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Added Value of Clinical Sequencing: WGS-Based Profiling of Pharmacogenes
Although several pharmacogenetic (PGx) predispositions affecting drug efficacy and safety are well established, drug selection and dosing as well as clinical trials are often performed in a non-pharmacogenetically-stratified manner, ultimately burdening healthcare systems. Pre-emptive PGx testing of...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178228/ https://www.ncbi.nlm.nih.gov/pubmed/32225115 http://dx.doi.org/10.3390/ijms21072308 |
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author | Caspar, Sylvan M. Schneider, Timo Meienberg, Janine Matyas, Gabor |
author_facet | Caspar, Sylvan M. Schneider, Timo Meienberg, Janine Matyas, Gabor |
author_sort | Caspar, Sylvan M. |
collection | PubMed |
description | Although several pharmacogenetic (PGx) predispositions affecting drug efficacy and safety are well established, drug selection and dosing as well as clinical trials are often performed in a non-pharmacogenetically-stratified manner, ultimately burdening healthcare systems. Pre-emptive PGx testing offers a solution which is often performed using microarrays or targeted gene panels, testing for common/known PGx variants. However, as an added value, whole-genome sequencing (WGS) could detect not only disease-causing but also pharmacogenetically-relevant variants in a single assay. Here, we present our WGS-based pipeline that extends the genetic testing of Mendelian diseases with PGx profiling, enabling the detection of rare/novel PGx variants as well. From our in-house WGS (PCR-free 60× PE150) data of 547 individuals we extracted PGx variants with drug-dosing recommendations of the Dutch Pharmacogenetics Working Group (DPWG). Furthermore, we explored the landscape of DPWG pharmacogenes in gnomAD and our in-house cohort as well as compared bioinformatic tools for WGS-based structural variant detection in CYP2D6. We show that although common/known PGx variants comprise the vast majority of detected DPWG pharmacogene alleles, for better precision medicine, PGx testing should move towards WGS-based approaches. Indeed, WGS-based PGx profiling is not only feasible and future-oriented but also the most comprehensive all-in-one approach without generating significant additional costs. |
format | Online Article Text |
id | pubmed-7178228 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71782282020-04-28 Added Value of Clinical Sequencing: WGS-Based Profiling of Pharmacogenes Caspar, Sylvan M. Schneider, Timo Meienberg, Janine Matyas, Gabor Int J Mol Sci Article Although several pharmacogenetic (PGx) predispositions affecting drug efficacy and safety are well established, drug selection and dosing as well as clinical trials are often performed in a non-pharmacogenetically-stratified manner, ultimately burdening healthcare systems. Pre-emptive PGx testing offers a solution which is often performed using microarrays or targeted gene panels, testing for common/known PGx variants. However, as an added value, whole-genome sequencing (WGS) could detect not only disease-causing but also pharmacogenetically-relevant variants in a single assay. Here, we present our WGS-based pipeline that extends the genetic testing of Mendelian diseases with PGx profiling, enabling the detection of rare/novel PGx variants as well. From our in-house WGS (PCR-free 60× PE150) data of 547 individuals we extracted PGx variants with drug-dosing recommendations of the Dutch Pharmacogenetics Working Group (DPWG). Furthermore, we explored the landscape of DPWG pharmacogenes in gnomAD and our in-house cohort as well as compared bioinformatic tools for WGS-based structural variant detection in CYP2D6. We show that although common/known PGx variants comprise the vast majority of detected DPWG pharmacogene alleles, for better precision medicine, PGx testing should move towards WGS-based approaches. Indeed, WGS-based PGx profiling is not only feasible and future-oriented but also the most comprehensive all-in-one approach without generating significant additional costs. MDPI 2020-03-26 /pmc/articles/PMC7178228/ /pubmed/32225115 http://dx.doi.org/10.3390/ijms21072308 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Caspar, Sylvan M. Schneider, Timo Meienberg, Janine Matyas, Gabor Added Value of Clinical Sequencing: WGS-Based Profiling of Pharmacogenes |
title | Added Value of Clinical Sequencing: WGS-Based Profiling of Pharmacogenes |
title_full | Added Value of Clinical Sequencing: WGS-Based Profiling of Pharmacogenes |
title_fullStr | Added Value of Clinical Sequencing: WGS-Based Profiling of Pharmacogenes |
title_full_unstemmed | Added Value of Clinical Sequencing: WGS-Based Profiling of Pharmacogenes |
title_short | Added Value of Clinical Sequencing: WGS-Based Profiling of Pharmacogenes |
title_sort | added value of clinical sequencing: wgs-based profiling of pharmacogenes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178228/ https://www.ncbi.nlm.nih.gov/pubmed/32225115 http://dx.doi.org/10.3390/ijms21072308 |
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