Abstract
Pharmacogenomics offers remarkable potential for the rapid translation of discoveries into changes in clinical practice. In the present work, we are interested in evaluating the ability of commercially available genome-wide association sequencing chips to cover genes that have high pharmacogenomics potential.We used a set of 2794 variations within 369 absorption, distribution, metabolism, and elimination (ADME) genes of interest, as previously defined in collaboration with the Pharma ADME consortium. We have compared the Illumina TrueSeq and both Agilent SureSelect and HaloPlex sequencing technologies. We have developed Python scripts to evaluate the coverage for each of these products. In particular, we considered a specific list of 155 allelic variants in 34 genes which present high pharmacogenomics potential. Both the theoretical and practical coverage was assessed.Given the need to have a good coverage to establish confidently the functionality of an enzyme, the observed rates are unlikely to provide sufficient evidence for pharmacogenomics studies. We assessed the coverage using enrichment technology for exome sequencing using the Illumina Trueseq exome, Agilent SureSelectXT1 V4 and V5, and Haloplex exome, which offer a coverage of 96.12%, 91.61%, and 88.38%, respectively.Although pharmacogenomic advances had been limited in the past due in part to the lack of coverage of commercial genotyping chips, it is anticipated that future studies that make use of new sequencing technologies should offer a greater potential for discovery.