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PharmGKB: A worldwide resource for pharmacogenomic information

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As precision medicine becomes increasingly relevant in healthcare, the field of pharmacogenomics (PGx) also continues to gain prominence in the clinical setting. Leading institutions have begun to implement PGx testing and the amount of published PGx literature increases yearly. The Pharmacogenomics Knowledgebase (PharmGKB; www.pharmgkb.org) is one of the foremost worldwide resources for PGx knowledge, and the organization has been adapting and refocusing its mission along with the current revolution in genomic medicine. The PharmGKB website provides a diverse array of PGx information, from annotations of the primary literature to guidelines for adjusting drug treatment based on genetic information. It is freely available and accessible to everyone from researchers to clinicians to everyday citizens. PharmGKB was found over 17 years ago, but continues to be a vital resource for the entire PGx community and the general public. This article is categorized under: Translational, Genomic, and Systems Medicine > Translational Medicine
The Pharmacogenomics Knowledgebase (PharmGKB) pathway diagram for thiopurines. PharmGKB pathways detail the pharmacokinetics or pharmacodynamics of pharmacogenomically important drugs, and include text providing detailed background and pharmacogenomic information. Most pathways are created in collaboration with experts in the field, and all pathways are available for download in multiple formats. An interactive version of this pathway can be found on the PharmGKB website at https://www.pharmgkb.org/pathway/PA2040
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A Pharmacogenomics Knowledgebase (PharmGKB) clinical annotation for HLA‐B*57:01 and abacavir. Clinical annotations accumulate all variant annotations that describe the same gene–drug relationship and present them on a single page with a short summary that describes the association. Each clinical annotation is also given a level of evidence based on the strength of the association. In this example, only one variant annotation is shown as evidence, but there are 12 studies supporting this association: see https://www.pharmgkb.org/clinicalAnnotation/981419257 for the full annotation
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A Pharmacogenomics Knowledgebase (PharmGKB) variant annotation for HLA‐B*57:01 and abacavir. PharmGKB curators read peer‐reviewed literature and add any relevant gene–drug associations to the knowledgebase. Variant annotations consist of a standardized summary sentence describing the association (seen in bold in the figure), as well as descriptive information about the association, such as p‐values, odds ratios, and cohort characteristics
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Rx Annotations on the Pharmacogenomics Knowledgebase (PharmGKB) website. In addition to annotating guidelines from organizations such as CPIC and DPWG, PharmGKB also annotates individual publications that provide PGx‐based dosing or prescribing advice. If available, these can be found below dosing guidelines under the “PGx Prescribing Info” tab
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The Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for azathioprine and TPMT on the Pharmacogenomics Knowledgebase (PharmGKB) website. In addition to providing the basic content of the CPIC guidelines, PharmGKB also provides its own functionality, allowing users to enter a genotype of interest and receive dosing advice as sourced from the guideline. In the figure, this functionality is shown in action: the TPMT genotype *1/*3A was selected, and detailed information on the implications and dosing recommendations was provided
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The Pharmacogenomics Knowledgebase (PharmGKB) Cancer PGx portal. Content regarding anticancer drug treatment affected by germline and somatic genetic variation is compiled on a single page for easy browsing
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The Food and Drug Administration (FDA)‐approved drug label for vemurafenib (Zelboraf), as annotated on the Pharmacogenomics Knowledgebase (PharmGKB). Vemurafenib is indicated for the treatment of patients with melanoma who have specific somatic mutations. In addition to annotating drug labels containing germline PGx information, PharmGKB also annotates drug labels containing somatic PGx information
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A small section of the drug labels available on the Pharmacogenomics Knowledgebase (PharmGKB). PharmGKB tags Food and Drug Administration (FDA) labels with a B inside a blue square if the label came from the FDA's Biomarker list (https://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm). A small set of labels contain specific dosing guidance based on genetic information; these labels are tagged as including dosing information. For example, in the above image, aripiprazole is tagged in this manner because the FDA label states that CYP2D6 poor metabolizers should have their dose reduced by 50%
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An overview of the annotated drug labels for abacavir on the Pharmacogenomics Knowledgebase (PharmGKB). PharmGKB annotates drug labels approved by the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), Health Canada (HCSC), and the Pharmaceutical and Medical Devices Agency (PMDA), Japan. PharmGKB has annotated drug labels available for over 250 drugs; not every drug has annotated labels available from all four of these medicine agencies
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The page for the TPMT gene on the Pharmacogenomics Knowledgebase (PharmGKB). Any information PharmGKB has on the TPMT gene or its variants is included on this page. This includes pathways that the TPMT gene appears in, such as the PharmGKB thiopurine pathway(Zaza et al., ) or the very important pharmacogene (VIP) summary article on the gene(Wang et al., ). Other types of data that discuss TPMT are also present on this page, such as Food and Drug Administration (FDA)‐approved drug labels or PharmGKB clinical or variant annotations. These data types are discussed in later sections of this review
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