Pharmacogenomic Profiling of ADME Gene Variants: Current Challenges and Validation Perspectives
Abstract
:1. Introduction
2. Pharmacogenomics Approaches for Germline SNP Identification
3. Pharmacogenomics Tools Currently Available
4. Candidate Biomarkers Discovery Process
5. Candidate Biomarkers Validation Process
6. Promise and Challenges of Pharmacogenomics Fallout in Clinical Practice
7. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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PGx Approach | GWAS | SNPs Panel | Candidate SNP |
---|---|---|---|
Sample size | Tailored for large populations | Tailored for small populations | Tailored for small populations |
Number of investigated markers | Larger numbers | 1–2 thousand | Smaller number |
Hypothesis | Hypothesis-free and hypothesis generating | Hypothesis-free and hypothesis generating/PK and PD coverage | Selected on a priori knowledge |
Study Design | Exploratory | Confirmatory/Exploratory | Confirmatory |
Limitations | False Negative/control for multiple testing | Coverage of limited genes | False positive/non-replication of results/low genetic coverage |
Platform | TaqMan Open Array PGx Express Panel (Thermo Fisher Scientific) | DMET Plus (Thermo Fisher Scientific) | PharmacoScan (Thermo Fisher Scientific) | Ion AmpliSeqPGx (Thermo Fisher Scientific) | iPLEX ADME PGx (Sequenom) |
---|---|---|---|---|---|
Markers (SNP/indels/CNV) | 60 | 1936 | 4627 | 141 | 192 |
Genes | 14 | 231 | 1191 | 40 | 38 |
Sample per assay | 46 | 48 | 22, 94 | 48 | 3, 12, 48 |
DNA input | 10 ng | 60 ng | 50 ng | 10 ng | 80 ng |
Technology | Real-Time PCR | Microarray | Microarray | Next-generation sequencing | Mass spectrometry |
Turnaround time | ~1 day | ~3 days | ~5 days | ~1.5 days | ~8 h |
Average Call Rate | >99.8% | >99.8% | >99.0% | 99.8% | >99.0% |
Concordance to reference | ≥99.5% | ≥99.5% | ≥99.5% | 99.9% | 98.9% |
Reproducibility | ≥99.8% | ≥99.8% | ≥99.8% | 99.7% | >99.7% |
For research only | Yes | Yes | Yes | Yes | Yes |
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Arbitrio, M.; Di Martino, M.T.; Scionti, F.; Barbieri, V.; Pensabene, L.; Tagliaferri, P. Pharmacogenomic Profiling of ADME Gene Variants: Current Challenges and Validation Perspectives. High-Throughput 2018, 7, 40. https://doi.org/10.3390/ht7040040
Arbitrio M, Di Martino MT, Scionti F, Barbieri V, Pensabene L, Tagliaferri P. Pharmacogenomic Profiling of ADME Gene Variants: Current Challenges and Validation Perspectives. High-Throughput. 2018; 7(4):40. https://doi.org/10.3390/ht7040040
Chicago/Turabian StyleArbitrio, Mariamena, Maria Teresa Di Martino, Francesca Scionti, Vito Barbieri, Licia Pensabene, and Pierosandro Tagliaferri. 2018. "Pharmacogenomic Profiling of ADME Gene Variants: Current Challenges and Validation Perspectives" High-Throughput 7, no. 4: 40. https://doi.org/10.3390/ht7040040