Pharmacogenomics, How to Deal with Different Types of Variants in Next Generation Sequencing Data in the Personalized Medicine Area

Abstract

Pharmacogenomics (PGx) is the knowledge of diverse drug responses and effects in people, based on their genomic profiles. Such information is considered as one of the main directions to reach personalized medicine in future clinical practices. Since the start of applying next generation sequencing (NGS) methods in drug related clinical investigations, many common medicines found their genetic data for the related metabolizing/shipping proteins in the human body. Yet, the employing of technology is accompanied by big obtained data, which most of them have no clear guidelines for consideration in routine treatment decisions for patients. This review article talks about different types of NGS derived PGx variants in clinical studies and try to display the current and newly developed approaches to deal with pharmacogenetic data with/without clear guidelines for considering in clinical settings.

PAnno: A pharmacogenomics annotation tool for clinical genomic testing

“…Furthermore, PGx genes have progressively gone beyond the longstudied range of drug-metabolizing enzymes and transporters. Clinical evidence for nuclear receptors, transcription regulators, and genes potentially related to ADME, etc., is increasing (Arbitrio et al, 2021;Tafazoli et al, 2021b;Lanillos et al, 2022). As the accumulation of associations between different genotypes and drug responses, the integrative strategy for genotype resolution and clinical annotation advocated by PAnno would become more valuable.…”

Measuring Pharmacogene Variant Function at Scale Using Multiplexed Assays

“…Clinical implementation of multiplexed functional data for PGx will require an increase in sequencing for precision medicine, which is promoted by variant functionalization: 85% of physicians do not routinely order PGx testing, mostly due to lack of guidelines for action based on test results (125). As more variants of actionable pharmacogenes are interpreted, the benefit of ordering PGx testing increases (9).…”

Applying Next-Generation Sequencing Platforms for Pharmacogenomic Testing in Clinical Practice

“…Secondly, as mentioned previously, the evolutionary conservation is less applicable to the drug-related genes and therefore the conventional computational algorithms have low predictive accuracy when applied to the pharmacogenetic variants. The difficulties with novel and big data interpretation could be overcome by applying combined and optimized calculation tools and algorithms (at least 6-7 of such bioinformatics tools) for allele imputation (see Appendix 1 ) of PGx single- or multi-marker signatures, as well as confirming such genetic variants as predictive for the drug response with more accuracy ( Zhou et al, 2019 ; Tafazoli et al, 2021 ). However, not all pharmacogenes have this limitation.…”

“…Table 4 lists some databases which are useful in interpreting the results of the clinical PGx analysis. We have also recently reviewed the software and the algorithms dedicated to the functional prediction alongside the related mechanism of action in such tools while using the PGx functional analysis ( Tafazoli et al, 2021 ). After finding a potentially strong relationship between the identified variant(s) and the drug response, particular in-vitro assessments as well as cell line modifications may be considered for exploring the functional consequences of the altered alleles and diplotypes on the activity of the related protein.…”