The PharmGKB homepage (retrieved July 21, 2008, from http://www.pharmgkb.org/). The homepage highlights easily accessible pharmacogenetics and pharmacogenomics knowledge and educational information.

Tamoxifen drug page. Drug pages are structured with a tab system (“Overview,” “Properties,” “Datasets,” “Pathways,” “Curated Publications,” “Non-curated Publications,” and “Downloads/Cross-references”) providing access to different information types. The “Datasets” tab provides curated primary phenotype data sets deposited by the research community. The “Curated Publications” tab links knowledge about drugs with genes and diseases and are similarly structured to the drug pages. The five categories of evidences are used by the curators to characterize the drug-gene and drug-disease relationship. Publication abstracts and PubMed IDs are available through the “View” link.

PharmGKB pathway diagrams. (A) The antiestrogen pathway: PK describes the hepatic metabolism of the drug tamoxifen (purple rectangle) to several primary and secondary metabolites (purple-yellow rectangles) by the cytochrome P450 (CYP) enzymes. Like tamoxifen, some of these metabolites exhibit antiestrogenic effects, indicated by arrows to the breast cancer cell. Along the arrows, the genes (blue ovals) are displayed, which code for the involved CYP isoforms. In the transformation to the potent antiestrogenic metabolite, 4-hydroxy-tamoxifen, CYP2D6 plays a significant role, indicated by the star. A summary explaining the different shapes and colors used in the graphic is available through the “legend” link. (B) The antiestrogen pathway: PD displays genes (blue ovals) involved in the synthesis of estrogens (green ovals) and the effect of estrogens on downstream signals by binding to estrogen receptors. Aromatase inhibitors (purple rectangle) are a group of drugs that reduce the amount of estrogens by blocking their transformation from androgens, whereas selective estrogen-receptor modulators (SERM) decrease the cellular effects of estrogens by binding to estrogen receptors in breast cells. The two drug groups are major pharmacological strategies in breast cancer therapy of estrogen receptor and/or progesterone receptor–positive breast tumors.

CYP2D6 Very Important Pharmacogene (VIP) gene. The CYP2D6 VIP contains a gene summary about CYP2D6 and its most important variants and haplotypes. CYP2D6 is an enzyme of the hepatic cytochrome P450 system and metabolizes many drugs as substrates. Throughout the introductory text, links to specific research articles are available that support the claims being made in the sentences. The “Important Variants” link opens the variant information page for CYP2D6, which contains 10 important polymorphisms. Each of them has a concise section containing a summary and an unambiguous identification of the variant by position and accession number for genomic DNA, mRNA, and protein. Also included are the dbSNP rsID and the UCSC Golden Path number.

Screenshot of the ABCB1 Variants page from the PharmGKB Web site (retrieved May 30, 2008, from http://www.pharmgkb.org/do/serve?ojbCls=Gene&objId=PA267&tabType=12). The rectangular box in the upper portion of the figure shows the genomic region containing the ABCB1 gene, with single-nucleotide polymorphism (SNP) locations represented as tick marks. The lower section of the figure is a table displaying ABCB1 variants, for which genotyping information has been submitted to PharmGKB. For each variant, the Golden Path position provides unambiguous polymorphism positioning information. The dbSNP rsID, the nucleotide(s) observed at the polymorphic position, the genetic feature in which the polymorphism occurs, and amino-acid translations of codons containing polymorphic nucleotides are listed. Additionally, two- and three-star designations reflect that the variant has been curated to supply brief (two-star) or detailed (three-star) descriptions of phenotype(s) observed for that variant. (Note: To include more curated variants in this image, some noncurated variants are not shown, as indicated by the white area between the second and third variants listed.).

Screenshot of marked-up text generated through an automated literature curation (retrieved July 21, 2008, from http://www.pharmgkb.org/do/serve?objId=PA161796011&objCls=AutomaticAnnotation#tabview=tab1). Genes are highlighted blue, diseases are highlighted green, drugs are highlighted red, variants are highlighted orange, and indeterminate terms are highlighted black.

Display of coding single-nucleotide polymorphisms (SNPs) mapped onto three-dimensional (3D) protein structure: (retrieved August 13, 2008, from “View Coding Variants on Protein Structure” link on https://preview.pharmgkb.org/do/serve?objId=PA139&objC1s=Gene#tabview=tab2). The coding SNPs for the angiotensin I converting enzyme (ACE) stored in PharmGKB are mapped onto the 3D protein structure of the ACE, somatic isoform stored in the Protein Data Bank (RCSB PDB; http://www.rcsb.org/pdb/explore/explore.do?structureId=2C6F). PharmGKB uses the MBT Protein Workshop software from the PDB for structure viewing. Variant locations are displayed in red.