Overview of PharmVIP analysis modules

The current release of PharmVIP (beta version) consists of three analysis modules.

1) Guideline module:

Function: Predict the haplotypes/alleles in 17 genes which are associated with 47 drugs and have information of CPIC (Clinical Pharmacogenetics Implementation Consortium) drug dosing guidelines.
Required Input: VCF/gVCF file (CYP2D6 analysis requires BAM file)
Features: User can choose to analyze from the gene list or the drug list (grouped by therapeutic category). Allele matching and dosing guideline assignment are performed by our own algorithm/method. CYP2D6 allele is predicted by Astrolabe software. The output can be filtered by selecting the displayed genes, phenotypes, and guideline strengths.
Output: Predicted diplotype, metabolizer status/phenotype, CPIC dosing recommendation with guideline strength
- CPIC guideline recommendations: PharmGKB (https://www.pharmgkb.org/) (downloaded on 20-02-2020)
- Allele definition tables: PharmGKB (https://www.pharmgkb.org/) (downloaded on 20-02-2020)

2) HLA module:

Function: Predict the alleles in all HLA genes and report the published adverse drug reactions (ADRs) associated with these HLA alleles.
Required Input: BAM file
Features: User can choose the cohort ethnicities of the reported ADR cases in the HLA-ADR association studies. The output can be filtered by selecting the displayed HLA genes, drugs, ADRs, cohort ethnicities, and diseases of patients with ADRs.
Output: Predicted HLA alleles, the associated drugs and adverse drug reactions, patient diseases and ethnicities, CPIC guideline recommendations (if available) with guideline strength
- Known adverse drug reactions with HLA alleles: The HLA and Adverse Drug Reaction Database (http://allelefrequencies.net/hla-adr) (downloaded on 20-02-2020)
- HLA sequence library: The IPD-IMGT/HLA Database (https://www.ebi.ac.uk/ipd/imgt/hla) (Release 3.35.0)

3) PGx genes module:

Function: Identify genomic variants (single nucleotide polymorphisms, insertions, deletions) in 3,533 pharmacogenes listed from different resources and predict their effects to gene function.
Required Input: VCF/gVCF file
Feature: User can choose a gene list to be analyzed. The output can be filtered by variant classes, types, consequences, impacts, and SIFT/PolyPhen classes
Output: List of known/novel variants, variant types, variant classes, consequences, impact level
- The list of pharmacogenes from:

Summary of user’s analysis workflow