Avtor/Urednik		Siamoglou, Stavroula; Koromina, Maria; Hishinuma, Eiji; Yamazaki, Shuki; Tsermpini, Evangelia Eirini; Kordou, Zoe; Fukunaga, Koya; Chantratita, Wasun; Zhou, Yitian; Lauschke, Volker M.
Naslov		Identification and functional validation of novel pharmacogenomic variants using a next-generation sequencing-based approach for clinical pharmacogenomics
Tip		članek
Vol. in št.		, št. Vol. 176
Leto izdaje		2022
Obseg		str. 1-8
ISSN		1096-1186 - Pharmacological research : the official journal of the Italian Pharmacological Society
Jezik		eng
Abstrakt		Inter-individual variability in pharmacokinetics and drug response is heavily influenced by single-nucleotide variants (SNVs) and copy-number variations (CNVs) in genes with importance for drug disposition. Nowadays, a plethora of studies implement next generation sequencing to capture rare and novel pharmacogenomic (PGx) variants that influence drug response. To address these issues, we present a comprehensive end-to-end analysis workflow, beginning from targeted PGx panel re-sequencing to in silico analysis pipelines and in vitro validation assays. Specifically, we show that novel pharmacogenetic missense variants that are predicted or putatively predicted to be functionally deleterious, significantly alter protein activity levels of CYP2D6 and CYP2C19 proteins. We further demonstrate that variant priorization pipelines tailored with functional in vitro validation assays provide supporting evidence for the deleterious effect of novel PGx variants. The proposed workflow could provide the basis for integrating next-generation sequencing for PGx testing into routine clinical practice.
Proste vsebinske oznake		pharmacogenomics enzyme kinetics clinical application farmakogenomika kinetika encimov klinična uporaba