Friday, August 3, 2018

Changes to the PharmGKB data licensing, downloads and user accounts

PharmGKB is changing its licensing policy in order to simplify access to files containing annotations and relationships. All of PharmGKB, including these files, are now licensed under the Creative Commons Attribution-ShareAlike 4.0 International License. Users who download or use PharmGKB annotations, knowledge, files, images or screen shots agree to the license requirements, including:

  1. Attribution: You must give appropriate credit to PharmGKB, provide a link to this license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests PharmGKB endorses you or approves of your use.
  2. ShareAlike: If you alter, amend, reuse or otherwise change PharmGKB data you agree that if you distribute such product, all recipients shall first agree to be subject to this license. Proof of such agreement shall be made available to PharmGKB. Under no circumstances can PharmGKB data be sold for other's private or commercial use.

More information can be found in the Data Usage Policy.

Users no longer need a PharmGKB account to download relationship or annotation files, nor do they need to fill out a request with detailed information about who they are or how they will use the information. However, we would appreciate it if users would fill out our survey when they download data to help us understand who our users are and what type(s) of information are useful to them so that we may continue to be responsive to user needs.

Another change to PharmGKB is that variant and clinical annotations are viewable on the website without logging in. In fact, PharmGKB users no longer need an account to view or download any data, and we will no longer ask users to create accounts.

For any questions or comments, please send email to feedback.

Thursday, July 26, 2018

New PharmGKB pathways for ondansetron and tropisetron

Ondansetron and tropisetron are 5-HT3 receptor antagonists used to treat nausea and vomiting and are commonly prescribed to patients who have undergone surgery or who are receiving chemotherapy. They are both covered by a CPIC guideline which can be accessed on the CPIC website.

PharmGKB has released two new pathways for these drugs; Ondansetron Pathway, Pharmacokinetics/Pharmacodynamics and Tropisetron Pathway, Pharmacokinetics/Pharmacodynamics. These pathways show the metabolism of both drugs as well as their action at 5-HT3 receptors on vagal afferent neurons. Key genes involved in the metabolism process are highlighted in the clickable images and described in the accompanying descriptions. Note that although ondansetron and tropisetron have very similar pharmacokinetic pathways, there are important differences between the two. This is why separate pathways have been produced for each drug.

You can view the Ondansetron Pathway,Pharmacokinetics/Pharmacodynamics and the Tropisetron Pathway,Pharmacokinetics/Pharmacodynamics on the PharmGKB website. Annotated versions of the CPIC guideline for ondansetron and tropisetron are also available at the PharmGKB website.

Friday, June 29, 2018

Curators' Favorite Papers

The growing number of individuals using direct to consumer (DTC) genetic tests has also led to an increase in physicians counseling patients on their results. In an effort to reveal the perspectives of physicians who receive these “unsolicited genomic results” (UGR), the Electronic Medical Records and Genomics (eMERGE) Network has conducted a survey, published in Genetics in Medicine (Physicians’ perspectives on receiving unsolicited genomic results) in which they ask physicians about their perspectives on the actionability of positive test results, what they believe their responsibilities are for UGRs, the impact of UGRs on patients and clinical workflow, and the the process and support involved in returning results. The 25 participants were selected because of their extensive experience as primary care physicians, pediatricians, cardiologists, or oncologists. The primary concern of physicians was that only actionable results should be returned to patients, and that any follow-up should include clinical decision support and be evidence-based. Additional concerns included the additional time that would need to be set aside to integrate results into clinical workflow, increased patient anxiety and confusion, and whose responsibility it was to “own” genetic test results. 

Pharmacogenetic algorithms have been demonstrated to improve the dosing of essential life-saving medications such as warfarin, as well as to reduce the incidence of adverse effects. However, dosing algorithms and recommendations often include genetic variants that come from cohorts of individuals who are predominantly of European descent and largely overlook variants that are prevalent in other populations. The authors of a new editorial in the journal Pharmacogenomics (Preventing the exacerbation of health disparities by iatrogenic pharmacogenomic applications: lessons from warfarin) review studies investigating warfarin dosing in underrepresented and admixed populations in Puerto Rico, Brazil, and the United States. In addition to noting the importance of cataloging variants in diverse populations, the authors also stress the complications that may arise when self-reported color or race categories, which vary by country, are used as proxies to infer the presence of pharmacogenetic variants. The authors also note that the 2017 update of the Clinical Pharmacogenetic Implementation Consortium (CPIC) for Warfarin Dosing reflects some of these new findings and it includes self-reported ancestry and variants that are more commonly found in African-American patients in the dosing algorithm.

You can find more information about pharmacogenetic guided dosing for warfarin on as well as on the PharmGKB’s annotation of the CPIC Guideline update for warfarin and CYP2C9, VKORC1, CYP4F2 and the single nucleotide polymorphism, rs12777823.

Monday, May 28, 2018

Curators' Favorite Papers

A critical component of pharmacogenetic/pharmacogenomics (PGx) implementation into clinical care is the integration of PGx data in clinical decision support (CDS) and electronic health records (EHRs). A new article in the journal Human Molecular Genetics (Genomics and electronic health record systems) discusses the benefits of, and current challenges to, the integration of genomics and PGx data, into EHRs. In particular, the article discusses how PGx data in EHRs relates to questions of standards and evidence generation, and how data should be represented so as not to be overwhelming for clinicians. The article adeptly outlines specific components of CDS pertaining to whole genome sequencing (WGS) (e.g. ordering and interpreting a test, importing data, trigger alerts and warning in EHRs, and evaluating outcomes) and describes existing tools, such as application programming interfaces (APIs), that link knowledgebases (including PharmGKB) to EHRs to assist with CDS.  The authors conclude that with continued developments in technology, and ambitious research programs with large, diverse cohorts, such as the NIH-sponsored All of Us program, the “goals of generating new knowledge and clinically relevant discoveries using population-based genomics data can someday be achieved by using EHRs”.

A patient’s diagnosis and medical treatment is frequently guided by where that patient’s laboratory values fall along a range of established “normal” values. A new “Viewpoint” (In the Era of Precision Medicine and Big Data, Who Is Normal?) in the Journal of the American Medical Association (JAMA) raises an important question in the context of laboratory values and precision medicine: if medicine is personalized, to what do we compare an individual’s laboratory values if “normal” is actually relative? The authors consider solutions to ensure that test results “be interpreted in reference to a population of ‘similar’, ‘healthy’ individuals”. For example, the authors propose 1) that longitudinal data on individual outcomes be accessible to researchers to determine whether selected reference values are truly useful 2) that large-scale analyses be carried out across data sets 3) that reference values be tailored to patients and delivered at point of care, and 3) that “computationally derived genetic ancestry” be linked to laboratory test values, so that race is not used as a proxy.

Tuesday, May 22, 2018

New PharmVar Downloads

PharmVar is delighted to announce a new feature that just went live!  Variants of genes in the PharmVar database can now be downloaded in sequence (FASTA and VCF) and table (TSV) formats. Options include to the download variants of interest, all variants of a gene or the entire PharmVar database. 

Check out the link “Additional Data Download Information” on the gene page for more information.

There are currently three genes in the database, CYPs 2C9, 2C19 and 2D6 – additional genes will be transitioned soon.

The PharmVar Team

Friday, May 4, 2018

Dr. Francis Collins discusses All of Us on CBS This Morning

The National Institutes of Health (NIH) director Dr. Francis Collins appeared on CBS This Morning to promote the All of Us program, a part of the Precision Medicine Initiative, which launches this Sunday, May 6th. 

When asked about what it hopes to accomplish, he explained:

“Do you ever feel when somebody is making recommendations to you about how to stay healthy or when you need a prescription and you’re wondering 'is this the right drug for me at the right dose?' A lot of what we do in medicine is one-size-fits-all. Precision medicine is this opportunity to make things much more individualized and more precise and more likely to result in a good outcome, but to get to that point we need to collect a lot of data on a lot of people…”

All of Us hopes to recruit 1 million Americans, and is particularly interested in recruiting subjects from communities that are typically underrepresented in biomedical research. Dr. Collins addressed questions about privacy concerns by explaining that all data will be de-identified, researchers pledged to not re-identify subjects and that data will be protected from use by law enforcement as a result of new legislation. 

You can find more information about pharmacogenomics (PGx) such as PGx-guided dosing/prescribing guidelines at CPIC and PharmGKB where you can also find curated information about drugs and genes, from the literature as well as from drug labels and other sources.

Tuesday, April 24, 2018

Curators' Favorite Papers

The first paper comes from the journal Pharmacogenomics (Clinical pharmacogenetics: how do we ensure a favorable future for patients?) and it discusses the factors that have impeded the implementation of pharmacogenomic (PGx) testing into routine clinical care. Randomized clinical trials (RCT) are the current gold-standard for clinical research for new drug approvals, but the nature of PGx studies is ill-suited to the RCT format. The authors propose alternatives to RCTs such as demonstration of non-inferiority to standard of care, N-of-1 trials for individuals or “hybrid effectiveness-implementation” clinical trials (trials that blend design components investigating clinical effectiveness with implementation research). They also emphasize that implementation of PGx data would require comprehensive, pre-emptive testing, population specific PGx considerations, and storage of results in electronic medical records (EMR) with adequate clinical decision support (CDS) tools. Finally, they make the case for testing for genetic variants with robust evidence of a PGx association, and specifically cite the Clinical Pharmacogenenomics Implementation Consortium (CPIC) as a “promising place to start” in selecting PGx genes to test as well as PharmGKB as a resource for information on gene-drug PGx associations.

The second paper, authored by the International Society for Biocuration (Biocuration: Distilling data into knowledge), comes from the journal PLoS Biology. It explains the specific role that biocurators play within teams that manage biological information resources and databases. Beginning with the premise that data is an asset whose value increases each time it is shared, the authors argue that biocurators maximize value by assuring the “accuracy, comprehensiveness, integration, accessibility, and reuse” of data through the process of extracting knowledge (such as data) from unstructured forms (usually publications) into structured and machine readable forms to enhance its usability and sharing. The authors note that there is encouraging development with regard to data reporting tools, an increase in demand and support for data standards and a growth in the use of biocuration tools by researchers, and all of these are expected to facilitate data curation, data sharing and ultimately, scientific progress.