New tutorial and walkthrough videos now available

We are pleased to announce the release of our PharmGKB walkthroughs and tutorial videos on YouTube. Users can now view detailed video walkthroughs of each of the main annotation types on PharmGKB as well as a longer video combining resources from across the site. We have also produced a series of tutorial videos to help users learn more about key concepts and issues in pharmacogenomics. These videos range from an introduction to the field to an explanation of the star allele nomenclature system for haplotypes. The videos are freely available on the PharmGKB YouTube channel. Links can also be found on our Educational Resources page. 

Ask a Curator for Healthcare Professionals on June 7th

We are holding an Ask a Curator zoom targeted towards healthcare professionals wanting to learn more about PharmGKB and pharmacogenomics. This is part of NHGRI’s Healthcare Professionals Genomics Education Week (#MedGeneEd22). Be sure to spread the word to colleagues who may find this useful.

We are asking people to please register in advance with their questions so curators can better focus these events. There will also be the opportunity to ask questions during the event. Events will be limited to 25 participants to allow enough time for everyone’s questions to be answered.

Sign up here for Tuesday June 7th at 12pm EST, 9am PST, 5pm GMT
Want to be notified about future Ask a Curator events? Join our mailing list here.

What does *1 really mean? And why does that matter?

A Haiku about PGx for National Poetry Month.

Diagnosed star one,

Yet severe toxicity.

What did the lab test?

What does *1 really mean? And why does that matter?

The star alleles of the drug metabolizing enzyme genes are an unusual way of defining variation and are perhaps one of the most misunderstood aspects of pharmacogenomics. Arising from attempts to describe and standardize the molecular basis of different drug phenotypes; debrisoquine poor metabolizer phenotype, etc [PMID: 7773298, PMID: 8807658].  Sometimes authors use the term “wild type”, even for humans, to describe the most common form of the gene or protein in a given population where it displays the expected drug metabolism phenotype. The *1 allele is generally used to denote the absence of the variants tested. However, it is not a stable assignment; a *1/*1 individual only tested at one locus may not have the same genetic sequence as a *1/*1 individual tested for a panel of 10 variants in the same gene. This really matters when evaluating the likelihood of drug phenotype - the "reference" is only as good as the number of variants that were checked. *1 is rather a placeholder, it is the absence of certainty, because even with a panel that covers variants that represent 99% of known variation (in the populations examined so far which are not representative of the full global population) there may still be rare variants with significant impact on protein function that we may not yet have documented. While a *1/*1 may not be at increased risk of toxicity (or other phenotypes), or require a change of dosage immediately, they still have the baseline level of risk and it shouldn’t be a huge surprise if they exhibit an adverse reaction to a drug. 

Recent publications of case studies that concluded a lack of involvement of known pharmacogenes without documenting what was tested: 

PMID:35180762 - “Acral Skin Rash Caused by Altered Mercaptopurine

Metabolism in Maintenance Therapy for B-Cell

Acute Lymphoblastic Leukemia”  excerpt “TPMT and NUDT15 genotype at diagnosis were wildtype alleles and therefore we started with full 6-MP dosing.”

This issue is not limited to pharmacogenes using star allele nomenclature: “5-Fluorouracil Neurotoxicity in the Absence of Dihydropyrimidine Dehydrogenase Deficiency Case Report” [PMID:35419161] excerpt “Our patient tested negative for DPD mutations, but it remains possible she harbored a genetic variant not accounted for in the genetic testing panel. Other known risk factors include mutations in the orotate phosphoribosyltransferase and thymidylate synthase genes… “

We recommend authors always include the list of all variants that were tested, and other features see [PMID:30406943].

"Ask a Curator" live zoom event

PharmGKB curators will hold a series of live Q&A events over Zoom to help people find and use different aspects of the knowledgebase. We hope this will be a great way to answer questions about PharmGKB and PGx which are specific to users’ individual needs or projects.  These events will demonstrate the full extent of the resources available on PharmGKB, as well as details about those resources and how to download, use, and cite data from PharmGKB. 

In order to tailor these events for users with similar needs from PharmGKB, the first event will focus on researchers. Future events geared towards educators and clinicians are in the works, as well as events hosted at different times for our global audience. We will also be recording this upcoming event along with future events for those who are unable to attend live. Recordings will be posted on the PharmGKB YouTube channel.

We are asking people to please register in advance with their questions so curators can better focus these events. There will also be the opportunity to ask questions during the event. Events will be limited to 20 participants to allow enough time for everyone’s questions to be answered.

Sign up here for Tuesday April 26th at 12pm EST, 9am PST, 5pm GMT

Can’t make it but want to sign up for a future Ask a Curator? Join our mailing list here.

PharmGKB Tutorial Published

We are pleased to announce that an updated PharmGKB tutorial has now been published in Current Protocols.

The paper describes how to navigate the PharmGKB website to retrieve information on how genes and genetic variations affect drug efficacy and toxicity. It also includes a protocol on how to use PharmGKB to facilitate interpretation of findings for a specific pharmacogenomic variant genotype or metabolizer phenotype. 

Further information about how to use PharmGKB, including a short guided page tour and training exercises, can be found on our website.

NHGRI/NCI survey on genomics education

The National Human Genome Research Institute (NHGRI), who are supportive of PharmGKB and CPIC, have teamed up with the National Cancer Institute (NCI) to survey research and healthcare professionals about genomics education. The results of this survey will help to determine the resource and training priorities for future genomics education.

PharmGKB and CPIC are both actively working on pharmacogenomic education initiatives and we encourage everyone working in pharmacogenomics to complete the survey. This will highlight the importance of pharmacogenomics in future genomics education.

The survey takes approximately 10 minutes to complete and is tailored to different roles in both research and healthcare. The questions aim to evaluate respondents’ knowledge of genomics and learning needs. It will also help to identify barriers to accessing genomics education as well as preferred training methods.

The survey is open now and can be accessed at https://www.surveymonkey.com/r/GenomicEducation until September 15. All responses are anonymous and the results will be presented at the NHGRI meeting on September 25-26.