FAQs

Questions about the website

• What is the PharmGKB?
  The Pharmacogenomics Knowledge Base, PharmGKB, is an interactive tool for researchers investigating how genetic variation effects drug response.
  A review of 10 years of PharmGKB can be found here PMID: 20350130.

• What kinds of data are available at PharmGKB?
  PharmGKB has data about genes, drugs and diseases and how these are interrelated. Data has been curated - extracted and sorted - from multiple sources to bring together information that builds a broader picture of the knowledge surrounding these relationships in a searchable or computable manner. The knowledge is presented as genomic variant annotations (that display the key data from individual publications), clinical annotations (that summarize several publications and interpret the data by genotype), VIP gene summaries (that give textual information about Very Important Pharmacogenes), drug centered pathways (in pictorial, textual and computer readable formats) and literature annotations (genes, drugs and diseases discussed in publications).

• Who compiles the Knowledge Base?
  The PharmGKB is run by a multidisciplinary team that brings together computer scientists, software engineers, developers and research scientists with advanced degrees in the biological sciences (referred to as curators at PharmGKB) to construct frameworks and displays to curate pharmacogenomic data.

• How do I register as a PharmGKB user?
  You can apply to become a registered user by clicking the "Register" sub-tab under the "About Us" tab at the top of the website. You will need to fill out an application form stating your reason for wanting to register and your contact information. You will be notified by email when your account is activated.

• Who is paying for PharmGKB?
  The United States National Institutes of Health (NIH) funded both the researchers that collected the data, as well as the researchers who are developing PharmGKB. These include the following NIH components:
  • National Institute of General Medical Sciences (NIGMS)
  • National Heart, Lung, and Blood Institute (NHLBI)
  • National Human Genome Research Institute (NHGRI)
  • National Institute of Environmental Health Sciences (NIEHS)
  • National Cancer Institute (NCI)
  • National Library of Medicine (NLM)

• Where is PharmGKB?
  The actual data reside on secured computers at the Stanford University campus.

• How may PharmGKB data be used?
  Details of our policies for data usage can be found here.

• How do I change my password?
  After signing in with the current password, click the "My PharmGKB" tab at the top of the web page. Click the second link listed on that page – "Change Password". Type in your current password and the new password (two times to confirm).

• How do I link to PharmGKB
  You are welcome to link to PharmGKB but you may not redistribute any data/information from PharmGKB. If you would like to link to PharmGKB please use the following formats for URLs. The PA numbers can be obtained from the Downloads section.
  For genes: http://www.pharmgkb.org/gene/PAxxx
  For drugs: http://www.pharmgkb.org/drug/PAxxx
  For diseases: http://www.pharmgkb.org/disease/PAxxx
  For RSID: http://www.pharmgkb.org/rsid/rsxxx

Questions about the data/knowledge in PharmGKB

• What is a variant annotation?
  This is a format to display the results from a single publication as they relate to a genomic variant or haplotype. This is done manually by reading the paper and extracting the relevant drugs, study size, population data, statistical values and mapping the variants to a common standard (dbSNP rs#).

• What standard do you use for variants?
  PharmGKB uses dbSNP rs identifiers to map genomic variants. This mapping is done manually by PharmGKB curators. We attempt to capture the multiple text-based names used in the literature as we come across them, so while we have common name information, these lists are not exhaustive. We also track how variants map to the UCSC Golden Path genome map and the genomic build from Entrez.

• What standard do you use for genes?
  PharmGKB imports and uses gene symbols and names from HGNC, the HUGO Gene Nomenclature Committee. Additional alternative names and symbols are imported from Entrez gene and manually curated from the literature to aid in searching. Gene boundaries and sequence data are imported from NCBI.

• What is a clinical annotation?
  This is a format to display a summary of the clinical impact of a genomic variant based on the information at PharmGKB. The genomic variant annotations, each from a single publication, are manually examined and the overall relevance described. The annotation is scored for the strength of evidence used to compile the annotation on a scale of 1 to 3 with 1 being the strongest evidence.

• How are clinical annotations scored for strength of evidence?
  See the pdf strength of evidence documentation

• Do you still have primary data?
  Yes PharmGKB still has primary data although it is no longer our primary focus. Primary data can be found in the datasets section of the Downloads/LinkOuts tab on a drug, gene or disease page, or the "Download" tab in the blue toolbar located on every PharmGKB page.
  If you wish to submit primary data please contact the curators at feedback.

• Drugs in PharmGKB
  PharmGKB imports the drug names and associated metadata (structures, properties, indications) mostly from DrugBank citation. Information from DrugBank is not routinely manually curated by PharmGKB and is labeled with the tag "Source:DrugBank" at the end of each section (however, if you find an error let us know and we will correct it and inform DrugBank of the problem). Additional drugs not found in DrugBank are occasionally imported from PubChem or other sources and are labeled as such.
  The top 100 drugs (a list compiled by combining the most frequently prescribed drugs of 2008 [citation] and those with the most reported adverse events from 2004-2008 in the FDA AERs database) also have short curator-written summaries of the pharmacogenomic knowledge and candidate genes and variants involved in PK and PD. These summaries are labeled "Pharmacogenetics" on the Overview tab of drug pages.

• Diseases in PharmGKB
  PharmGKB imports the standardized disease vocabulary found in MeSH: Medical Subject Headings or SnoMED. The overview page shows the inter-related MeSH, SnoMED and UMLS terms.
  Known Caveats: While we recognize that the term "disease" does not accurately describe some of the phenotypes in MeSH (eg. Death) and that there are several terms that are hierarchically related, we do not have an alternative freely available structured ontology for diseases/phenotypes at present. If you wish to assist PharmGKB in this matter please contact feedback.
  PharmGKB does not routinely annotate variant-disease associations, including causal or associated SNPs. Most disease annotations are tangentially related to variant-drug associations, eg. the study population may be disease-based but the drug discussed may or may not be used for that indication and the gene/variant is typically associated with the drug, not the disease.

• How do I get the data from PharmGKB?
  Data can be viewed using the website or downloaded from links under the Download tab on the dark blue toolbar at the top of every PharmGKB webpage. A user account and agreement to the PharmGKB database license agreement is necessary for downloading data. This can be done in bulk using web services or as zipped up packages of spreadsheets with literature annotations, variant annotations, clinical annotations or pathway relationships.
  See data usage agreement.

• How do I cite PharmGKB?
  In citing the PharmGKB please refer to:
  E.M. McDonagh, M. Whirl-Carrillo, Y. Garten, R.B. Altman and T.E. Klein, "From pharmacogenomic knowledge acquisition to clinical applications: the PharmGKB as a clinical pharmacogenomic biomarker resource." Biomarkers in Medicine (2011) Dec; 5(6):795-806.
  If you are citing a pathway please check the pathway diagram page to find out whether the pathway has been published in the Pharmacogenetics and Genomics journal. If there is such a citation on the pathway page, please use that. If not, please use the PharmGKB citation below.
  Also, please send a brief email to feedback@pharmgkb.org to inform us of which data you are using and for what purpose.

• What is a literature annotation?
  A literature annotation is the tagging of a single publication with the genes, drugs and diseases discussed in the article. A literature annotation does not necessarily imply a direct relationship between the genes, drugs and diseases discussed.

• Does PharmGKB have all the pharmacogenomics articles from PubMed?
  No. PharmGKB manually curates articles on a routine basis from the major pharmacogenomics journals and individual articles found in the process of compiling literature reviews for VIPs and pathways. This corpus of articles does not represent the entire pharmacogenomics literature in PubMed. PharmGKB is developing methods to automatically identify pharmacogenomics literature in PubMed and the results of these are available in the "Non-Curated Information" section at the bottom of the pages of the "Related To" tab.

• What is a Publication?
  PharmGKB uses the term publication to refer to a published article that has been catalogued in the PubMed database.

• How are pharmacogenomics articles annotated for pharmacokinetics (PK) or pharmacodynamics (PD)?
  Genetic variants that are generally associated with drug response or outcomes are tagged with PD, those specifically associated with ADME of a drug are tagged with PK.

• What is a genotype-based dosing guideline?
  The dosing guidelines are suggested modulations to the existing dosing guidelines that incorporate genotype based recommendations that have been published by the Clinical Pharmacogenetics Implementation Consortium (CPIC) or the Royal Dutch Association for the Advancement of Pharmacy - Pharmacogenetics Working Group (DPWG).

• What is a drug label page?
  The drug label pages have the FDA drug label for drugs that have pharmacogenomic information and the relevant sections are manually highlighted by PharmGKB. The list of drugs with label information is derived from the information found at the "Table of Pharmacogenomic Biomarkers in Drug Labels". PharmGKB does NOT contain all drug labels, only those for which the drug is implicated in a PGx association, i.e. those listed in the FDA's Table of Pharmacogenomic Biomarkers.

• Does PharmGKB have data on genomic variants associated with disease risk?
  While PharmGKB does not routinely curate genomic variants associated with disease risk, some publications encountered during routine work may have these associations and they may be entered into the PharmGKB at the curators' discretion.

• Does PharmGKB have information on all the variants associated with drug response?
  No, curating genomic variant data is a highly time consuming process. While PharmGKB strives to routinely curate those associations reported in the major pharmacogenomics journals as well as historically important studies encountered during literature reviews for VIPs and pathways, we acknowledge that we cannot manually curate the literature in its entirety. If you see something you think we should have, please send us feedback.

• What is a VIP?
  VIP stands for Very Important Pharmacogene. It is a gene for which there are known pharmacogenetic relationships. For example, the gene may have variants that have been associated with drug response or metabolism, or it may be a gene known to be involved in drug or xenobiotic metabolism or target of a drug action. In some cases there may be extensive evidence of variants that have known pharmacogenomic relevance, while in other cases the summary may serve to highlight the gaps in the knowledge where further study would aid the field. Many PharmGKB VIPs have been published in the Pharmacogenetics and Genomics Journal [PMIDs: 19940803, 19512959, 19451861, 20154640, 20150829, 19927042, 19952871, 19898265, 20150828, 20216335, 20084049, 20648701, 20739908, 20736885, 20811316, 21063235, 21989077].
  PharmGKB has a wish-list of VIP genes to develop, based on a survey of the PGRN. If you would like to work with PharmGKB to develop a VIP summary please contact feedback.

• What is a Pathway?
  PharmGKB pathways are manually curated gene-centered drug pathway graphics underpinned by references for each arrow and described in a short review. The genes and drugs on the pathways can be clicked to link out. The references can be seen in the components tab. The pathway can be downloaded as picture or BioPax-compatible data files.
  Many PharmGKB pathways have been published in the Pharmacogenetics and Genomics Journal [PMIDs: 19512958, 19512957, 19512956 , 19952870, 19525887, 19741567, 20023594, 21151855, 20124951, 20440227, 20601926, 21048526, 20938371, 21317831, 21546862, 21738081].
  PharmGKB has a wish-list of drug pathways to develop. If you would like to work with PharmGKB to develop a drug pathway please contact feedback.
  External pathways are pathways that have been imported from other sources such as the Pathway Interaction Database and Reactome.

• Can I use PharmGKB Pathway diagrams in my presentation or paper?
  Yes, please acknowledge the copyright to PharmGKB and state that permission has been given by PharmGKB and Stanford University. In addition, please check the pathway diagram page to find out whether the pathway has been published in the Pharmacogenetics and Genomics journal. If there is such a citation on the pathway page, please use that. If not, please use the PharmGKB citation below.
  Also, please send a brief email to feedback@pharmgkb.org to inform us of which pathway diagram you are using and for what purpose.

• How do I find frequency data on genomic variants?
  PharmGKB collects some frequency data for genomic variants involved in pharmacogenomic relationships although it is not a primary focus and other resources may be better for finding extensive information. The frequency data of variants within individual studies is noted in the population section of variant annotations where available. This frequency data is taken directly from the annotated article. The primary datasets submitted to PharmGKB by the PGRN also contain some frequency data. Some of the VIP variant summaries also have frequency tables listing data from various publications.
  Other resources that have frequency data include dbSNP, Alfred and HapMap.

• What data are manually curated?
  Clinical annotations, genotype-based dosing guidelines, drug labels, genetic tests, variant annotations, haplotypes, VIP summaries, drug pathways, literature annotations and pharmacogenetics summaries for top drugs (see "Drugs in PharmGKB" section) are manually curated in PharmGKB.

• What should I do if I see an error in the data?
  Please contact us using the feedback button on the page with the error and describe the problem. Thank you for taking the time to do this and improving the resource for all users.

• How can I request addition/curation of a paper?
  Please contact us using the feedback button and give the details of the publication you would like us to consider annotating. Thank you for taking the time to do this and improving the resource for all users.

• I found a link to data at PharmGKB in a paper but it no longer works, so how do I find the data?
  If there is a PA number in the paper do a search on that. Alternatively, do a keyword search for a gene or drug studied in the paper and look at the datasets listed under the Downloads/Linkout tab. Or if the data are from a consortium there is a link to the submissions on the right panel of the consortium page (found by doing a keyword search for the consortium). If you still don't find what you are looking for please contact feedback for assistance.

• How often is PharmGKB updated?
  Literature annotations and variant annotations are added in real time as a curator annotates the paper, so the tables on the "PGx Research" and "Is related to" tabs can change during the course of a day. VIPs, pathways and clinical annotations are reviewed periodically (VIPs and pathways have about a 2 year cycle, shorter if new evidence is readily apparent, clinical annotations are reviewed annually). New guidelines, drug labels and tests are added as they become evident.
  Gene, drug and disease data that is automatically retrieved is updated in response to scheduled updates at the external resource. Build number/database release can be found at link.

Questions about Pharmacogenomics

• What is the difference between pharmacogenetics and pharmacogenomics?
  In general pharmacogenetics usually refers to how variation in one single gene influences the response to a single drug. Pharmacogenomics is a broader term, which studies how all of the genes (the genome) can influence responses to drugs. However, these terms are often used interchangeably.

• What is PK?
  PK is short for Pharmacokinetics, the movement and change of drugs in the body over a period of time. Genetic variation in processes involved in the absorption, distribution, metabolism, or elimination of a drug can result in changes in drug availability. Data in this category are primarily concerned with demonstrating that genetic polymorphisms lead to variations in the levels or concentrations of drugs or their metabolites at the site of action.

• What is PD?
  PD is short for Pharmacodynamics and Drug Response, the study of the biochemical and physiological effects of drugs and the mechanisms of their actions. Genetic variation in drug targets can cause measurable differences in the response of an organism to a drug. Data in this category document that the biological or physiological response to a drug varies, and that this variation can be associated with the variation of one or more genes. This variation is often measured at the whole-organism level.

• What is personalized medicine? Is it different from pharmacogenomics?
  Personalized medicine is using information specific to a patient to tailor their health care. Pharmacogenomics can be used as part of a personalized medicine approach.

• Why is pharmacogenomics not used routinely in patient care?
  There are currently many obstacles to the use of pharmacogenomics in routine patient care. These include but are not exclusive to: lack of evidence that pharmacogenomics guided therapy is better than regular therapy; cost or lack of insurance coverage of pharmacogenetic testing; physicians not feeling sufficiently trained to apply results of pharmacogenetic tests; lack of guidelines in how to interpret test results; lack of studies showing how to develop pharmacogenomic associations into predictive tests. This is discussed further in these articles - PMIDs: 21326263, 21884816, 21691271, 21619429, 20485318.

• How is a genetic study different from a pharmacogenetic study?
  A pharmacogenetic study is a subset of genetic studies. The tests in a pharmacogenetic study attempt to predict how a person will respond to a drug. It might be a test that has nothing to do with a disease at all, but about how quickly the body breaks down the drug so the person's doctor could give a different dose if the person is likely to break down the drug very slowly or very fast. Or the test result might suggest that the person has a risk of a bad reaction to a drug so the doctor should use a different drug. But sometimes it might be a test that relates to the person's disease profile. E.g. for the cancer drug Herceptin, a drug that works on tumors that have a particular biomarker,the pharmacogenetic test is performed to assess if the tumor will be attacked by the Herceptin drug.
  The same as with genetic tests to determine risk of a disease, the results of pharmacogenetics tests are not deterministic. Even if a person's genetic test shows they have a gene variant associated with an increased risk for heart disease, they may not develop heart disease. Even if the pharmacogenetic test says a person doesn't have the marker for high risk for a bad response to codeine, they might still have a bad response to codeine due to some other factor. Multiple genetic and environmental factors can contribute to an individual's response to a drug, as well as interactions with drugs taken concomitantly.

• Does the database include results from GWAS?
  PharmGKB does contain data from a few pharmacogenomics GWAS studies, including primary data from the International Warfarin Pharmacogenetics Consortium - Genome Wide Associated Studies group. However, in general, rather than storing data from GWA studies, we annotate and link out to a NIH/NCBI database dedicated to storing data from GWA studies (dbGAP ). PharmGKB also contains literature annotations about published genetic variant - drug response or genetic variant -disease associations from GWA studies in PubMed.

• How is the PharmGKB different from other databases that have drug or gene data?
  There are many databases that have some of the information in PharmGKB, such as PubMed, Drug Bank and dbSNP, and we rely on their resources. PharmGKB brings together the relevant data in a single place and adds value by combining disparate data on the same relationship, making it easier to search and easier to view the key aspects and by interpreting the data. We provide clinical interpretations of this data, curated pathways and VIP summaries which are not found elsewhere.

• Does PharmGKB sell drugs or recommend suppliers?
  No, PharmGKB does not sell any drugs or recommend suppliers of drugs.