TY - JOUR
T1 - PGRNseq
T2 - A targeted capture sequencing panel for pharmacogenetic research and implementation
AU - Gordon, Adam S.
AU - Fulton, Robert S.
AU - Qin, Xiang
AU - Mardis, Elaine R.
AU - Nickerson, Deborah A.
AU - Scherer, Steve
N1 - Funding Information:
The authors wish to acknowledge the Pharmacogenomics Research Network (PGRN) for supporting the development of the PGRNseq platform as well as the contributions of Richard Wilson from the Genome Institute at Washington University and Richard Gibbs and Donna Muzny from the Human Genome Sequencing Center at Baylor College of Medicine. This work was supported by the following grants: GM061388, HL069757, and GM097119.
Publisher Copyright:
© 2016 Wolters Kluwer Health, Inc.
PY - 2016
Y1 - 2016
N2 - Objectives Although the costs associated with whole-genome and whole-exome next-generation sequencing continue to decline, they remain prohibitively expensive for large-scale studies of genetic variation. As an alternative, custom-target sequencing has become a common methodology on the basis of its favorable balance between cost, throughput, and deep coverage. Methods We have developed PGRNseq, a custom-capture panel of 84 genes with associations to pharmacogenetic phenotypes, as a tool to explore the relationship between drug response and genetic variation, both common and rare. We utilized a set of 32 diverse HapMap trios and two clinical cohorts to assess platform performance, accuracy, and ability to discover novel variation. Results We found that PGRNseq generates ultra-deep coverage data (mean=496x) that are over 99.8% concordant with orthogonal datasets. In addition, in our testing sets, PGRNseq identified many novel, rare variants of interest, underscoring its value in both research and clinical settings. Conclusion PGRNseq is an ideal platform for carrying out sequencing-based analyses of pharmacogenetic variation in large cohorts. In addition, the high accuracy associated with genotypes from PGRNseq highlight its utility as a clinical test.
AB - Objectives Although the costs associated with whole-genome and whole-exome next-generation sequencing continue to decline, they remain prohibitively expensive for large-scale studies of genetic variation. As an alternative, custom-target sequencing has become a common methodology on the basis of its favorable balance between cost, throughput, and deep coverage. Methods We have developed PGRNseq, a custom-capture panel of 84 genes with associations to pharmacogenetic phenotypes, as a tool to explore the relationship between drug response and genetic variation, both common and rare. We utilized a set of 32 diverse HapMap trios and two clinical cohorts to assess platform performance, accuracy, and ability to discover novel variation. Results We found that PGRNseq generates ultra-deep coverage data (mean=496x) that are over 99.8% concordant with orthogonal datasets. In addition, in our testing sets, PGRNseq identified many novel, rare variants of interest, underscoring its value in both research and clinical settings. Conclusion PGRNseq is an ideal platform for carrying out sequencing-based analyses of pharmacogenetic variation in large cohorts. In addition, the high accuracy associated with genotypes from PGRNseq highlight its utility as a clinical test.
KW - pharmacogenomics
KW - rare variation
KW - targeted sequencing
UR - http://www.scopus.com/inward/record.url?scp=84953212338&partnerID=8YFLogxK
U2 - 10.1097/FPC.0000000000000202
DO - 10.1097/FPC.0000000000000202
M3 - Article
C2 - 26736087
AN - SCOPUS:84953212338
SN - 1744-6872
VL - 26
SP - 161
EP - 168
JO - Pharmacogenetics and Genomics
JF - Pharmacogenetics and Genomics
IS - 4
ER -