We have developed a Pharmacogenetics-Cell line database for use as a central repository of pharmacology-related phenotypes that integrates genotypic, gene expression, and pharmacological data obtained via lymphoblastoid cell lines. Since genetic polymorphisms may impact a drug response phenotype through either gene expression or through their effects on miRNA, Affymetrix Human Exon Array 1.0 expression data from 90 CEU and 90 YRI LCLs as well as Exiqon miRNA baseline data from 60 unrelated CEU and 60 unrelated YRI have been deposited in the PACdb database.
The database provides results from:
- Whole genome analysis of genotype and cytotoxicity association in populations;
- Summary analysis which identifies differentially expressed transcript clusters between populations;
- Analysis of genotype and gene expression association;
- Summary information of correlations between gene expression and pharmacological phenotypes
- Summary analysis of miRNA / mRNA and miRNA / genotype associations
- Increasingly large dataset of summary data including functional and physical annotations of single nucleotide polymorphisms (SNPs) and genes currently distributed across several public databases.
The database employs a genome-wide model, making available correlations between genotype, gene expression, and cytotoxicity in lymphoblastoid cell lines. This large set of easily-queried data serves to allow for the determination of (and the prioritization of) a list of potentially functional polymorphisms and/or haplotypes associated with a drug response phenotype. For each gene that comes out of an analysis, the database provides physical and functional annotations for the gene and SNPs within or related to the gene via expression.
Data generated on the following drugs are included in the database: carboplatin, cisplatin, etoposide, daunorubicin, busulfan, ara-C, doxyfluridine (capecitabine), hydroxyurea, and pemetrexed.