PGMD: a comprehensive manually curated pharmacogenomic database

The PharmacoGenomic Mutation Database (PGMD) is a comprehensive manually curated pharmacogenomics database. Two major sources of PGMD data are peer-reviewed literature and Food and Drug Administration (FDA) and European Medicines Agency (EMA) drug labels. PGMD curators capture information on exact genomic location and sequence changes, on resulting phenotype, drugs administered, patient population, study design, disease context, statistical significance and other properties of reported pharmacogenomic variants. Variants are annotated into functional categories on the basis of their influence on pharmacokinetics, pharmacodynamics, efficacy or clinical outcome. The current release of PGMD includes over 117 000 unique pharmacogenomic observations, covering all 24 disease superclasses and nearly 1400 drugs. Over 2800 genes have associated pharmacogenomic variants, including genes in proximity to intergenic variants. PGMD is optimized for use in annotating next-generation sequencing data by providing genomic coordinates for all covered variants, including Single Nucleotide Polymorphisms (SNPs), insertions, deletions, haplotypes, diplotypes, Variable Number Tandem Repeats (VNTR), copy number variations and structural variations.


Search by variant
Searching by variant is the most direct approach when you are interested in a specific variant and know the dbSNP accession (rsID), the resulting amino acid change, or the genomic coordinates for the variant. For example, you've read a recent publication describing a NOD2 variant (rs2066844) as a marker for early intensive treatment of Crohn's disease. To quickly find the report for this variant, select the Variants radio button in the search options box, select the Identifier radio button, enter the accession in the search field and click the search button. The matched variant, and any haplotypes containing the matched variant, will be listed in the search results. A short overview is provided including the gene(s) that the variant falls within or is surrounded by, as well as the drug that is affected by the variant and the disease context of the variant-drug association. Click the hyperlinked variant name to navigate to the variant report which provides details of the phenotype observed for the variant. If you have a list of accession to search by, use the Upload a list of variants option.
Know the amino acid change caused by the variation? Select the Amino acid change radio button and enter the amino acid change (three letter format, i.e. Arg702Trp) in the search field.
Want to find the variant at a specific genomic coordinate or the list of variants within a genomic coordinate range? Select the Coordinate radio button and enter your coordinates in .bed format in the search field. If you have a list of coordinates to search by, use the Upload a list of variants option.
To quickly obtain a list of all genes, drugs or diseases associated with the variant use the search within results option within the results header. The resulting list of variants can be downloaded in txt format using Export these results link.

Search by drug
Searching by drug is most appropriate when you are interested in learning about the drug itself (including information about the protein(s) it target(s), which enzyme(s) metabolize the drug, as well as general properties) or are interested in identifying all or a subset of variants that have been shown to affect response to the drug. To quickly find the report for a drug, select the Drugs radio button in the search options box, enter the drug name in the search field and click the search button. The matched drug will be listed in the search results. A short description of the drug (provided by DrugBank) is provided when available. Click the hyperlinked drug name to navigate to the drug report which provides details of the drug, its targets, its metabolizers and the variants that influence patient response.
To quickly obtain a list of all variants associated with the drug use the search within results option within the results header. The resulting list of variants can be downloaded in txt format using Export these results link.

Search by disease
Searching by disease is most appropriate when you are interested in learning about the disease itself (including information about the genes and miRNAs associated with the disease as well as clinical trials underway or already completed) or are interested in identifying all or a subset of variants that have been shown to affect response to a drug administered in the context of the disease. To quickly find the report for a disease, select the Diseases radio button in the search options box, enter the disease name in the search field and click the search button. The matched disease will be listed in the search results. A short description of the disease (provided by MeSH) is provided when available. Click the hyperlinked disease name to navigate to the disease report which provides details of the disease, the genes and miRNAs involved, ongoing and completed clinical trials and the variants associated with altered drug response in the treatment of the disease.
To quickly obtain a list of all variants associated with drug response in the treatment of the disease use the search within results option within the results header. The resulting list of variants can be downloaded in txt format using Export these results link.

Search by gene
Searching by gene is most appropriate when you are interested in learning about a particular gene or are interested in identifying all or a subset of pharmacogenomic variants that fall within the gene. To quickly find the report for a gene, select the Genes and proteins radio button in the search options box, select the Name radio button, enter the gene name in the search field and click the search button. The matched gene will be listed in the search results. A short description of the gene (curated by BIOBASE curators) is provided. Click the hyperlinked gene name to navigate to the locus report which provides details about the gene and its encoded protein(s) and the pharmacogenomic variants that fall within the gene.
To quickly obtain a list of all variants that fall within a gene use the search within results option within the results header. The resulting list of variants can be downloaded in txt format using Export these results link.

1
Each variant report provides detailed information about a site that has been known to affect drug response in humans.
The introduction provides basic information gene, type of variant, snpEff predicted effect, coordinate, reference allele, and an average frequency based off of Exome Variant Server, 1000 Genomes, and HapMap.

2
Studies are grouped by the drug that was 2 administered to patients in a clinical trial, and display how one genotype versus another has been shown to respond to a treatment.

3
A default set of columns is provided in the 3 study tables, but additional information may be selected for display by clicking the "Show/hide columns" option. Link outs to gene, drug, and disease reports are also included.

4
Linkage disequilibrium data, when available from HapMap, is provided organized by population. To limit the data by population type the desired population into the Search box.

5
All references, linked to PubMed or FDA label, are listed in the last table.