Cross-comparison of exome analysis, next-generation sequencing of amplicons, and the iPLEX® ADME PGx panel for pharmacogenomic profiling

Eng Wee Chua, Simone L. Cree, Kim N T Ton, Klaus Lehnert, Phillip Shepherd, Nuala Helsby, Martin A. Kennedy

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Whole-exome sequencing (WES) has been widely used for analysis of human genetic diseases, but its value for the pharmacogenomic profiling of individuals is not well studied. Initially, we performed an in-depth evaluation of the accuracy of WES variant calling in the pharmacogenes CYP2D6 and CYP2C19 by comparison with MiSeq® amplicon sequencing data (n = 36). This analysis revealed that the concordance rate between WES and MiSeq® was high, achieving 99.60% for variants that were called without exceeding the truth-sensitivity threshold (99%), defined during variant quality score recalibration (VQSR). Beyond this threshold, the proportion of discordant calls increased markedly. Subsequently, we expanded our findings beyond CYP2D6 and CYP2C19 to include more genes genotyped by the iPLEX® ADME PGx Panel in the subset of twelve samples. WES performed well, agreeing with the genotyping panel in approximately 99% of the selected pass-filter variant calls. Overall, our results have demonstrated WES to be a promising approach for pharmacogenomic profiling, with an estimated error rate of lower than 1%. Quality filters, particularly VQSR, are important for reducing the number of false variants. Future studies may benefit from examining the role of WES in the clinical setting for guiding drug therapy.

Original languageEnglish
Article number1
JournalFrontiers in Pharmacology
Volume7
Issue numberJAN
DOIs
Publication statusPublished - 26 Jan 2016

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Exome
Pharmacogenetics
Cytochrome P-450 CYP2D6
Inborn Genetic Diseases
Medical Genetics
Drug Therapy
Genes

Keywords

  • Multiplexed genotyping panel
  • Next-generation amplicon sequencing
  • Pharmacogenomic profiling
  • Variant quality score recalibration
  • Whole-exome sequencing

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Cross-comparison of exome analysis, next-generation sequencing of amplicons, and the iPLEX® ADME PGx panel for pharmacogenomic profiling. / Chua, Eng Wee; Cree, Simone L.; Ton, Kim N T; Lehnert, Klaus; Shepherd, Phillip; Helsby, Nuala; Kennedy, Martin A.

In: Frontiers in Pharmacology, Vol. 7, No. JAN, 1, 26.01.2016.

Research output: Contribution to journalArticle

Chua, Eng Wee ; Cree, Simone L. ; Ton, Kim N T ; Lehnert, Klaus ; Shepherd, Phillip ; Helsby, Nuala ; Kennedy, Martin A. / Cross-comparison of exome analysis, next-generation sequencing of amplicons, and the iPLEX® ADME PGx panel for pharmacogenomic profiling. In: Frontiers in Pharmacology. 2016 ; Vol. 7, No. JAN.
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