Wednesday, February 25, 2015

Our 10-step guide to enabling your PGx study to be curated

At PharmGKB we manually curate pharmacogenetic (PGx) associations found in published articles and add them to our database. However, lack of information or clarity is unfortunately common in publications and these hurdles make it difficult or impossible to curate a particular association.

We have published a guideline in Clinical Pharmacology & Therapeutics of 10 simple rules to help your publication be curated:

Enabling the curation of your pharmacogenetic study

1. Use standard gene nomenclature. 

2. Provide dbSNP rsIDs, a reference sequence and mapping information for genetic variants. 

3. Clearly state which allele/genotype of the variant is associated with the phenotype and the direction of the association.  

4. Clearly state population size, ethnicity, gender and drug regimen. 

5. State the minor allele for the variant in the given population/cohort.

6. Clearly state on which chromosomal strand the alleles are reported. 

7. State all genetic variants that were screened (including SNPs, indels, copy number variations and structural variations). 

8. Specify how * alleles or haplotypes were defined. 

9. Report which genotypes/diplotypes were found in the study population and map them to phenotype groups. 

10. State the statistical tests used for each association analysis. Include methods used for multiple hypothesis correction. 

Why follow these steps? 

Here are some benefits to you for enabling us to add your study findings to our public database:
  • Be part of the largest collection of curated PGx literatures, which is often used for identifying clinically relevant variants, interpreting genomes and used as a standard for evaluating methods and models for mining scientific literatures as well as drug discovery.
  • Your results and a link to your publication on PubMed become accessible to a broad audience, including students, bioinformaticians, researchers and clinicians.
  • By becoming part of our data set, your results may contribute to further research studies.
  • Your findings can aid in the clinical interpretation of a PGx association (whether the association you found was negative or positive) by contributing evidence to a Clinical Annotation.
  • These in turn may aid towards establishing a PGx-based dosing guideline for a particular drug.

    Wednesday, February 18, 2015

    PharmGKB VIP summary for CFTR published

    The PharmGKB summary describing CFTR as a pharmacogene has been published by Pharmacogenetics & Genomics. Genetic variants within the CFTR gene are the target of new Cystic Fibrosis therapies and drugs in development. The hope is that patients will be better treated with personalized medicines tailored to the underlying defects within CFTR. The VIP summary details these treatment strategies and clinically important variants within the CFTR gene.

    • Read the article: 
    McDonagh EM, Clancy JP, Altman RB, Klein TE.   
    Pharmacogenetics & Genomics. 2014 Dec 15. (Epub ahead of print)

    Sunday, February 8, 2015

    FDA Proposed Regulation of Laboratory Developed Tests (LDTs)

    Dear Colleagues,

    As you may know, the FDA is considering regulating laboratory developed tests (LDTs) and had an open comment period that ended February 2, 2015.  We would like to share with you a response that we wrote from our perspective at PharmGKB, working with the Stanford Law School “IP and Innovation Clinic” directed by Prof. Phil Malone.   Several law students worked on this with us on a very tight schedule since their clinic just started in January.  We anticipate other opportunities to comment on this important issue, and would be interested if any of you filed comments that you are willing to share.  This is a confusing situation and not directly in our expertise, but we saw an opportunity to get some things about PGx on the record.

    Russ & Teri

    Friday, February 6, 2015

    Genomic CDS Sandbox

    A multidisciplinary team of genomics experts is planning to create and distribute a freely available, open source genomic clinical decision support (CDS) sandbox that experts could use to create and evaluate genomic CDS knowledge and novel approaches. This resource will be preconfigured with many open source health IT applications on a easily distributable virtual machine.

    At this point, they are assessing the level of interest among potential users and determining desired features. They have created a short survey (< 10 min) for genomic and CDS domain experts to assess this important information.

    They would appreciate your time completing this survey and look forward to your input. The survey will close February 28th, so a prompt response is appreciated.

    For more information, contact Brandon M Welch, MS, PhD (

    Wednesday, February 4, 2015

    Pathways of acetaminophen metabolism at therapeutic versus toxic doses

    We have updated the acetaminophen pharmacokinetic pathway, which depicts the metabolism at therapeutic doses. In addition we added a new pathway illustrating the metabolism of acetaminophen at toxic doses.

    Acetaminophen (paracetamol) is widely used for its analgesic and antipyretic properties. Acetaminophen is mostly converted by glucuronidation and sulfation. A minor fraction of acetaminophen is oxidized to a reactive metabolite NAPQI, which is primarily responsible for acetaminophen-induced hepatotoxicity. A higher proportion of the drug gets oxidized at toxic doses leading to an increased risk of hepatotoxicity. 

    For more information on differences in the PK of acetaminophen between therapeutic vs toxic doses go to Acetaminophen Pathway (therapeutic doses), Pharmacokinetics and Acetaminophen Pathway (toxic doses), Pharmacokinetics.

    View all pathways at PharmGKB.

    Tuesday, February 3, 2015

    CPIC Term Standardization Survey Has Been Released

    In December 2014, we wrote a blog entry about the CPIC term standardization project. CPIC (Clinical Pharmacogenetics Implementation Consortium) is leading an effort to standardize terms for clinical pharmacogenetic tests, and the terms will be used in future CPIC guidelines. The hope is for the terminology to be adopted by the larger pharmacogenetics community as well.  CPIC will use a modified Delphi method in order to refine the term list based on expert opinions.

    The initial survey has been released and is available at:

    The survey is to be completed by February 20th.  CPIC has prepared webinars to assist participants taking the survey.

    There are two upcoming live webinars:

    February 11th at 1:00 pm ET/12:00 pm CT/10:00 am PT 
    Live Webinar link

    February 19th at 3:00 pm ET/ 2:00 pm CT/ 12:00 pm PT
    Live Webinar link
    If those are not convenient, you can access a streaming version and downloadable version of the webinar at any time:

    Streaming recording link

    Download recording link

    If you have questions or comments regarding this project, please contact us at

    Monday, February 2, 2015

    President Obama Unveils Details of the Precision Medicine Initiative

    President Obama has requested that congress authorize $215 million dollars to fund the newly announced Precision Medicine Initiative. In addition to focusing on the development of cancer treatments tailored to individual cancers the initiative proposes to develop a research consortium to do a longitudinal cohort study of one million people. Patient data could include electronic medical records, health, genomic, pharmaceutical and lifestyle information. The cohort would leverage data from existing longitudinal cohort studies, such as the Framingham Heart Study, as well as from new volunteers. These data would be integrated and available to researchers in secure databases to advance precision medicine discoveries. The proposed funding will be partitioned between the National Institutes of Health, the National Cancer Institute, the Food and Drug Administration and the Office of the National Coordinator for Health Information Technology. If approved, the funding would go into effect for the 2016 fiscal year. 

    Read more: