Cross-comparison of exome analysis, next-generation sequencing of amplicons, and the iPLEX® ADME PGx Panel for pharmacogenomic profiling
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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2016-01-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00001/full |
| _version_ | 1811238301501227008 |
|---|---|
| author | Eng Wee eChua Eng Wee eChua Martin A Kennedy Simone L Cree Kim N. T. Ton Klaus eLehnert Phillip eShepherd Nuala eHelsby |
| author_facet | Eng Wee eChua Eng Wee eChua Martin A Kennedy Simone L Cree Kim N. T. Ton Klaus eLehnert Phillip eShepherd Nuala eHelsby |
| author_sort | Eng Wee eChua |
| collection | DOAJ |
| description | 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. 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 variant quality score recalibration, 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. |
| first_indexed | 2024-04-12T12:39:23Z |
| format | Article |
| id | doaj.art-63c37df4538d4808af558c0d98fc4ee5 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T12:39:23Z |
| publishDate | 2016-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-63c37df4538d4808af558c0d98fc4ee52022-12-22T03:32:49ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122016-01-01710.3389/fphar.2016.00001172401Cross-comparison of exome analysis, next-generation sequencing of amplicons, and the iPLEX® ADME PGx Panel for pharmacogenomic profilingEng Wee eChua0Eng Wee eChua1Martin A Kennedy2Simone L Cree3Kim N. T. Ton4Klaus eLehnert5Phillip eShepherd6Nuala eHelsby7University of Otago, ChristchurchUniversiti Kebangsaan MalaysiaUniversity of Otago, ChristchurchUniversity of Otago, ChristchurchUniversity of Otago, ChristchurchUniversity of AucklandUniversity of AucklandUniversity of AucklandWhole-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. 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 variant quality score recalibration, 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.http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00001/fullWhole-exome sequencingnext-generation amplicon sequencingmultiplexed genotyping panelvariant quality score recalibrationpharmacogenomic profiling |
| spellingShingle | Eng Wee eChua Eng Wee eChua Martin A Kennedy Simone L Cree Kim N. T. Ton Klaus eLehnert Phillip eShepherd Nuala eHelsby Cross-comparison of exome analysis, next-generation sequencing of amplicons, and the iPLEX® ADME PGx Panel for pharmacogenomic profiling Frontiers in Pharmacology Whole-exome sequencing next-generation amplicon sequencing multiplexed genotyping panel variant quality score recalibration pharmacogenomic profiling |
| title | Cross-comparison of exome analysis, next-generation sequencing of amplicons, and the iPLEX® ADME PGx Panel for pharmacogenomic profiling |
| title_full | Cross-comparison of exome analysis, next-generation sequencing of amplicons, and the iPLEX® ADME PGx Panel for pharmacogenomic profiling |
| title_fullStr | Cross-comparison of exome analysis, next-generation sequencing of amplicons, and the iPLEX® ADME PGx Panel for pharmacogenomic profiling |
| title_full_unstemmed | Cross-comparison of exome analysis, next-generation sequencing of amplicons, and the iPLEX® ADME PGx Panel for pharmacogenomic profiling |
| title_short | Cross-comparison of exome analysis, next-generation sequencing of amplicons, and the iPLEX® ADME PGx Panel for pharmacogenomic profiling |
| title_sort | cross comparison of exome analysis next generation sequencing of amplicons and the iplex 174 adme pgx panel for pharmacogenomic profiling |
| topic | Whole-exome sequencing next-generation amplicon sequencing multiplexed genotyping panel variant quality score recalibration pharmacogenomic profiling |
| url | http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00001/full |
| work_keys_str_mv | AT engweeechua crosscomparisonofexomeanalysisnextgenerationsequencingofampliconsandtheiplex174admepgxpanelforpharmacogenomicprofiling AT engweeechua crosscomparisonofexomeanalysisnextgenerationsequencingofampliconsandtheiplex174admepgxpanelforpharmacogenomicprofiling AT martinakennedy crosscomparisonofexomeanalysisnextgenerationsequencingofampliconsandtheiplex174admepgxpanelforpharmacogenomicprofiling AT simonelcree crosscomparisonofexomeanalysisnextgenerationsequencingofampliconsandtheiplex174admepgxpanelforpharmacogenomicprofiling AT kimntton crosscomparisonofexomeanalysisnextgenerationsequencingofampliconsandtheiplex174admepgxpanelforpharmacogenomicprofiling AT klauselehnert crosscomparisonofexomeanalysisnextgenerationsequencingofampliconsandtheiplex174admepgxpanelforpharmacogenomicprofiling AT phillipeshepherd crosscomparisonofexomeanalysisnextgenerationsequencingofampliconsandtheiplex174admepgxpanelforpharmacogenomicprofiling AT nualaehelsby crosscomparisonofexomeanalysisnextgenerationsequencingofampliconsandtheiplex174admepgxpanelforpharmacogenomicprofiling |