Nomic	g-Nomic is PGx interpretation software that provides recommendations on the suitability of a given combination of drugs for each patient according to their genes and polymedication	Sabater et al. (2019)
PHARMIP	PHARMIP uses drug modeled structure and up-to-date bioinformatics tools and/or databases to understand the genetic factors that cause drug-related adverse reactions	Zidan et al. (2020)
Cyrius	Superior, accurate genotyping of CYP2D6 compared to other existing methods as well as Aldy and Stargazer. All types of variants and haplotype calling in addition to the structural and homology analysis will be covered for both GRCh38 and 37 genome builds	Chen et al. (2021)