Development of an extensive workflow for comprehensive clinical pharmacogenomic profiling: lessons from a pilot study on 100 whole exome sequencing data

Alireza Tafazoli; Maaike van der Lee; Jesse J Swen; Anna Zeller; Natalia Wawrusiewicz-Kurylonek; Hailiang Mei; Ruben H P Vorderman; Krzysztof Konopko; Andrzej Zankiewicz; Wojciech Miltyk

doi:10.1038/s41397-022-00286-4

Development of an extensive workflow for comprehensive clinical pharmacogenomic profiling: lessons from a pilot study on 100 whole exome sequencing data

Pharmacogenomics J. 2022 Dec;22(5-6):276-283. doi: 10.1038/s41397-022-00286-4. Epub 2022 Aug 13.

Authors

Affiliations

¹ Department of Analysis and Bioanalysis of Medicines, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Bialystok, 15-089, Bialystok, Poland.
² Clinical Research Centre, University Hospital of Bialystok, 15-276, Bialystok, Poland.
³ Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.
⁴ Department of Clinical Genetics, Medical University of Białystok, 15-089, Białystok, Poland.
⁵ Sequencing Analysis Support Core, Department of Biomedical Data Sciences, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.
⁶ Department of Photonics, Electronics, and Lighting Technology, Faculty of Electrical Engineering, Bialystok University of Technology, 15-351, Bialystok, Poland.
⁷ Department of Analysis and Bioanalysis of Medicines, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Bialystok, 15-089, Bialystok, Poland. Wojciech.miltyk@umb.edu.pl.

Abstract

This pilot study is aimed at implementing an approach for comprehensive clinical pharmacogenomics (PGx) profiling. Fifty patients with cardiovascular diseases and 50 healthy individuals underwent whole-exome sequencing. Data on 1800 PGx genes were extracted and analyzed through deep filtration separately. Theoretical drug induced phenoconversion was assessed for the patients, using sequence2script. In total, 4539 rare variants (including 115 damaging non-synonymous) were identified. Four publicly available PGx bioinformatics algorithms to assign PGx haplotypes were applied to nine selected very important pharmacogenes (VIP) and revealed a 45-70% concordance rate. To ensure availability of the results at point-of-care, actionable variants were stored in a web-hosted database and PGx-cards were developed for quick access and handed to the study subjects. While a comprehensive clinical PGx profile could be successfully extracted from WES data, available tools to interpret these data demonstrated inconsistencies that complicate clinical application.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Algorithms*
Exome Sequencing
Humans
Pharmacogenetics*
Pilot Projects
Workflow